МУЛЬТИСПЕЦИФИЧЕСКИЕ АНТИТЕЛА, АНАЛОГИ АНТИТЕЛ, КОМПОЗИЦИИ И СПОСОБЫ

Изобретение относится к области биотехнологии. Представлен способ синтеза панели мультиспецифических антител для терапии, диагностики или исследований, где проводят реакцию первого фрагмента антитела, имеющего первую моноспецифичность, полученного из первого исходного антитела, и обладающего свободной сульфгидрильной группой, с тио-реактивным кросслинкером для получения группы фрагмент антитела-кросслинкер и где проводят реакцию группы фрагмент антитела-кросслинкер попарно с каждым из трех или более дополнительных фрагментов антител, имеющих различную моноспецифичность, отличную от первого фрагмента антитела, каждый из которых имеет свободную сульфгидрильную группу, для получения панели мультиспецифических антител. Кроме того, также предложен способ синтеза панели аналогов антител для терапии, диагностики или исследований, где проводят реакцию первого фрагмента антитела, обладающего свободной сульфгидрильной группой, с тио-реактивным кросслинкером для получения группы фрагмент антитела-кросслинкер ...

МЫШИ ADAM6

Изобретение относится к области биотехнологии и генной инженерии. Предложены мыши со сниженной или отсутствующей активностью ADAM6, обеспечиваемой эндогенным локусом ADAM6, либо с отсутствующим эндогенным локусом, кодирующим белок ADAM6 мыши, отличающиеся тем, что у указанных мышей присутствует последовательность, кодирующая ADAM6, либо его ортолог, гомолог или фрагмент, функциональный у мышей-самцов. Согласно одному из вариантов реализации указанная последовательность представляет собой эктопическую последовательность ADAM6 или последовательность, придающую самцам мыши способность производить потомство посредством спаривания. Также предложены мыши и клетки с генетически модифицированными локусами тяжелой цепи иммуноглобулина, содержащими эктопическую последовательность нуклеотидов, кодирующую ADAM6 мыши, либо его функциональный фрагмент, гомолог или ортолог. Предложенное изобретение может быть использовано в иммунологии. 6 н. и 17 з.п. ф-лы, 41 ил., 13 табл., 11 пр.

АНТИТЕЛО ПРОТИВ МИТОХОНДРИАЛЬНОГО ИЗОФЕРМЕНТА АДЕНИЛАТКИНАЗЫ ЧЕЛОВЕКА, ДИАГНОСТИЧЕСКАЯ КОМПОЗИЦИЯ И ДИАГНОСТИЧЕСКИЙ НАБОР ДЛЯ ДИАГНОСТИКИ БОЛЕЗНЕЙ СЕРДЦА

Изобретение относится к области медицинской иммунологии, в частности к иммунологической композиции и набору для диагностики болезней сердца с использованием митохондриальных изоферментов аденилаткиназы человека. Сущность изобретения состоит в том, что в качестве маркера используют митохондриальные изоферменты аденилаткиназы человека из мышечных клеток, присутствующие в клетках миокарда. Эти маркеры позволяют более точно и легко диагностировать болезнь сердца. Технический результат - расширение арсенала средств для диагностики болезней сердца. 5 н. и 9 з.п. ф-лы, 20 ил., 5 табл.

ПРЕПАРАТЫ В ФОРМЕ РАСТВОРОВ, СОДЕРЖАЩИЕ АНТИТЕЛА

Изобретение относится к области медицины, а именно к производству лекарственных средств. Предложены препараты в форме стабилизированного раствора, содержащие антитело против рецептора интерлейкина-6 или НМ1.24, включающие сахарозу в качестве стабилизатора. Указанные препараты дополнительно могут включать поверхностно-активное вещество в качестве стабилизатора. Использование изобретения дает значимый эффект в предотвращении ассоциации молекул указанных антител при хранении растворов. 2 н. и 6 з.п. ф-лы, 18 табл.

КОМПОЗИЦИЯ ДЛЯ ИММУНИЗАЦИИ (ВАРИАНТЫ), СПОСОБ ЕЕ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЕ ДЛЯ ЛЕЧЕНИЯ АЛЛЕРГИЧЕСКИХ ЭОЗИНОФИЛЬНЫХ ЗАБОЛЕВАНИЙ

Изобретение относится к областям молекулярной биологии, вирусологии, иммунологии и медицины. Композиция содержит вирусоподобную частицу и по меньшей мере один связанный с ней белок или пептид IL-5, IL-13 или человеческого эотоксина. Также раскрыты способ ее получения и применения, фармацевтическая композиция и композиции вакцины, содержащие такую композицию. Композиции применимы для получения вакцин для лечения аллергических заболеваний с эозинофильным компонентом. Кроме того, композиции особенно применимы для эффективной индукции специфичных для аутоантигенов иммунных ответов. Изобретение может быть использовано в медицине. 9 н. и 31 з.п. ф-лы, 12 ил., 1 табл.

НОВЫЕ МОДУЛЯТОРЫ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

Изобретение относится к биохимии. Представлено химерное, CDR-привитое, гуманизированное или рекомбинантное человеческое антитело или его фрагмент, который специфически связывается с человеческим EFNA4. Также представлен конъюгат указанного антитела с цитотоксическим агентом. Представлена фармацевтическая композиция и способ лечения EFNA4-ассоциированного расстройства. Изобретение расширяет арсенал средств борьбы с EFNA4-ассоциированными расстройствами. 10 н. и 41 з.п. ф-лы, 20 ил., 5 табл., 20 пр.

АНТИТЕЛА ЧЕЛОВЕКА К PCSK9 ДЛЯ ПРИМЕНЕНИЯ В СПОСОБАХ ЛЕЧЕНИЯ КОНКРЕТНЫХ ГРУПП ИНДИВИДУУМОВ

Настоящая группа изобретений относится к медицине, а именно к терапии, и касается лечения заболеваний, опосредованных экспрессией конвертазы пробелков типа субтилизина/кексина 9 (PCSK9). Для этого вводят фармацевтическую композицию, содержащую антитело, которое специфически связывается с пропротеином конвертазы hPCSK9, или его антигенсвязывающий фрагмент. Фармацевтическая композиция содержит указанное антитело в фиксированных дозах – 75, 150 или 300 мг. Введение композиции осуществляют раз в две или четыре недели. Такой режим введения обеспечивает эффективное лечение указанных заболеваний или патологических состояний при минимальных побочных эффектах. 4 н. и 20 з.п. ф-лы, 6 ил., 2 табл., 4 пр.

КОМПОЗИЦИИ И СПОСОБЫ ИММУНОТЕРАПИИ

Настоящее изобретение относится к иммунологии. Предложена Т-клетка для снижения опухолевой нагрузки и/или лечения неоплазии, содержащая T-клеточный рецептор (TCR) или химерный рецептор антигена (CAR), который связывается с антигеном В-клеточного лейкоза, и ингибирующий химерный рецептор антигена (iCAR), который содержит домен внутриклеточной передачи сигнала CTLA-4 или PD-1. Кроме того, описано применение такой Т-клетки для снижения опухолевой нагрузки и/или размера опухоли и фармацевтическая композиция. Также представлены вектор, композиция и способ получения Т-клетки. Использование iCAR позволяет снизить цитотоксичность Т-клетки в отношении клеток ненеопластической ткани. 8 н. и 10 з.п. ф-лы, 23 ил., 1 пр.

САЙТ-СПЕЦИФИЧЕСКАЯ КОНЪЮГАЦИЯ АНТИТЕЛО-ЛЕКАРСТВЕННОЕ СРЕДСТВО ПОСРЕДСТВОМ ГЛИКОИНЖЕНЕРИИ

Изобретение относится к области биотехнологии. Описана группа изобретений, включающая конъюгат антитела или его антигенсвязывающего фрагмента и цитотоксина для доставки цитотоксина субъекту (варианты), композицию для терапевтического применения, содержащую вышеуказанный конъюгат, способ лечения нуждающегося в этом пациента, включающий введение эффективного количества композиции, выделенный полинуклеотид, кодирующий антитело для получения вышеуказанного конъюгата, вектор экспрессии, клетку-хозяина для продуцирования вышеуказанного конъюгата, способ получения конъюгата, конъюгат антитело-лекарственное средство для доставки группы лекарственного средства субъекту. В одном из вариантов реализации конъюгат антитела или его антигенсвязывающего фрагмента и цитотоксина содержит по меньшей мере один гликан, содержащий по меньшей мере одну группу формулы -Gal-Sia-C(H)=N-Q-CON-X. Изобретение расширяет арсенал средств для доставки цитотоксинов субъекту. 13 н. и 29 з.п. ф-лы, 36 ил., 16 табл., 15 пр ...

РЕКОМБИНАНТНЫЙ ВЕКТОР, ЭКСПРЕССИРУЮЩИЙ ПОЛИПЕПТИД С АКТИВНОСТЬЮ ГЛЮКОЗООКСИДАЗЫ, ТРАНСФОРМИРОВАННЫЙ ШТАММ SACCHAROMYCES CEREVISIAE, РЕКОМБИНАНТНЫЙ ПОЛИПЕПТИД С АКТИВНОСТЬЮ ГЛЮКОЗООКСИДАЗЫ И СПОСОБ ЕГО ПОЛУЧЕНИЯ

Изобретение относится к биотехнологии и может быть использовано для получения глюкозооксидазы. Рекомбинантный вектор для экспрессии полипептида с активностью глюкозооксидазы (ГО) содержит нуклеотидную последовательность, кодирующую полипептид или его мутеин, имеющий Ser в положении Cys у аминокислотного остатка 521, и оперативно связанные регуляторные последовательности. Сконструированным вектором трансформируют клетки, в частности клетки Saccharomyces cerevisiae. Рекомбинантный полипептид с активностью ГО получают путем культивирования трансформированных клеток. Изобретение позволяет получать глюкозооксидазу из грибов рекомбинантным путем. 4 с. и 6 з.п. ф-лы, 17 ил., 5 табл.

АНТИТЕЛО, БЛОКИРУЮЩЕЕ AGR2, И ЕГО ПРИМЕНЕНИЕ

Изобретение относится к области биотехнологии и иммунологии. Описано блокирующее AGR2 моноклональное антитело и, в частности, гуманизированное моноклональное антитело для блокирования AGR2. Также описаны фармацевтическая композиция, содержащая антитело, способ ее получения и применение антитела для блокирования роста и метастазирования опухоли. Предложенная группа изобретений может быть использована в медицине. 7 н. и 13 з.п. ф-лы, 28 ил., 11 пр.

ГУМАНИЗИРОВАННЫЕ АНТИТЕЛА ПРОТИВ AXL

Изобретение относится к биохимии. Описано моноклональное гуманизированное антитело, которое специфически связывается с внеклеточным доменом рецепторной тирозинкиназы AXL и которое, по меньшей мере, частично ингибирует активность AXL. Представлена молекула нуклеиновой кислоты, кодирующая описанное антитело. Также представлен экспрессионный вектор и клетка-хозяин. Раскрыт способ производства описанного антитела. Также раскрыта фармацевтическая композиция, содержащая описанное антитело. Описан способ диагностики состояния здоровья, связанного с экспрессией AXL. Раскрыто применение описанного антитела для лечения рака, устойчивого к лекарствам. Изобретение расширяет арсенал лекарственных средств, в частности, применяемых для терапии рака. 13 н. и 4 з.п. ф-лы, 39 ил., 2 табл., 29 пр.

АНТИТЕЛА С РН-ЗАВИСИМЫМ СВЯЗЫВАНИЕМ АНТИГЕНА

Группа изобретений относится к области медицины и фармакологии и касается выделенного антитела, которое специфически связывает человеческий PCSK9, содержащее: гипервариабельный участок вариабельной области тяжелой цепи 1 (VH CDR1) с аминокислотной последовательностью, показанной в SEQ ID NO: 6; VH CDR2 с аминокислотной последовательностью, показанной в SEQ ID NO: 7; VH CDR3 с аминокислотной последовательностью, показанной в SEQ ID NO: 8 или 9, и дополнительно содержащее: CDR1 вариабельной области легкой цепи (VL) с аминокислотной последовательностью, показанной в SEQ ID NO: 10; VL CDR2 с аминокислотной последовательностью, показанной в SEQ ID NO: 11; и VL CDR3 с аминокислотной последовательностью, показанной в SEQ ID NO: 12, а также антитела, кодируемого плазмидами, депонированными в Американской коллекции типовых культур (АТСС) и имеющими номер в АТСС No. РТА-10547 или РТА-10548 и РТА-10549, где указанное антитело специфически связывает человеческий PCSK9, и способа снижения уровня холестерина ...

СПОСОБЫ И КОМПОЗИЦИИ ДЛЯ МОДУЛЯЦИИ ГЕПСИНОМ СТИМУЛИРУЮЩЕГО МАКРОФАГИ БЕЛКА

Изобретение относится к биохимии. Представлен способ идентификации вещества-кандидата, ингибирующего активацию гепсином стимулирующего макрофаги пробелка (про-MSP). 9 з.п. ф-лы, 10 ил., 1 табл., 1 пр.

АНТИТЕЛО, КОТОРОЕ РАСПОЗНАЕТ ПЕПТИД Т14 АСНЕ

Изобретение относится к области биохимии, в частности к антителу или его антигенсвязывающему фрагменту, которое специфически связывается с полипептидом Т14. Также раскрыты набор для диагностики субъекта, страдающего нейродегенеративным расстройством, содержащее указанное антитело, а также способ диагностики субъекта, страдающего нейродегенеративным расстройством, с помощью указанного антитела. Изобретение позволяет эффективно диагностировать нейродегенеративное расстройство. 3 н. и 12 з.п. ф-лы, 25 ил., 3 табл., 9 пр.

СПОСОБ ЛЕЧЕНИЯ ДИССЕМИНИРОВАННОГО ВНУТРИСОСУДИСТОГО СВЕРТЫВАНИЯ КРОВИ ПУТЕМ ИНГИБИРОВАНИЯ MASP-2 ЗАВИСИМОЙ АКТИВАЦИИ КОМПЛЕМЕНТА

Настоящее изобретение относится к биохимии, в частности к применению композиции, содержащей агент, ингибирующий MASP-2, в количестве, эффективном для ингибирования или предупреждения образования бляшек в сосудистой системе пациента, для приготовления лекарственного средства для лечения указанного пациента, страдающего или подверженного риску развития комплемент-опосредованного нарушения свертывания крови, такого как диссеминированное внутрисосудистое свертывание крови (ДВС). Настоящее изобретение также раскрывает применение указанной композиции в производстве лекарственного средства для лечения или профилактики инфекции менингококка Neisseria meningitidis у пациента. Настоящее изобретение также раскрывает способ лечения комплемент-опосредованного нарушения свертывания крови и способ лечения или профилактики инфекции менингококка Neisseria meningitidis у пациента. Настоящее изобретение раскрывает новые применения агента, ингибирующего MASP-2, и позволяет расширить арсенал средств для лечения ...

ПРИМЕНЕНИЕ ИНГИБИТОРОВ VAP-1 ДЛЯ ЛЕЧЕНИЯ ФИБРОЗНЫХ БОЛЕЗНЕЙ

Настоящее изобретение относится к способу лечения фиброзных болезней у человека, включающему введение указанному пациенту эффективного количества ингибитора VAP-1, в котором указанный ингибитор VAP-1 выбран из группы, состоящей из анти-VAP-1-антител и ингибиторов SSAO, где указанный ингибитор SSAO выбран из производных гидразина, производных 4,5,6,7-тетрагидроимидазо[4,5-с]пиридина, тиокарбамоильных производных, карбоксамидов, сульфонамидов, тиазолов, включающих производные гуанидина, оксимных производных, дигидразина, арилалкиламинов, оксазолидинонов, галогеналкиламинов, производных бенфотиамина и производных имидазопиридина. Заявленное изобретение эффективно в лечении фиброзных болезней. 4 з.п. ф-лы, 19 ил., 7 табл., 8 пр.

ГУМАНИЗИРОВАННЫЕ АНТИТЕЛА К ФАКТОРУ D И ИХ ПРИМЕНЕНИЯ

Группа изобретений относится к иммунологии. Предложены гуманизированное моноклональное антитело к фактору D человека или его антигенсвязывающий фрагмент, его нуклеотидная последовательность, клетка и вектор, которые несут эти антитела, способ его получения и применение для получения композиций для лечения заболеваний и нарушений, ассоциированных с избыточной или неконтролируемой активацией системы комплемента. Антитело к фактору D или его антигенсвязывающий фрагмент содержит (i) вариабельный домен легкой цепи, содержащий аминокислотную последовательность с по меньшей мере 97% идентичности с SEQ ID NO:5, и вариабельный домен тяжелой цепи, содержащий аминокислотную последовательность с по меньшей мере 97% идентичности с SEQ ID NO: 6; или (ii) вариабельный домен легкой цепи, содержащий аминокислотную последовательность с по меньшей мере 97% идентичности с SEQ ID NO:7, и вариабельный домен тяжелой цепи, содержащий аминокислотную последовательность с по меньшей мере 97% идентичности с SEQ ID ...

АНТИТЕЛА И СОДЕРЖАЩИЕ ИХ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ, ПОДХОДЯЩИЕ ДЛЯ ИНГИБИРОВАНИЯ АКТИВНОСТИ МЕТАЛЛОПРОТЕИНОВ

Настоящее изобретение относится к соединению, имеющему общую формулу (I):где m и n являются независимо целыми числами от 1 до 6; каждый из X-Xи Y-Yявляется О; R-Rкаждый независимо выбирают из группы, состоящей из водорода или алкила; и R является O-(CH)x-C(=O)NR'-(CH)y-NHR', причем: x и y каждый являются независимо целыми числами от 1 до 6; и R' выбирают из группы, состоящей из водорода и алкила. Также предложены антитело, содержащее область распознавания антигена, использование соединения, фармацевтическая композиция, применение антитела, способ ингибирования активности ММП-2 или ММП-9 в пробе и композиция для определения ММП-2 или ММП-9. Изобретение позволяет получить соединения, способные ингибировать активность ММП-2 и ММП-9. 7 н. и 4 з.п. ф-лы, 16 ил., 4 табл., 11 пр.

PCSK9 ВАКЦИНЫ

Изобретение относится к области биотехнологии, конкретно к вакцине против пропротеиновой конвертазы субтилизин-кексинового типа 9 (PCSK9), и может быть использовано в медицине для лечения или предотвращения заболеваний, связанных с PCSK9, выбранных из гиперлипидемии, гиперхолестеринемии, атеросклероза или неопластических болезней. Конъюгат варианта фрагмента PCSK9 с SEQ ID NO:1 с иммуногенным белковым носителем может быть использован в составе вакцины для усиленной индукции образования антител к PCSK9, по сравнению с конъюгатом фрагмента природного PCSK9. 4 н. и 3 з.п. ф-лы, 6 ил., 2 табл., 1 пр.

СПОСОБ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С MASP-2-ЗАВИСИМОЙ АКТИВАЦИЕЙ КОМПЛЕМЕНТА (ВАРИАНТЫ)

Изобретение относится к области биотехнологии, конкретно к способам ингибирования последствий MASP-2-зависимой активации комплемента, и может быть использовано в медицине. В качестве лекарственного средства для ингибирования MASP-2-зависимой активации комплемента применяют агент, включающий антитело или его фрагмент, связывающийся с полноразмерным полипептидом MASP-2, но не связывающийся с MASP-2 N-терминальным фрагментом, состоящим из CUBI-EGF-CUBII доменов, и не связывающийся с MASP-2 С-терминальным фрагментом, состоящим из CCPII-SP доменов. Изобретение позволяет выборочно ингибировать MASP-2-зависимую активацию комплемента, при этом оставляя функционально незатронутым Clq-зависимый классический путь активации комплемента. 4 н. и 5 з.п. ф-лы, 39 ил., 7 табл., 31 пр.

ОДНОДОМЕННЫЕ АНТИТЕЛА, НАПРАВЛЕННЫЕ ПРОТИВ ФАКТОРА НЕКРОЗА ОПУХОЛЕЙ АЛЬФА, И ИХ ПРИМЕНЕНИЕ

Настоящее изобретение относится к иммунологии. Предложена полипептидная конструкция, способная специфически связывать фактор некроза опухолей альфа (TNF-альфа), содержащая два-четыре антагонистических однодоменных антитела, направленных против TNF-альфа, и одно однодоменное антитело, направленное против сывороточного белка. Кроме того, рассмотрена содержащая ее композиция и кодирующая нуклеиновая кислота. Данное изобретение может найти применение в терапии расстройств, связанных с воспалительными процессами или аутоиммунными заболеваниями. 3 н. и 9 з.п. ф-лы, 18 ил., 11 табл., 9 пр.

НОВЫЕ АНТИТЕЛА К ТКАНЕВОМУ ФАКТОРУ В КАЧЕСТВЕ АНТИКОАГУЛЯНТОВ

Настоящее изобретение относится к биотехнологии. Описано антикоагулирующее антитело, которое связывается с большей аффинностью с комплексом FVIIa/ТФ, чем со свободным ТФ. Раскрыта фармацевтическая композиция для предупреждения и лечения тромбоза, содержащая описанное антитело. Предложен способ предупреждения образования тромба, заключающийся в том, что вводят терапевтически эффективное количество описанного антитела. Также предложен способ снижения и лечения тромбоза глубоких вен (ТГВ), диссеминированного внутрисосудистого свертывания крови (ДВС), острого коронарного тромбоза или рака с признаками коагулопатии у пациента, заключающийся в том, что пациенту вводят терапевтически эффективное количество описанного антитела. Раскрыт способ регуляции воспалительного ответа у пациента, заключающийся в том, что пациенту вводят терапевтически эффективное количество описанного антитела. Представлена полинуклеотидная последовательность, кодирующая описанное антитело. Настоящее изобретение позволяет ...

МОНОКЛОНАЛЬНОЕ АНТИТЕЛО, ИНГИБИРУЮЩЕЕ ФЕРМЕНТАТИВНУЮ АКТИВНОСТЬ СОСУДИСТОЙ ЭНДОТЕЛИАЛЬНОЙ ЛИПАЗЫ

Изобретение относится к области биохимии, в частности к моноклональному антителу к сосудистой эндотелиальной липазе человека или его антигенсвязывающему фрагменту, а также к фармацевтической композиции, содержащей его. Изобретение позволяет эффективно осуществлять лечение или профилактику дислипидемии или атеросклероза. 2 н. и 1 з.п. ф-лы, 7 ил., 6 табл., 14 пр.

СИНТЕТИЧЕСКАЯ ЛЕТАЛЬНОСТЬ И ЛЕЧЕНИЕ РАКА

Настоящая группа изобретений относится к медицине, а именно к онкологии, и касается лечения рака. Для этого субъекту со снижением или отсутствием N-миристоилтрансферазы 2 (NMT2) вводят эффективное количество ингибитора NMT. Это обеспечивает эффективное лечение данной формы рака. 5 н. и 56 з.п. ф-лы, 6 ил., 7 пр., 1 табл.

PSCAXCD3, CD19XCD3, C-METXCD3, ЭНДОСИАЛИНXCD3, EPCAMXCD3, IGF-1RXCD3 ИЛИ FAP-АЛЬФАXCD3 БИСПЕЦИФИЧЕСКОЕ ОДНОЦЕПОЧЕЧНОЕ АНТИТЕЛО С МЕЖВИДОВОЙ СПЕЦИФИЧНОСТЬЮ

Настоящее изобретение относится к области иммунологии. Предложена молекула биспецифического одноцепочечного антитела, содержащая первый связывающий домен, способный связываться с эпитопом CD3-эпсилон-цепи человека и Callithrix jacchus (игрунка), Saguinus oedipus (эдипов тамарин) и Saimiri sciureus (беличья обезьяна), и второй связывающий домен, способный связываться с антигеном, выбранным из группы, состоящей из: PSCA, CD19, С-МЕТ, эндосиалина, EGF-подобного домена 1 ЕрСАМ, кодируемого экзоном 2, FAP-альфа или IGF-IR (или IGF-1R) человека и/или примата. Эпитоп СD3ε включает аминокислотную последовательность, раскрытую в описании. Раскрыта нуклеиновая кислота, кодирующая указанную молекулу биспецифического одноцепочечного антитела, экспрессирующий вектор, клетка-хозяин и способ получения антитела, а также полученное способом антитело. Описывается фармацевтическая композиция, содержащая молекулу биспецифического одноцепочечного антитела и способ предупреждения, лечения или ослабления рака ...

САЙТ-СПЕЦИФИЧНАЯ КОНЪЮГАЦИЯ ЛИНКЕРНЫХ ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ С АНТИТЕЛАМИ И ПОЛУЧАЕМЫЕ В РЕЗУЛЬТАТЕ ADC

Изобретение относится к области биотехнологии. Описана группа изобретений, включающая соединение конъюгат антитело-лекарственное средство для лечения солидных опухолей и гематологических злокачественных образований и фармацевтическая композиция для лечения солидных опухолей и гематологических злокачественных образований. В одном из вариантов реализации соединение конъюгат антитело-лекарственное средство содержит в себе лекарственное средство, конъюгированное при помощи линкера сайт-специфичным образом с антителом или его антигенсвязывающим фрагментом, которые связываются с антигеном-мишенью, экспрессируемым опухолевой клеткой, через встроенный цистеин в указанном антителе или его антигенсвязывающем фрагменте в положении 40 или 41 легкой цепи согласно нумерации Kabat. Изобретение расширяет арсенал средств для лечения солидных опухолей и гематологических злокачественных образований. 2 н. и 11 з.п. ф-лы, 4 ил., 7 табл., 1 пр.

ММР13-СВЯЗЫВАЮЩИЕ ИММУНОГЛОБУЛИНЫ

Настоящее изобретение относится к области биотехнологии, конкретно к иммуноглобулинам, которые специфически связываются с матриксной металлопротеиназой 13 (MMP13), и может быть использовано в медицине для лечения и профилактики заболеваний или расстройств у индивидуума, которые связаны с активностью MMP13. Предложенные полипептиды, включающие по меньшей мере 1 одиночный вариабельный домен иммуноглобулина (ISVD), связывающийся с матриксной металлопротеиназой 13, являются антагонистами MMP13 с улучшенными профилактическими, терапевтическими и/или фармакологическими свойствами, включая более безопасный профиль по сравнению со сравнительными молекулами. 3 н. и 42 з.п. ф-лы, 4 ил., 28 табл., 6 пр.

АНТАГОНИСТЫ ALK1 И ИХ ПРИМЕНЕНИЕ В ЛЕЧЕНИИ ПОЧЕЧНО-КЛЕТОЧНОЙ КАРЦИНОМЫ

Изобретение относится к медицине, а именно к онкологии, и может быть использовано для лечения почечно-клеточной карциномы (ПКК). Способ по изобретению включает введение млекопитающему с ПКК эффективного количества сунитиниба и полипептида ALK1, содержащего лиганд-связывающую часть внеклеточного домена ALK1. Использование изобретения позволяет замедлить рост опухоли и усилить активность сунитиниба. 9 з.п. ф-лы, 20 ил., 15 пр.

БЕЛКИ, СВЯЗЫВАЮЩИЕ СПЕЦИФИЧЕСКИЙ МЕМБРАННЫЙ АНТИГЕН ПРОСТАТЫ, И СООТВЕТСТВУЮЩИЕ КОМПОЗИЦИИ И СПОСОБЫ

Изобретение относится к области биотехнологии, конкретно к биспецифическим связывающим полипептидным терапевтическим средствам, специфично нацеленным на клетки, экспрессирующие специфический мембранный антиген простаты (ПСМА), что может быть использовано в медицине. Полученный полипептид, а также его димер и композиции их содержащие используют в составе фармацевтических композиций для лечения рака предстательной железы и кастрационно-резистентного рака предстательной железы. Изобретение позволяет связываться и с ПСМА-экспрессирующими клетками, и с Т-клеточным рецепторным комплексом на Т-клетках, индуцируя мишенезависимую Т-клеточную цитотоксичность, активацию и пролиферацию, что обеспечивает эффективную противоопухолевую терапию. 9 н. и 17 з.п. ф-лы, 8 ил., 3 табл., 9 пр.

ПРОФИЛАКТИКА И ЛЕЧЕНИЕ ПАТОЛОГИЧЕСКИХ СОСТОЯНИЙ ГЛАЗ, ВЫЗВАННЫХ КОМПЛЕМЕНТОМ

Настоящее изобретение относится к области иммунологии и медицины. Предложен способ профилактики или лечения состояния глаза, связанного с высокой экспрессией или активностью фактора комплемента D, включающий введение субъекту антитела или его антигенсвязывающего фрагмента. Рассмотрено антитело 20D12 против фактора D и его антигенсвязывающий фрагмент, их применение для получения лекарственного средства, а также содержащий такое антитело или его антигенсвязывающий фрагмент набор для лечения состояния глаз, связанного с высокой активностью или экспрессией фактора D. Данное изобретение может найти дальнейшее применение в терапии заболеваний, связанных с системой комплемента. 4 н. и 10 з.п. ф-лы, 6 ил., 3 табл.

КОНЪЮГАТЫ АНТИ-РТК7 АНТИТЕЛО-ЛЕКАРСТВЕННОЕ СРЕДСТВО

Изобретение относится к области биохимии, в частности к конъюгату антитело-лекарственное средство для доставки лекарственного средства в PTK7-экспрессирующие клетки, его применению в изготовлении лекарственного средства для лечения расстройства, ассоциированного с экспрессией PTK7, а также к способу его получения. Также раскрыта композиция для доставки лекарственного средства в PTK7-экспрессирующие клетки, содержащая эффективное количество вышеуказанного конъюгата. Изобретение также относится к способу лечения расстройства, ассоциированного с экспрессией PTK7, включающему введение субъекту вышеуказанного конъюгата антитело-лекарственное средство. Изобретение позволяет эффективно осуществлять доставку лекарственного средства в PTK7-экспрессирующие клетки. 6 н. и 20 з.п. ф-лы, 23 ил., 38 табл., 16 пр.

РЕГУЛЯТОРЫ ММР-9 И ИХ ПРИМЕНЕНИЕ

Изобретение относится к медицине и касается способа идентификации агента для лечения рака и воспалительных заболеваний, заключающегося в определении способности агента взаимодействовать с OG-доменом ММР-9, где упомянутый агент является предполагаемым понижающим регулятором коллагенолитической активности ММР, и определении способности указанного агента понижающе регулировать коллагенолитическую активность ММР-9. Изобретение обеспечивает снижение коллагенолитической активности ММР-9. 2 н. и 8 з.п. ф-лы, 7 пр., 7 ил., 2 табл.

СПОСОБ ВЫДЕЛЕНИЯ И ОЧИСТКИ ЦЕЛЕВОГО БЕЛКА БЕЗ ПРИМЕСИ ПРИОНОВОГО БЕЛКА PrP

Группа изобретений относится к области биохимии. Предложен способ выделения и очистки целевого белка посредством хроматографии, в котором хроматография удаляет или уменьшает содержание прионов (PrP). Осуществляют взаимодействие потенциально PrP-загрязненного образца, содержащего целевой белок, с комбинированным хроматографическим материалом, содержащим лиганд. Лиганд выбирают из положительно заряженного N-бензил-N-метилэтаноламинового лиганда; отрицательно заряженного лиганда 2-(бензоиламино)бутановой кислоты; фенилпропилового лиганда; N-гексилового лиганда; 4-меркаптоэтилпиридинового лиганда; лиганда 3-[{3-метил-5-((тетрагидрофуран-2-илметил)амино)-фенил}амино]бензойной кислоты. Затем создают буферные условия в хроматографических условиях, таких, чтобы целевой белок связывался с комбинированным хроматографическим материалом, а PrPне связывался с комбинированным хроматографическим материалом. Затем элюируют целевой белок. Также предложена фракция фармацевтически применимого целевого белка ...

НОВЫЕ ЛЮЦИФЕРАЗЫ И СПОСОБЫ ИХ ИСПОЛЬЗОВАНИЯ

Группа изобретений относится к биохимии. Предложена нуклеиновая кислота, кодирующая люциферазу или ее функциональный фрагмент и выбранная из группы, состоящей из нуклеиновой кислоты, кодирующей белок, характеризующийся аминокислотной последовательностью, представленной в SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 или 34, нуклеиновой кислоты, кодирующей белок, имеющий последовательность, которая по крайней мере на 65% идентична аминокислотной последовательности, представленной в SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 или 34, и нуклеиновой кислоты, кодирующей белок, в состав которого входит консенсусная последовательность SEQ ID NO: 35. Предложены также люцифераза или ее функциональный фрагмент, кодируемые указанной нуклеиновой кислотой. Также предложены экспрессионная кассета, клетка-хозяин, трансгенный организм, содержащие указанные молекулы нуклеиновых кислот. Кроме того, предложены набор для мечения организмов и способ мечения ...

ОДНОДОМЕННЫЕ АНТИТЕЛА, НАПРАВЛЕННЫЕ ПРОТИВ ВНУТРИКЛЕТОЧНЫХ АНТИГЕНОВ

Изобретение относится к области биохимии, в частности к однодоменному антителу sdAb к арахидонат-12-липоксигеназе ALOX12, способному специфически связываться с антигеном ALOX12. Также раскрыто применение вышеуказанного антитела для лечения заболевания, опосредованного ALOX12, для предотвращения развития заболевания, опосредованного ALOX12, а также для предотвращения рецидива заболевания, опосредованного ALOX12. Изобретение также относится к выделенному полипептиду, способному специфически связываться с антигеном ALOX12. Изобретение позволяет эффективно осуществлять лечение заболевания, опосредованного ALOX12 у субъекта. 5 н. и 12 з.п. ф-лы, 10 ил., 4 табл., 5 пр.

СПОСОБЫ ЛЕЧЕНИЯ СОСТОЯНИЙ, СВЯЗАННЫХ С MASP-2 ЗАВИСИМОЙ АКТИВАЦИЕЙ КОМПЛЕМЕНТА

Изобретение относится к медицине, а именно к иммунологии, и может быть использовано при лечении атипичного гемолитического уремического синдрома (aHUS). Применение по изобретению включает введение MASP-2-ингибирующего агента, представляющего собой ингибирующее моноклональное антитело против MASP-2 или его антигенсвязывающий фрагмент, которые специфически связываются с MASP-2 человека, представленной как SEQ ID NO:6, и селективно ингибируют MASP-2-зависимую активацию комплемента без ингибирования C1q-зависимого пути комплемента. Использование изобретения позволяет уменьшить проявления симптомов анемии, тромбоцитопении, почечной недостаточности и увеличивающегося креатинина. 10 з.п. ф-лы, 15 табл., 36 пр., 45 ил.

АНТИТЕЛА ПРОТИВ НtrА1 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

Изобретение относится к области биохимии, в частности к антителу или его антигенсвязывающему фрагменту, которое специфически связывает HtrA1. Раскрыты нуклеиновая кислота, кодирующая указанное антитело, фармацевтическая композиция, содержащая указанное антитело. Также раскрыты способ получения указанного антитела, комбинированная терапия с применением указанного антитела, применение указанного антитела в производстве лекарственного средства. Изобретение позволяет эффективно лечить заболевания, ассоциированные с HtrA1. 9 н. и 34 з.п. ф-лы, 32 ил., 14 табл., 5 пр.

СРЕДСТВО, ОБЛАДАЮЩЕЕ АНАЛЬГЕТИЧЕСКОЙ АКТИВНОСТЬЮ

Изобретение касается применения протеина С или активированного протеина С в качестве средства, обладающего анальгетической активностью. Препарат пригоден для лечения болезненных состояний, которые вызываются острыми или хроническими воспалительными процессами (ревматоидный артрит, миозит, гастрит, колит, воспаления в мочеполовом тракте). 3 табл.

МУЛЬТИСПЕЦИФИЧЕСКАЯ СВЯЗЫВАЮЩАЯ АНТИГЕН МОЛЕКУЛА, КОТОРАЯ ОБЛАДАЕТ АЛЬТЕРНАТИВНОЙ ФУНКЦИЕЙ К ФУНКЦИИ ФАКТОРА СВЕРТЫВАНИЯ КРОВИ VIII

Настоящее изобретение относится к области биохимии. Предложено биспецифическое антитело, которое связывается как с фактором свертывания крови IX/активированным фактором свертывания крови IX, так и с фактором свертывания крови X, и функционально заменяет функцию фактора свертывания крови VIII. Рассмотрены нуклеиновая кислота, кодирующая антитело по изобретению, вектор, клетка и способ получения антитела, а также фармацевтическая композиция и набор для применения в способе предупреждения и/или лечения кровотечения или болезней, связанных или вызванных кровотечением. Данное изобретение может найти дальнейшее применение в терапии заболеваний, связанных с нарушением свертывания крови. 8 н. и 8 з.п. ф-лы, 2 пр., 6 ил.

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ АНТИТЕЛО, СПЕЦИФИЧНО СВЯЗЫВАЮЩЕЕСЯ С N-КОНЦОМ ЛИЗИЛ-тРНК-СИНТЕТАЗЫ, В КАЧЕСТВЕ ЭФФЕКТИВНОГО ИНГРЕДИЕНТА ДЛЯ ПРОФИЛАКТИКИ ИЛИ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЯ, ОБУСЛОВЛЕННОГО МИГРАЦИЕЙ КЛЕТОК

Группа изобретений относится к области медицины и фармацевтики. Первый объект представляет собой фармацевтическую композицию, содержащую эффективное количество антитела или его функционального фрагмента, специфично связывающихся с N-концом лизил-тРНК-синтетазы (KRS), для профилактики или лечения заболевания, связанного с миграцией иммунных клеток, выбранного из группы, состоящей из сердечно-сосудистого заболевания, фиброзного заболевания, воспалительного заболевания и синдрома Альпорта, где антитело содержит: (a) вариабельную область тяжелой цепи, включающую CDR1, содержащую последовательность SYDMS; CDR2, содержащую последовательность X1IX2X3X4X5GX6X7YYADSVKG, и где X1представляет собой A или V, X2– S, D или G, X3– Y, P, S или A, X4– D, Q, L или Y, X5– N, M, S или G, X6– N, R или P, X7– T, V, I или S; и CDR3, содержащую последовательность X8ALDFDY, где X8представляет собой M или L, и (b) вариабельную область легкой цепи, включающую CDR1, содержащую последовательность TGSSSNIGSNYVT; CDR2 ...

АНТАГОНИСТЫ PCSK9

... 1. Водный состав, содержащий:от около 1 мг/мл до около 200 мг/мл антитела-антагониста, которое специфически связывается с PCSK9, содержащим аминокислотную последовательность с номером доступа Q8NBP7 в Uniрrot;от около 1 мM до около 100 мM буфера;от около 0,01 мг/мл до около 10 мг/мл поверхностно-активного вещества; иот около 100 мM до около 400 мM стабилизатора;где состав имеет pH от около 5,0 до около 6,5.2. Водный состав, содержащий:от около 1 мг/мл до около 200 мг/мл антитела-антагониста, которое специфически связывается с PCSK9, содержащим аминокислотную последовательность с номером доступа Q8NBP7 в Uniрrot;от около 1 мM до около 100 мM буфера;от около 0,01 мг/мл до около 10 мг/мл поверхностно-активного вещества;от около 100 мM до около 400 мM стабилизатора; иот около 0,01 мM до около 1,0 мM хелатообразующего агента;где состав имеет pH от около 5,0 до около 6,5.3. Состав по п. 1 или 2, где антитело содержит первую определяющую комплементарность область (CDR1) вариабельной области тяжелой ...

КОМПОЗИЦИИ ДЛЯ АНТИФИБРИНОЛИТИЧЕСКОГО ЛЕЧЕНИЯ

... 1. Применение нейтрализующего антитела к матриксной металлопротеиназе-10 (ММР-10) для приготовления лекарственного средства, которое можно применять для антифибринолитического лечения. ! 2. Применение по п.1 для приготовления лекарственного средства, которое можно применять для лечения кровотечений и геморрагических осложнений. ! 3. Применение по п.2 для приготовления лекарственного средства, предназначенного для лечения кровотечений и геморрагических осложнений у пациентов с гиперфибринолитическими состояниями, обусловленными врожденными патологиями. ! 4. Применение по п.2 для приготовления лекарственного средства, предназначенного для лечения кровотечений и геморрагических осложнений у пациентов, подвергающихся лечению с помощью антикоагулянтов. ! 5. Применение по п.2 для приготовления лекарственного средства, предназначенного для лечения кровотечений и геморрагических осложнений у пациентов с диссеминированным внутрисосудистым свертыванием крови. ! 6. Применение по п.2 для приготовления ...

НОВЫЕ ПОЛНОСТЬЮ ЧЕЛОВЕЧЕСКИЕ МОНОКЛОНАЛЬНЫЕ АНТИТЕЛА ПРОТИВ VAP-1

... 1. Полипептид тяжелой цепи антитела против VAP-1, отличающийся тем, что является полностью человеческим. ! 2. Полипептид по п.1, содержащий по меньшей мере одну аминокислотную последовательность CDR, выбранную из ! первой группы, состоящей из SEQ ID NO: с 4 по 8 и консервативных вариантов их последовательностей, и/или ! второй группы, состоящей из SEQ ID NO: с 9 по 13 и консервативных вариантов их последовательностей, и/или !третьей группы, состоящей из SEQ ID NO: с 14 по 18 и консервативных вариантов их последовательностей. ! 3. Полипептид по п.2, содержащий аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: с 19 по 23 и консервативных вариантов их последовательностей. ! 4. Полипептид по п.3, содержащий аминокислотную последовательность, описанную в SEQ ID NO:47 или консервативный вариант ее последовательности. ! 5. Полипептид легкой цепи антитела против VAP-1, отличающийся тем, что является полностью человеческим. ! 6. Полипептид по п.5, содержащий по меньшей ...

МОНОКЛОНАЛЬНЫЕ АНТИТЕЛА ПРОТИВ АКТИВИРОВАННОГО ПРОТЕИНА С

... 1. Моноклональное антитело, где указанное антитело связывается с активированным протеином C и ингибирует антикоагулянтную активность, но не связывается или не ингибирует активацию неактивированного протеина С. ! 2. Моноклональное антитело по п.1, где указанное связывание с активированным протеином С происходит в активном центре активированного протеина C, и не ингибирует цитопротективных эффектов активированного протеина C. ! 3. Моноклональное антитело по п.1, дополнительно обозначенное далее как HAPC1573. ! 4. Моноклональное антитело по п.1, где указанное ингибирование активированного или неактивированного протеина C происходит in vivo. ! 5. Моноклональное антитело по п.1, где указанное ингибирование активированного или неактивированного протеина C происходит in vitro. ! 6. Моноклональное антитело по п.1, где антитело является антителом мыши. ! 7. Моноклональное антитело по п.1, где антитело является антителом человека. ! 8. Моноклональное антитело по п.1, где антитело является гуманизированным ...

СИНТЕТИЧЕСКАЯ ЛЕТАЛЬНОСТЬ И ЛЕЧЕНИЕ РАКА

... 1. Способ лечения субъекта, больного раком с недостатком NMT2, включающий введение упомянутому субъекту ингибитора NMT.2. Способ по п. 1, где упомянутый ингибитор NMT включает ингибитор NMT1.3. Способ по п. 2, где упомянутый ингибитор NMT1 включает небольшую молекулу, антитело, пептидный фрагмент, нуклеиновую кислоту или их комбинации.4. Способ по п. 3, где упомянутая небольшая молекула включает Tris-DBA, НМА или DDD85646, DDD86481 или их производные.5. Способ по п. 3, где упомянутое антитело является моноклональным антителом или поликлональным антителом.6. Способ по п. 3, где упомянутая нуклеиновая иклсота включает молекулу дцРНК (двухцепочечная РНК), молекулу иРНК, молекулу микроРНК, рибозим, молекулу кшРНК (короткая шпилечная РНК) или молекулу миРНК.7. Способ по любому из пп. 1-6, где упомянутый рак представляет собой лимфому, В-клеточную лимфому, фолликулярную лимфому, диффузную В-крупноклеточную лимфому, мантийноклеточную лимфому, В-ХЛЛ/ЛЛ, иммуноцитому/болезнь Вальденстрема, лимфому ...

СПОСОБЫ ДИАГНОСТИКИ

... 1. Способ идентификации млекопитающего с повышенной предрасположенностью к эрозии зубной эмали, включающий:a. получение образца цельной слюны из ротовой полости млекопитающего;b. измерение концентрации одного или нескольких следующих биомаркеров:i) муцина 5B;ii) карбоангидразы 6 иiii) статерина; иc. сравнение концентрации муцина B; концентрации карбоангидразы 6 и/или концентрации статерина с контрольным значением для каждого из указанных биомаркеров;где указанное контрольное значение представляет собой концентрацию указанного биомаркера в образце цельной слюны, полученного из ротовой полости млекопитающего, не страдающего эрозией; игде сниженная относительно указанного контрольного значения для муцина 5B концентрация муцина 5B является показателем повышенной предрасположенности к эрозии зубной эмали;где сниженная относительно указанного контрольного значения для карбоангидразы 6 концентрация карбоангидразы 6 является показателем повышенной предрасположенности к эрозии зубной эмали; игде ...

МУТАНТНЫЕ АНТИГЕНЫ GAS57 И АНТИТЕЛА ПРОТИВ GAS57

... 1. Выделенное антитело, которое связывается с полипептидом GAS57, содержащим аминокислотную последовательность SEQ ID NO:1, и снижает или ингибирует способность GAS57 дикого типа расщеплять человеческий IL-8.2. Выделенное антитело, полученное способом, включающим иммунизацию животного, не являющегося человеком, полипептидом GAS57 дикого типа, содержащим аминокислотную последовательность SEQ ID NO:1, где указанное антитело связывается с полипептидом GAS57 дикого типа и за счет этого снижает или ингибирует способность GAS57 дикого типа расщеплять человеческий IL-8.3. Выделенное антитело по п.1 или 2, где антитело является поликлональным антителом.4. Выделенное антитело по п.1 или 2, где антитело является моноклональным антителом.5. Выделенное антитело по п.1 или 2, где антитело используется для снижения или ингибирования способности GAS57 дикого типа расщеплять человеческий IL-8 in vitro.6. Композиция, включающая выделенное антитело по п.1 и фармацевтически приемлемый носитель.7. Композиция ...

ПЕПТИДЫ ТОРК И СОДЕРЖАЩИЕ ИХ ВАКЦИНЫ

... 1. Выделенный пептид, выбранный из указанной ниже группы, состоящей из (i) и (ii):(i) выделенного пептида из указанных ниже (a) или (b):(a) выделенного пептида, содержащего аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 2, 3, 6, 27 и 28;(b) выделенного пептида, содержащего аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 2, 3, 6, 27 и 28, в которой 1, 2 или несколько аминокислот заменены, введены, удалены и/или добавлены, где пептид обладает способностью к индукции CTL;(ii) выделенного пептида из указанных ниже (c) или (d):(c) выделенного пептида, содержащего аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 42, 45, 47, 50, 51, 53, 54, 62, 63, 64, 66, 71, 72 и 76;(d) выделенного пептида, содержащего аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 42, 45, 47, 50, 51, 53, 54, 62, 63, 64, 66, 71, 72 и 76, в которой 1, 2 или несколько аминокислот заменены, введены, удалены ...

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... 1. Способ обнаружения нежизнеспособных неопластических клеток у субъекта, включающий скрининг уровня белка теломеразы и/или экспрессии гена нежизнеспособными клетками у указанного субъекта или в биологическом образце, полученном от указанного субъекта, согласно которому увеличение уровня нежизнеспособных клеток, экспрессирующих указанную теломеразу относительно нормальных уровней, указывает на присутствие нежизнеспособных неопластических клеток. ! 2. Способ оценки и/или мониторинга неопластического состояния у субъекта, включающий скрининг уровня белка теломеразы и/или экспрессии гена нежизнеспособными клетками у указанного субъекта или в биологическом образце, полученном от указанного субъекта, согласно которому увеличение уровня нежизнеспособных клеток, экспрессирующих указанную теломеразу, относительно нормальных уровней указывает на присутствие нежизнеспособных неопластических клеток. ! 3. Способ оценки и/или мониторинга эффективности режима терапевтического лечения новообразования ...

МОЛЕКУЛЯРНЫЕ МАССИВЫ АНТИГЕНОВ

... 1. Вирусоподобная частица, предназначенная для использования в вакцинации, содержащая по меньшей мере один белок, выбранный из группы, состоящей из: ! (а) белка, имеющего аминокислотную последовательность, представленную в SEQ ID NO:1; ! (b) белка, имеющего аминокислотную последовательность, представленную в SEQ ID NO:3; и ! (с) мутеина указанного белка (а) или (b), где указанный мутеин имеет аминокислотную последовательность, представленную в SEQ ID NO:1 или представленную в SEQ ID NO:3, где ! (i) один, два или три аминокислотных остатка добавлены, делетированы или заменены, и/или ! (ii) один или два остатка цистеина делетированы или заменены, и/или ! (iii) три, два или один остаток лизина добавлен, делетирован или заменен. ! 2. Вирусоподобная частица по п.1, где указанный мутеин имеет аминокислотную последовательность, представленную в SEQ ID NO:1 или представленную в SEQ ID NO:3, где три аминокислотных остатка добавлены, делетированы или заменены. ! 3. Вирусоподобная частица по п.1, ...

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Предложенное изобретение относится к области иммунологии. Описаны варианты гуманизированных моноклональных антител к фактору D или их функциональные фрагменты. Предложены: кодирующая нуклеиновая кислота, вектор экспрессии, а также клетка для получения антитела, содержащая вектор. Описан способ получения антитела к фактору D путем культивирования клетки и очистки экспрессируемого антитела. Кроме того, предлагаются: композиция на основе антител и применение антител для лечения нарушений, опосредованных системой комплемента. Использование изобретения может найти применение в медицине для лечения заболеваний, связанных с избыточной или неконтролируемой активацией системы комплемента. 18 н. и 14 з.п. ф-лы, 9 ил., 4 табл., 6 пр.

PCSK9 АНТИТЕЛО, ЕГО АНТИГЕНСВЯЗЫВАЮЩИЙ ДОМЕН И ИХ МЕДИЦИНСКОЕ ПРИМЕНЕНИЕ

ТЕСИДОЛУМАБ ДЛЯ ПРИМЕНЕНИЯ В ЛЕЧЕНИИ ОТТОРЖЕНИЯ ТРАНСПЛАНТАТА

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ГУМАНИЗИРОВАННЫЕ АНТИТЕЛА ПРОТИВ ФАКТОРА D И ИХ ПРИМЕНЕНИЯ

... 1. Антитело против фактора D, содержащее HVRs легкой цепи контрольного антитела, где указанное антитело против фактора D дополнительно содержит замену в одной или нескольких позициях указанного контрольного антитела, где указанное контрольное антитело содержит HVR-1 легкой цепи, содержащую ITSTDIDDDMN (SEQ ID №: 30), HVR-2 легкой цепи, содержащую GGNTLRP (SEQ ID №: 35), и HVR-3 легкой цепи, содержащую LQSDSLPYT (SEQ ID №: 38), и где указанная замена представляет собой одно или несколько из следующего: ! (a) аминокислота в позиции 33 легкой цепи представляет собой L или I, ! (b) аминокислота в позиции 34 легкой цепи представляет собой A или Q, ! (c) аминокислота в позиции 52 легкой цепи представляет собой S или A, ! (d) аминокислота в позиции 104 легкой цепи представляет собой V, ! (e) аминокислота в позиции 1 тяжелой цепи представляет собой E, ! (f) аминокислота в позиции 99 тяжелой цепи представляет собой A или Q, или ! (g) аминокислота в позиции 100 тяжелой цепи представляет собой A или ...

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БЛОКАДА CD73

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ЛЕЧЕНИЕ ОСЛОЖНЕНИЙ ХРОНИЧЕСКОГО ЗАБОЛЕВАНИЯ ПЕЧЕНИ

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СПОСОБЫ ЛЕЧЕНИЯ СОСТОЯНИЙ, СВЯЗАННЫХ С MASP-2 ЗАВИСИМОЙ АКТИВАЦИЕЙ КОМПЛЕМЕНТА

ИММУНОГЛОБУЛИН С ДВУМЯ ВАРИАБЕЛЬНЫМИ ДОМЕНАМИ И ЕГО ПРИМЕНЕНИЕ

... 1. Связывающийся белок, включающий полипептидную цепь, где указанная полипептидная цепь содержит VD1-(X1)n-VD2-C-(X2)n, где:VD1 представляет собой первый вариабельный домен тяжелой цепи, полученный от первого родительского антитела или его антигенсвязывающей части;VD2 представляет собой второй вариабельный домен тяжелой цепи, полученный от второго родительского антитела или его антигенсвязывающей части;C представляет собой константный домен тяжелой цепи;(X1)представляет собой линкер, при условии, что он не является СН1, где указанный (X1)присутствует или отсутствует, и(X2)представляет собой Fc-область, где указанный (X2)присутствует или отсутствует;где VD1 и VD2 содержат аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 323, 325 и 327.2. Связывающийся белок по п.1, где указанный связывающийся белок обладает способностью связываться с парой антигенов, выбранных из группы, состоящей из EGFR и CD- ...

МОЛЕКУЛЫ ФИБРОНЕКТИНА, СОДЕРЖАЩИЕ КАРМАН, И ИХ БИБЛИОТЕКИ

... 1. Полипептид, содержащий карман, на основе домена фибронектина III-го типа (FnIII), содержащий одну или несколько замен аминокислот по меньшей мере в двух петлеобразных участках и по меньшей мере в двух непетлеобразных участках.2. Полипептид с карманом по п.1, при этом непетлеобразные участки выбраны из группы, состоящей из β-нити С, β-нити D, β-нити F и β-нити G, а петлеобразные участки выбраны из группы, состоящей из петли АВ, петли ВС, петли CD, петли DE, петли EF и петли FG.3. Полипептид с карманом по п.2, при этом по меньшей мере два непетлеобразных участка представляют собой β-нити С и F, а по меньшей мере два петлеобразных участка представляют собой петли CD и FG.4. Полипептид с карманом по п.3, при этом вводится одна или несколько замен аминокислот в остатки β-нитей в кармане.5. Полипептид с карманом по п.1, дополнительно включающий вставку и/или делению по меньшей мере одной аминокислоты в петлеобразных участках и непетлеобразных участках.6. Полипептид с карманом по п.5, при этом ...

АНТИТЕЛА ПРОТИВ РЕЦЕПТОРА ЭПИДЕРМАЛЬНОГО ФАКТОРА РОСТА (EGFR) И ИХ ПРИМЕНЕНИЕ

... 1. Композиция, содержащая тройку антител против EGFR, включающую первое антитело, второе антитело и третье антитело, при этом (i) первое антитело является антителом, выбранным из группы, или конкурирует за с EGFR с антителом, выбранным из группы, или связывается с тем же эпитопом, что и антитело, выбранное из группы, состоящей из са, cb и cc; (ii) второе антитело является антителом, выбранным из группы, или конкурирует за с EGFR с антителом, выбранным из группы, или связывается с тем же эпитопом, что и антитело, выбранное из группы, состоящей из cd, се и cf; и (iii) третье антитело является антителом, выбранным из группы, или конкурирует за с EGFR с антителом, выбранным из группы, или связывается с тем же эпитопом, что и антитело, выбранное из группы, состоящей из cg, ch, ci, cj и ck.2. Композиция по п.1, отличающаяся тем, что (i) первое антитело является антителом, или конкурирует за с EGFR с антителом, или связывается с тем же эпитопом, что и антитело ca (содержащее CDR 1, 2 и 3 тяжелой ...

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... 1. Синергическая комбинация антитела, специфичного к CD38, содержащего HCDR1 участок с последовательностью GFTFSSYYMN (SEQ ID NO: 1) или SYYMN (SEQ ID NO: 14), HCDR2 участок с последовательностью GISGDPSNTYYADSVKG (SEQ ID NO: 2), HCDR3 с последовательностью DLPLVYTGFAY (SEQ ID NO: 3), LCDR1 участок с последовательностью SGDNLRHYYVY (SEQ ID NO: 4), LCDR2 участок с последовательностью GDSKRPS (SEQ ID NO: 5) и LCDR3 участок с последовательностью QTYTGGASL (SEQ ID NO: 6), и(a) талидомида или его аналога или(b) ингибитора протеасомдля применения при лечении множественной миеломы и/или неходжкинской лимфомы.2. Комбинация по п.1, где антитело содержит вариабельный участок тяжелой цепи с последовательностьюQVQLVESGGGLVQPGGSLRLSCAASGFTFSSYYMNWVRQAPGKGLEWVSGISGDPSNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLPLVYTGFAYWGQGTLVTVSS (SEQ ID NO: 10) и вариабельный участок легкой цепи с последовательностьюDIELTQPPSVSVAPGQTARISCSGDNLRHYYVYWYQQKPGQAPVLVIYGDSKRPSGIPERFSGSNSGNTATLTISGTQAEDEADYYCQTYTGGASLVFGGGTKLTVLGQ ...

ГЛИКОЗИЛ-ТРАНСФЕРАЗА КИТАЙСКОГО ХОМЯЧКА И СОПУТСТВУЮЩИЕ СПОСОБЫ

... 1. Выделенная молекула нуклеиновой кислоты, включающая нуклеотидную последовательность, имеющую идентичность последовательности по меньшей мере 90% с (а) молекулой ДНК, которая имеет последовательность, кодирующую последовательность остатков аминокислот в SEQ ID NO: 2, или в SEQ ID NO: 4, или в SEQ ID NO: 7, или с ее биологически активным фрагментом, или с (b) комплементарной цепью молекулы ДНК из (а).2. Выделенная молекула нуклеиновой кислоты, кодирующая последовательность, приведенную в SEQ ID NO: 2, или в SEQ ID NO: 4, или в SEQ ID NO: 7.3. Выделенная молекула нуклеиновой кислоты, имеющая идентичность последовательности по меньшей мере 90% с последовательностью в SEQ ID NO: 1, или в SEQ ID NO: 3, или в SEQ ID NO: 5, или в SEQ ID NO: 6.4. Выделенная молекула нуклеиновой кислоты, которая в жестких условиях гибридизуется с молекулой нуклеиновой кислоты, имеющей последовательность, приведенную в SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5 или SEQ ID NO: 6, или с ее комплементарной цепью.5.

АНТИТЕЛА ПРОТИВ ГЕПСИНА И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

... 1. Выделенное антитело против гепсина, где одновалентная форма антитела связывается с гепсином человека с аффинностью, меньшей или равной 10 нМ или лучшей, где одновалентная форма антитела связывается с гепсином мыши с аффинностью, меньшей или равной 330 нМ, и где антитело связывается с гепсином в комплексе, содержащем гепсин и ингибитор сериновой протеазы, который связывает субсайт S1 гепсина человека.2. Антитело по п.1, где ингибитором сериновой протеазы является 3,4-дихлоризокумарин (DCI).3. Антитело по п.1, где антитело связывает область связывания домена Кунитца гепсина.4. Антитело по п.1, где антитело блокирует связывание субстрата с субсайтом 2 гепсина и/или субсайтом 3 гепсина.5. Антитело по п.1, где антитело ингибирует опосредуемую гепсином активацию стимулирующего макрофаги белка (MSP).6. Антитело по п.1, где антитело ингибирует ламинин-зависимую миграцию клеток.7. Антитело по п.1, где антитело содержит (a) HVR-H1, который содержит последовательность GFNFSYSYMH (SEQ ID NO:4); ...

КОМПОЗИЦИИ RON И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

ПЕПТИДЫ TTLL4 И СОДЕРЖАЩИЕ ИХ ВАКЦИНЫ

... 1. Выделенный пептид, имеющий CTL-индуцибельность, где пептид состоит из аминокислотной последовательности TTLL4 или ее иммунологически активного фрагмента.2. Выделенный пептид по п.1, где пептид содержит аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 1, 6, 11, 12, 16, 20, 21, 22, 28, 29, 32, 37, 38, 39, 44 и 59.3. Выделенный пептид, содержащий аминокислотную последовательность, в которой 1, 2 или несколько аминокислот являются замененными, делетированными, инсертированными и/или добавленными в аминокислотной последовательности, выбранной из SEQ ID NO: 1, 6, 11, 12, 16, 20, 21, 22, 28, 29, 32, 37, 38, 39, 44 и 59, и где указанный пептид имеет индуцибельность цитотоксических Т-лимфоцитов (CTL).4. Выделенный пептид по любому из пп.1-3, где указанный пептид связывается с HLA-антигеном.5. Выделенный пептид по п.4, где указанный HLA-антиген представляет собой HLA-А24 или HLA-А2.6. Пептид по п.5, где пептид имеет одну или обе из следующих характеристик:(a) вторая ...

МУТАНТЫ СТРЕПТОКИНАЗЫ И ИХ КОВАЛЕНТНО МОДИФИЦИРОВАННЫЕ ФОРМЫ

... 1. Полипептид, содержащий аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID N0:22-24.2. Фармецевтическая композиция, содержащая полипептид с аминокислотной последовательностью, выбранной из группы, состоящей из SEQ ID N0:22-24.3. Способ лечения тромбоза, включающий введение полипептида с аминокислотной последовательностью, выбранной из группы, состоящей из SEQ ID N0:22-24.4. Применение полипептида с аминокислотной последовательностью, выбранной из группы, состоящей из SEQ ID N0:22-24 при производстве медикамента для лечения тромбоза.5. Полипептид, содержащий аминокислотную последовательность SEQ ID N0:24.6. Фармацевтическая композиция, содержащая полипептид последовательности SEQ ID N0:24.7. Способ лечения тромбоза полипептидом последовательности SEQ ID NO:24.

ПРИМЕНЕНИЕ ИНГИБИТОРОВ VAP-1 ДЛЯ ЛЕЧЕНИЯ ФИБРОЗНЫХ БОЛЕЗНЕЙ

... 1. Ингибитор VAP-1, который представляет:i) полностью человеческое анти-VAP-1-антитело, содержащее одну-три консенсусных CDR-последовательности, выбранных из группы, состоящей из последовательностей SEQ ID NO: 1-3, и/или полипептид легкой цепи, содержащий одну-три консенсусных CDR-последовательности, выбранных из группы, состоящей из последовательностей SEQ ID NO: 24-26; илиii) ингибитор SSAO, выбранный из производных гидразина, производных 4,5,6,7-тетрагидроимидазо[4,5-с]пиридина, тиокарбамоильных производных, карбоксамидов, сульфонамидов, производных тиазола и/или гуанидина, оксимных производных, дигидразина, арилалкиламинов, оксазолидинонов, галогеналкиламинов, производных бенфотиамина и имидазопиридина для применения в качестве антифиброзного средства.2. Ингибитор VAP-1 по п.1, где указанное анти-VAP-1-антитело содержит полипептид тяжелой цепи, содержащий первую CDR-последовательность, выбранную из последовательностей SEQ ID NO: 4-8, вторую CDR-последовательность, выбранную из последовательностей ...

Антитела против фактора IX/фактора IXа и производные антител

... 1. Антитело или производное антитела против фактора IX/фактора IXa, которое увеличивает прокоагулянтную активность FIXa. 2. Антитело или производное антитела по п.1, где указанное антитело или производное антитела увеличивает прокоагулянтную активность FIXa в присутствии ингибиторов FVIII. 3. Антитело по п.1, где указанное антитело выбрано из группы, состоящей из антител IgG, IgM, IgA и IgE. 4. Антитело или производное антитела по п.1, где указанное антитело или производное антитела выбрано из группы, состоящей из моноклональных антител, фрагментов антител, химерных антител, гуманизированных антител, одноцепочечных антител, биспецифичных антител, диантител и их ди-, олиго- или мультимеров. 5. Производное антитела по п.1, где указанное производное антитела содержит пептид района, определяющего комплементарность (CDR). 6. Производное антитела по п.5, где указанным CDR-пептидом является пептид CDR3. 7. Производное антитела по п.6, где указанный CDR3-пептид содержит аминокислотную последовательность ...

КОМПОЗИЦИИ И СПОСОБЫ ОБНАРУЖЕНИЯ И КОЛИЧЕСТВЕННОГО ОПРЕДЕЛЕНИЯ БЕЛКА КЛЕТОК-ХОЗЯЕВ В КЛЕТОЧНЫХ ЛИНИЯХ И РЕКОМБИНАНТНЫЕ ПОЛИПЕПТИДНЫЕ ПРОДУКТЫ

СПОСОБ ЛЕЧЕНИЯ ВОСПАЛИТЕЛЬНЫХ ЗАБОЛЕВАНИЙ МУЛЬТИВАЛЕНТНЫМИ FC СОЕДИНЕНИЯМИ

Эпитоп тиоредоксина 1 и моноклональное антитело, специфически связывающееся с ним

ПРОТИВОРАКОВЫЕ ВАКЦИНЫ, НАЦЕЛЕННЫЕ НА СУРВИВИН, И ИХ ПРИМЕНЕНИЯ

КОМБИНИРОВАННАЯ ТЕРАПИЯ ДЛЯ ЛЕЧЕНИЯ СВЯЗАННЫХ С BCMA РАКОВЫХ ЗАБОЛЕВАНИЙ И АУТОИММУННЫХ РАССТРОЙСТВ

ТЕРАПЕВТИЧЕСКИЕ СПОСОБЫ И КОМПОЗИЦИИ

... 1. Способ ингибирования активации фибробластов, уменьшения количества фибробластов или уменьшения десмоплазии в окружении опухоли или у субъекта с фиброзным заболеванием, который включает:введение выделенного ингибитора лизилоксидазоподобного фермента-2 (LOXL2) в окружение опухоли или субъекту с фиброзным заболеванием,при этом ингибируется активация фибробластов, уменьшается количество фибробластов или уменьшается десмоплазия.2. Способ по п.1, в котором ингибитором является антитело против LOXL2.3. Способ по п.1 или 2, в котором антитело содержит:тяжелую цепь, содержащую CDR3 с аминокислотной последовательностью NWMNFDY; илегкую цепь, содержащую CDR3 с аминокислотной последовательностью MQHLEYPYT.4. Способ по п.3, в котором:тяжелая цепь дополнительно содержит CDR1 с аминокислотной последовательностью GYAFTYYLIE и CDR2 с аминокислотной последовательностью VINPGSGGTNYNEKFKG; илегкая цепь дополнительно содержит CDR1 с аминокислотной последовательностью RSSKSLLHSNGNTYLY и CDR2 с аминокислотной ...

ПОЛИПЕПТИДЫ АНТИТЕЛ И ИХ ПРИМЕНЕНИЯ

Antibodies against fatty acid synthase

The present invention relates to antibodies that immunospecifically bind to FAS and certain FAS related proteins. The invention encompasses human and humanized forms of the antibodies and their use in treating cancers and other proliferative disorders. The invention also relates to FAS-derived peptides useful for preparing the antibodies. Methods and compositions for detecting, diagnosing, treating or ameliorating a disease or disorder, especially cancer and other proliferative disorders using the present antibodies also are disclosed.

Hk1-binding proteins

The invention features hK1 binding polypeptides as well as compositions comprising such polypeptides and methods of making and using such polypeptides.

Aminoacyl trna synthetases for modulating hematopoiesis

Hematopoietic-modulating compositions are provided comprising aminoacyl-tRNA synthetase polypeptides, including active fragments and/or variants thereof, as well as compositions comprising related agents such as antibodies and other binding agents. Also provided are methods of using such compositions in the treatment of conditions that benefit from the modulation of hematopoiesis.

Antagonists of pcsk9

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Antagonists of pcsk9

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Antagonists of pcsk9

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Agents and Methods Related to Reducing Resistance to Apoptosis-Inducing Death Receptor Agonists

Provided herein is a method of reversing or preventing a target cell's resistance to a death receptor agonist. Also provided are methods of screening for biomarkers resistance of and monitoring resistance to death receptor agonists. Also provided are methods of selectively inducing apoptosis in a target cell, treating a subject with cancer, autoimmune or inflammatory diseases, comprising administering compositions provided herein. Further provided are compositions comprising agents that modulate CARD containing proteins.

Diagnosis and treatment of cancer using anti-tmprss11e antibody

[Problem to be Solved] An object of the present invention is to provide novel means for the treatment and diagnosis of cancer. [Solution] The present inventors have obtained a monoclonal antibody against TMPRSS11E and found that this antibody binds to a native form of TMPRSS11E, and TMPRSS11E is highly expressed on the cell membranes of cancer cell lines in flow cytometry. This antibody exhibits antibody-dependent cell-mediated cytotoxicity activity (ADCC activity) and antitumor effect based on internalization activity and is promising as a therapeutic target. Moreover, this antibody has neutralization activity against protease activity and is also expected to have effect brought about by the inhibition of TMPRSS11E functions.

Antibodies and Methods of Use Thereof

The disclosure relates to protease-binding agent specific for a protease. The agent may be an antibody capable of specifically binding and inhibiting a protease, such as a P1-Arg-specific protease. The disclosure also provides methods of producing, and compositions comprising the subject agent. Methods and kits related to the protease-binding agent find use in protection against, detection, diagnosing, treating cancer and infections due to pathogens containing active proteases.

Aldehyde-Tagged Immunoglobulin Polypeptides and Methods of Use Thereof

The present disclosure provides aldehyde-tagged immunoglobulin (Ig) polypeptides that can be converted by a formylglycine-generating enzyme to produce a 2-formylglycine (FGly)-modified Ig polypeptide. An FGly-modified Ig polypeptide can be covalently and site-specifically bound to a moiety of interest to provide an Ig conjugate. The disclosure also encompasses methods of production of such aldehyde-tagged Ig polypeptides, FGly-modified Ig polypeptides, and Ig conjugates, as well as methods of use of same.

Bispecific death receptor agonistic antibodies

The present invention relates to bispecific antibodies comprising a first antigen binding site specific for a death receptor and a second antigen binding site specific for a second antigen, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

Anti-pcsk9 antibodies and methods of use

The invention provides anti-PCSK9 antibodies and methods of using the same.

Antibody Substituting for Function of Blood Coagulation Factor VIII

The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

Novel heparanase splice variant

The present invention, in at least some aspects, is of splice variants of heparanase, as well as diagnostic kits and methods of use, and therapeutic agents and methods of use based thereon, and antibodies specifically binding thereof.

Adam6 Mice

Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

Methods of treating hematological proliferative disorders by targeting epha3 expressed on aberrant vasculature in bone marrow

The invention provides diagnostic and therapeutic methods for the treatment of hematological proliferative disorders.

Compositions and Methods for Preventing and Treating Cancer via Modulating UBE1L, ISG215 and/or UBP43

Compositions and methods of using compositions that induce UBE1L or a ubiquitin-like protein ISG15, or inhibit a deconjugase UBP43 to degrade oncogenic proteins and enhance apoptosis of cancer (neoplastic) or pre-cancerous (pre-neoplastic) cells are provided. Methods for the prevention or treatment of cancer via administration of these compositions are also provided.

MONOMERIC FORMS OF HUMAN AMINOACYL-t-RNA SYNTHETASES HAVING NON-CANONICAL BIOLOGICAL ACTIVITIES

Isolated monomelic aminoacyl-tRNA synthetase polypeptides and polynucleotides having non-canonical biological activities are provided, as well as compositions and methods related thereto.

Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (pcsk9)

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described.

Methods of treating or preventing cholesterol related disorders

The present invention relates to methods of treating or preventing cholesterol related disorders, such as hypercholesterolemia, hyperlipidemia or dyslipidemia, using antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9). Formulations and methods of producing said formulations are also described.

1B20 PCSK9 ANTAGONISTS

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure. 1. An isolated PCSK9-specific antagonist which comprises:(a) a heavy chain variable region comprising a CDR3 domain comprising SEQ ID NO: 17 or an equivalent thereof, said equivalent characterized as having one or more conservative amino acid substitutions in the CDR3 domain; and/or(b) a light chain variable region comprising a CDR3 domain comprising SEQ ID NO: 7 or an equivalent thereof, said equivalent characterized as having one or more conservative amino acid substitutions in the CDR3 domain;wherein said PCSK9-specific antagonist antagonizes PCSK9's inhibition of cellular LDL uptake.2. The PCSK9-specific antagonist of wherein the CDR3 domain(s) are in a human germline region in the CDR3 region thereof.3. The PCSK9-specific antagonist of that binds to human PCSK9 with an equilibrium dissociation constant (K) of less than 1200 nM.4. The PCSK9-specific antagonist of that binds to human PCSK9 with a Kof less than 500 nM.5. The PCSK9-specific antagonist of that binds to human PCSK9 with a Kof less than 100 nM.6. The PCSK9-specific antagonist of that binds to human PCSK9 with a Kof less than 5 nM.7. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an ICof less than 500 nM.8. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an ICof less than ...

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described. 1. (canceled)2. An antibody that binds specifically to PCSK9 , wherein the antibody binds to PCSK9 with a higher affinity at pH 7.4 than at pH 6.0.3. The antibody of claim 2 , wherein the antibody binds to PCSK9 with a lower Kat pH 7.4 than at pH 6.0.4. The antibody of claim 2 , wherein the antibody binds to PCSK9 with a ratio of a Kat pH 6.0 to a Kat pH 7.4 that is at least about 2:1.5. The antibody of claim 2 , wherein the antibody binds to PCSK9 with a ratio of a Kat pH 6.0 to a Kat pH 7.4 that is at least about 3:1.6. The antibody of claim 2 , wherein the antibody binds to PCSK9 with a lower kat pH 7.4 than at pH 6.0.7. The antibody of claim 2 , wherein the antibody binds to PCSK9 with a ratio of a kat pH 6.0 to a kat pH 7.4 that is at least about 2:1.8. An antibody that binds specifically to PCSK9 claim 2 , wherein the antibody binds to PCSK9 with a higher affinity at pH 7.4 than at pH 5.5.9. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a lower Kat pH 7.4 than at pH 5.5.10. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a ratio of a Kat pH 5.5 to a Kat pH 7.4 that is at least about 2:1.11. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a ratio of a Kat pH 5.5 to a Kat pH 7.4 that is at least about 3:1.12. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a ratio of a Kat pH 5.5 to a Kat pH 7.4 that is at least about 4:1.13. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a lower kat pH 7.4 than at pH 5.5.14. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a ratio ...

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described. 136-. (canceled)37. A antigen binding protein variant comprising:a heavy chain variable region that is at least 85% identical to the amino acid sequence of SEQ ID NO: 459; anda light chain variable region that is at least 85% identical to the amino acid sequence of SEQ ID NO: 461.38. The antigen binding protein variant of claim 37 , wherein the heavy chain variable region is at least 90% identical to the amino acid sequence of SEQ ID NO: 459 claim 37 , and wherein the light chain variable region is at least 90% identical to the amino acid sequence of SEQ ID NO: 461.39. The antigen binding protein variant of claim 37 , wherein the heavy chain variable region is at least 95% identical to the amino acid sequence of SEQ ID NO: 459 claim 37 , and wherein the light chain variable region is at least 95% identical to the amino acid sequence of SEQ ID NO: 461.40. The antigen binding protein variant of claim 37 , wherein the antigen binding protein specifically binds to PCSK9.41. The antigen binding protein variant of claim 37 , wherein the antigen binding protein is an antibody or a binding part thereof.42. A antigen binding protein variant comprising:a heavy chain variable region that is at least 85% identical to the amino acid sequence of SEQ ID NO: 463; anda light chain variable region that is at least 85% identical to the amino acid sequence of SEQ ID NO: 465.43. The antigen binding protein variant of claim 42 , wherein the heavy chain variable region is at least 90% identical to the amino acid sequence of SEQ ID NO: 463 claim 42 , and wherein the light chain variable region is at least ...

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described. 136-. (canceled)37. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake.38. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake and binds to human PCSK9 with an equilibrium dissociation constant (KD) of less than 1200 nM.39. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 500 nM.40. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 100 nM.41. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 5 nM.42. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake at an ICof less than 500 nM.43. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an ICof less than 200 nM.44. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an ICof less than 100 nM.45. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 20%.46. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 50%.47. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 60%.48. An isolated PCSK9-specific antibody molecule that antagonizes PCSK9's inhibition of cellular uptake by at least 20%.49. An isolated antigen binding molecule that binds to PCSK9 and reduces PCSK9's ability to inhibit cellular LDL uptake.50. The isolated antigen binding molecule of claim 49 ...

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described. 136-. (canceled)37. An antigen binding protein that competes for binding to PCSK9 with at least one of the following antigen binding proteins:a) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 79 and a light chain variable region of SEQ ID NO: 35;b) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 80 and a light chain variable region of SEQ ID NO: 36;c) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 76 and a light chain variable region of SEQ ID NO: 37;d) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 77 and a light chain variable region of SEQ ID NO: 38;e) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 78 and a light chain variable region of SEQ ID NO: 39;f) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 83 and a light chain variable region of SEQ ID NO: 40;g) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 67 and a light chain variable region of SEQ ID NO: 12;h) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 483 and a light chain variable region of SEQ ID NO: 485;i) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 459 and a light chain variable region of SEQ ID NO: 461; orj) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 463 and a light chain variable region of SEQ ID NO: 465.38. The antigen binding protein of claim 37 , wherein the antigen ...

ANTI-PCSK9 ANTIBODIES WITH pH-DEPENDENT BINDING CHARACTERISTICS

The present invention provides antibodies and antigen-binding fragments thereof that specifically bind human proprotein convertase subtilisin/kexin type 9 (hPCSK9) which do not exhibit enhanced binding affinity for hPCSK9 at acidic pH relative to neutral pH. In certain embodiments, the antibodies and antigen-binding fragments of the invention bind hPCSK9 with a lower affinity at acidic pH than at neutral pH. 15-. (canceled)6. An isolated antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin/kexin type 9 (hPCSK9) , wherein the antibody or antigen-binding fragment thereof does not exhibit an enhanced binding affinity for hPCSK9 at an acidic pH relative to a neutral pH , as measured by surface plasmon resonance.7. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment thereof binds hPCSK9 with a lower affinity at acidic pH than at neutral pH.8. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment thereof binds hPCSK9 with a shorter t½ at acidic pH than at neutral pH claim 6 , as measured by surface plasmon resonance.9. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment thereof: (a) binds hPCSK9 with a lower affinity at acidic pH than at neutral pH; and (b) binds hPCSK9 with a shorter t½ at acidic pH than at neutral pH claim 6 , as measured by surface plasmon resonance.10. An isolated antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin/kexin type 9 (hPCSK9) claim 6 , wherein the antibody or antigen-binding fragment thereof: (a) binds hPCSK9 with a lower affinity at acidic pH than at neutral pH; and (b) exhibits a serum half-life which is greater than the serum half-life of an anti-hPCSK9 antibody that does not exhibit lower affinity binding to hPCSK9 at acidic pH.11. An isolated antibody ...

TUMOR TARGETED ANTIBODIES AND METHOD FOR USING THE SAME

Isolated and recombinant antibodies, such as EGFR-binding antibodies. Antibodies can comprising the sequence of an immunoglobulin heavy constant gamma-1 region encoded by a human G1M3 allele. For example, antibodies of the embodiments can comprise an immunoglobulin heavy constant gamma-1 region wherein position 214 is arginine; position 356 is glutamic acid; position 358 is methionine and/or position 431 is alanine. Methods for treating diseases, such as cancer, in a human subject with such antibodies are also provided. 1. A pharmaceutical composition comprising a purified EGFR-binding antibody which has a human immunoglobulin heavy constant gamma-1 region with arginine at position 214 and a pharmaceutically acceptable carrier.2. The composition of claim 1 , wherein the human immunoglobulin heavy constant gamma-1 region has glutamic acid claim 1 , methionine claim 1 , and alanine at positions 356 claim 1 , 358 claim 1 , and 431 claim 1 , respectively.3. The composition of claim 1 , wherein the human immunoglobulin heavy constant gamma-1 region is encoded by a human G1M3 allele.4. The composition of claim 1 , wherein the antibody is a humanized antibody.5. The composition of claim 1 , wherein the antibody is a human antibody.6. The composition of claim 1 , wherein the antibody is a chimeric antibody.7. The composition of claim 1 , wherein the EGFR is HER2 (human epidermal growth factor receptor 2).8. The composition of claim 1 , wherein the EGFR is HER1 (human epidermal growth factor receptor 1).9. The composition of claim 1 , wherein the antibody is coupled to a therapeutic claim 1 , a reporter claim 1 , or a targeting moiety.10. The composition of claim 9 , wherein the therapeutic is a nucleotide claim 9 , a peptide claim 9 , a small molecule claim 9 , a therapeutic radionuclide claim 9 , a chemotherapeutic claim 9 , a tumor suppressor claim 9 , an apoptosis inducer claim 9 , an enzyme claim 9 , a second antibody claim 9 , an siRNA claim 9 , a hormone claim 9 , a ...

Antibodies Directed to ERBB2

The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that specifically bind to ErbB2, preferably human ErbB2. In another embodiment, the antibodies or antigen-binding portions thereof inhibit ErbB2. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins or portions thereof derived from human anti-ErbB2 antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-ErbB2 antibodies. The invention also relates to transgenic animals or plants comprising nucleic acid molecules of the present invention 1. A targeted binding agent that specifically binds to ErbB2.2. The targeted binding agent according to claim 1 , wherein said targeted binding agent possesses at least one of the following properties:(a) binds to human cells;(b) binds to cells expressing cynomolgus ErbB2;(c) competes partially with Herceptin® but does not compete with 2C4;(d) inhibits ErbB2 phosphorylation in MCF7 cells with a EC50 of less than 50 ng/ml;(e) inhibits cell proliferation with an EC50 of less than 50 ng/ml in SKBR3 cells;(f) binds to ErbB2 with a KD of 13.5 nM or less; or(g) has an off rate (koff) for ErbB2 of 2.14×10-4 s-1 or smaller.3. The targeted binding agent to claim 2 , wherein said targeted binding agent binds ErbB2 with a KD of 13.5 nM or less and inhibits activation of ErbB2.4. The targeted binding agent of claim 1 , wherein said targeted binding agent is a monoclonal antibody selected from the group consisting of a chimeric antibody claim 1 , a human antibody and a humanized antibody.5. ...

ACYLGLYCEROL ACYLTRANSFERASE-LIKE PROTEIN MGAT-X1 AND USES THEREOF

The present invention is directed to a polynucleotide sequence of a novel acylglycerol acyltransferase-like protein MGAT-X1. The invention also provides the human MGAT-X1 associated with the dermatological diseases, urological diseases, muscle-skeleton disorders, hematological diseases, cancer, reproduction disorders, neurological diseases, metabolic diseases, cardiovascular diseases or gastroenterological diseases. The invention also provides assays for the identification of compounds useful for the modulation of dermatological diseases, urological diseases, muscle-skeleton disorders, hematological diseases, cancer, reproduction disorders, neurological diseases, metabolic diseases, cardiovascular diseases or gastroenterological diseases for treating of such diseases associated with expression of the MGAT-X1. The invention also features compounds which bind to and/or activate or inhibit the activity of MGAT-X1 as well as pharmaceutical compositions comprising such compounds. 1. A preparation of purified antibodies which specifically bind to a polypeptide comprising the amino acid sequence SEQ ID NO:2.2. The preparation of claim 1 , wherein the antibodies are selected from the group consisting of intact immunoglobulin molecules claim 1 , Fab fragments claim 1 , F(ab′)fragments claim 1 , Fv fragments claim 1 , monoclonal antibodies claim 1 , chimeric antibodies claim 1 , partially humanized antibodies claim 1 , fully humanized antibodies claim 1 , and single chain antibodies.3. A pharmaceutical composition comprising:purified antibodies which specifically bind to a polypeptide comprising the amino acid sequence SEQ ID NO:2; anda pharmaceutically acceptable carrier.4. The pharmaceutical composition of claim 3 , wherein the antibodies are selected from the group consisting of intact immunoglobulin molecules claim 3 , Fab fragments claim 3 , F(ab′)fragments claim 3 , Fv fragments claim 3 , monoclonal antibodies claim 3 , chimeric antibodies claim 3 , partially humanized ...

Methods and compositions for treatment and diagnosis of fibrosis, tumor invasion, angiogenesis, and metastasis

Provided are methodology, compositions and kits to prevent and treat diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, using processed lysyl oxidase or lysyl oxidase-like protein inhibitors, LOX inhibitors and LOXL inhibitors, or synergistic combinations of such inhibitors with therapeutic agents. Provided are methods for selecting tumor invasion, angiogenesis and metastasis inhibiting agents, by contacting cells in EMT states with candidate agents and detecting changes in such states; and methods, compositions, and kits for diagnosing or monitoring diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, using molecules or agents specifically recognizing processed LOX or LOXL. Provided are methods, compositions, medical devices, systems and kits for preventing or treating diseases and conditions associated with fibrosis, including pathological cardiovascular conditions and diseases, e.g., hypertension, hypertensive heart disease, myocardial infarction, atherosclerosis, restenosis, liver fibrosis, kidney fibrosis, lung fibrosis, dermal scaring, keloid formation, and Alzheimer's disease, with LOX or LOXL inhibitors.

FACTOR XII INHIBITORS FOR TREATING INTERSTITIAL LUNG DISEASE

The present invention provides methods for treating interstitial lung diseases, comprising administering to an individual an effective amount of an inhibitor of coagulation factor XII. The invention further provides uses and pharmaceutical kits for that treatment. 1. Non-endogenous inhibitor of the cellular activity of factor XII and/or factor XIIa (FXII/FXIIa) for treating and/or preventing a fibroproliferative interstitial lung disease.2. The inhibitor of claim 1 , which is a compound capable of inhibiting the catalytic activity of factor XIIa.3. The inhibitor of claim 1 , which is a compound capable of reducing or abolishing expression of factor XII in a cell.4. The inhibitor of claim 1 , which is a compound capable of inhibiting the conversion of factor XII into factor XIIa.54. The inhibitor any one of to claim 1 , which is a serine protease inhibitor.6. The inhibitor of claims 1 , which is selected of the group consisting of (a) the N-terminal amino acids 2-13 of the wild type Infestin-4 sequence and at least one and up to five amino acid mutations outside said N-terminal amino acids that result in differences from the wild type Infestin-4 sequence; and/or', '(b) six conserved cysteine residues from the wild type Infestin-4 sequence and a homology of at least 70% to the wild type Infestin-4 sequence;, '(i) the wild type Infestin-4 polypeptide sequence (SEQ ID NO: 33), or a variant thereof, wherein a variant comprises'} a) the N-terminal amino acids 2-13 of the wild type Infestin-4 sequence; and at least one and up to five amino acid mutations outside said N-terminal amino acids that result in differences from the wild type SPINK-1 sequence and which increase the homology of the variant to the wild type Infestin-4 sequence; and/or', 'b) six conserved cysteine residues from the wild type SPINK-1 sequence and a homology of at least 70% to the wild type SPINK-1 sequence;, '(ii) SPINK-1 (SEQ ID NO:29), which is mutated to include the N-terminal amino acids 2-13 of ...

COMPOSITIONS AND METHODS FOR TREATING NEUROLOGICAL DISORDERS

The present disclosure provides methods for treating neurological disorders, generally involving modulating protein kinase D1 (PKD1) activity levels in a neuron or glial cell in an individual in need thereof. The present disclosure provides antibodies specific for PKD1. The present disclosure provides a genetically modified non-human mammal deficient in PKD1 activity. 1. A method for treating a neurological disorder or a neurodegenerative disease in an individual , the method comprising administering to the individual an effective amount of an agent that inhibits activity of protein kinase D1 (PKD1) in a neuronal cell and/or a glial cell in the individual.2. The method of claim 1 , wherein the agent is a small molecule inhibitor of PKD1.3. The method of claim 1 , wherein the agent is an inhibitory nucleic acid that reduces the level of active PKD1 in the neuronal cell.4. The method of claim 1 , wherein the agent is an antibody that specifically binds PKD1.5. The method of claim 1 , wherein the neurodegenerative disease is Parkinson's disease claim 1 , Huntington's disease claim 1 , amyotrophic lateral sclerosis claim 1 , multiple sclerosis claim 1 , or Alzheimer's disease.6. The method of claim 1 , wherein the neurological disorder is stroke claim 1 , spinal cord injury claim 1 , or head injury.7. An isolated interfering nucleic acid that specifically reduces the level of protein kinase D1 (PKD1) in a cell.8. The interfering nucleic acid of claim 7 , wherein the interfering nucleic acid is a short interfering RNA (siRNA).9. A recombinant construct comprising a nucleotide sequence encoding the interfering nucleic acid of .10. An isolated antibody that specifically binds protein kinase D1 (PKD1).11. The antibody of claim 10 , wherein the antibody is a polyclonal antibody.12. The antibody of claim 10 , wherein the antibody is a monoclonal antibody.13. The antibody of claim 10 , wherein the antibody binds a PKD1 polypeptide with an affinity of at least about 10M.14. A ...

Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) Single Chain FV Antibody Fragment Conjugates and Methods of Use Thereof

Compositions including an antibody single-chain variable fragment (scFv) conjugate that specifically binds to ROR1 tumor-associated antigen are provided. The anti-ROR1 scFv antibody and conjugates may include a biologically-active molecule. Such conjugates may comprise a chimeric receptor to direct T cells to respond to ROR1 cancer cells, Methods to use the scFV conjugates to target cells expressing ROR1 for therapeutic and diagnostic purposes are also provided. 1. An antibody single-chain variable fragment (scFv) conjugate comprising ,an scFv having an amino acid sequence at least 90% identical to SEQ ID NO: 1 or SEQ ID NO: 2; anda biologically active molecule.2. The conjugate of claim 1 , wherein the amino acid sequence of the scFv is at least 95% identical to SEQ ID NO: 1 or SEQ ID NO: 2.3. The conjugate of claim 1 , wherein the amino acid sequence of the scFv is 100% identical to SEQ LD NO: 1 or SEQ LD NO: 2.4. The conjugate of claim 1 , wherein the scFv has a binding specificity of an antibody as produced by a hybridoma having Accession No. PTA 8634 by the American Type Culture Collection.5. The conjugate of claim 1 , wherein the biologically active molecule is selected from the group consisting of a polypeptide claim 1 , a peptidomimetic claim 1 , a nucleic acid molecule claim 1 , a lipid claim 1 , a drug compound claim 1 , chemotherapeutic agent claim 1 , an antagonist and an agonist.6. The conjugate of claim 5 , wherein the biologically active molecule is a polypeptide.7. The conjugate of claim 6 , wherein the polypeptide is an antibody or an antibody fragment.8. The conjugate of claim 7 , wherein the antibody fragment is selected from the group consisting of a Fab fragment claim 7 , a F(ab)2 fragment claim 7 , an FV fragment claim 7 , a single chain FV (scFV) fragment claim 7 , a dsFV fragment claim 7 , a CH fragment and a dimeric scFV.9. The conjugate of claim 8 , wherein the CH fragment is an IgG CH fragment.10. The conjugate of claim 9 , wherein the IgG ...

Actriib binding agents and uses thereof

The disclosure provides, among other aspects, neutralizing antibodies and portions thereof that bind to ActRIIB and uses for same.

Usp2a peptides and antibodies

The invention relates to novel USP2a peptides and antibodies, as well as nucleic acids related to them. The peptides, antibodies and the nucleic acids are useful for the detection, staging and monitoring of the progression of cancer, as well as for determining or monitoring the efficacy of treatment.

ANTI-cMET ANTIBODY

Antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region. A composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer. 1. A monoclonal antibody , or a divalent functional fragment or derivative thereof , capable of inhibiting c-Met dimerization , wherein the antibody comprises:a heavy chain comprising CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences SEQ ID Nos. 1, 2, and 3, respectively;a light chain comprising CDR-L1, CDR-L2, and CDR-L3 comprising amino acid sequences SEQ ID Nos. 5, 6, and 7; anda modified hinge region comprising the amino acid sequence SEQ ID No. 56.233.-. (canceled) The present invention relates to a novel divalent antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, as well as the amino acid and nucleic acid sequences coding for said antibody. More particularly, the antibody according to the invention is capable of inhibiting the c-Met dimerization. The invention likewise comprises the use of said antibody as a medicament for the prophylactic and/or therapeutic treatment of cancers or any pathology connected with the overexpression of said receptor as well as in processes or kits for diagnosis of illnesses connected with the over-expression of c-Met. The invention finally comprises products and/or compositions comprising such an antibody in combination with other antibodies and/or chemical compounds directed against other growth factors involved in tumor progression or metastasis and/or compounds and/or anti-cancer agents or agents conjugated with toxins and their use for the prevention and/or the treatment of certain cancers.Receptor tyrosine kinase (RTK) targeted agents such as trastuzumab, ...

ANTI-cMET ANTIBODY

Antibody capable of binding specifically to the luman c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region. A composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer. 1. A monoclonal antibody , or a divalent functional fragment or derivative thereof , capable of inhibiting c-Met dimerization , wherein the antibody comprises:a heavy chain comprising CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences SEQ ID Nos. 1, 2, and 3, respectively;a light chain comprising CDR-L1, CDR-L2, and CDR-L3 comprising amino acid sequences SEQ ID Nos. 5, 6, and 7; anda modified hinge region comprising the amino acid sequence SEQ ID No. 56.233.-. (canceled) The present invention relates to a novel divalent antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, as well as the amino acid and nucleic acid sequences coding for said antibody. More particularly, the antibody according to the invention is capable of inhibiting the c-Met dimerization. The invention likewise comprises the use of said antibody as a medicament for the prophylactic and/or therapeutic treatment of cancers of any pathology connected with, the overexpression of said receptor as well as in processes or kits for diagnosis of illnesses connected with the over-expression of c-Met. The invention finally comprises products and/or compositions comprising such an antibody in combination with other antibodies and/or chemical, compounds directed against, other growth factors involved in tumor progression or metastasis and/or compounds and/or anti-cancer agents or agents conjugated with toxins and their use for the prevention and/or the treatment of certain cancers.Receptor tyrosine kinase (RTK) targeted, agents such, as trastuzumab, ...

ANTI-cMET ANTIBODY

Antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region. A composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer. 1. A monoclonal antibody , or a divalent functional fragment or derivative thereof , capable of inhibiting c-Met dimerization , wherein the antibody comprises:a heavy chain comprising CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences SEQ ID Nos. 1, 2, and 3, respectively;a light chain comprising CDR-L1, CDR-L2, and CDR-L3 comprising amino acid sequences SEQ ID Nos. 5, 6, and 7; anda modified hinge region comprising the amino acid sequence SEQ ID No. 56.233.-. (canceled) The present invention relates to a novel divalent antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, as well as the amino acid and nucleic acid sequences coding for said antibody. More particularly, the antibody according to the invention is capable of inhibiting the c-Met dimerization. The invention likewise comprises the use of said antibody as a medicament for the prophylactic and/or therapeutic treatment of cancers or any pathology connected with the overexpression of said receptor as well as in processes or kits for diagnosis of illnesses connected with the over-expression of c-Met. The invention finally comprises products and/or compositions comprising such an antibody in combination with other antibodies and/or chemical compounds directed against other growth factors involved in tumor progression or metastasis and/or compounds and/or anti-cancer agents or agents conjugated with toxins and their use for the prevention and/or the treatment of certain cancers.Receptor tyrosine kinase (RTK) targeted agents such as trastuzumab, ...

ISOLATED HIGH AFFINITY ENTITIES WITH T-CELL RECEPTOR LIKE SPECIFICITY TOWARDS NATIVE COMPLEXES OF MHC CLASS II AND GLUTAMIC ACID DECARBOXYLASE (GAD) AUTOANTIGENIC PEPTIDES

Provided are isolated complexes comprising a major histocompatibility complex (MHC) class II and a type I diabetes-associated GAD autoantigenic peptide, the isolated complex having a structural conformation which enables isolation of a high affinity entity which comprises an antigen binding domain capable of specifically binding to a native conformation of a complex composed of the MHC class II and the type I diabetes-associated GAD autoantigenic peptide; and isolated high affinity entities comprising an antigen binding domain capable of specifically binding the complex, wherein the isolated high affinity entity does not bind to the MHC class II in an absence of the diabetes-associated GAD autoantigenic peptide, wherein the isolated high affinity entity does not bind to the diabetes-associated GAD autoantigenic peptide in an absence of the MHC class II; and methods and kits using same for diagnostic and therapeutic purposes. 1. An isolated complex comprising a major histocompatibility complex (MHC) class II and a Glutamic acid decarboxylase (GAD) autoantigenic peptide , wherein said GAD autoantigenic peptide comprises a core amino acid sequence set forth by SEQ ID NO:14 (GAD556-565 , FFRMVISNPA) , wherein said GAD autoantigenic peptide is covalently attached to a beta chain of said MHC class II.2. The isolated complex of claim 1 , wherein said GAD autoantigenic peptide is covalently bound at a C terminus thereof to an N-terminus of an extracellular domain of a beta chain of said MHC class II.3. The isolated complex of claim 1 , wherein said GAD autoantigenic peptide is covalently embedded between amino acids 1-6 of an extracellular domain of a beta chain of said MHC class II.4. The isolated complex of claim 1 , wherein said GAD autoantigenic peptide is covalently attached to said beta chain between the third and forth amino acid of a mature polypeptide of said MHC class II beta chain.5. An isolated antibody comprising an antigen binding domain capable of ...

ANTAGONISTS OF PCSK9

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure. 1. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake and comprises:(a) a heavy chain variable region comprising a CDR3 domain comprising SEQ ID NO: 17 or an equivalent thereof characterized as having one or more conservative amino acid substitutions in the CDR3 domain; and/or(b) a light chain variable region comprising a CDR3 domain comprising SEQ ID NO: 7 or an equivalent thereof characterized as having one or more conservative amino acid substitutions in the CDR3 domain.2. The PCSK9-specific antagonist of that binds to human PCSK9 with an equilibrium dissociation constant (KD) of less than 1200 nM.3. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 500 nM.4. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 100 nM.5. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 5 nM.6. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an IC50 of less than 500 nM.7. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an IC50 of less than 200 nM.8. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an IC50 of less than 100 nM.9. The PCSK9-specific antagonist of that ...

ANTIBODIES IMMUNOREACTIVE WITH HEREGULIN-COUPLED HER3

Antibodies which specifically bind heregulin-coupled HERS, at a site distinct from the heregulin binding site, are described. These antibodies are particularly useful in treating cancer. 1. One or more nucleic acid molecules which comprise nucleotide sequences that encode a monoclonal antibody or fragment thereof which binds to HER3 not complexed to heregulin , and binds to HER3:heregulin complex with greater affinity as compared to binding uncomplexed HER3.2. A recombinant expression system which comprises the encoding nucleotide sequences of operably linked to control sequences for expression.3. Recombinant host cells that contain the expression system of .4. A method to produce monoclonal antibodies including fragments thereof which bind to HER3 but which bind to HER3:heregulin complex with greater affinity as compared to binding uncomplexed HER3{'claim-ref': {'@idref': 'CLM-00003', 'claim 3'}, 'which method comprises culturing the cells of and recovering said antibodies.'}5. One or more nucleic acid molecule(s) which comprise nucleotide sequences that encode a monoclonal antibody or fragment wherein the heavy chain comprises CDR1:GYTFTDYVS (SEQ ID NO:4) claim 2 , CDR2:IYPSGRY (SEQ ID NO:5) and CDR3:TRSLQRLRYFDV (SEQ ID NO:6).6. The nucleic acid molecule of wherein the monoclonal antibody or fragment further comprises a light chain that comprises CDR1:RASQSISDYLH (SEQ ID NO:10) claim 5 , CDR2:YGSQSIS (SEQ ID NO:11) and CDR3:QQSNSWPLT (SEQ ID NO:12).7. A recombinant expression system which comprises the encoding nucleotide sequences of operably linked to control sequences for expression.8. A recombinant expression system which comprises the encoding nucleotide sequences of operably linked to control sequences for expression.9. Recombinant host cells that contain the expression system of .10. Recombinant host cells that contain the expression system of .11. A method to produce monoclonal antibodies including fragments thereof which bind to HER3 but which bind to ...

HUMAN FGF RECEPTOR AND BETA-KLOTHO BINDING PROTEINS

The present invention provides compositions and methods relating to or derived from antigen binding proteins and antigen binding protein-FGF21 fusions that specifically bind to β-Klotho, or β-Klotho and one or more of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins and antigen binding protein-FGF21 fusions induce FGF21-like signaling. In some embodiments, an antigen binding protein or antigen binding protein-FGF21 fusion antigen binding component is a fully human, humanized, or chimeric antibody, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to β-Klotho, or β-Klotho and one or more of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins and antigen binding protein-FGF21 fusions, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins and antigen binding protein-FGF21 fusions, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins and antigen binding protein-FGF21 fusions, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions. 1. An isolated antigen binding protein comprising one or more of: (i) a light chain CDR3 sequence that differs by no more than two amino acid additions, substitutions, deletions and combinations thereof from a CDR3 sequence of L1-L11, SEQ ID NOs:17-27;', {'sub': '1', '(ii) MQAXEFPWT (SEQ ID NO: 174);'}, {'sub': 2', '3, '(iii) GTWDSSLSXVX(SEQ ID NO: 175);'}, '(iv) QQYDNLFT (SEQ ID NO: 122);', '(v) QQYGSAPLT (SEQ ID NO: 123);', '(vi) VLYMGSGIWV (SEQ ID NO: 124);', '(vii) ETWDSSLSAGV (SEQ ID NO: 127);, '(a) a light chain CDR3 comprising one or more of [{'sub': '1', 'Xis L or I;'}, {'sub': '2', 'Xis V or A; and'}, {' ...

ANTI C-MET ANTIBODY AND USES THEREOF

An anti c-Met antibody or antigen-binding fragment thereof comprising a heavy-chain variable region having heavy-chain complementarity determining region (CDR) amino acid sequences of SEQ ID NOs: 1, 2 and 3, and a light-chain variable region having light-chain CDR amino acid sequences of SEQ ID NOs: 4, 5, and 6; and a method of wound healing, tissue regeneration, or cell proliferation comprising administration of same; as well as related compositions and methods. 1. An anti c-Met antibody or antigen-binding fragment thereof comprising a heavy-chain variable region having heavy-chain complementarity determining region (CDR) amino acid sequences of SEQ ID NOs: 1 , 2 and 3 , and a light-chain variable region having light-chain CDR amino acid sequences of SEQ ID NOs: 4 , 5 , and 6.2. The anti c-Met antibody or antigen-binding fragment of comprising a heavy-chain variable region having an amino acid sequence of SEQ ID No. 7 claim 1 , and a light-chain variable region having an amino acid sequence of SEQ ID No. 8.3. The anti c-Met antibody or antigen-binding fragment thereof of claim 1 , wherein the c-Met is human c-Met claim 1 , monkey c-Met claim 1 , mouse c-Met claim 1 , or rat c-Met.4. The anti c-Met antibody or antigen-binding fragment thereof of claim 1 , wherein the anti c-Met antibody is a monoclonal antibody.5. An antigen-binding fragment of an anti c-Met antibody according to .6. The antigen-binding fragment of claim 5 , wherein the antigen-binding fragment is selected from the group consisting of scFv claim 5 , (scFv) claim 5 , Fab claim 5 , Fab′ claim 5 , and F(ab′).7. A polynucleotide comprising a nucleotide sequence encoding the antibody or antigen-binding fragment of .8. A polynucleotide comprising a nucleotide sequence encoding the antibody or antigen-binding fragment of .9. A recombinant vector comprising the polynucleotide of .10. A recombinant vector comprising the polynucleotide of .11. A host cell comprising the polynucleotide of .12. A host cell ...

Group B Streptococcus Polypeptides Nucleic Acids and Therapeutic Compositions and Vaccines Thereof

This invention provides an isolated nucleic acid encoding a polypeptide comprising amino acid sequences of a streptococcal matrix adhesion E (EmaE) polypeptide. Antibodies to the EmaE polypeptide and immunogenic fragments thereof are also provided. This invention provides pharmaceutical compositions, immunogenic compositions, vaccines, and diagnostic and therapeutic methods of use of the isolated polypeptide, antibodies thereto, and nucleic acids. 112-. (canceled)13. An isolated streptococcal Extracellular Matrix Adhesion Protein E (EmaE) which comprises the amino acid sequence set forth in SEQ ID NO:10.14. A vaccine comprising an isolated streptococcal polypeptide EmaE comprising the amino acid sequence set forth in SEQ ID NO:10 and a pharmaceutically acceptable adjuvant.15. The vaccine of claim 14 , further comprising an antigen selected from the group consisting of:a) the polypeptide Spbl or an immunogenic fragment thereof;b) the polypeptide Spb2 or an immunogenic fragment thereof;c) the polypeptide C protein alpha antigen or an immunogenic fragment thereof;d) the polypeptide Rib or an immunogenic fragment thereof;e) the polypeptide Lmb or an immunogenic fragment thereof;f) the polypeptide C5a-ase or an immunogenic fragment thereof;g) Group B streptococcal polysaccharides or oligosaccharides; andh) any combination of one or more of the foregoing.16. An immunogenic composition comprising an isolated streptococcal polypeptide EmaE comprising the amino acid sequence set forth in SEQ ID NO:10 and a pharmaceutically acceptable adjuvant.17. The immunogenic composition of claim 16 , further comprising an antigen selected from the group consisting of:a) the polypeptide Spbl of an immunogenic fragment thereof;b) the polypeptide Spb2 or an immunogenic fragment thereof;c) the polypeptide C protein alpha antigen or an immunogenic fragment thereof;d) the polypeptide Rib or an immunogenic fragment thereof;e) the polypeptide Lmb or an immunogenic fragment thereof;f) the ...

ANTI-HtrA1 ANTIBODIES AND METHODS OF USE

The invention provides anti-HtrA1 antibodies and methods of using the same.

Methods, Compositions and Kits Relating to Chitnases and Chitnase-Like Molecules and Inflammation Disease

The present invention includes compositions and methods for the treatment of inflammatory disease (e.g., asthma, COPD, inflammatory bowel disease, atopic dermatitis, atopy, allergy, allergic rhinitis, scleroderma, and the like), relating to inhibiting a chitinase-like molecule. The invention further includes methods to identify new compounds for the treatment of inflammatory disease, including, but not limited to, asthma, COPD and the like. This is because the present invention demonstrates, for the first time, that expression of IL-13, and of a chitinase-like molecule, mediates and/or is associated with inflammatory disease and that inhibiting the chitinase-like molecule treats and even prevents, the disease. Thus, the invention relates to the novel discovery that inhibiting a chitinase-like molecule treats and prevents an inflammatory disease. 1. A method of treating an inflammatory disease in a mammal wherein said disease is associated with an increased level of a chitinase-like molecule , wherein said chitinase-like molecule is YKL0-40 , said method comprising administering an effective amount of an antibody inhibitor of said YKL-40 to said mammal , thereby treating said inflammatory disease , wherein said inflammatory disease is asthma.2. The method of claim 1 , wherein said mammal is a human.3. A method of preventing an inflammatory disease in a mammal wherein said disease is associated with an increased level of a chitinase-like molecule claim 1 , wherein said chitinase-like molecule is YKL0-40 claim 1 , said method comprising administering an effective amount of an antibody inhibitor of said YKL-40 to said mammal claim 1 , thereby treating said inflammatory disease claim 1 , wherein said inflammatory disease is asthma.4. The method of claim 3 , wherein said mammal is a human.5. A method for treating an inflammatory disease in a mammal wherein said disease is associated with an increased level of interleukin-13 claim 3 , said method comprising administering ...

ANTICANCER DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF

Provided herein are compounds of formula (I): 2. The compound according to in which U═U′ and/or W═W′ and/or R═R′ and/or R═R′ and/or Y═Y′ and/or the two groups ALK and ALK′ attached to the phenyl or pyridyl nucleus are identical.5. The compound according to in which Y and Y′ represent a group (C-C)alkoxy.6. The compound according to in which M represents N.7. The compound according to in which if Lrepresents a single bond claim 1 , Lrepresents —(CHCHO)—CHCH— or —(CHCHO)—CHCHNR″—(C-C)ALK-.8. The compound according to in which G represents a group —OH claim 1 , —O(C-C)alkyl claim 1 , —NH claim 1 , —NH(C-C)alkyl or —N(C-C)alkylor G represents a group —NRR′ in which R and R′ form claim 1 , together with the nitrogen atom to which they are attached claim 1 , a group (C-C)heterocycloalkyl which may comprise in the ring another heteroatom chosen from N claim 1 , O and S and which may be optionally substituted with at least one substituent chosen from a group (C-C)alkyl claim 1 , a halogen atom and a hydroxyl group.9. The compound according to in which:{'sub': 1', '1', '6', '2', '6', '6, 'L=-D-(C-C)ALK- and L=-(C-C)ALK-; or'}{'sub': 1', '2', '2', 'i', '2', '1', '6, 'L=-(OCHCH)— and L=-(C-C)ALK-; or'}{'sub': 1', '2', '2', '2', 'j', '2', '2', '1', '6, 'L=single bond and L=-(CHCHO)—CHCHNR″—(C-C)ALK-; or'}{'sub': 1', '1', '6', '2', '2', '2', 'j', '2', '2', '1', '6, 'L=-D-(C-C)ALK-, and L=-(CHCHO)—CHCHNR″—(C-C)ALK-; or'}{'sub': 1', '1', '6', '2', '2', '2', 'j', '2', '2, 'L=-D-(C-C)ALK- and L=-(CHCHO)—CHCH—.'}10. The compound according to in which:{'sub': 1', '1', '6', '2', '1', '6', 'a, 'L=-D-(C-C)ALK-, L=-(C-C)ALK-, Q=single bond, k=1-10, G=OR, RCG1=-SZ;'}{'sub': 1', '1', '6', '2', '1', '6', 'a, 'L=-D-(C-C)ALK-, L=-(C-C)ALK-, Q=CO, k=1-10, G=OR, RCG1=-SZ;'}{'sub': 1', '2', '2', 'i', '2', '1', '6', 'a, 'L=-(OCHCH)—, L=-(C-C)ALK-, Q=single bond, k=1-10, G=OR, RCG1=-SZ;'}{'sub': 1', '2', '2', 'i', '2', '1', '6', 'a, 'L=-(OCHCH)—, L=-(C-C)ALK-, Q=CO, k=1-10, G=OR, RCG1=-SZ;'}{'sub': ...

Innovative discovery of therapeutic, diagnostic, and antibody compositions related protein fragments of arginyl-trna synthetases

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

MST1/STK4 PHOSPHO-THREONINE 120 (pMST-T120) ANTIBODY

The present invention relates to prostate cancer (PCa). More specifically, the invention provides a MST1 phosphothreonine (pMST1-T120) antibody that can be used in various assays to study correlations between Mst1 function and T120 site phosphorylation. The present invention can also be used to determine disease development and/or progression of prostate cancer in a subject using the antibodies disclosed herein. 1. An isolated antibody that specifically binds to MST1 phospho-T120.2. A composition comprising an antibody that specifically binds to MST phospho-T120.3. A method of detecting MST1 phospho-T120 in a sample comprising:(a) providing a sample;(b) contacting the sample with an antibody that binds to MST1 phospho-T120;(c) allowing the antibody to bind to MST1 phospho-T120 in the sample; and(d) detecting the presence of MST1 phospho-T120 in the sample.4. The method according to claim 3 , wherein the sample is obtained from a tumor.5. The method according to claim 3 , wherein the detection is accomplished by immunohystochemical analysis.6. A method of determining late stage cancer in a subject comprising:(a) providing a sample of cells from a subject;(b) contacting the sample from the subject with an antibody that binds to MST1 phospho-T120;(c) allowing the antibody to bind to MST1 phospho-T120 in the sample; and(d) detecting the presence of MST1 phospho-T120 in the nucleus of the cells and not in the cytoplasm of the cells, wherein detection of MST1 phospho-T120 in the nucleus of the cells and not in the cytoplasm indicates late stage cancer.7. The method according to claim 6 , wherein the sample is obtained from a tumor.8. The method according to claim 6 , wherein the detection is accomplished by using immunohystochemical analysis.9. The method according to claim 6 , wherein the cancer is prostate cancer.10. A method of determining the amount of MST1 phospho-T120 in the cells of a sample claim 6 , comprising:(a) providing a sample of cells from a subject;(b) ...

BARD1 Isoforms in Lung and Colorectal Cancer and Use Thereof

The present invention relates to new BARD1 isoforms specific to lung cancer and colorectal cancer, a method for detecting thereof and a method for treating and/or preventing lung cancer and colorectal cancer.

COMPOSITIONS AND METHODS FOR TREATING CANCER AND MODULATING STRESS GRANULE FORMATION

The invention provides methods for treating or decreasing the likelihood of developing a stress-granule related disorder and/or cancer by administering one or more poly-ADP-ribose polymerase (PARP) inhibitors, one or more PARP activators, one or more poly-ADP-ribose glycosylase (PARG) activators, and/or one or more poly-ADP-ribose glycohydrolase ARH3 activators. The invention also provides corresponding methods of decreasing stress granule formation and/or proliferation in a cell or a population of cells. The invention further provides methods of increasing the number of stress granules and proliferation in a cell or a population of cells by administering one or more PARP activators, one or more PARP inhibitors, one or more PARG inhibitors, and/or one or more ARH3 inhibitors. The invention also provides methods for screening for agents for treating or decreasing the likelihood of developing a stress granule-related disorder or cancer, and methods for determining the propensity for developing a stress granule-related disorder or cancer, as well as compositions and kits containing one or more PARP inhibitors, one or more PARP activators, one or more PARG activators, and one or more ARH3 activators. 1. A method of treating or decreasing the likelihood of developing a stress granule-related disorder in a subject comprising administering to said subject a therapeutically effective amount of one or more poly-ADP-ribose polymerase (PARP) inhibitor(s) , one or more poly-ADP ribose glycolase (PARG) activators , and/or one or more PARP11 activators.2. The method of claim 1 , wherein said one or more PARP inhibitor(s) selectively decrease the expression and/or one or more activities of one or more PARP(s) selected from the group consisting of PARP5a claim 1 , PARP12 claim 1 , PARP13 isoform 1 (PARP13.1) claim 1 , PARP13 isoform 2 (PARP13.2) claim 1 , and PARP15.3. The method of claim 2 , wherein:(a) said decrease in expression is a decrease in the level of one or more nucleic ...

NOVEL DIAGNOSTIC AND THERAPEUTIC TARGET IN INFLAMMATORY AND/OR CARDIOVASCULAR DISEASES

Methods for diagnosing inflammatory and/or cardiovascular diseases by assaying for Fibroblast Activation Protein (FAP) expression in a body fluid is provided as well as therapeutic means based thereon. 1. A method of determining the presence of an inflammatory and/or cardiovascular disease or condition in a patient comprising assaying(i) a sample of a body fluid taken from said patient for expression of Fibroblast Activation Protein (FAP), wherein expression or an increased expression of said FAP compared to a control sample is indicative for the disease or condition in said patient; and/or(ii) a sample of a thrombus or plaque taken from said patient for expression of FAP, wherein an increased expression of FAP as compared to its expression in a sample of a body fluid taken from said patient is indicative for the disease or condition.2. The method of claim 1 , wherein said body fluid is blood.3. The method of claim 1 , wherein said disease is selected from the group atherosclerosis claim 1 , rheumatoid arthritis claim 1 , stroke or an acute coronary syndrome such as myocardial infarction claim 1 , heart attack claim 1 , chronic liver disease claim 1 , cerebral venous thrombosis claim 1 , deep venous thrombosis or pulmonary embolism.4. The method of claim 2 , wherein the condition is vulnerable atherosclerotic plaques or atherothrombosis.5. The method of claim 1 , comprising assaying said sample for FAP protein or mRNA.6. The method of claim 5 , wherein said assay is an immunoassay.7. The method of claim 6 , wherein said assay is an immunohistochemical assay.8. The method of claim 7 , wherein said assay comprises fluorescence activated cytometry (FACS) claim 7 , indirect ELISA claim 7 , sandwich ELISA or cell culture ELISA.9. The method of claim 6 , wherein said immunoassay comprises contacting said sample with a monoclonal or polyclonal antibody which binds specifically to FAP.10. The method of claim 9 , wherein said monoclonal antibody is a mouse anti-human ...

Fc FUSION PROTEINS

The embodiments of the invention relate to compositions, methods, and kits comprising a fusion protein. The fusion proteins of the embodiments include monomer polypeptides which in one embodiment have at least a binding domain, an optional hinge region, a collagen-like domain and the Fc domain of a human IgG.

Antibodies Directed to the Unprocessed Receptor Tyrosine Kinase c-Met

The present invention relates to antibodies that specifically bind to unprocessed c-Met present on the surface of tumor cells. These antibodies are useful in the diagnosis and treatment of cancer or as agents for delivering moieties to cancer cells. The antibodies of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents. 147-. (canceled)48. An isolated antibody or antigen-binding fragment thereof that specifically binds to unprocessed c-Met present on the surface of a tumor cell.49. The isolated antibody or antigen-binding fragment thereof according to wherein the antibody or fragment specifically binds to the epitope sequence VVDTYYDDQL (SEQ ID NO:2) claim 48 , RHFQSCSQCLSAPPFVQCGW (SEQ ID NO:5) or RHFQSCSQCLSAPPF (SEQ ID NO:6).50. The isolated antibody or antigen-binding fragment thereof according to claim 48 , the antibody comprising an immunoglobulin heavy chain and light chain having a sequence selected from:(i) an immunoglobulin heavy chain variable region amino acid sequence comprising the complementarity determining region (CDR) sequences SEQ ID NO:15, SEQ ID NO:16 and SEQ ID NO:17, and an immunoglobulin light chain variable region comprising the CDR sequences SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:20;(ii) an immunoglobulin heavy chain variable region amino acid sequence which is at least 90% identical to SEQ ID NO:21 and an immunoglobulin light chain variable region amino acid sequence which is at least 90% identical to SEQ ID NO:22;(iii) an immunoglobulin heavy chain variable region amino acid sequence comprising the complementarity determining region (CDR) sequences SEQ ID NO:7, SEQ ID NO:8 and SEQ ID NO:9, and an immunoglobulin light chain variable region comprising the CDR sequences SEQ ID NO:10, SEQ ID NO:11 and SEQ ID NO:12; and(ii) an immunoglobulin heavy chain variable region amino acid sequence which is at least 90% identical to SEQ ID NO:13 and an immunoglobulin light chain variable region ...

Humanized Anti-Factor D Antibodies And Uses Thereof

The invention relates to humanized anti-human Factor D monoclonal antibodies, their nucleic acid and amino acid sequences, the cells and vectors that harbor these antibodies and their use in the preparation of compositions and medicaments for treatment of diseases and disorders associated with excessive or uncontrolled complement activation. These antibodies are useful for diagnostics, prophylaxis and treatment of disease. 137-. (canceled)38. A method for detecting Factor D in a diagnostic assay comprising binding an anti-Factor D antibody or an anti-Factor D antibody fragment thereof to Factor D , wherein the antibody comprises a variable light chain comprising a CDR-L 1 having the sequence of SEQ ID NO: 16; a CDR-L2 having the sequence of SEQ ID NO: 17 , 21 or 24 , and a CDR-L3 having the sequence of SEQ ID NO: 18 , 19 or 22 , wherein the variable light chain does not comprise the sequence of SEQ ID NO: 2.39. A method for detecting Factor D in a diagnostic assay comprising binding an anti-Factor D antibody or an anti-Factor D antibody fragment thereof to Factor D , wherein the antibody comprises a variable heavy chain comprising a CDR-H1 having the sequence of SEQ ID NO: 13 , 23 or 25; a CDR-H2 having the sequence of SEQ ID NO: 14; and a CDR-H3 having the sequence of SEQ ID NO: 15 or 20 , wherein the variable heavy chain does not comprise the sequence of SEQ ID NO: 1.40. A method for detecting Factor D in a diagnostic assay comprising binding an anti-Factor D antibody or an anti-Factor D antibody fragment thereof to Factor D , wherein the antibody comprises:(i) a variable light chain comprising a CDR-L1 having the sequence of SEQ ID NO: 16; a CDR-L2 having the sequence of SEQ ID NO: 17.21 or 24, and a CDR-L3 having the sequence of SEQ ID NO: 18, 19 or 22; and(ii) a variable heavy chain comprising a CDR-H1 having the sequence of SEQ ID NO: 13, 23 or 25; a CDR-H2 having the sequence of SEQ ID NO: 14; and a CDR-H3 having the sequence of SEQ ID NO: 15 or 20.wherein (i ...

Targeting compounds

The present invention provides antibody targeting compounds in which the specificity of the antibody has been reprogrammed by covalently or noncovalently linking a targeting agent to the combining site of an antibody. By this approach, the covalently modified antibody takes on the binding specificity of the targeting agent. The compound may have biological activity provided by the targeting agent or by a separate biological agent. Various uses of the invention compounds are provided.

ANTI-CD38 ANTIBODIES

Isolated antibodies that bind to human CD38 and cynomolgus CD38 are disclosed. Also disclosed are pharmaceutical compositions comprising the disclosed antibodies, and therapeutic and diagnostic methods for using the disclosed antibodies. 1. A method of inhibiting the biological activity of human CD38 protein (SEQ ID NO: 1) by contacting said protein with an antibody that interacts with at least K121 , F135 , Q139 , D141 , E239 , W241 , C275 , K276 , F284 , P291 and E292 of SEQ ID NO:1.2. The method according to claim 1 , wherein said antibody specifically binds human CD38 (SEQ ID NO:1) and cynomolgus CD38 (SEQ ID NO:2) and comprises: i) a first CDR comprising SEQ ID NO:3;', 'ii) a second CDR comprising SEQ ID NO:4;', 'iii) a third CDR comprising SEQ ID NO:5; and, 'a) a heavy chain variable region comprising i) a first CDR comprising SEQ ID NO:6;', 'ii) a second CDR comprising SEQ ID NO:7;', 'iii) a third CDR comprising SEQ ID NO:8., 'b) a light chain variable region comprising3. The method according to wherein said heavy chain variable region comprises SEQ ID NO:9.4. The method according to wherein said light chain variable region comprises SEQ ID NO:10.5. The method according to wherein said heavy chain variable region comprises SEQ ID NO:9 and said light chain variable region comprises SEQ ID NO:10.6. The method according to wherein the heavy chain comprises SEQ ID NO:21 and the light chain comprises SEQ ID NO:22.7. The method of claim 1 , wherein said antibody specifically binds human CD38 (SEQ ID NO: 1) and cynomolgus CD38 (SEQ ID NO:2) and comprises: i) a first CDR comprising SEQ ID NO:13;', 'ii) a second CDR comprising SEQ ID NO: 14;', 'iii) a third CDR comprising SEQ ID NO: 15; and, 'a) a heavy chain variable region comprising i) a first CDR comprising SEQ ID NO: 16;', 'ii) a second CDR comprising SEQ ID NO: 17;', 'iii) a third CDR comprising SEQ ID NO: 18., 'b) a light chain variable region comprising8. The method according to wherein said heavy chain ...

Inhibitors Of Complement Activation

The invention relates to factor D inhibitors, which bind to factor D and block the functional activity of factor D in complement activation. The inhibitors include antibody molecules, as well as homologues, analogues and modified or derived forms thereof, including immunoglobulin fragments like Fab, F(ab′)and Fv, small molecules, including peptides, oligonucleotides, peptidomimetics and organic compounds. A monoclonal antibody which bound to factor D and blocked its ability to activate complement was generated and designated 166-32. The hybridoma producing this antibody was deposited at the American Type Culture Collection, 10801 University Blvd., Manassas, Va. 20110-2209, under Accession Number HB-12476. 1. An inhibitor of complement activation which specifically binds factor D which at a molar ratio of about 1.5:1 (inhibitor:factor D) can substantially inhibit complement activation.2. An inhibitor of complement activation which specifically binds to human factor D which at a molar ratio of less than 80:1 (inhibitor:factor D) can substantially completely inhibit complement activation.3. The inhibitor of or wherein the inhibition of complement activation is determined in vitro.4. The inhibitor of or wherein the inhibition of complement activation is determined in vitro by an extracorporeal assay.5. An inhibitor of complement activation which binds to a region of human factor D between (and including) amino acid residue numbers Cys154 and Cys170.6. The inhibitor of which does not bind to human factor D if amino acid residues Arg156 claim 5 , His159 and Leu168 are absent.7. The inhibitor of any of claim 5 , claim 5 , or which is an antibody or a homologue claim 5 , analogue or fragment thereof claim 5 , a peptide claim 5 , a peptidomimetic or an organic compound.8. The inhibitor of wherein the antibody fragment is Fab claim 7 , F(ab′) claim 7 , Fv or single chain Fv.9. The inhibitor of wherein the antibody is a chimeric claim 7 , humanized claim 7 , deimmunised or ...

PROCESS FOR PROTEIN EXTRACTION

The invention includes a process for extracting a target protein from cells that includes lowering the pH of a whole cell solution to form an acidic solution, disrupting the cells to release the protein into the acidic solution, and separating the cellular debris from the released protein to obtain a protein product enriched in the heterologous target protein. The invention also includes addition of a solubility enhancer. 111-. (canceled)12Escherichia coli. A recombinant protein product produced by a method for extracting a heterologous target protein from cells , comprising the following steps:{'i': 'E. coli', 'a) lowering the pH of a solution containing whole cells expressing said heterologous target protein to form an acidic cell solution;'}{'i': 'E. coli', 'b) adding at least one solubility enhancer to the solution containing the cells;'}c) disrupting the cells to release the heterologous target protein into the acidic solution; andd) separating cellular debris from the released heterologous target protein to obtain a protein preparation enriched in the heterologous target protein.13. The recombinant protein product of claim 12 , wherein the protein is an antibody or antibody fragment.14. The recombinant protein product of claim 13 , wherein the antibody or antibody fragment is an anti-VEGF antibody fragment.15. The recombinant protein product of claim 13 , wherein the antibody or antibody fragment is Fab VEGF or Anti-Tissue Factor Antibody.16. The recombinant protein product of claim 12 , wherein the pH is lowered to a pH of about 4.0 to about 5.0.17. The recombinant protein product of claim 12 , wherein the pH is lowered to a pH of about 4.0 to about 4.5.18. The recombinant protein product of claim 12 , wherein the pH is lowered to no more than 4.0.19. The recombinant protein product of claim 12 , wherein said separating step comprises centrifugation.20. The recombinant protein product of claim 12 , wherein said at least one solubility enhancer is added to the ...

Aberrant cell-restricted immunoglobulins provided with a toxic moiety

Described are immunoglobulins provided with a toxic moiety, comprising at least an immunoglobulin variable region that specifically binds to an MHC-peptide complex preferentially associated with aberrant cells. These immunoglobulins provided with a toxic moiety are preferably used in selectively modulating biological processes. The provided immunoglobulins provided with a toxic moiety are of particular use in pharmaceutical compositions for the treatment of diseases related to cellular aberrancies, such as cancers and autoimmune diseases.

Methods and compositions for the inhibition of stat5 in prostate cancer cells

The present invention relates to compositions and methods for the treatment of prostate cancer. In certain embodiments, the invention relates to compositions and methods for the inhibition of prostate cancer cell growth, comprising inhibiting the activity of Stat5 in prostate cancer cells.

Transgenic plants modified for reduced cadmium transport, derivative products, and related methods

Various embodiments are directed to transgenic plants, including transgenic tobacco plants and derivative seeds, genetically modified to impede the transport of Cadmium (Cd) from the root system to aerial portions of transgenic plants by reducing the expression levels of HMA-related transporters. Various embodiments are directed to transgenic tobacco plants genetically modified to stably express a RNAi construct encoding RNAi polynucleotides that enable the degradation of endogenous NtHMA RNA variants. Reduced expression of NtHMA transporters in transgenic plants results in substantially reduced content of Cadmium (Cd) in the leaf lamina. Various consumable products that are substantially free or substantially reduced in Cd content can be produced by incorporating leaves derived from transgenic tobacco plants modified to reduce the expression of NtHMA transporters.

Inhibition of AXL/GAS6 Signaling in the Treatment of Disease

Compositions and methods are provided for alleviating endometriosis, kidney disease, inflammatory disease and/or transplant rejection in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits AXL, MER or Tyro3 protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL, MER or Tyro3 and its ligand GAS6. 1. A method of treating , reducing , or preventing endometriosis , kidney disease , inflammatory disease and/or transplant rejection in a mammalian patient , the method comprising:administering one or more inhibitor agents selected from the group consisting of (a) an inhibitor of AXL, MER and/or Tyro3 activity (b) an inhibitor of GAS6 activity; and (c) an inhibitor of AXL, MER or Tyro3-GAS6 interaction.2. A method of determining the susceptibility of a subject to endometriosis , kidney disease , inflammatory disease and/or transplant rejection , said method comprising:detecting the level of AXL, MER or Tyro3 activity in a biological sample from a subject; andcomparing the level of the AXL, MER or Tyro3 activity in the biological sample to a predetermined level,wherein an increase over the predetermined level is indicative of a predisposition of the subject to develop endometriosis, kidney disease, inflammatory disease and/or transplant rejection (GVHD).3. A method of determining the susceptibility of a subject to endometriosis , kidney disease , inflammatory disease and/or transplant rejection , said method comprising:detecting the level of GAS6 activity in a biological sample from a subject; andcomparing the level of the GAS6 activity in the biological sample to a predetermined level,wherein an increase over the predetermined level is indicative of a predisposition of the subject to develop endometriosis, kidney disease, inflammatory disease and/or transplant rejection (GVHD).4. A method of determining treatment efficacy of administering an inhibitor agent comprising detecting ...

ACTRIIB BINDING AGENTS AND USES THEREOF

The disclosure provides, among other aspects, neutralizing antibodies and portions thereof that bind to ActRIIB and uses for same. 1. An anti-ActRIIB antibody or functional fragment thereof that binds to ActRIIB between amino acids 19-134 of SEQ ID NO:1.2. The anti-ActRIIB antibody or functional fragment thereof according to claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof binds to ActRIIB with a Kof 1 nM or less.3. The anti-ActRIIB antibody or functional fragment thereof according to claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof inhibits myostatin binding to ActRIIB.4. The anti-ActRIIB antibody or functional fragment thereof according to claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof inhibits myostatin induced signaling as measured by a Smad dependent reporter gene assay.5. The anti-ActRIIB antibody or functional fragment thereof according to claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof binds to ActRIIB with a 10-fold or greater affinity that it binds to ActRIIA.6. The anti-ActRIIB antibody or functional fragment thereof according to claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof binds to an epitope selected from the group consisting of: amino acids 77-83 of SEQ ID NO:1 claim 1 , amino acids 60-64 of SEQ ID NO:1 claim 1 , 73-74 of SEQ ID NO:1 claim 1 , amino acids 73-83 of SEQ ID NO:1 claim 1 , amino acids 98-101 of SEQ ID NO:1; amino acids 35-39 of SEQ ID NO:1 and amino acids 52-55 of SEQ ID NO:1.7. The anti-ActRIIB antibody or functional fragment thereof according to claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof is of the IgG1 isotype.8. The anti-ActRIIB antibody or functional fragment thereof according to claim 1 , wherein the anti-ActRIIB antibody or functional fragment thereof is characterized by an altered effector function through mutation of the Fc region.9. An isolated polynucleotide ...

ANTAGONISTS OF PCSK9

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure. 1. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake.2. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake and binds to human PCSK9 with an equilibrium dissociation constant (1(D) of less than 1200 nM.3. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 500 nM.4. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 100 nM.5. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 5 nM.6. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake at an IC50 of less than 500 nM.7. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an IC50 of less than 200 nM.8. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an IC50 of less than 100 nM.9. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 20%.10. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 50%.11. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 60%.12. An isolated PCSK9-specific antibody ...

INNOVATIVE DISCOVERY OF THERAPEUTIC, DIAGNOSTIC, AND ANTIBODY COMPOSITIONS RELATED TO PROTEIN FRAGMENTS OF PHENYLALANYL-ALPHA-TRNA SYNTHETASES

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications. 1125-. (canceled)126. A therapeutic composition , comprising an isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% , 85% , 90% , 95% , 98% , or 100% identical to a sequence in any of Table(s) 1-3 , or Table(s) 4-6 , or Table(s) 7-9 , wherein the polypeptide has a solubility of at least about 5 mg/mL , and wherein the composition has a purity of at least about 95% on a protein basis and less than about 10 EU endotoxin/mg protein.127. The therapeutic composition of claim 126 , wherein the polypeptide specifically binds to a binding partner to exert a physiological effect.128. The therapeutic composition of claim 126 , wherein said polypeptide differs from an amino acid sequence set forth in any of Table(s) 1-3 claim 126 , or Table(s) 4-6 claim 126 , or Table(s) 7-9 claim 126 , by substitution claim 126 , deletion claim 126 , and/or addition of about 0 claim 126 , 1 claim 126 , 2 claim 126 , 3 claim 126 , 4 claim 126 , 5 claim 126 , 6 claim 126 , 7 claim 126 , 8 claim 126 , 9 claim 126 , 10 claim 126 , or 11 amino acids claim 126 , and wherein the altered polypeptide substantially retains a non-canonical activity of the unaltered protein.129. The therapeutic composition of claim 126 , wherein the AARS polypeptide is fused to a heterologous polypeptide.130. The therapeutic composition of claim 126 , wherein at least one moiety or a solid substrate is covalently or non-covalently attached to said polypeptide.131. An isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% claim 126 , 85% ...

Therapeutics and processes for treatment of immune disorders

Processes of diagnosing or treating an autoimmune abnormality are provided whereby the presence of IgA anti-neutrophil cytoplasmic antibodies (ANCA) in a subject are detected correlating with both presence and severity of disease such as Wegener's granulomatosis (WG). The FCAR genotype predicts whether IgA ANCA will be stimulatory or inhibitory of neutrophil activation such that in subjects with an inhibitory genotype, IgA ANCA will act as an inhibitor of disease severity, and in subjects with a proinflammatory genotype, IgA ANCA will increase disease severity as observed by increased prevalence of renal disease in WG. Thus, individualized medical treatment is possible based on determination of the presence of IgA ANCA and FCAR genotype.

Biomarkers for Non-Hodgkin Lymphomas and Uses Thereof

The disclosure provides a method of identifying a subject as having B-cell non-Hodgkin lymphoma (NHL) such as testing a sample from a subject for a mutation in one or more biomarkers. Also described are methods for classifying or monitoring a subject having, or suspected of having, B-cell non-Hodgkin lymphoma comprising testing the sample for a mutation in one or more biomarkers. 1. An isolated nucleic acid molecule encoding an EZH2 protein with a mutation at position Y641 with respect to the amino acid sequence set forth in SEQ ID NO: 1.2. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule is a cDNA or an mRNA.3. The isolated nucleic acid molecule of claim 2 , wherein the nucleic acid molecule has at least 90% sequence identity to SEQ ID NO: 2.4. The isolated nucleic acid molecule of claim 1 , wherein the mutation at position Y641 is selected from Y641N claim 1 , Y641H claim 1 , Y641F claim 1 , Y641S and Y641C.6. An isolated EZH2 protein with a mutation at position Y641 with respect to the amino acid sequence set forth in SEQ ID NO: 1.7. The isolated EZH2 protein of claim 6 , wherein the protein has at least 90% sequence identity to SEQ ID NO: 1.8. The isolated EZH2 protein of claim 6 , wherein the mutation at position Y641 is selected from Y641N claim 6 , Y641H claim 6 , Y641F claim 6 , Y641S and Y641C.9. An antibody that selectively binds to the EZH2 protein of .10. A method for identifying a subject as having B-cell non-Hodgkin lymphoma (NHL) claim 6 , the method comprising testing a sample from the subject for a mutation in EZH2 corresponding to a mutation at position Y641 with respect to the amino acid sequence set forth in SEQ ID NO: 1.11. The method of claim 10 , wherein the presence of the Y641 mutation in the sample identifies the subject as having follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL).12. The method of claim 10 , wherein the mutation at position Y641 is Y641N claim 10 , Y641H claim 10 , Y641F ...

Antibody targeting through a modular recognition domain

The present invention provides antibodies containing one or more modular recognition domains (MRDs) for targeting the antibodies to specific sites. The use of the antibodies containing one or more modular recognition domains to treat disease, and methods of making antibodies containing one or more modular recognition domains are also provided in the invention. 1. An isolated full length antibody comprising a modular recognition domain (MRD).2. The antibody of claim 1 , wherein the antibody and the MRD are operably linked through a linker peptide.313-. (canceled)14. The antibody of claim 1 , wherein the target of the MRD is an integrin.1518-. (canceled)19. The antibody of claim 1 , wherein the target of the MRD is an angiogenic cytokine.2025-. (canceled)26. The antibody of claim 1 , wherein the target of the MRD is ErbB2.27. The antibody of claim 1 , wherein the target of the MRD is VEGF.28. (canceled)29. The antibody of claim 1 , wherein the target of the MRD is an insulin-like growth factor-I receptor.30. (canceled)31. The antibody of claim 1 , wherein the target of the MRD is a tumor antigen.32. The antibody of claim 1 , wherein the target of the MRD is CD20.33. The antibody of claim 1 , wherein the target of the MRD is an epidermal growth factor receptor (EGFR).3437-. (canceled)38. The antibody of claim 1 , wherein the target of the MRD is the ErbB3 receptor.39. The antibody of claim 1 , wherein the target of the MRD is tumor-associated surface antigen epithelial cell adhesion molecule (Ep-CAM).40. The antibody of claim 1 , wherein the target of the MRD is an angiogenic factor.41. The antibody of claim 40 , wherein the antibody binds to a cell surface antigen selected from the group consisting of EGFR claim 40 , ErbB2 claim 40 , ErbB3 claim 40 , ErbB4 claim 40 , CD20 claim 40 , insulin-like growth factor-I receptor claim 40 , or prostate specific membrane antigen.42. The antibody of claim 1 , wherein the target of the MRD is an angiogenic receptor.4345-. ( ...

SERUM AMYLOID P-ANTIBODY FUSION PROTEINS

Functionalized pentraxin-2 (PTX-2) protomers and functionalized PTX-2 pentamers, methods for preparing functionalized PTX-2 protomers and functionalized PTX-2 pentamers, pharmaceutical compositions including functionalized PTX-2 pentamers, and methods for using the same are described herein. 1. A composition comprising a serum amyloid P (PTX-2) pentamer having at least one PTX-2 protomer with an attached antibody or antibody fragment.2. The composition of claim 1 , wherein the PTX-2 pentamer comprises five protomers with attached antibodies or antibody fragments.3. The composition of claim 1 , wherein the PTX-2 pentamer comprises one or more unmodified PTX-2 protomers.4. The composition of claim 1 , wherein the PTX-2 pentamer comprises one or more PTX-2 protomers that are modified to eliminate a ligand binding site on naturally occurring PTX-2 protomers claim 1 , a Cabinding site on naturally occurring PTX-2 protomers claim 1 , or a combination thereof.5. The composition of claim 1 , wherein the antibody or antibody fragment are attached to the C-terminus or the N-terminus of at least one PTX-2 protomer.6. The composition of claim 5 , wherein the at least one PTX-2 protomer further comprises a linker between the antibody or antibody fragment and at least one PTX-2 protomer.7. The composition of claim 1 , wherein antibody or antibody fragment inserted within at least one PTX-2 protomer.8. The composition of claim 7 , wherein at least one PTX-2 protomer further comprises a linker between the antibody or antibody fragment and at least one PTX-2 protomer.9. The composition of claim 1 , wherein the PTX-2 pentamer comprises one or more PTX-2 protomers having at least one additional cysteine amino acid that is not present in naturally occurring PTX-2 protomers.10. The composition of claim 9 , wherein at least one cysteine amino acid participates in a disulfide bond with the antibody or antibody fragment.11. The composition of claim 9 , wherein at least one cysteine amino ...

INNOVATIVE DISCOVERY OF THERAPEUTIC, DIAGNOSTIC, AND ANTIBODY COMPOSITIONS RELATED TO PROTEIN FRAGMENTS OF VALYL-TRNA SYNTHETASES

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications. 1125-. (canceled)126. A therapeutic composition , comprising an isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% , 85% , 90% , 95% , 98% , or 100% identical to a sequence in any of Table(s) 1-3 , or Table(s) 4-6 , or Table(s) 7-9 , wherein the polypeptide has a solubility of at least about 5 mg/mL , and wherein the composition has a purity of at least about 95% on a protein basis and less than about 10 EU endotoxin/mg protein.127. The therapeutic composition of claim 126 , wherein the polypeptide specifically binds to a binding partner to exert a physiological effect.128. The therapeutic composition of claim 126 , wherein said polypeptide differs from an amino acid sequence set forth in any of Table(s) 1-3 claim 126 , or Table(s) 4-6 claim 126 , or Table(s) 7-9 claim 126 , by substitution claim 126 , deletion claim 126 , and/or addition of about 0 claim 126 , 1 claim 126 , 2 claim 126 , 3 claim 126 , 4 claim 126 , 5 claim 126 , 6 claim 126 , 7 claim 126 , 8 claim 126 , 9 claim 126 , 10 claim 126 , or 11 amino acids claim 126 , and wherein the altered polypeptide substantially retains a non-canonical activity of the unaltered protein.129. The therapeutic composition of claim 126 , wherein the AARS polypeptide is fused to a heterologous polypeptide.130. The therapeutic composition of claim 126 , wherein at least one moiety or a solid substrate is covalently or non-covalently attached to said polypeptide.131. An isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% claim 126 , 85% ...

INNOVATIVE DISCOVERY OF THERAPEUTIC, DIAGNOSTIC, AND ANTIBODY COMPOSITIONS RELATED TO PROTEIN FRAGMENTS OF PHENYLALANYL-BETA-TRNA SYNTHETASES

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications. 1125-. (canceled)126. A therapeutic composition , comprising an isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% , 85% , 90% , 95% , 98% , or 100% identical to a sequence in any of Table(s) 1-3 , or Table(s) 4-6 , or Table(s) 7-9 , wherein the polypeptide has a solubility of at least about 5 mg/mL , and wherein the composition has a purity of at least about 95% on a protein basis and less than about 10 EU endotoxin/mg protein.127. The therapeutic composition of claim 126 , wherein the polypeptide specifically binds to a binding partner to exert a physiological effect.128. The therapeutic composition of claim 126 , wherein said polypeptide differs from an amino acid sequence set forth in any of Table(s) 1-3 claim 126 , or Table(s) 4-6 claim 126 , or Table(s) 7-9 claim 126 , by substitution claim 126 , deletion claim 126 , and/or addition of about 0 claim 126 , 1 claim 126 , 2 claim 126 , 3 claim 126 , 4 claim 126 , 5 claim 126 , 6 claim 126 , 7 claim 126 , 8 claim 126 , 9 claim 126 , 10 claim 126 , or 11 amino acids claim 126 , and wherein the altered polypeptide substantially retains a non-canonical activity of the unaltered protein.129. The therapeutic composition of claim 126 , wherein the AARS polypeptide is fused to a heterologous polypeptide.130. The therapeutic composition of claim 126 , wherein at least one moiety or a solid substrate is covalently or non-covalently attached to said polypeptide.131. An isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% claim 126 , 85% ...

INNOVATIVE DISCOVERY OF THERAPEUTIC, DIAGNOSTIC, AND ANTIBODY COMPOSITIONS RELATED TO PROTEIN FRAGMENTS OF HISTIDYL-TRNA SYNTHETASES

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications. 1125-. (canceled)126. A therapeutic composition , comprising an isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% , 85% , 90% , 95% , 98% , or 100% identical to a sequence in any of Table(s) 1-3 , or Table(s) 4-6 , or Table(s) 7-9 , wherein the polypeptide has a solubility of at least about 5 mg/mL , and wherein the composition has a purity of at least about 95% on a protein basis and less than about 10 EU endotoxin/mg protein.127. The therapeutic composition of claim 126 , wherein the polypeptide specifically binds to a binding partner to exert a physiological effect.128. The therapeutic composition of claim 126 , wherein said polypeptide differs from an amino acid sequence set forth in any of Table(s) 1-3 claim 126 , or Table(s) 4-6 claim 126 , or Table(s) 7-9 claim 126 , by substitution claim 126 , deletion claim 126 , and/or addition of about 0 claim 126 , 1 claim 126 , 2 claim 126 , 3 claim 126 , 4 claim 126 , 5 claim 126 , 6 claim 126 , 7 claim 126 , 8 claim 126 , 9 claim 126 , 10 claim 126 , or 11 amino acids claim 126 , and wherein the altered polypeptide substantially retains a non-canonical activity of the unaltered protein.129. The therapeutic composition of claim 126 , wherein the AARS polypeptide is fused to a heterologous polypeptide.130. The therapeutic composition of claim 126 , wherein at least one moiety or a solid substrate is covalently or non-covalently attached to said polypeptide.131. An isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% claim 126 , 85% ...

Autotaxin pathway modulation and uses thereof

Disclosed are methods for preventing, treating, or reducing symptoms of a disorder involving the autotaxin (ATX) pathway. In one embodiment, the method features administering to a mammal a sufficient amount of an autotaxin (ATX) or lysophosphatidic acid (LPA) signaling inhibitor, to prevent, treat or reduce symptoms of an inflammatory disorder, autoimmune disorder, fibrosis or malignancy of the lung. Further disclosed are methods for diagnosing an autotaxin-related disorder as well as kits for performing the methods of the invention.

COMPOSITIONS AND METHODS FOR IMMUNIZATION AGAINST BACTERIA EXPRESSING A CARBAPENEMASE

The present invention provides vaccine and pharmaceutical compositions for treating or preventing bacterial inventions. The vaccine compositions of the invention include a carbapenemase such as a serine carbapenemase, a metallo-β-lactamase or an immunogenic fragment thereof. The pharmaceutical compositions include an anti-carbapenemase antibody or fragment thereof. Also provided are methods for treating and preventing a bacterial infection using the vaccine and pharmaceutical compositions of the invention. The invention further provides antibody conjugates that include an antibody or fragment thereof conjugated to a siderophore or an analog thereof. 1. A vaccine composition comprising a serine carbapenemase or immunogenic fragment thereof and a pharmaceutically acceptable carrier.2K. pneumoniaSerratia marcescens. The vaccine composition of claim 1 , wherein said serine carbapenemase is selected from the group consisting of a carbapenemase (KPC) claim 1 , a enzyme (SME) claim 1 , a imipenem-hydrolyzing β-lactamase (IMI) claim 1 , a not metalloenzyme carbapenemase (NMC-A) claim 1 , an integron-borne cephalosporinase (IBC) and a Guiana extended spectrum (GES) enzyme.37-. (canceled)8. A method for treating or preventing a bacterial infection in a subject in need thereof comprising administering a therapeutically effective amount of a vaccine composition of to said subject.915-. (canceled)16. A pharmaceutical composition comprising an anti-serine carbapenemase antibody or a fragment thereof and a pharmaceutically acceptable carrier.1719-. (canceled)20. The pharmaceutical composition of claim 16 , wherein said anti-serine carbapenemase antibody is conjugated to a siderophore or an analog thereof.21. The pharmaceutical composition of claim 20 , wherein said siderophore is selected from the group consisting of enterobactin claim 20 , bacillibactin claim 20 , vibrobactin claim 20 , ferrichrome claim 20 , desferrioxamine claim 20 , fusarinine C claim 20 , ornibactin claim 20 ...

Anti-Tumor Antigen Antibodies and Methods of Use

Antibodies that bind to tumor associated antigen CD44 or to tumor associated antigen EphA2, are disclosed herein, as well as related compositions and methods of use. Methods of use encompass cancer therapies, diagnostics, and screening methods. 143-. (canceled)44. A monoclonal antibody that specifically binds an epitope of EphA2 that is specifically bound by antibody 2D6 , D2-1A7 , D2-1A9 or D2-1B1 , or that competes with antibody 2D6 , D2-1A7 , D2-1A9 or D2-1B1 , for binding to EphA2.45. The monoclonal antibody of claim 44 , wherein said antibody comprises:{'sub': H', 'H', 'H, 'a) a VCDR1, a VCDR2 and a VCDR3 of 2D6;'}{'sub': H', 'H', 'H, 'b) a VCDR1, a VCDR2 and a VCDR3 of D2-1A7;'}{'sub': H', 'H', 'H, 'c) a VCDR1, a VCDR2 and a VCDR3 of D2-1A9;'}or{'sub': H', 'H', 'H, 'd) a VCDR1, a VCDR2 and a VCDR3 of D2-1B1.'}46. The monoclonal antibody of claim 44 , wherein said antibody comprises:{'sub': L', 'L', 'L, 'a) a VCDR1, a VCDR2 and a VCDR3 of 2D6;'}{'sub': L', 'L', 'L, 'b) a VCDR1, a VCDR2 and a VCDR3 of D2-1A7;'}{'sub': L', 'L', 'L, 'c) a VCDR1, a VCDR2 and a VCDR3 of D2-1A9;'}or{'sub': L', 'L', 'L, 'd) a VCDR1, a VCDR2 and a VCDR3 of D2-1B1;'}47. A monoclonal antibody that specifically binds an epitope of EphA2 that is specifically bound by an antibody selected from A3H9 claim 44 , A3G3 claim 44 , A3D10 claim 44 , A3D1 claim 44 , A3C8 claim 44 , 1A3 claim 44 , 1A5 claim 44 , 1A8 claim 44 , 1A12 claim 44 , 1B2 claim 44 , 1C2 claim 44 , 1C7 claim 44 , 1D8 claim 44 , and 15H11 or that competes with an antibody selected from A3H9 claim 44 , A3G3 claim 44 , A3D10 claim 44 , A3D1 claim 44 , A3C8 claim 44 , 1A3 claim 44 , 1A5 claim 44 , 1A8 claim 44 , 1A12 claim 44 , 1B2 claim 44 , 1C2 claim 44 , 1C7 claim 44 , 1D8 claim 44 , and 15H11 for binding to EphA2.48. A monoclonal antibody that specifically binds an epitope of CD44 that is specifically bound by antibody F2-1A6 or F2-1H9 claim 44 , or that competes with antibody F2-1A6 or F2-1H9 claim 44 , for binding to CD44.49 ...

METHODS OF GENERATING ANTIBODIES TO METALLOENZYMES

A method of generating an antibody which inhibits a metalloenzyme is disclosed. The method comprises immunizing a subject with: 1. A method of generating an antibody which inhibits a metalloenzyme , the method comprising immunizing a subject with:(i) a synthetic zinc mimicry compound having structural and electronic properties similar to a catalytic domain of the metalloenzyme; and(ii) the metalloenzyme,thereby generating the antibody which inhibits the metalloenzyme.2. The method of claim 1 , wherein said metalloenzyme is MMP-7 or ALF.4. The method of claim 1 , wherein said immunizing is effected by initially immunizing with (i) and subsequently immunizing with (ii).5. The method of claim 1 , wherein said immunizing is effected by co-immunizing with (i) and (ii).6. The method of claim 1 , wherein said metalloenzyme is not naturally expressed by the subject.8. (canceled)9. The antibody of claim 7 , wherein said antigen recognition region binds the metal ion coordinating amino acids within said catalytic zinc site of said ALF and to said metal ion of said metal ion coordinating amino acids within said catalytic zinc site of said ALF.10. (canceled)11. An antibody comprising an antigen recognition region which binds a catalytic site of MMP-7 claim 7 , wherein the antibody inhibits the activity of said MMP-7 and wherein the Ki of the antibody towards said MMP-7 is at least 5 times lower than a Ki of the antibody towards MMP2 or MMP9.1215-. (canceled)16. The antibody of attached to a detectable moiety or a therapeutic moiety.17. A method of treating a disease associated with imbalanced or abnormal activity of MMP-7 in a subject in need thereof claim 11 , the method comprising administering to the subject a therapeutically effective amount of the antibody of claim 11 , thereby treating the disease associate with imbalanced or abnormal activity of MMP-7 in the subject.18. The method of claim 17 , wherein the disease is cancer or an inflammatory bowel disease.19. A method ...

Anti-Tie2 Antibodies and Uses Thereof

The present invention provides antibodies that bind to Tie2 and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human Tie2 and block the interaction between Tie2 and one or more Tie2 ligands such as angiopoietin 1 (Ang1), angiopoietin 2 (Ang2), angiopoietin 3 (Ang3) and/or angiopoietin 4 (Ang4). The antibodies of the invention are useful, inter alia, for the treatment of diseases and disorders associated with one or more Tie2 biological activities including angiogenesis. 1. An isolated antibody or antigen-binding fragment thereof that specifically binds human Tie2 and blocks the interaction between Tie2 and a Tie2 ligand.2. The isolated antibody or antigen-binding fragment of claim 1 , wherein the Tie2 ligand is selected from the group consisting of Ang1 claim 1 , Ang2 claim 1 , Ang3 and Ang4.3. The isolated antibody or antigen-binding fragment of claim 1 , wherein antibody or antigen-binding fragment thereof blocks the interaction between Tie2 and all four of Ang1 claim 1 , Ang2 claim 1 , Ang3 and Ang4.4. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment thereof specifically binds a polypeptide consisting of Ig1-Ig2-EGF domains of human Tie2 (SEQ ID NO:7) claim 1 , or a polypeptide consisting of Ig2-EGF domains of human Tie2 (SEQ ID NO:8).5. The antibody or antigen-binding fragment of claim 4 , wherein the antibody or antigen-binding fragment interacts with one or more amino acids located within one or more amino acid segments selected from the group consisting of amino acids 96-106 of SEQ ID NO:7 claim 4 , amino acids 139-152 of SEQ ID NO:7; and amino acids 166-175 of SEQ ID NO:7.6. The antibody or antigen-binding fragment of claim 5 , wherein the antibody or antigen-binding fragment interacts with amino acids 96-106 of SEQ ID NO:7 claim 5 , amino acids 139-152 of SEQ ID NO:7; and amino acids 166-175 of SEQ ID NO:7 claim 5 ...

Egfr-related polypeptides and methods of use

Described herein are truncated EGF receptor polypeptides, nucleic acids encoding them, and methods of using them to help select a method of treatment for an EGFR-related cancer, to predict clinical outcome, and to detect micrometastases or minimal residual disease. High EGFR expression and phosphorylated EGFR predicts poor survival in head and neck cancer patients, but does not correlate with advanced stage disease. In our studies, we determined that clinical biological correlates are likely to be more accurate when different aspects of EGFR are evaluated in combination. We analyzed EGFR phosphorylation, expression and mutations in 60 primary head and neck tumors. We not only found that head and neck tumors with either truncated or activated EGFR tend to have higher tumor and nodal stage, but also discovered three EGFR truncations.

HUMANEERED ANTI-FACTOR B ANTIBODY

This invention relates to humaneered anti-factor B antibodies and antigen-binding fragments thereof with reduced immunogenicity. The humaneered anti-factor B antibodies and antigen-binding fragments thereof are derived from murine monoclonal antibody 1379, which binds factor B in the third short consensus repeat (“SCR”) domain and selectively inhibits activation of the alternative complement pathway by preventing formation of the C3bBb complex. The invention also relates to methods of treating diseases or disorders in which activation of the alternative complement pathway plays a role, and methods of selectively inhibiting activation of the alternative complement pathway in an individual in need thereof. 1. A humaneered anti-factor B antibody or antigen-binding fragment thereof derived from murine monoclonal antibody 1379 (“mAb 1379”) that selectively binds to factor B within the third short consensus repeat (“SCR”) domain and prevents formation of the C3bBb complex , wherein the humaneered antibody or antigen-binding fragment thereof has an equilibrium dissociation constant (“K”) between about 1.0×10M and about 1.0×10M.2. The humaneered anti-factor B antibody or antigen binding fragment thereof of claim 1 , wherein the Kis between about 1.0×10M and about 9.0×10M.3. The humaneered anti-factor B antibody or antigen-binding fragment thereof of claim 1 , wherein the Kis between about 3.0×10M and about 7.0×10M.4. The humaneered anti-factor B antibody or antigen-binding fragment thereof of claim 1 , wherein the Kis about 3.7×10M or less.5. The humaneered anti-factor B antibody or antigen-binding fragment thereof of claim 1 , wherein the Kis about 4.5×10M or less.6. The humaneered anti-factor B antibody or antigen-binding fragment thereof of claim 1 , wherein the Kis about 5.4×10M or less.7. The humaneered anti-factor B antibody or antigen-binding fragment thereof of claim 1 , wherein the Kis about 6.5×10M or less.8. The humaneered anti-factor B antibody or antigen- ...

MONOCLONAL ANTIBODIES AGAINST C-MET

Isolated monoclonal antibodies which bind to human c-Met, the hepatocyte growth factor receptor, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and therapeutic and diagnostic methods for using the antibodies are also disclosed.

INNOVATIVE DISCOVERY OF THERAPEUTIC, DIAGNOSTIC, AND ANTIBODY COMPOSITIONS RELATED TO PROTEIN FRAGMENTS OF GLYCYL-TRNA SYNTHETASES

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications. 1125-. (canceled)126. A therapeutic composition , comprising an isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% , 85% , 90% , 95% , 98% , or 100% identical to a sequence in any of Table(s) 1-3 , or Table(s) 4-6 , or Table(s) 7-9 , wherein the polypeptide has a solubility of at least about 5 mg/mL , and wherein the composition has a purity of at least about 95% on a protein basis and less than about 10 EU endotoxin/mg protein.127. The therapeutic composition of claim 126 , wherein the polypeptide specifically binds to a binding partner to exert a physiological effect.128. The therapeutic composition of claim 126 , wherein said polypeptide differs from an amino acid sequence set forth in any of Table(s) 1-3 claim 126 , or Table(s) 4-6 claim 126 , or Table(s) 7-9 claim 126 , by substitution claim 126 , deletion claim 126 , and/or addition of about 0 claim 126 , 1 claim 126 , 2 claim 126 , 3 claim 126 , 4 claim 126 , 5 claim 126 , 6 claim 126 , 7 claim 126 , 8 claim 126 , 9 claim 126 , 10 claim 126 , or 11 amino acids claim 126 , and wherein the altered polypeptide substantially retains a non-canonical activity of the unaltered protein.129. The therapeutic composition of claim 126 , wherein the AARS polypeptide is fused to a heterologous polypeptide.130. The therapeutic composition of claim 126 , wherein at least one moiety or a solid substrate is covalently or non-covalently attached to said polypeptide.131. An isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% claim 126 , 85% ...

NOTUM PROTEIN MODULATORS AND METHODS OF USE

Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat hyperproliferative disorders are provided. 1101-. (canceled)102. An isolated anti-Notum antibody which competes with hSC2.D2.2 antibody for binding to Notum.103. The anti-Notum antibody of claim 102 , comprising a heavy chain and a light chain; whereinthe heavy chain comprises CDR1 comprising the amino acid sequence of SEQ ID NO:122, CDR2 comprising the amino acid sequence of SEQ ID NO:160, and CDR3 comprising the amino acid sequence of SEQ ID NO:198; andthe light chain comprises CDR1 comprising the amino acid sequence of SEQ ID NO:236, CDR2 comprising the amino acid sequence of SEQ ID NO:274, and CDR3 comprising the amino acid sequence of SEQ ID NO:312.104. The anti-Notum antibody of claim 103 , wherein the heavy chain comprises a variable region comprising the amino acid sequence of SEQ ID NO:331 and the light chain comprises a variable region comprising the amino acid sequence of SEQ ID NO:332.105. The anti-Notum antibody of claim 103 , wherein the antibody is hSC2.D2.2 antibody.106. An isolated anti-Notum antibody comprising CDR1 claim 103 , CDR2 claim 103 , and CDR3 of the heavy chain and CDR1 claim 103 , CDR2 claim 103 , and CDR3 of the light chain of an antibody selected from SC2.A1 antibody claim 103 , SC2.A3 antibody claim 103 , SC2.A6 antibody claim 103 , SC2.A8 antibody claim 103 , SC2.A11 antibody. SC2.A12 antibody claim 103 , SC2.A13 antibody claim 103 , SC2.A101 antibody claim 103 , SC2.A109 antibody claim 103 , SC2.A113 antibody claim 103 , SC2.A106 antibody claim 103 , SC2.A122 antibody claim 103 , SC2.10E11 antibody claim 103 , SC2.9E7 antibody claim 103 , SC2.A118 antibody claim 103 , SC2.A126 antibody claim 103 , SC2.5C4 antibody claim 103 , SC2.A110 antibody claim 103 , SC2.D1 antibody claim 103 , SC2.D3 antibody claim 103 , SC2.D4 antibody claim 103 , SC2.D7 antibody claim 103 , SC2.D12 antibody claim 103 , SC2.D14 antibody claim 103 , ...

ANTIBODIES TO MATRIX METALLOPROTEINASE 9

The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), such as where the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an Ig light chain (or functional fragment thereof). 1. A method of inhibiting Matrix Metalloproteinase 9 (MMP9) activity in a subject in need thereof , comprising:administering to the subject an effective amount of a pharmaceutical composition comprising an isolated antibody or fragment thereof that binds to MMP9, and a pharmaceutically acceptable excipient.2. The method of claim 1 , wherein the subject in need thereof has a disease or condition associated with MMP9 selected from the group consisting of a cancer claim 1 , an autoimmune disease or condition claim 1 , an inflammatory disease or condition claim 1 , and fibrotic disease or condition.3. The method of claim 2 , wherein the cancer is pancreatic cancer claim 2 , esophagogastric adenocarcinoma claim 2 , non-small cell lung cancer claim 2 , lung squamous cell carcinoma claim 2 , lung adenocarcinoma claim 2 , gastric adenocarcinoma claim 2 , colorectal carcinoma claim 2 , pancreatic adenocarcinoma claim 2 , head and neck squamous cell carcinoma claim 2 , hepatocellular carcinomacolorectal cancer claim 2 , colorectal adenocarcinoma claim 2 , or hepatocellular carcinoma.4. The method of claim 2 , wherein the autoimmune or inflammatory disease or condition is rheumatoid arthritis claim 2 , an inflammatory bowel disease (IBD) claim 2 , septicemia claim 2 , multiple sclerosis claim 2 , muscular dystrophy claim 2 , lupus claim 2 , allergy claim 2 , or asthma.5. The method of claim 4 , wherein the IBD is ulcerative colitis (UC) claim 4 , Crohn's disease (CD) claim 4 , or indeterminate colitis.6. The method of claim 1 , wherein the isolated antibody or fragment ...

METHODS AND PRODUCTS RELATING TO GSK3SS REGULATION

The invention relates to methods and compositions for regulation of GSK3β activity. The invention provides phosphorylated GSK3β polypeptides and antibodies that recognize such polypeptides. The invention further includes methods for treating disorders that are associated with elevated or reduced GSK3β activity. 1. An isolated GSK3β polypeptide , wherein the polypeptide is a full-length GSK3β protein or is a fragment of a full-length GSK3β protein and comprises a phosphorylated residue that corresponds to residue Thrin a full-length , wild-type , human GSK3β amino acid sequence , or corresponds to residue Serin a full-length , wild-type , mouse GSK3β amino acid sequence.2. The isolated GSK3β polypeptide of claim 1 , wherein the GSK3β polypeptide is a human GSK3β polypeptide.3. The isolated GSK3β polypeptide of claim 1 , wherein the phosphorylated residue corresponds to the Thrresidue.4. The isolated GSK3β polypeptide of claim 3 , wherein the polypeptide comprises the amino acid sequence set forth as: RIQAAAST(POH)PTN (SEQ ID NO:7).5. A composition comprising the isolated GSK3β polypeptide of .6. The composition of claim 5 , further comprising a pharmaceutically acceptable carrier.7. A fusion protein comprising the GSK3β polypeptide of .8. A method of producing an antibody that specifically binds to a phosphorylated GSK3β polypeptide claim 1 , the method comprising claim 1 ,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'sup': 390', '389, 'inoculating an animal with a polypeptide of , that comprises a phosphorylated residue that corresponds to residue Thrin a full-length, wild-type, human GSK3β amino acid sequence, or corresponds to residue Serin a full-length, wild-type, mouse GSK3β amino acid sequence, wherein the polypeptide elicits an immune response in the animal to produce the antibody; and'}isolating the antibody from the animal; wherein the antibody specifically binds to a phosphorylated GSK3β polypeptide.9. The method of claim 8 , wherein the polypeptide ...

ErbB3 BINDING ANTIBODY

The present invention relates to an antibody, particularly a monoclonal antibody, which binds to the ErbB3 receptor, compositions comprising such an antibody as well as methods using such an antibody. 1. Antibody or fragment thereof which binds to the ErbB3 receptor and which comprises:(a) a heavy chain amino acid sequence as encoded by SEQ ID NO: 1 or at least the variable domain thereof or an amino acid sequence having a sequence identity of at least 80%, preferably 90%, thereto and/or(b) a light chain amino acid sequence as encoded by SEQ ID NO: 2 or at least the variable domain thereof or an amino acid sequence having a sequence identity of at least 80%, preferably 90%, thereto.2. The antibody according to claim 1 , wherein binding of said antibody to ErbB3 reduces ErbB3 mediated signal transduction.3. The antibody of claim 2 , wherein said reduction of signal transduction is caused by a down-regulation of ErbB3.4. The antibody according to claim 2 , having the ability to decrease levels of ErbB3 on cell surfaces.5. The antibody of claim 1 , which is a polyclonal antibody or a monoclonal antibody claim 1 , in particular a recombinant antibody claim 1 , a humanized antibody claim 1 , a chimeric antibody claim 1 , a multispecific antibody claim 1 , in particular a bispecific antibody claim 1 , or a fragment thereof.6. The antibody according to claim 1 , which is a Fab fragment claim 1 , a Fab′ fragment claim 1 , a F(ab′) fragment claim 1 , a Fv-fragment claim 1 , a diabody claim 1 , ScFv claim 1 , SMIP claim 1 , single chain antibody claim 1 , affibody claim 1 , avimer claim 1 , nanobody and/or a domain antibody.7. The antibody according to claim 1 , wherein the antibody isotype is selected from the group consisting of an IgG1 claim 1 , an IgG2 claim 1 , an IgG3 claim 1 , an IgG4 claim 1 , an IgM claim 1 , an IgA1 claim 1 , an IgA2 claim 1 , an IgAsec claim 1 , an IgD claim 1 , and an IgE antibody.8. The antibody according to claim 1 , which is MP-RM-1 claim 1 , ...

Ttll4 peptides and vaccines containing the same

Peptide vaccines against cancer are described herein. In particular, epitope peptides derived from the TTLL4 gene that elicit CTLs are provided. Antigen-presenting cells and isolated CTLs that target such peptides, as well as methods for inducing the antigen-presenting cell, or CTL are also provided. The present invention further provides pharmaceutical compositions containing peptides derived from TTLL4 or polynucleotides encoding the polypeptides as active ingredients. Furthermore, the present invention provides methods for the treatment and/or prophylaxis of (i.e., preventing) cancers (tumors), and/or the prevention of a postoperative recurrence thereof, as well as methods for inducing CTLs, methods for inducing anti-tumor immunity, using the peptides derived from TTLL4, polynucleotides encoding the peptides, or antigen-presenting cells presenting the peptides, or the pharmaceutical compositions of the present invention.

ENDOTHELIAL NITRIC OXIDE SYNTHASE

The activity of endothelial nitric oxide synthase (eNOS) was modulated by contact with an effective amount of a mitogen-activated protein (MAP) kinase, resulting in phosphorylation of S602, T46, and/or S58. Kinetics and stoichiometry are disclosed. The contact strongly reduced nitric oxide (NO) synthesis, and also inhibited the cytochrome c reductase activity of eNOS reductase domains. Three sites of phosphorylation were determined that matched the serine-proline (SP) and threonine-proline (TP) motifs of typical MAP kinase phosphorylation sites. 1. A method for modulating nitric oxide synthase activity , the method comprising contacting a nitric oxide synthase (NOS) with an effective amount of a mitogen-activated protein (MAP) kinase , wherein contacting the NOS with the MAP kinase results in phosphorylation of at least one amino acid selected from the group of S602 , T46 , and S58 resulting in NOS activity modulation.2. The method of wherein the MAP kinase is selected from the group consisting of extracellular signal-regulated kinase (ERK) claim 1 , p38 MAP kinase claim 1 , and c-Jun N-terminal kinase (JNK).3. The method of wherein the MAP kinase is ERK.4. A method for modulating the cytochrome C reductase activity of a nitric oxide synthase (NOS) claim 2 , the method comprising contacting a NOS reductase domain with an effective amount of a mitogen-activated protein (MAP) kinase to result in phosphorylation of at least one amino acid from the NOS reductase results in cytochrome C reductase activity modulation.5. The method of wherein the MAP kinase is selected from the group consisting of extracellular signal-regulated kinase (ERK) claim 4 , p38 MAP kinase claim 4 , and c-Jun N-terminal kinase (JNK).6. The method of wherein the MAP kinase is ERK.7. A polypeptide comprising a pentabasic site claim 4 , wherein the pentabasic site is in an autoinhibitory element in an endothelial nitric oxide synthase (eNOS) and the pentabasic site is capable of binding a peptide ...

Cyanine compounds

Compounds used as labels with properties comparable to known fluorescent compounds. The compounds can be conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

INNOVATIVE DISCOVERY OF THERAPEUTIC, DIAGNOSTIC, AND ANTIBODY COMPOSITIONS RELATED TO PROTEIN FRAGMENTS OF P38 MULTI-TRNA SYNTHETASE COMPLEX

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications. 1125-. (canceled)126. A therapeutic composition , comprising an isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% , 85% , 90% , 95% , 98% , or 100% identical to a sequence in any of Table(s) 1-3 , or Table(s) 4-6 , or Table(s) 7-9 , wherein the polypeptide has a solubility of at least about 5 mg/mL , and wherein the composition has a purity of at least about 95% on a protein basis and less than about 10 EU endotoxin/mg protein.127. The therapeutic composition of claim 126 , wherein the polypeptide specifically binds to a binding partner to exert a physiological effect.128. The therapeutic composition of claim 126 , wherein said polypeptide differs from an amino acid sequence set forth in any of Table(s) 1-3 claim 126 , or Table(s) 4-6 claim 126 , or Table(s) 7-9 claim 126 , by substitution claim 126 , deletion claim 126 , and/or addition of about 0 claim 126 , 1 claim 126 , 2 claim 126 , 3 claim 126 , 4 claim 126 , 5 claim 126 , 6 claim 126 , 7 claim 126 , 8 claim 126 , 9 claim 126 , 10 claim 126 , or 11 amino acids claim 126 , and wherein the altered polypeptide substantially retains a non-canonical activity of the unaltered protein.129. The therapeutic composition of claim 126 , wherein the AARS polypeptide is fused to a heterologous polypeptide.130. The therapeutic composition of claim 126 , wherein at least one moiety or a solid substrate is covalently or non-covalently attached to said polypeptide.131. An isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% claim 126 , 85% ...

NOVEL ANTIBODY TO A CARBONIC ANHYDRASE

The present invention relates to an antibody binding to a carbonic anhydrase, wherein the antibody comprises (a) the amino acid sequences SEQ ID NOS. 1 (CDR 1), 2 (CDR 2) and 3 (CDR 3) determining the CDRs of the Vregion, and the amino acid sequences SEQ ID NOS. 4 (CDR 1), 5 (CDR 2) and 6 (CDR 3) determining the CDRs of the Vregion; or (b) the amino acids sequences of (a), wherein at least one amino acid is conservatively substituted in any one of the amino acid sequences SEQ ID NOS. 1 to 6. 115-. (canceled)16. An antibody binding to a carbonic anhydrase , wherein the antibody comprises the amino acid sequences SEQ ID NOS: 1 (CDR 1) , 2 (CDR 2) and 3 (CDR 3) determining the CDRs of the Vregion , and the amino acid sequences SEQ ID NOS: 4 (CDR 1) , 5 (CDR 2) and 6 (CDR 3) determining the CDRs of the Vregion.17. The antibody of claim 16 , which binds to carbonic anhydrase XII.18. The antibody of claim 16 , wherein said antibody comprises the Vregion determined by the amino sequence of SEQ ID NO. 7 and the Vregion determined by the amino sequence of SEQ ID NO. 8.19. The antibody of claim 16 , wherein said antibody is a monoclonal antibody.20. The antibody according of claim 16 , wherein said antibody is coupled to(a) a labelling group,(b) a toxin, or(c) an anti-tumor drug.21. A nucleic acid molecule encoding the antibody of .22. A vector comprising the nucleic acid molecule of in an expressible form.23. A non-human host comprising the vector of .24. A method for producing the antibody of claim 16 , comprising the steps of:(a) culturing a non-human host under conditions that allow synthesis of said antibody; and(b) recovering said antibody from said culture.25. A diagnostic composition comprising a component selected from the group consisting of the antibody of claim 16 , a nucleic acid molecule encoding the antibody claim 16 , a vector comprising the nucleic acid molecule in an expressible form claim 16 , and a non-human host comprising the vector.26. A pharmaceutical ...

INNOVATIVE DISCOVERY OF THERAPEUTIC, DIAGNOSTIC, AND ANTIBODY COMPOSITIONS RELATED TO PROTEIN FRAGMENTS OF METHIONYL-TRNA SYNTHETASES

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications. 1125-. (canceled)126. A therapeutic composition , comprising an isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% , 85% , 90% , 95% , 98% , or 100% identical to a sequence in any of Table(s) 1-3 , or Table(s) 4-6 , or Table(s) 7-9 , wherein the polypeptide has a solubility of at least about 5 mg/mL , and wherein the composition has a purity of at least about 95% on a protein basis and less than about 10 EU endotoxin/mg protein.127. The therapeutic composition of claim 126 , wherein the polypeptide specifically binds to a binding partner to exert a physiological effect.128. The therapeutic composition of claim 126 , wherein said polypeptide differs from an amino acid sequence set forth in any of Table(s) 1-3 claim 126 , or Table(s) 4-6 claim 126 , or Table(s) 7-9 claim 126 , by substitution claim 126 , deletion claim 126 , and/or addition of about 0 claim 126 , 1 claim 126 , 2 claim 126 , 3 claim 126 , 4 claim 126 , 5 claim 126 , 6 claim 126 , 7 claim 126 , 8 claim 126 , 9 claim 126 , 10 claim 126 , or 11 amino acids claim 126 , and wherein the altered polypeptide substantially retains a non-canonical activity of the unaltered protein.129. The therapeutic composition of claim 126 , wherein the AARS polypeptide is fused to a heterologous polypeptide.130. The therapeutic composition of claim 126 , wherein at least one moiety or a solid substrate is covalently or non-covalently attached to said polypeptide.131. An isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% claim 126 , 85% ...

MONOSPECIFIC AND BISPECIFIC ANTI-IGF-1R AND ANTI-ERBB3 ANTIBODIES

Provided are monospecific and bispecific antibodies that are useful as anti-neoplastic agents and that bind specifically to human IGF-1R and human ErbB3. Exemplary antibodies inhibit signal transduction through either or both of IGF-1R and ErbB3. Exemplary polyvalent proteins comprise at least one anti-IGF-1R binding site and at least one anti-ErbB3 binding site. In certain embodiments the binding sites may be linked through an immunoglobulin constant region. AntiErbB3 and anti-IGF-1R antibodies (e.g., monoclonal antibodies) are also provided. 1194-. (canceled)196. A polyvalent bispecific antibody that is: two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:212; and', 'two light chains, each comprising a light chain sequence of SEQ ID NO:202, or;, 'a. an SF-G1-P1 polyvalent bispecific antibody comprising two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:214; and', 'two light chains, each comprising a light chain amino acid sequence of SEQ ID NO:202, or;, 'b. an SF-G1-M1.3 polyvalent bispecific antibody comprising two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:216; and', 'two light chains, each comprising a light chain amino acid sequence of SEQ ID NO:202, or;, 'c. an SF-G1-M27 polyvalent bispecific antibody comprising two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:218; and', 'two light chains, each comprising a light chain amino acid sequence of SEQ ID NO:202, or;, 'd. an SF-G1-P6 polyvalent bispecific antibody comprising two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:220; and', 'two light chains, each comprising a light chain amino acid sequence of SEQ ID NO:202, or;, 'e. an SF-G1-B69 polyvalent bispecific antibody comprising two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:224; and', 'two light chains, each comprising a light chain amino acid sequence of SEQ ID NO:204, or;, ...

EPIDERMAL GROWTH FACTOR RECEPTOR VARIANT LACKING EXON

The present invention provides an epidermal growth factor receptor variant-de4 EGFR protein. The variant lacks the fourth exon of the epidermal growth factor receptor, and promotes tumor cell invasion/metastasis. The present invention also provides an encoding gene for the variant and a method of producing the variant by means of recombination technology. 1. An isolated polypeptide of human epidermal growth factor receptor variant de4 EGFR , wherein it is selected from the following groups:(a) Polypeptide comprising the amino acid sequence of SEQ ID NO: 2;(b) Polypeptide generated by replacement, deletion or addition of amino acid sequence of SEQ ID NO: 2 with one or more amino acids, which can promote tumor cell invasion and/or migration and is derived from (a);(c) Polypeptide possessing ≧95% homology to the amino acid sequence of SEQ ID NO: 2, which can promote tumor cell invasion or migration and is derived from (a).2. The polypeptide according to of claim 1 , wherein the amino acid sequence of the polypeptide is shown as SEQ ID NO: 2.3. An isolated polynucleotide claim 1 , wherein it comprises a nucleotide sequence selected from the following groups:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) Polynucleotide encoding the polypeptide according to ;'}(b) Polynucleotide complementary to the polynucleotide (a).4. The polynucleotide according to claim 3 , wherein it encodes amino acid sequence of SEQ ID NO: 2 claim 3 , (i) Sequence of 1st-3495th in SEQ ID NO: 1;', '(ii) Sequence of 1 st-3498th in SEQ ID NO: 1., 'more preferably, the polynucleotide sequence is selected from the following groups5. A vector claim 3 , wherein it contains the polynucleotide according to .6. A genetically engineered host cell claim 3 , wherein it contains the vector according to or its chromosome is integrated by the polynucleotide according to .7. A method for preparing a polypeptide claim 3 , wherein it comprises:{'claim-ref': {'@idref': 'CLM-00006', 'claim 6'}, '(a) culturing ...

USP2A PEPTIDES AND ANTIBODIES

The invention relates to novel USP2a peptides and antibodies, as well as nucleic acids related to them. The peptides, antibodies and the nucleic acids are useful for the detection, staging and monitoring of the progression of cancer, as well as for determining or monitoring the efficacy of treatment. 1. An isolated antibody specifically reactive with a USP2a peptide , said peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO. 1 , SEQ ID NO. 2 , and variants thereof.2. The isolated antibody of comprising a detectable label.3. The isolated antibody of which is a humanized antibody.4. The isolated antibody of which is a monoclonal antibody.5. An isolated antibody obtained by a method claim 1 , said method comprising:a) contacting a subject with at least one USP2a peptide comprising a portion of a USP2a protein, wherein the USP2a peptide is from about 5 to about 30 amino acids in length and has a sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO 2 and variants thereof; andb) collecting a sample containing the USP2a antibody from the subject.6. The isolated antibody of wherein the sample contains antiserum that has been immunopurified. This application is a divisional application of U.S. patent application Ser. No. 13/659,173, filed Oct. 24, 2012, which claims priority to U.S. Provisional Patent Application No. 61/551,567 filed Oct. 26, 2011 which is incorporated by reference in its entirety.The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled 20151007USDIVSEQLST.txt, created on May 16, 2013 which is 12,400 bytes in size. The information in the electronic format of the sequence listing is incorporated herein by reference in its entirety.The invention relates to peptides and antibodies having immunospecificity for USP2a polypeptides and proteins, as well as nucleic acids related to these peptides and antibodies, and methods ...

INNOVATIVE DISCOVERY OF THERAPEUTIC, DIAGNOSTIC, AND ANTIBODY COMPOSITIONS RELATED TO PROTEIN FRAGMENTS OF LYSYL-TRNA SYNTHETASES

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications. 1125-. (canceled)126. A therapeutic composition , comprising an isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% , 85% , 90% , 95% , 98% , or 100% identical to a sequence in any of Table(s) 1-3 , or Table(s) 4-6 , or Table(s) 7-9 , wherein the polypeptide has a solubility of at least about 5 mg/mL , and wherein the composition has a purity of at least about 95% on a protein basis and less than about 10 EU endotoxin/mg protein.127. The therapeutic composition of claim 126 , wherein the polypeptide specifically binds to a binding partner to exert a physiological effect.128. The therapeutic composition of claim 126 , wherein said polypeptide differs from an amino acid sequence set forth in any of Table(s) 1-3 claim 126 , or Table(s) 4-6 claim 126 , or Table(s) 7-9 claim 126 , by substitution claim 126 , deletion claim 126 , and/or addition of about 0 claim 126 , 1 claim 126 , 2 claim 126 , 3 claim 126 , 4 claim 126 , 5 claim 126 , 6 claim 126 , 7 claim 126 , 8 claim 126 , 9 claim 126 , 10 claim 126 , or 11 amino acids claim 126 , and wherein the altered polypeptide substantially retains a non-canonical activity of the unaltered protein.129. The therapeutic composition of claim 126 , wherein the AARS polypeptide is fused to a heterologous polypeptide.130. The therapeutic composition of claim 126 , wherein at least one moiety or a solid substrate is covalently or non-covalently attached to said polypeptide.131. An isolated aminoacyl-tRNA synthetase (AARS) polypeptide of about 100 to about 750 amino acids in length and comprising an amino acid sequence that is at least 80% claim 126 , 85% ...

Compositions and methods comprising histidyl-trna synthetase splice variants having non-canonical biological activities

Isolated histidyl-tRNA synthetase splice variant polynucleotides and polypeptides having non-canonical biological activities are provided, as well as compositions and methods related thereto.

Compounds having activity of suppressing activation of tgf-beta receptor, method for screening of the compounds, and composition for preventing or treating disease caused by hepatitis c virus

An object is to provide a compound capable of inhibiting activation of TGF-β receptors due to HCV, and a screening method for the compound. It has been found that a HCV-derived NS3 protease binds to type I TGF-β receptor, and this binding results in activation of TGF-β receptors. Moreover, binding sites between the NS3 protease and type I TGF-β receptor were identified, and it has been found that antibodies recognizing these binding sites inhibit activation of TGF-β receptors due to NS3 protease. Furthermore, it has been also found that screening for a compound capable of inhibiting activation of TGF-β receptors can be performed by using the inhibition of the binding between NS3 protease and type I TGF-β receptor or the like as an index.

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described. 1. (canceled)2. An isolated monoclonal antibody , wherein , when bound to PCSK9 , the monoclonal antibody is positioned at a location 8 angstroms or less from at least one of the following residues: S153 , I154 , P155 , W156 , N157 , L158 , E159 , H193 , R194 , E195 , H229 , R237 , D238 , A239 , G240 , K243 , D367 , I368 , 1369 , G370 , A371 , S372 , S373 , D374 , C375 , S376 , T377 , C378 , F379 , V380 , S381 , or Q382 of SEQ ID NO: 3 , and wherein said monoclonal antibody inhibits binding of an EGFa domain of LDLR to PCSK9.3. The isolated monoclonal antibody of claim 2 , wherein claim 2 , when bound to PCSK9 claim 2 , the monoclonal antibody is positioned within 8 angstroms or less from at least one of the following residues: S153 claim 2 , I154 claim 2 , P155 claim 2 , R194 claim 2 , D238 claim 2 , A239 claim 2 , I369 claim 2 , S372 claim 2 , D374 claim 2 , C375 claim 2 , T377 claim 2 , C378 claim 2 , F379 claim 2 , V380 claim 2 , or S381.4. The isolated monoclonal antibody of claim 2 , wherein claim 2 , when bound to PCSK9 claim 2 , the monoclonal antibody is positioned within 8 angstroms or less from at least one of the following residues: W156 claim 2 , N157 claim 2 , L158 claim 2 , E159 claim 2 , H193 claim 2 , E195 claim 2 , H229 claim 2 , R237 claim 2 , G240 claim 2 , K243 claim 2 , D367 claim 2 , I368 claim 2 , G370 claim 2 , A371 claim 2 , S373 claim 2 , S376 claim 2 , or Q382.5. The isolated monoclonal antibody of claim 2 , wherein claim 2 , when bound to PCSK9 claim 2 , the monoclonal antibody is positioned within 5 angstroms or less from at least one of the following ...

ANTI-ROR1 ANTIBODIES

The invention provides antibodies which bind to the extracellular domain of the Tyrosine-protein kinase transmembrane receptor ROR1. Nucleic acid molecules encoding the antibodies, expression vectors, host cells and methods for expressing the antibodies are also provided. The antibodies may be used for the treatment of cancer, including non-small cell lung carcinoma, B-cell chronic lymphocytic leukemia and colon cancer. 134-. (canceled)35. An antibody that specifically binds to the extracellular domain of ROR1 (SEQ ID NO:272) on a cell expressing ROR1 , said antibody comprising: i) a first vhCDR comprising SEQ ID NO:275;', 'ii) a second vhCDR comprising SEQ ID NO: 277; and', 'iii) a third vhCDR comprising SEQ ID NO:279; and, 'a) a heavy chain variable region comprising i) a first vlCDR comprising SEQ ID NO:281;', 'ii) a second vlCDR comprising SEQ ID NO: 283; and', 'iii) a third vlCDR comprising SEQ ID NO:285., 'b) a light chain variable region comprising36. An antibody according to wherein said first vhCDR is selected from the group consisting of SEQ ID NOs: 57 claim 35 , 58 claim 35 , 59 claim 35 , 60 claim 35 , 58 claim 35 , 61 claim 35 , 62 claim 35 , 63 claim 35 , 64 claim 35 , 65 claim 35 , 66 claim 35 , 67 claim 35 , 68 claim 35 , 69 claim 35 , 70 claim 35 , 71 claim 35 , 72 claim 35 , 73 claim 35 , 74 claim 35 , 75 claim 35 , 76 and 77 claim 35 , or a sequence that has 1 claim 35 , 2 or 3 amino acid variants as compared to SEQ ID NOs: 57 claim 35 , 58 claim 35 , 59 claim 35 , 60 claim 35 , 58 claim 35 , 61 claim 35 , 62 claim 35 , 63 claim 35 , 64 claim 35 , 65 claim 35 , 66 claim 35 , 67 claim 35 , 68 claim 35 , 69 claim 35 , 70 claim 35 , 71 claim 35 , 72 claim 35 , 73 claim 35 , 74 claim 35 , 75 claim 35 , 76 and 77.37. An antibody according to wherein said second vhCDR is selected from the group consisting of SEQ ID NOs: 99 claim 35 , 100 claim 35 , 101 claim 35 , 102 claim 35 , 103 claim 35 , 104 claim 35 , 105 claim 35 , 106 claim 35 , 107 claim 35 , ...