ПРИМЕНЕНИЕ ПРОСОМАТОСТАТИНА В ДИАГНОСТИКЕ

Группа изобретений относится к медицине и касается способа диагностики и мониторинга у пациентов нарушений активности и/или функции желудочно-кишечного тракта, за исключением соматостатиномы, где указанный способ включает стадии взятия образца физиологической жидкости у пациента, определения уровня просоматостатина 1-64 или его фрагментов в указанном образце, определения корреляции уровня просоматостатина 1-64 или его фрагментов с диагнозом у указанного пациента нарушений активности и/или функции желудочно-кишечного тракта, за исключением соматостатиномы. Группа изобретений также касается набора для определения уровня просоматостатина 1-64 или его фрагментов, содержащего по меньшей мере два антитела. Группа изобретений обеспечивает диагностику и мониторинг нарушений активности и/или функции желудочно-кишечного тракта, выбранных из группы, состоящей из болезни Крона, панкреатита, дивертикулита, карциномы поджелудочной железы, неокарциномы поджелудочной железы, карциномы пищевода, карциномы ...

КОМПОЗИЦИИ И СПОСОБЫ БОРЬБЫ С НАКОПЛЕНИЕМ ЖИРОВОЙ ТКАНИ

Предложены способ лечения ожирения, диабета II типа или метаболического синдрома с использованием композиции, содержащей фармацевтически эффективное количество молекулярного антагониста желудочного ингибиторного полипептида (GIP), а также способ снижения накопления жировой ткани в печени, снижения накопления жировой ткани в сальнике или снижения накопления подкожной жировой ткани с использованием композиции, содержащей фармацевтически эффективное количество молекулярного антагониста GIP. Предложен также молекулярный антагонист GIP. При этом молекулярный антагонист GIP содержит вариабельный домен легкой цепи и вариабельный домен тяжелой цепи, где вариабельный домен легкой цепи имеет 100% идентичности с аминокислотной последовательностью SEQ ID NO: 17, SEQ ID NO: 18 или SEQ ID NO: 19, а вариабельный домен тяжелой цепи имеет 100% идентичности с аминокислотной последовательностью SEQ ID NO: 28, SEQ ID NO: 29 или SEQ ID NO: 30. Группа изобретений обеспечивает снижение скорости набора веса, снижение ...

НЕПРИРОДНЫЕ СЕМАФОРИНЫ КЛАССА 3 И ИХ МЕДИЦИНСКОЕ ПРИМЕНЕНИЕ

Изобретение относится к области биохимии, в частности к мутантному семафорину 3 или его функциональному фрагменту, к гибридному белку, содержащему вышеуказанный семафорин 3 или его функциональный фрагмент, а также к способу их получения. Также раскрыта молекула нуклеиновой кислоты, кодирующая вышеуказанный мутантный семафорин 3 или его функциональный фрагмент, молекула нуклеиновой кислоты, кодирующая вышеуказанный гибридный белок, а также вектор и клетка-хозяин, содержащие вышеуказанную молекулу нуклеиновой кислоты. Изобретение также относится к фармацевтической композиции, содержащей вышеуказанный мутантный семафорин 3 или его функциональный фрагмент, гибридный белок и/или молекулу нуклеиновой кислоты, а также к применению вышеуказанного мутантного семафорина 3 или его функционального фрагмента, гибридного белка, молекулы нуклеиновой кислоты, вектора, клетки-хозяина, фармацевтической композиции для лечения ангиогенного нарушения и для лечения опухолевого заболевания. Изобретение позволяет ...

Блокаторы рецептора гормона роста при предупреждении заболеваний и лечении

Изобретение относится к способу ингибирования GH, GHR, STAT5, SOCS и с-fos, который включает идентификацию субъекта, имеющего заболевание или состояние с изменениями экспрессии или активности генов/белков, относящихся к GH, GHR, STAT5 и SOCS человека, или на которого изменения экспрессии или активности генов/белков, относящихся к GH, GHR, STAT5 и SOCS человека, могут оказывать благоприятный эффект; и введение терапевтически эффективного количества соединения, выбранного из группы, состоящей из:и их фармацевтически приемлемых солей. Технический результат - выявлена новая активность известных соединений и разработан способ ингибирования на их основе, который может найти применение в медицине для лечения рака, диабета, иммуносупрессии, болезни Альцгеймера и заболеваний и состояний, в отношении которых клеточная и тканевая регенерация оказывает благоприятный эффект. 16 з.п. ф-лы, 23 ил.

АНТИТЕЛА К ГЕПСИДИНУ И ИХ ПРИМЕНЕНИЯ

Изобретение относится к области биотехнологии, конкретно к антителам, которые специфично связываются с гепсидином, что может быть использовано в медицине. Получают моноклональные антитела к пептиду N-концевой части гепсидина, которые используют в составе композиции и применяют для лечения заболеваний, ассоциированных с повышенным уровнем гепсидина, или нарушений гомеостаза железа. Изобретение позволяет получить терапевтически пригодные антитела к гепсидину, обладающие высокой специфичностью и низкой константой диссоциации по сравнению с имеющимися в уровне техники аналогами. 6 н. и 21 з.п. ф-лы, 32 ил., 10 пр.

СПОСОБЫ ЛЕЧЕНИЯ ВИСЦЕРАЛЬНОЙ БОЛИ ПУТЕМ ВВЕДЕНИЯ АНТИТЕЛ-АНТАГОНИСТОВ, НАПРАВЛЕННЫХ ПРОТИВ ПЕПТИДА, СВЯЗАННОГО С ГЕНОМ КАЛЬЦИТОНИНА

Предложенная группа изобретений относится к области медицины. Предложен способ лечения висцеральной боли и/или одного или более чем одного симптома висцеральной боли, включающий введение терапевтически эффективного количества антитела-антагониста против пептида, связанного с геном кальцитонина (CGRP), индивиду, страдающему от висцеральной боли, или индивиду с риском висцеральной боли, где антитело-антагонист против CGRP изготовлено для периферического введения. Предложена также фармацевтическая композиция, содержащая антитело-антагонист против CGRP и фармацевтически приемлемый носитель, изготовленная для периферического введения. Предложенная группа изобретений обеспечивает эффективное лечение висцеральной боли без использования опиатов. 2 н. и 16 з.п. ф-лы, 3 ил., 2 табл., 3 пр.

АНТИТЕЛА И ПЕПТИДНЫЕ АНТИГЕНЫ ДЛЯ ПОЛУЧЕНИЯ АНТИТЕЛ, ИМЕЮЩИХ СЕЛЕКТИВНУЮ СПЕЦИФИЧНОСТЬ СВЯЗЫВАНИЯ С БИОЛОГИЧЕСКИ АКТИВНЫМ ИНТАКТНЫМ ПАРАТИРЕОИДНЫМ ГОРМОНОМ (ПТГ(РТН))1-84

Изобретение относится к иммунологии. Предложен способ получения поликлональной антисыворотки, которая иммуноспецифически связывается с биологически активным паратиреоидным гормоном (ПТГ) в части трех или четырех N-концевых аминокислотных остатков (1-84) ПТГ. Вводят первый пептидный антиген животному-хозяину, не являющемуся человеком. Проводят мониторинг титра продуцируемых антител. Экстрагируют антисыворотку. Выделяют и отбирают по меньшей мере одно антитело из антисыворотки с помощью аффинной хроматографии с использованием второго пептидного антигена. Удаляют по меньшей мере одно антитело, обладающее специфичностью в отношении пептидного антигена, выбранного из группы, состоящей из (4-34) ПТГ, (5-34) ПТГ, (4-84) ПТГ и (5-84) ПТГ, посредством аффинной хроматографии с использованием третьего пептидного антигена, выбранного из группы, состоящей из (4-34) ПТГ, (5-34) ПТГ, (4-84) ПТГ и (5-84) ПТГ, соответственно. Выделяют поликлональную сыворотку, обладающую связывающей аффинностью в отношении ...

Белки, связывающиеся с гепсидином

Изобретение относится к области биотехнологии, конкретно к мутеинам белка липокалина, а также к полученным на их основе специфично связывающимся терапевтическим или диагностическим белкам, направленным против гепсидина, и может быть использовано в медицине. Получают мутеин липокалина, по меньшей мере на 90% идентичный последовательности белка, выбранной из группы, состоящей из последовательностей SEQ ID NO: 1-14. Изобретение позволяет получить мутеин липокалина, способный связываться с гепсидином с аффинностью, определенной по константе диссоциации (KD), равной приблизительно 10 нМ или менее. 19 н. и 54 з.п. ф-лы, 12 ил., 11 пр.

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 ...

СПОСОБ ОБНАРУЖЕНИЯ N-КОНЦЕВОГО ПРО-МНП

Изобретение относится к области медицины, а именно к способу обнаружения N-концевого про-МНП, рекомбинантному N-концевому про-МНП, его применению в качестве стандарта в способе обнаружения N-концевого про-МНП, а также к антителам, которые распознают рекомбинантный N-концевой про-МНП, и их получению. Сущность изобретения состоит в том, что для обнаружения N-концевого про-МНП в пробе используют по меньшей мере два антитела, которые распознают различные эпитопы N-концевого про-МНП. Техническим результатом является разработка высокочувствительного способа обнаружения N-концевого про-МНП в пробе, позволяющего дифференцировать здоровых людей и больных с сердечной недостаточностью. 7 с. и 12 з.п.ф-лы, 5 табл.

СПОСОБ ПРОГНОЗИРОВАНИЯ РИСКА РАЗВИТИЯ СЕРДЕЧНО-СОСУДИСТОЙ ПАТОЛОГИИ У ОСОБИ ЖЕНСКОГО ПОЛА

... 1. Способ прогнозирования риска развития сердечно-сосудистой патологии у особи женского пола, который включает:- определение уровня про-нейротензина 1-117 или его фрагментов из по меньшей мере 5 аминокислот или про-нейротензина 1-117, содержащего пептиды, в биологической жидкости, полученной из указанной особи женского пола; и- корреляцию указанного уровня про-нейротензина 1-117 или его фрагментов или про-нейротензина 1-117, содержащего пептиды, с риском развития сердечно-сосудистой патологии, где повышенный уровень является прогностическим для повышенного риска развития сердечно-сосудистой патологии.и где указанная сердечно-сосудистая патология представляет собой острую сердечно-сосудистую патологию, выбранную из группы, включающей инфаркт миокарда, удар, острую сердечную недостаточность и смерть по причине сердечно-сосудистой патологии, связанную с инфарктом миокарда, ударом или острой сердечной недостаточностью и где уровень про-нейротензина 1-117 или его фрагментов из по меньшей мере ...

БЕЛКИ, СВЯЗЫВАЮЩИЕСЯ С ГЕПСИДИНОМ

... 1. Мутеин липокалина, способный связываться с гепсидином с аффинностью, определенной по константе диссоциации (K), приблизительно 10 нМ или менее, содержащий:а) по меньшей мере 2 мутированных аминокислотных остатка в любом из положений 96, 100 и 106 линейной полипептидной последовательности липокалина, ассоциированного с желатиназой нейтрофилов (NGAL); иб) по меньшей мере один мутированный аминокислотный остаток в любом из положений 36, 40, 41, 49, 52, 68, 70, 72, 73, 77, 79, 81, 103, 125, 127, 132 и 134 линейной полипептидной последовательности NGAL.2. Мутеин липокалина по п.1, аффинность которого, определенная по K, составляет приблизительно 1 нМ или менее.3. Мутеин липокалина по п.2, аффинность которого, определенная по K, составляет приблизительно 0,1 нМ или менее.4. Мутеин липокалина по любому из пп.1-3, способный нейтрализовать биологическую активность человеческого гепсидина-25.5. Мутеин липокалина по п.4 со значением средней ингибирующей концентрации (IC50) приблизительно 80 нМ ...

ШТАММ КЛЕТОК CHO-SE-9/4 - ПРОДУЦЕНТ ХИМЕРНОГО АНТИТЕЛА ПРОТИВ ЭРИТРОПОЭТИНА ЧЕЛОВЕКА И ХИМЕРНОЕ АНТИТЕЛО, ПРОДУЦИРУЕМОЕ ДАННЫМ ШТАММОМ

Настоящее изобретение относится к области иммунологии. Предложено антитело, способное специфически связываться с эритропоэтином человека. Также рассмотрен штамм-продуцент такого антитела. Данное изобретение может найти дальнейшее применение в выделении и/или очистке рекомбинантного эритропоэтина человека методом иммуноаффинной хроматографии. 2 н.п. ф-лы, 6 ил., 6 пр.

Блокаторы рецептора гормона роста при профилактике заболеваний и лечении

КОМПОЗИЦИЯ ДЛЯ ЛЕЧЕНИЯ РАКА, ЭКСПРЕССИРУЮЩЕГО IGF-1R

АНАЛОГИ КОРТИСТАТИНА, ИХ СИНТЕЗ И ПРИМЕНЕНИЯ

СПОСОБ ДИАГНОСТИКИ ЗАБОЛЕВАНИЙ ПУТЕМ СКРИНИНГА ТКАНЕЙ, КРОВИ ИЛИ ЭИДКОСТЕЙ ОРГАНИЗМА ЖИВОТНЫХ ИЛИ ЧЕЛОВЕКА[НА ПРЕДМЕТ ОБНАРУЖЕНИЯ НЕФИЗИОЛОГИЧЕСКИХ УРОВНЕЙ]ЕПЦИДИНА И ЕГО ТЕРАПЕВТИЧЕСКОЕ ПРИМЕНЕНИЕ

... 1. Способ диагностики патологического состояния, характеризующегося нефизиологическими уровнями гепцидина, подразумевающий получение образца ткани или жидкости от субъекта; приведение образца в контакт с антителом или его фрагментом, которые специфически связываются с одним или более эпитопами средней части или эпитопами карбоксильного конца гепцидина, и количественное определение уровня гепцидина в образце; где нефизиологический уровень гепцидина является показателем патологического состояния. 2. Способ по п.1, в котором антитело специфически связывает эпитоп средней части, находящийся между аминокислотами с 28 по 47 гепцидина. 3. Способ по п.1, в котором антитело специфически связывает эпитоп карбоксильного конца, содержащий аминокислоты с 70 по 84 гепцидина. 4. Способ по п.1, в котором количественное определение подразумевает проведение анализа, выбранного из группы, состоящей из радиоиммуноанализа, иммуноферментного анализа, сэндвич-метода, реакции с преципитином, теста иммунодиффузии ...

СПОСОБ ПОЛУЧЕНИЯ ПОЛИПЕПТИДОВ

... 1. Способ получения полипептида, гетерологичного для E. coli, предусматривающий (a) культивирование клеток E. coli, содержащих кодирующую полипептид нуклеиновую кислоту, в культуральной среде при подпитке культуральной среды транспортабельным органофосфатом, так что нуклеиновая кислота экспрессируется, и (b) выделение полипептида из клеток. 2. Способ по п.1, где органофосфат представляет собой глицерофосфат. 3. Способ по п.2, где глицерофосфат представляет собой альфа-глицерофосфат или бета-глицерофосфат или их смесь. 4. Способ по п.3, где глицерофосфат представляет собой смесь глицерол-2-фосфата и глицерол-3-фосфата или представляет собой глицерол-3-фосфат. 5. Способ по любому из пп.1-4, где культивирование проводят во встряхиваемой колбе или ферментере. 6. Способ по любому из пп.1-4, где полипептид выделяют из цитоплазмы, периплазмы или культуральной среды клеток. 7. Способ по любому из пп.1-4, где экспрессию нуклеиновой кислоты регулируют индуцибельным промотором. 8. Способ по п.7, где ...

EINZELKETTENFORMEN DES CLYCOPROTEIN-HORMON-QUARTETTS

INHIBITOREN VON KATALYTISCHEN ANTIKÖRPERN

Humaner Endothelinrezeptor bindender Antikörper und dessen Verwendung

Ein speziell an Human-Endothelin-Rezeptoren bindender Antikörper, dadurch gekennzeichnet, dass der Antikörper eines der nachfolgenden Schemata von Aminosäuresequenzen umfasst:a. CDR3-Sequenz einer leichten Kette ausgewählt aus einer der nachfolgenden Sequenzen:CDR3-Sequenzen einer leichten Kette, die sich von einer CDR3-Sequenz einer leichten Kette ausgewählt aus L1-L12: SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 66, SEQ ID NO: 68 durch insgesamt nicht mehr als drei Aminosäurezusätze, - substitutionen und/oder -deletionen unterscheiden;b. CDR3-Sequenz einer schweren Kette aus einer der nachfolgenden Sequenzen: CDR3-Sequenzen einer schweren Kette, die sich von einer CDR3-Sequenz einer schweren Kette ausgewählt aus H1-H12: SEQ ID NO: 116, SEQ ID NO: 118, SEQ ID NO: 120, SEQ ID NO: 122, SEQ ID NO: 124, SEQ ID NO: 126, SEQ ID NO: 128, SEQ ID NO: 130, SEQ ID NO: 132, SEQ ID NO: 134, SEQ ID NO: 136 durch insgesamt ...

Antikörper gegen den menschlichen gastrinfreisetzenden Peptidvorläufer und deren Verwendung

Hormones de croissance humaines mutantes et leur utilisation

IMMUNTEST FÜR HUMAN CHROMOGRANINE A (CgA), ANTIKÖRPER, REAGENZ UND DAZU GEEIGNETER TESTSATZ

ANTIBODIES

BINDING SUBSTANCE

In vitro protein expression process comprising Ck fusion molecules

The invention relates to an in vitro protein expression process comprising preparation of a nucleic acid molecule which comprises a fusion of a gene encoding a target protein and a gene encoding an immunoglobulin K light chain constant domain (CK) followed by cell-free protein expression. The invention also relates to proteins expressed by said process and to a composition and kit for performing said in vitro protein expression process.

METHOD OF IMMUNOASSAY

IMPROVEMENTS IN AND RELATING TO HORMONES

In vitro protein expression process comprising Ck fusion molecules

RADIOLABELLED -ENDORPHIN

An obesity (ob) polypeptide capable of modulating body weight, nucleic acids therefore, and diagnostic and therapeutic use thereof.

The present invention relates generally to the concrol of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of weight, and to the diagnostic and therapeutic uses to which such modulators may be put. In its broadest aspect, the present invention relates to the elucidation and discovery of nuc'cotide sequences, and proteins putatively expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability to participate In the control of mammalian body weight. The nucleotidc sequences in object represent the genes corresponding to the murinc and human OB gene, that have been postulated to play a critical role in the regulation of body weight and adiposity. Preliminary data, presented herein, suggests that the polypcptidc product of [he gene in question functions as a hormone. The present invention further provides nucleic acid molecules for use as molecular probes, or as primers for polyrncrasc chain ...

Modulators of body weight corresponding acids and proteins diagnostic and therapeutic uses thereof

Antagonist antibodies directed against calcitonin generelated peptide anf methods using same

CORTISTATIN ANALOGUES AND SYNTHESES AND USES THEREOF

Compositions and methods for antibodies targeting epo

Monoclonal antibodies to progastrin and their uses.

Bispecific binding molecules binding to VEGF and ANG2

Anti-CGRP compositions and use thereof

Modulators of body weight corresponding nucleic acids and proteins and diagnostic and therapeutic uses thereof

CORTISTATIN ANALOGUES AND SYNTHESES AND USES THEREOF

Monoclonal antibodies to progastrin and their uses.

Antagonist antibodies directed against calcitonin generelated peptide anf methods using same

Monoclonal antibodies to progastrin and their uses.

Compositions and methods for antibodies targeting epo

Anti-CGRP compositions and use thereof

Modulators of body weight corresponding acids and proteins diagnostic and therapeutic uses thereof

Anti-CGRP compositions and use thereof

CORTISTATIN ANALOGUES AND SYNTHESES AND USES THEREOF

Compositions and methods for antibodies targeting epo

Antagonist antibodies directed against calcitonin generelated peptide anf methods using same

PRODUCTION OF LUMINESZIERENDER OF 10.10 ' - SUBSTITUTING 9.9 ' - UNTIL ACRIDIN DERIVATIVES AND SIGNAL SOLUTIONS

BACTERIOPHAGE PARTICLES, THE DABS PRESENTATION

PROCEDURE FOR DIFFERENTIATING AND SUPERVISING PARATHYROID AND DISEASES, WHICH ARE WITH THE CONDITION OF THE BONES GROUPS

APPROXIMATELY PROCALCITONIN ARRANGED ANTIBODIES, YOUR PRODUCTION AND USE

SELFARRANGING MOLECULES

GENE REGULARIZATION IN TRANSGENEN ANIMALS USING A VECTOR ON TRANSPOSONBASIS

MODULATION OF THE POLYPEPTIDEXPRESSION ON MODIFIED FILAMENT EYES PHAGES

IMMUNOLOGICAL ASSAYS AND ANTIBODY FOR THE ANTI-MUELLER HORMONE

ANTIBODY MODULATING THE BIOLOGICAL ACTIVITY OF HORSE CHORIONGONADOTROPIN

READY HORMONE ANTI-BODY AND WITH IT BEING CONNECTED PROCEDURE

ANALYTIC SAND YIELDING TEST FOR THE REGULATION OF NTPROBNP

PROCEDURE FOR THE SELECTIVE REGULATION FROM PROCALCITONIN 1-116 FOR DIAGNOSTIC PURPOSES AS WELL AS ANTIKÍRPER AND KITS TO THE EXECUTION OF THIS PROCEDURE

MORE ANTIKÍRPER AGAINST 25-HYDROXYVITAMIN D

EVALUATION OF SKELETON GROWTH USING MEASUREMENTS OF NT-CNP-PEPTIDEN

ANTIBODY AGAINST PARATH HORMONE (PTH) AND YOUR USES

FAB FRAGMENT LIBRARIES AND PROCEDURES FOR THEIR USE

PROCEDURE FOR THE PROOF OF PROBNP WITH A MONOCLONAL ANTIBODY, WHICH BINDS THE AMINO SAÜRE 3843

HUMAN RINGSPEZIFI BNP ANTIKÖRPER ONES

PROCEDURE FOR THE PROOF OF N-TERMINAL PROBNP

ANTIBODY AND PEPTIDANTIGENE FOR THE PRODUCTION OF ANTIBODIES WITH A SELECTIVE CONNECTION SPECIFICITY TO BIOACTIVE INTACT ONE PARATHYROIDHORMON (PTH) 1-84

ZELLPROLIFERATION INHIBITORS

PROCEDURE FOR THE PRODUCTION OF FUNCTIONAL, EINKETTIGER FV OF ANTIKOERPER FRAGMENTS ON BACTERIOPHAGE SURFACES

PROCEDURE FOR THE MEASUREMENT OF THE ACTIVITY ANGIOTENSINKONVERTIERENDEN OF ENZYME IN BIOLOGICAL SAMPLES

HCG PEPTIDE FOR USE IN ANTI-BODY CLEANING METHOD

TRANSKARYOTI IMPLANTING

PROCEDURE AND REAGENT FOR THE DETERMINATION THE FOLLICLES OF THE STIMULATING HORMONE AS WELL AS FOR THIS APTITUDE MONOCLONAL ANTIBODIES

IMMUNOLOGICAL INCREASE OF THE SOMATOGENI EFFECT OF SOMATOTROPIN WITH AN ANTIBODY.

USE OF A AMYLINANTAGONISTEN FOR THE PRODUCTION OF A ARTZNEIMITTELS TO THE TREATMENT OF FAT CRAZE AND ESSENTIAL HYPERTONIA AND THUS COHERENT DISEASES.

MONOCLONAL ANTIBODY AGAINST ACETYLATED LYSINABFÄLLE IN REKOMBINANTEM RINDSOMATOTROPIN.

MONOCLONAL ANTI-BODIES AGAINST ATRIALE, NATRIURETHI PEPTIDE.

EFFECT OF HORMONES.

IMPROVEMENTS ON DELIVERY SYSTEMS FOR DRUGS

PROCEDURE FOR THE ANIMAL GROWTH PROMOTION.

USE FROM AGAINST A DARMPEPTID ARRANGED ANTIBODY TO THE PROMOTION OF THE FODDER UTILIZATION

PRODUCTION OF ANTIBODIES ON PHAGE SURFACES ON THE BASIS OF ANTI-BODY SEGMENT LIBRARIES.

BNP ANTIBODY AND IMMUNOLOGICAL PROOF IT USE

METHOD FOR THE PRODUCTION OF FILAMENT EYES, ANTI-BODY-PRESENTING BACTERIOPHAGE PARTICLES BY USE OF PHAGEMIDEN AND THE DADUCH MANUFACTURE BACTERIOPHAGE PARTICLE

MAGNETIC POLYMER PARTICLES ON THE BASIS OF POLYVINYL ALCOHOL, PROCEDURE FOR YOUR PRODUCTION AND USE

SANDWICH IMMUNOTESTVERFAHREN FOR N-PEPTIDE

SINGLE CHAIN FORMS THE CLYCOPROTEIN HORMONE OF THE QUARTET

PROCEDURE FOR THE CONNECTION OF AN ANTIGEN TO A MOLECULE WITH HIGH CONNECTION AFFINITY FOR THE ANTIGEN

HUMAN THYMOSIN BETA 15 GENE, PROTEIN AND ITS USES

POLYPEPTIDPRODUKTION

ENHANCEMENT OF PORCINE SOMATOTROPIN ACTIVITY

Relaxin diagnostic assays and kits, and methods and uses the reof

High affinity antibodies to human il-6 receptor

A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hIL-6R) with a K D of about 500 pM or less and blocks IL-6 activity with an IC 50 of 200 pM or less, is provided. In preferred embodiments, the antibody the antibody or antigen-binding fragment binds hIL-6R with an affinity at least 2-fold higher relative to its binding monkey IL-6R.

Natriuretic activities

This document provides methods and material related to natriuretic polypeptides. For example, substantially pure polypeptides having a natriuretic peptide activity, nucleic acids encoding polypeptides having a natriuretic peptide activity, host cells containing such nucleic acids, and methods for inducing a natriuretic or diuretic activity within a mammal are provided.

Methods and compositions for liver cancer therapy

The present disclosure provides methods of treating liver cancer and preventing liver cancer recurrence with anti-progastrin antibodies, methods of monitoring treatment efficacy of anti-progastrin therapy for liver cancer, and compositions useful therefore.

Anti-estrogen and immune modulator combinations for treating breast cancer

Compositions for treating cancers of mucosal tissues including breast, prostate, ovary, colon are disclosed which include various combinations of new or conventional anti-estrogen compounds, aromatase inhibitors, immune modulators, immune inhibitors, immune inhibitor mimicking compounds and steroid or thyroid hormones. Methods of predicting susceptibility of a cancer of mucosal origin to treatment with a composition containing an immune inhibitor or an immune inhibitor mimicking compound are also disclosed. Preferred methods include identifying in a specimen of cancer cells the presence of a Poly-Ig (Fe) receptor or Poly-Ig-like (Fc) receptor capable of binding to an immune inhibitor or an immune inhibitor mimicking compound and of mediating immune inhibition of cancer cell growth.

METHODS OF TREATING DIABETES AND COMPOSITIONS CAPABLE OF SAME

A composition of matter is disclosed which comprises isolated oligomers of human islet amyloid polypeptide (IAPP). Antibodies recognizing same are also disclosed. Use of the composition of matter and the antibodies are also disclosed. 1. A composition of matter comprising isolated oligomers of human islet amyloid polypeptide (IAPP).2. The composition of matter of claim 1 , wherein said oligomers comprise dimers and/or trimers.3. The composition of matter of claim 1 , wherein said oligomers have a molecular weight between 4 kDa and 90 kDa.4. The composition of matter of claim 1 , wherein the composition is devoid of fibrils of IAPP.5. The composition of matter of claim 1 , further comprising sodium dodecyl sulfate (SDS).6. The composition of matter of claim 1 , wherein said oligomers have an alpha helical conformation.7. The composition of matter of claim 1 , wherein said oligomers are crosslinked.8. The composition of matter of claim 1 , wherein said oligomers are non-crosslinked.9. The composition of matter of claim 8 , wherein said oligomers consist of dimers and/or trimers.10. The composition of matter of claim 1 , being stable for up to 7 days.11. A method of generating a composition of matter comprising isolated oligomers of human islet amyloid polypeptide (IAPP) claim 1 , the method comprising:(a) dissolving human IAPP in an agent that eliminates structured forms of IAPP;(b) removing said agent; and(c) redissolving said non-structured form of IAPP in a solvent and an anionic surfactant, thereby generating the composition of matter.12. The method of claim 11 , wherein said agent is selected from the group consisting of 1 claim 11 ,1 claim 11 ,1 claim 11 ,3 claim 11 ,3 claim 11 ,3 hexafluoro-2-propanol (HFIP) claim 11 , trifluoroethanol (TFE) claim 11 , and trifluoroacetic acid (TFA).13. The method of claim 11 , wherein said solvent is selected from the group consisting of sodium hydroxide claim 11 , potassium hydroxide claim 11 , ammonium hydroxide claim 11 , ...

Bispecific binding molecules binding to vegf and ang2

Bispecific binding molecules binding to both VEGF and Ang2, preferably in the form of immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing the same and their use in the treatment of diseases that are associated with VEGF- and/or Ang2-mediated effects on angiogenesis are disclosed. Further, nucleic acids encoding bispecific binding molecules, host cells and methods for preparing same are also described.

Immunoassay for chromogranin a, antibodies and kit

The invention relates to monoclonal antibodies which are reactive with an epitope in the polypeptide represented by amino acid sequence 236 to 251 or 264 to 279 of the human CGA amino acid sequence. The invention further relates to the use of these monoclonal antibodies in an immunoassay for CGA, to immunoreagents comprising any of these two antibodies, and to test kits for the determination of CGA containing immunoreagents based on both of the monoclonal antibodies.

Epitope regions of a thyrotrophin (tsh) receptor, uses thereof and antibodies thereto

The present invention is concerned with epitope regions of a thyrotrophin (TSH) receptor, uses thereof and antibodies thereto.

Isoforms of brain natriuretic peptide

Methods and materials for diagnosing and treating heart conditions (e.g., heart failure) and kidney conditions (e.g., kidney failure) are described.

Methods of Determination of Activation or inactivation of Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) Hormonal Systems

An in vivo method of determining activation or inactivation of the atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) hormonal systems, the method comprising simultaneously detecting the presence or amount of atrial and brain natriuretic peptide prohormones (proANP and proBNP) or fragments thereof in a sample.

ANTI-HEPCIDIN ANTIBODIES AND USES THEREOF

Monoclonal antibodies are provided that selectively bind human hepcidin-25 and are characterized as having high affinity for human hepcidin-25 and strong human mature hepcidin neutralizing properties. The antibodies of the invention are useful therapeutically for increasing serum iron levels, reticulocyte count, red blood cell count, hemoglobin, and/or hematocrit in a human and for the treatment and diagnosis of mature hepcidin-promoted disorders such as anemia, in a human subject. 1. An antibody that comprises six CDRs selected from the group consisting of:(i) LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 having the amino acid sequences as shown in SEQ ID NOs: 41, 53, 31, 63, 84, and 46, respectively;(ii) LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 having the amino acid sequences as shown in SEQ ID NOs: 43, 30, 31, 32, 44, and 46, respectively;(iii) LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 having the amino acid sequences as shown in SEQ ID NOs: 43, 53, 61, 63, 85, and 46, respectively; and(iv) LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, and HCDR3 having the amino acid sequences as shown in SEQ ID NOs: 43, 57, 61, 63, 84, and 46, respectively.217-. (canceled)18. A method of increasing serum iron levels claim 1 , reticulocyte count claim 1 , red blood cell count claim 1 , hemoglobin claim 1 , and/or hematocrit comprising administering to a subject an effective amount of the antibody of .19. A method of treating anemia in a subject claim 1 , comprising administering to the subject an effective amount of the antibody of .2025-. (canceled)26. A pharmaceutical composition comprising the antibody of claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent claim 1 , or excipient.27. (canceled)28. An immunoassay comprising a) obtaining a sample to be assayed for human mature hepcidin; b) contacting the sample with an antibody of under suitable conditions for antibody binding and allowing any human mature hepcidin present to form a complex with the antibody; and c) ...

Anti-adrenomedullin (adm) antibody or anti-adm antibody fragment or an anti-adm non-ig scaffold for use in therapy

Subject matter of the present invention is an anti-adrenomedullin antibody or an anti-adrenomedullin antibody fragment or anti-ADM non-Ig scaffold wherein said antibody or said fragment or scaffold is a non-neutralizing antibody, antibody fragment or non-Ig scaffold, respectively. Subject matter of the present invention is also an anti-adrenomedullin antibody or an anti-adrenomedullin antibody fragment or anti-ADM non-Ig scaffold for use in a treatment of a chronic or acute disease wherein said antibody or fragment or scaffold is: an ADM stabilizing antibody or an adrenomedullin stabilizing antibody fragment or an ADM stabilizing non-Ig scaffold that enhances the t 1/2 half retention time of adrenomedullin in serum, blood, plasma at least 10%, preferably at least, 50%, more preferably >50%, most preferably 100% and/or wherein said anti-ADM antibody or an anti-adrenomedullin antibody fragment or anti-ADM non-Ig scaffold blocks the bioactivity of ADM to not more than 80%, or not more than 50%.

Antibodies That Bind Myostatin, Compositions And Methods

There are disclosed selective myostatin antagonists (including antibodies), nucleic acids encoding them, and methods of making and using them. Neutralizing antibodies recognizing the conformational epitope near position 21 to 31 and position 50 to 60. 1. An isolated myostatin-specific antibody comprising at least one light chain and at least one heavy chain , wherein the light chain comprises a constant region and a variable region that comprises three complementarity determining regions (CDRs) and the heavy chain comprises a constant region and a variable region that comprises three CDRs , wherein the light chain CDRs are those disclosed in SEQ ID NO:10 , and the heavy chain CDRs are those disclosed in SEQ ID NO:20.2. The antibody of claim 1 , wherein the light chain CDRs are selected from the group consisting of:a) the light chain CDRs disclosed in SEQ ID NO:1;b) the light chain CDRs disclosed in SEQ ID NO:2;c) the light chain CDRs disclosed in SEQ ID NO:3;d) the light chain CDRs disclosed in SEQ ID NO:4;e) the light chain CDRs disclosed in SEQ ID NO:5;f) the light chain CDRs disclosed in SEQ ID NO:6;g) the light chain CDRs disclosed in SEQ ID NO:7;h) the light chain CDRs disclosed in SEQ ID NO:8; andi) the light chain CDRs disclosed in SEQ ID NO:9;and wherein the heavy chain CDRs are selected from the group consisting of:a′) the heavy chain CDRs disclosed in SEQ ID NO:11;b′) the heavy chain CDRs disclosed in SEQ ID NO:12;c′) the heavy chain CDRs disclosed in SEQ ID NO:13;d′) the heavy chain CDRs disclosed in SEQ ID NO:14;e′) the heavy chain CDRs disclosed in SEQ ID NO:15;f) the heavy chain CDRs disclosed in SEQ ID NO:16;g′) the heavy chain CDRs disclosed in SEQ ID NO:17;h′) the heavy chain CDRs disclosed in SEQ ID NO:18; andi′) the heavy chain CDRs disclosed in SEQ ID NO:19.3. The antibody of claim 1 , wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:10 claim 1 , and the heavy chain variable region comprises the ...

Human antibodies to human angiopoietin-like protein 4

A fully human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human angiopoietin-like protein 4 (hANGPTL4) is provided. The human anti-hANGPTL4 antibodies are useful in treating diseases or disorders associated with ANGPTL4, such as hyperlipidemia, hyperlipoproteinemia and dyslipidemia, including hypertriglyceridemia, hypercholesterolemia, chylomicronemia, and so forth. Furthermore, the anti-hANGPTL4 antibodies can be administered to a subject in need thereof to prevent or treat diseases or disorders, for which abnormal lipid metabolism is a risk factor. Such diseases or disorders include cardiovascular diseases, such as atherosclerosis and coronary artery diseases; acute pancreatitis; nonalcoholic steatohepatitis (NASH); diabetes; obesity; and the like.

DIAGNOSIS AND RISK STRATIFICATION BY MEANS OF THE NOVEL MARKER CT-PROADM

The invention relates to a novel diagnostic marker CT-proADM (C-terminal fragment of preproADM, SEQ ID No. 1) for diagnosing and/or stratifying the risk of diseases. Also disclosed is a method for diagnosing and/or stratifying the risk of diseases, particularly cardiovascular diseases, cardiac insufficiency, and infections and/or inflammations of the lungs and respiratory tract. In said method, the CT-proADM (SEQ ID No. 1) marker, or a partial peptide of fragment thereof, or said marker contained in a marker combination (panel, cluster) is determined in a patient who is to be examined. The invention further relates to a diagnostic apparatus as well as a kit for carrying out said method. 1. Diagnostic marker consisting of CT-proADM (SEQ ID No. 1) , or partial peptides or fragments thereof.2. A method for diagnosing and/or stratifying the risk of diseases , comprising determining CT-proADM (SEQ ID No , 1) , or a partial peptide of fragment thereof , in a patient.3. The method of claim 2 , wherein the method is an in-vitro diagnosis.4. The method of claim 2 , wherein the diagnosis or risk stratification of diseases is an in vitro diagnosis or risk stratification of cardiovascular diseases claim 2 , cardiac insufficiency claim 2 , infections and/or inflammations of the lungs and respiratory.5. The method of claim 4 , wherein the cardiac diseases comprise a disease selected from the group consisting of high blood pressure claim 4 , coronary heart diseases claim 4 , especially acute coronary syndrome claim 4 , (acute) myocardial infarct claim 4 , and angina pectoris.6. The method of claim 4 , wherein the cardiac insufficiency comprises a chronic cardiac insufficiency claim 4 , hypertensive heart disease with (congestive) cardiac insufficiency claim 4 , hypertensive heart and kidney disease with (congestive) cardiac insufficiency claim 4 , primary right-ventricular heart failure claim 4 , secondary right-ventricular heart failure claim 4 , left-ventricular heart failure ...

ANTI-ERYTHROPOIETIN ANTIBODIES

The present disclosure provides compositions and methods relating to antibodies that specifically bind to human erythropoietin. The disclosure provides nucleic acids encoding such antibodies and methods of making and using such antibodies. 1. An isolated antibody or fragment of an antibody , wherein the antibody or the fragment specifically binds to human erythropoietin and comprises:a. a VH CDR1 having an amino acid sequence identical to or comprising 0, 1, 2, or 3 amino acid residue substitutions relative to SEQ ID NO: 36;b. a VH CDR2 having an amino acid sequence identical to or comprising 0, 1, 2, or 3 amino acid residue substitutions relative to SEQ ID NO: 37;c. a VH CDR3 having an amino acid sequence identical to or comprising 0, 1, 2, or 3 amino acid residue substitutions relative to SEQ ID NO: 38;d. a VL CDR1 having an amino acid sequence identical to or comprising 0, 1, 2, or 3 amino acid residue substitutions relative to SEQ ID NO: 6;e. a VL CDR2 having an amino acid sequence identical to or comprising 0, 1, 2, or 3 amino acid residue substitutions relative to SEQ ID NO: 7; andf. a VL CDR3 having an amino acid sequence identical to or comprising 0, 1, 2, or 3 amino acid residue substitutions relative to SEQ ID NO: 8; org. a VH CDR1 having an amino acid sequence identical to or comprising 1, 2, or 3 amino acid residue substitutions relative to SEQ ID NO: 42;h. a VH CDR2 having an amino acid sequence identical to or comprising 1, 2, or 3 amino acid residue substitutions relative to SEQ ID NO: 43;i. a VH CDR3 having an amino acid sequence identical to or comprising 1, 2, or 3 amino acid residue substitutions relative to SEQ ID NO: 44;j. a VL CDR1 having an amino acid sequence identical to or comprising 1, 2, or 3 amino acid residue substitutions relative to SEQ ID NO: 12;k. a VL CDR2 having an amino acid sequence identical to or comprising 1, 2, or 3 amino acid residue substitutions relative to SEQ ID NO: 13; andl. a VL CDR3 having an amino acid sequence ...

PNEUMONIA BIOMARKERS

Ghrelin signal peptide fragment assays and kits useful in the diagnosis, prognosis, risk stratification, assessing, staging, monitoring, categorizing and determination of further diagnoses and treatment regimens in subjects with various disorders, diseases and conditions including, pneumonia, heart failure, or pneumonia and heart failure or suspected pneumonia, heart failure, or pneumonia and heart failure, and methods for monitoring treatment.

LUTEINIZING-HORMONE LIGAND AND LIGAND-GONADOTROPHIN COMPLEX

The invention relates to a ligand of a luteinizing hormone (LH), characterized in that it comprises the paratope of an ovine anti-LH antibody of which the variable domain of the heavy chain contains the following CDRs: —VH-CDR1, defined by the sequence GYTFTNYW (SEQ ID NO: 13); —VH-CDR2, defined by the sequence IYPGGGYT (SEQ ID NO: 14); —VH-CDR3, defined by the sequence ARTPLYGSSYGGFAY (SEQ ID NO: 15); and the variable domain of the light chain contains the following CDRs: —VL-CDR1, defined by the sequence QGISNY (SEQ ID NO: 16); —VL-CDR2, defined by the sequence YTS; —VL-CDR3, defined by the sequence QQYSKLPWT (SEQ ID NO: 17). The invention also relates to a ligand-gonadotrophin (LH, hCG, FSH) complex. The ligand or the complex according to the invention can be used to induce ovulation in a female mammal. 2. The ligand as claimed in claim 1 , wherein the heavy chain contains a framework region FR1 characterized in that the N-terminal portion of the framework region FR1 of the heavy chain is defined by the sequence XVQLQXSGAE (SEQ ID NO: 24) in which Xrepresents a glutamine or a glutamic acid.3. The ligand as claimed in claim 2 , wherein the heavy chain contains a framework region FR1 characterized in that the N-terminal portion of the framework region FR1 of the heavy chain is defined by the sequence SEQ ID NO: 24 in which Xrepresents a glutamine.4. The ligand as claimed in claim 2 , wherein the light chain contains a framework region FR1 characterized in that the N-terminal portion of the framework region FR1 of the light chain contains the sequence XTQXTSS (SEQ ID NO: 25) claim 2 , in which Xrepresents a methionine or a lysine and Xrepresents a threonine or an alanine.5. The ligand as claimed in claim 2 , selected from:a) the monoclonal antibody 1A6 C4 G11 produced by the hybridoma CNCM I-4332;b) a Fab, Fab′, or Fab′2 fragment of an antibody a), above; orc) a recombinant protein comprising the paratope of an antibody a) above.6. The ligand as claimed in claim 3 , ...

Low Dead Volume Extraction Column Device

The invention provides extraction columns for the purification of an analyte (e.g., a biological macromolecule, such as a peptide, protein or nucleic acid) from a sample solution, as well as methods for making and using such columns. The invention is characterized by the use of low dead volume columns, which is achieved in part by the use of low pore volume frits (e.g., membrane screens) to contain a bed of extraction media in the column. Low dead volume facilitates the elution of the captured analyte into a very small volume of desorption solution, allowing for the preparation of low volume samples containing relatively high concentrations of analyte. 1. A method for extracting an analyte , comprising: i) a column body having an open upper end for attachment to a pump, an open lower end for passing fluid into and out of the column body, and an open channel between the upper and lower end of the column body, wherein the column body comprises a pipette tip,', 'ii) a bottom frit bonded to and extending across the open channel, the bottom frit having a pore volume,', 'iii) a top frit bonded to and extending across the open channel between the bottom frit and the open upper end of the column body, the top frit having a pore volume, wherein the top frit or bottom frit are less than 350 microns thick, wherein the bottom frit is a membrane screen and the top frit is optionally a membrane screen and wherein the top frit or the bottom frit is comprised of nylon, polyester, polyamide, polycarbonate, cellulose, polyethylene, nitrocellulose, cellulose acetate, or polypropylene, and wherein the top frit, bottom frit, and channel surface define an extraction media chamber, and', 'iv) a bed of extraction media positioned inside the extraction media chamber;, 'a. providing a low dead volume extraction column, wherein the low dead volume extraction column is comprised of'}b. passing a sample solution through the low dead volume extraction column; andc. passing a desorption solvent ...

COMPOSITIONS, METHODS AND KITS RELATING TO RESISTIN

The invention relates to novel nucleic acids encoding a mammalian resistin gene, and proteins encoded thereby, whose expression is suppressed by the antidiabetic compounds thiazolidinediones. The invention further relates to methods of treating and detecting type 2 diabetes and Syndrome X comprising modulating or detecting resistin expression and/or production and activity of resistin polypeptide. 1. An isolated mammalian resistin polypeptide comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4 or a sequence sharing at least 80% sequence identity with SEQ ID NO: 2 or SEQ ID NO: 4.2. (canceled)3. The isolated polypeptide of claim 1 , wherein said resistin is encoded by a nucleic acid sequence having at least about 80% sequence identity with a nucleic acid having the sequence of SEQ ID NO:1 or SEQ ID NO: 3.4. (canceled)5. An isolated nucleic acid sequence encoding the polypeptide of .67-. (canceled)8. The nucleic acid of claim 5 , said nucleic acid further comprising a nucleic acid encoding a tag polypeptide covalently linked thereto.9. The nucleic acid of claim 8 , wherein said tag polypeptide is selected from the group consisting of a myc tag polypeptide claim 8 , a glutathione-S-transferase tag polypeptide claim 8 , a green fluorescent protein tag polypeptide claim 8 , a myc-pyruvate kinase tag polypeptide claim 8 , a His6 tag polypeptide claim 8 , an influenza virus hemagglutinin tag polypeptide claim 8 , a flag tag polypeptide claim 8 , and a maltose binding protein tag polypeptide.10. The nucleic acid of claim 5 , said nucleic acid further comprising a nucleic acid encoding a promoter or regulatory sequence operably linked thereto.11. A vector comprising the nucleic acid of .12. The vector of claim 11 , said vector further comprising a nucleic acid encoding a promoter or regulatory sequence operably linked thereto.13. A recombinant cell comprising the isolated nucleic acid of .14. A recombinant cell comprising the vector of .15. An antibody that ...

METHOD FOR SELECTING PLASMA CELLS OR PLASMABLASTS, METHOD FOR PRODUCING TARGET ANTIGEN SPECIFIC ANTIBODIES, AND NOVEL MONOCLONAL ANTIBODIES

[Problem] To provide a method that efficiently produces antigen-specific monoclonal antibodies from a wide range of animal species, and to provide a new antigen-specific monoclonal antibody using this technique. [Solution] A nonhuman animal is immunized with a target antigen, lymph fluid or the like is collected from the immunized nonhuman animal, or lymph fluid or the like is collected from a human having antibodies to the target antigen, the collected lymph fluid or the like is combined with (1) a labeled target antigen and (2) a marker that can selectively binds to plasma cells and/or plasmablasts, and cells that have bound to (1) the labeled target antigen and (2) the marker are then selected. The plasma cells and or the plasmablasts that have specifically bound to the target antigen by the method are selected, an gene of an antibody for the target antigen is collected from the selected cells, the base sequence thereof is identified, an antibody or antibody fragment is prepared on the basis of the base sequence of the identified gene, and an antibody or antibody fragment specific to the target antigen is produced. 1. A method for selecting a plasma cell(s) and/or plasmablast(s) that specifically bind to a target antigen , comprising:either collecting lymph fluid, lymphoid tissue, blood cell sample, or bone marrow derived cells from a nonhuman animal, and sensitizing the lymphocytes, lymphoid tissue, blood cell sample, or bone marrow derived cells in vitro to the target antigen, orimmunizing a nonhuman animal to the target antigen, and collecting lymph fluid, lymphoid tissue, blood cell sample, or bone marrow derived cells from the nonhuman animal once immunization has been established;mixing the sensitized or collected lymph fluid, lymphoid tissue, blood cell sample, or bone marrow derived cells with (1) a labeled target antigen and (2) a marker that selectively binds to plasma cells and/or plasmablasts; andselecting a cell(s) to which (1) the labeled target ...

MITIGATING TISSUE DAMAGE AND FIBROSIS VIA LATENT TRANSFORMING GROWTH FACTOR BETA BINDING PROTEIN (LTBP4)

The disclosure relates to compositions and methods of mitigating tissue damage and fibrosis in a patient by modulating latent transforming growth factor beta binding protein (LTBP4)-induced proteolysis of a TGFβ superfamily protein. 1. (canceled)2. A method of treating , delaying onset or preventing a transforming growth factor beta (TGFβ) superfamily protein-related disease , comprising administering an effective amount of an agent that modulates proteolysis of latent TGFβ binding protein 4 (LTBP4) to a patient in need thereof.3. The method of wherein the patient suffers from a disease selected from the group consisting of Duchenne Muscular Dystrophy claim 2 , Limb Girdle Muscular Dystrophy claim 2 , Becker Muscular Dystrophy claim 2 , myopathy claim 2 , cystic fibrosis claim 2 , pulmonary fibrosis claim 2 , cardiomyopathy claim 2 , acute lung injury claim 2 , acute muscle injury claim 2 , acute myocardial injury claim 2 , radiation-induced injury and colon cancer.4. The method of wherein the agent is selected from the group consisting of an anti-LTBP4 antibody and a peptide.5. The method of further comprising administering an effective amount of a second agent claim 2 , wherein the second agent is selected from the group consisting of a modulator of an inflammatory response claim 2 , a promoter of muscle growth claim 2 , a chemotherapeutic agent claim 2 , and a modulator of fibrosis.6. (canceled)7. A method of treating claim 2 , delaying onset or preventing a transforming growth factor beta (TGFβ) superfamily protein-related disease claim 2 , comprising administering to the patient an effective amount of an agent that upregulates the activity of latent TGFβ binding protein 4 (LTBP4).8. The method of wherein LTBP4 interacts with a TGFβ superfamily protein.9. The method of any one of wherein the TGFβ superfamily protein is selected from the group consisting of TGFβ claim 8 , a growth and differentiation factor (GDF) claim 8 , activin claim 8 , inhibin claim 8 , and ...

Antibodies to TTR and Methods of Use

The disclosure pertains to antibodies and binding fragments thereof that specifically binds all or part of EHAEVVFTA. Also provided are isolated peptides, isolated nucleic acids, immunogens, compositions, immunoassays and kits and method of using said reagents to detect misfolded TTR. 1. An antibody or binding fragment thereof that specifically binds all or part of EHAEVVFTA , wherein the part comprises at least 4 or at least 5 or more contiguous amino acids of EHAEVVFTA.2. The antibody or binding fragment thereof of claim 1 , wherein the antibody or binding fragment specifically binds misfolded and/or monomeric TTR claim 1 , optionally TTR fibrils.3. The antibody or binding fragment thereof of claim 1 , wherein the antibody or binding fragment thereof is capable of disrupting or reducing TTR fibril formation when monomeric TTR or misfolded TTR intermediates in solution is/are contacted with the antibody or binding fragment.4. The antibody or binding fragment thereof of claim 1 , wherein the antibody is a monoclonal or polyclonal antibody and/or a chimeric and/or a humanized antibody or binding fragment thereof.5. The antibody binging fragment of claim 1 , wherein the antibody fragment is a Fab claim 1 , Fab′ claim 1 , F(ab′) claim 1 , scFv claim 1 , dsFv claim 1 , ds-scFv claim 1 , dimer claim 1 , minibody claim 1 , diabody claim 1 , or multimer thereof or a bispecific antibody fragment.6. The antibody of claim 1 , wherein the antibody is affinity purified.7. An isolated peptide comprising all or part of EHAEVVFTA claim 1 , the part comprising at least 4 or at least 5 or more contiguous amino acids.8. The isolated peptide of claim 7 , further comprising one or more amino acid linkers conjugated to one or more of the peptide N and/or C termini claim 7 , optionally wherein the amino acid linkers include one or more G or K or S residues and for example the amino acid linker or linkers each independently comprise GG or GGKG or glycine serine linkers.9. The isolated ...

Ion Exchange Chromatography with Improved Selectivity for the Separation of Polypeptide Monomers, Aggregates and Fragments by Modulation of the Mobile Phase

Herein is reported a method for producing a polypeptide in monomeric form comprising the following step: recovering the polypeptide in monomeric form from an ion exchange chromatography material by applying a solution comprising a non-ionic polymer and an additive. 1. A method for producing an antibody of the IgG class in monomeric form comprising the following steps:applying a first solution that optionally comprises poly (ethylene glycol) and sorbitol to a cation exchange chromatographic material and thereby equilibrating the material,applying the solution comprising the antibody of the IgG class to the equilibrated chromatography material and thereby loading the chromatography material,producing the antibody of the IgG class in monomeric form by applying a solution to the chromatographic material comprising poly (ethylene glycol) and sorbitol, and thereby desorbing/eluting the antibody of the IgG class in monomeric form from the chromatographic material,whereby the poly (ethylene glycol) polymer has a concentration of about 10% by weight and the sorbitol has a concentration of from 5% to 20% by weight.2. A method for producing an antibody of the IgG class preparation with reduced host cell protein content comprising the following steps:applying a first solution that optionally comprises poly (ethylene glycol) and sorbitol to a cation exchange chromatographic material and thereby equilibrating the materialapplying the solution comprising the antibody of the IgG class to the equilibrated chromatography material and thereby loading the chromatography material,producing the antibody of the IgG class in monomeric form by applying a solution to the chromatographic material comprising poly (ethylene glycol) and sorbitol and thereby desorbing/eluting the antibody of the IgG class in monomeric form from the chromatographic material,whereby the poly (ethylene glycol) has a concentration of about 10% by weight and the sorbitol has a concentration of from 5% to 20% by weight ...

METHODS FOR DECREASING INFLUENZA-INDUCED LETHALITY USING GASTRIN-RELEASING PEPTIDE (GRP) INHIBITORS OR GASTRIN-RELEASING PEPTIDE RECEPTOR (GRPR) ANTAGONISTS

Gastrin-releasing peptide (GRP) is a neuroendocrine peptide that acts as a novel contributor to the inflammatory response to influenza infection. Thus, inhibition of GRP or antagonizing the GRP receptor (GRPR) during influenza infection represents a novel therapeutic approach to mitigating lung damage. The present invention encompasses methods of treatment based on these novel findings and observations. 1. A method for reducing GRP-induced pulmonary inflammation in a subject , comprising administering a therapeutically effective amount of a GRP inhibitor or a GRPR antagonist , or a combination thereof , to a subject having GRP-induced pulmonary inflammation.2. A method for reducing GRP-induced lung pathology in a subject , comprising administering a therapeutically effective amount of a GRP inhibitor or a GRPR antagonist , or a combination thereof , to a subject at risk for GRP-induced lung pathology.3. The method of claim 2 , wherein the lung pathology is one or more of increased numbers of mononuclear cell masses surrounding conducting airways; increased numbers of neutrophil masses in alveoli; increased numbers of PNEC; degradation of airway parenchyma at bronchiole/alveoli foci due claim 2 , for example claim 2 , to infiltrating inflammatory cells; breakdown of pulmonary capillary integrity; and leaky vasculature.48-. (canceled)9. A method for treating a viral infection in a subject claim 2 , comprising administering a therapeutically effective amount of a GRP inhibitor or a GRPR antagonist claim 2 , or a combination thereof claim 2 , to a subject infected with a virus.10. The method of claim 9 , wherein said treatment is a reduction in one or more of pulmonary inflammation claim 9 , lung damage claim 9 , decreased PNECs claim 9 , GRP gene expression claim 9 , GRP protein production claim 9 , GRPR activation claim 9 , GRPR signaling claim 9 , inflammatory cytokine and/or chemokine production claim 9 , and HMGB1 release in the subject in comparison to a subject ...

Monoclonal antibodies to progastrin and their uses

The present disclosure is directed to progastrin monoclonal antibodies, fragments thereof, compositions comprising progastrin monoclonal antibodies, and methods of making and using progastrin monoclonal antibodies and compositions thereof. The present disclosure is directed to methods of treating colorectal cancer with progastrin monoclonal antibodies and compositions comprising progastrin monoclonal antibodies or fragments thereof. The present disclosure is further directed to methods comprising detection of progastrin, including methods of diagnosing colorectal cancer and methods of monitoring efficacy of anti-cancer therapy in subjects suffering from colorectal cancer.

ANTIGEN-BINDING PROTEINS TO MARINOBUFAGENIN

The present invention provides monoclonal antigen-binding proteins that bind to the cardiac glycoside marinobufagenin (MBG), and methods of use. In various embodiments of the invention, the antigen-binding proteins are fully human antigen-binding proteins that bind to MBG. In some embodiments, the antigen-binding proteins of the invention are useful for inhibiting or neutralizing MBG activity, thus providing a means of treating or preventing a MBG-associated disease or disorder selected from the group consisting of hypertension, myocardial fibrosis, uremic cardiomyopathy, heart failure, myocardial infarction, renal failure, renal fibrosis and pre-eclampsia. 1. A recombinant antigen-binding protein comprising an antigen-binding domain that specifically binds to marinobufagenin (MBG) with a dissociation constant (K) of less than 50 nM as measured in an isothermal titration calorimetry assay at 25° C.2. The antigen-binding protein of claim 1 , wherein the antigen-binding protein shows one or more characteristics selected from the group consisting of:{'sub': 'D', '(a) binds to MBG with a dissociation constant (K) of less than 25 nM, as measured in a isothermal titration calorimetry assay at 25° C.;'}{'sub': 'D', '(b) binds to MBG with a dissociation constant (K) of less than 10 nM, as measured in a surface plasmon resonance assay at 25° C.;'}(c) blocks binding of MBG to Na+/K+ ATPase;{'sub': '50', '(d) releases inhibition of Na+/K+ ATPase and facilitates membrane repolarization of a cell with ECless than 300 nM, less than 200 nM, less than 150 nM or less than 100 nM, as measured in a membrane potential assay;'}(e) does not bind to digitalis or digoxin;(f) is fully human; and(g) the antigen-binding domain comprises at least one immunoglobulin variable region comprising three complementarity determining regions (CDRs).3. The antigen-binding protein of claim 2 , wherein the at least one immunoglobulin variable region is not a heavy chain variable region.4. The antigen- ...

Novel t cell receptors and immune therapy using the same

The present invention pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular the TAA Serine protease inhibitor Kazal-type 2 (SPINK2). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and SPINK2 binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of SPINK2 expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Mitigating tissue damage and fibrosis via latent transforming growth factor beta binding protein (ltbp4)

The disclosure relates to compositions and methods of mitigating tissue damage and fibrosis in a patient by modulating latent transforming growth factor beta binding protein (LTBP4)-induced proteolysis of a TGFβ superfamily protein.

ADRENOMEDULLIN TO GUIDE THERAPY OF BLOOD PRESSURE DECLINE

Subject matter of the present invention is an in vitro method for identifying a subject in need of administration of fluid resuscitation or a vasopressor comprising the following steps: 1. An in vitro method for identifying a subject in need of fluid resuscitation or administration of a vasopressor comprising the following steps:Determining the level of proADM (SEQ ID No. 1) and/or fragments thereof having at least 6 amino acids in a bodily fluid of said subjectCorrelating said level with the need of said subject for fluid resuscitation or administration of a vasopressor wherein said subject is identified as having such a need if the level of proADM (SEQ ID No. 1) and/or fragments thereof having at least 6 amino acids in the bodily fluid of said subject is above a threshold.2. An in vitro method for identifying a subject in need of fluid resuscitation or administration of a vasopressor according to wherein said proADM (SEQ ID No. 1) and/or fragments thereof having at least 6 amino acids are selected from the group comprising mature ADM (SEQ ID No. 4) and/or mature ADM 1-52-Gly (SEQ ID No. 5) and MR-proADM (SEQ ID No.3) and CT-ADM (SEQ ID No. 6).3. An in vitro method for identifying a subject in need of fluid resuscitation or administration of a vasopressor according to wherein either the level of mature ADM (SEQ ID No. 4) immunoreactivity and/or the level of mature ADM 1-52-Gly (SEQ ID No. 5)—immunoreactivity or the level of MR-proADM (SEQ ID No.3) immunoreactivity or the level of CT-ADM (SEQ ID No.6) immunoreactivity is determined and correlated with the need of said patient for fluid resuscitation or administration of a vasopressor wherein said patient is identified as having such a need if the level of mature ADM (SEQ ID No. 4) immunoreactivity and/or the level of mature ADM 1-52-Gly (SEQ ID No. 5)—immunoreactivity or the level of MR-proADM (SEQ ID No.3) immunoreactivity or the level of CT-ADM (SEQ ID No.6) immunoreactivity in the bodily fluid of said subject is ...

ANTI-NEUROTENSIN LONG FRAGMENT ANTIBODIES AND USES THEREOF

The present invention relates to a neutralising antibody which is capable of binding to neurotensin with high affinity. The antibody of the present invention neutralises the activity of neurotensin, in particular the oncogenic activities of neurotensin. In particular, the present invention relates to a neutralising antibody which binds to the human neurotensin long fragment, and having a heavy chain variable region which comprises a H-CDR1 region having at least 90% of identity with SEQ ID NO:2, a H-CDR2 region having at least 90% of identify with SEQ ID NO:3 and a H-CDR3 region having at least 90% of identity with SEQ ID NO:4; and a light chain variable region comprising a L-CDR1 region having at least 90% of identity with SEQ ID NO:6, a L-CDR2 having at least 90% of identity with SEQ ID NO:7 and a L-CDR3 region having at least 90% of identity with SEQ ID NO:8. The present invention also provides the use of such antibodies in the treatment of cancer. 110-. (canceled)11. A nucleic acid sequence which encodes a neutralizing antibody which binds to human neurotensin , said neutralizing antibody comprising one or more of a heavy chain variable region which comprises a H-CDR1 region having at least 90% identity with SEQ ID NO:2 , a H-CDR2 region having at least 90% identify with SEQ ID NO:3 and a H-CDR3 region having at least 90% identity with SEQ ID NO:4; and a light chain variable region comprising a L-CDR1 region having at least 90% identity with SEQ ID NO:6 , a L-CDR2 having at least 90% identity with SEQ ID NO:7 and a L-CDR3 region having at least 90% identity with SEQ ID NO:8.12. A vector which comprises the nucleic acid sequence of .13. A host cell which has been transfected claim 11 , infected or transformed to include the nucleic acid sequence of .1423-. (canceled)24. The nucleic acid of wherein neutralizing antibody hasa heavy chain variable region comprising a H-CDR1 region as set forth in SEQ ID NO:2, a H-CDR2 region as set forth in SEQ ID NO:3 and a H-CDR3 ...

COMBINATION THERAPY BETWEEN ANTI-PROGASTRIN ANTIBODY AND IMMUNOTHERAPY TO TREAT CANCER

The present invention relates to combinations comprising anti-progastrin (anti-hPG) monoclonal antibodies and immune checkpoint inhibitors, as well as pharmaceutical compositions comprising said combinations. Methods of treatment of cancer using said combinations are also provided. 120.-. (canceled)21. A combination comprising: a heavy chain comprising CDR-H1, CDR-H2 and CDR-H3 of amino acid sequences SEQ ID NOs 28, 29, and 30, respectively, and', 'a light chain comprising CDR-L1, CDR-L2 and CDR-L3 of amino acid sequences SEQ ID NOs 31, 32, and 33, respectively,, 'an anti-progastrin (anti-hPG) monoclonal antibody comprisingandan immune checkpoint inhibitor, wherein said immune checkpoint inhibitor is an anti-PD1 antibody.22. The combination of claim 21 , wherein said anti-hPG antibody is selected among single chain antibodies claim 21 , camelised antibodies claim 21 , chimeric antibodies claim 21 , IgA1 antibodies claim 21 , IgA2 antibodies claim 21 , IgD antibodies claim 21 , IgE antibodies claim 21 , IgG1 antibodies claim 21 , IgG2 antibodies claim 21 , IgG3 antibodies claim 21 , IgG4 antibodies claim 21 , and IgM antibodies.23. The combination of claim 21 , wherein said anti-hPG antibody is a C-terminal anti-progastrin antibody.24. The combination of claim 21 , wherein said anti-hPG antibody is a neutralising antibody.25. The combination of claim 21 , wherein said anti-hPG antibody is a monoclonal antibody comprising:a heavy chain of amino acid sequence SEQ ID NO:49 anda light chain of amino acid sequence SEQ ID NO:50.26. The combination of claim 21 , wherein said anti-hPG antibody is a humanised antibody.28. The combination of claim 26 , wherein said anti-hPG antibody comprises:a heavy chain variable region of amino acid sequence SEQ ID NO:71 anda light chain variable region of amino acid sequence SEQ ID NO:72, said antibody further comprising constant regions of the light-chain and the heavy-chain derived from a human antibody.29. The combination of claim 26 , ...

PEPTIDE ANALOGS

Analogs for CLR/RAMP receptor ligands are provided that have agonist, superagonist, antagonist or superantagonist activity. The analogs can be selective for one or more CLR/RAMP receptors, or can be pan-specific. 1. A CLR/RAMP receptor agonist peptide , comprising a structure of Formula I:{'br': None, 'sup': a', 'a', 'a, 'B—C-D\u2003\u2003(I)'}wherein:{'sup': 'a', 'Bis a modified N-terminal fragment of adrenomedullin peptide family member comprising from twenty to twenty eight amino acid residues, wherein two amino acid residues of the fragment are cysteine (Cys), wherein the C-terminal residue of the fragment is threonine (Thr);'}{'sup': 'a', 'Cis a central core consist of 3-12 amino acids; and'}{'sup': 'a', 'Dis a modified C-terminal fragment of intermedin (IMD) comprising from 3-6 amino acid residues with a C-terminal amide, where at least one amino acid of the C-terminal fragment is histidine (His), proline (P), serine (Ser), tyrosine (Tyr).'}2. The agonist of claim 1 , wherein Cis a core of 3-12 residues.3. The agonist of or wherein the N-terminal fragment Bcomprises: B—B—B—B—B—B-G-B—C—B—B—B—B—B—B—B—B—B—B—B—B—B(SEQ ID NO: 1) where: Bis absent or present claim 1 , or an amino string of KTKKTLRT; Bis selected from the group consisting of an empty residue claim 1 , histidine (His) claim 1 , acylated histidine (acy-His) claim 1 , double acylated histidine (acy-His(acy)) claim 1 , ace-histidine(acy) (ace-His(acy)) claim 1 , mini-PEG-acylated-histidine (mini-PEG-His(acy)) claim 1 , arginine (Arg) claim 1 , acylated arginine (acy-Arg) claim 1 , double acylated arginine (acy-Arg(acy)) claim 1 , ace-arginine(acy) (ace-Arg(acy)) claim 1 , mini-PEG-acylated-arginine (mini-PEG-Arg(acy)) claim 1 , lysine (Lys) claim 1 , acylated lysine (acy-Lys) claim 1 , double acylated lysine (acy-Lys(acy)) claim 1 , ace-lysine(acy) (ace-Lys(acy)) claim 1 , and mini-PEG-acylated-lysine (mini-PEG-Lys(acy)); Bis selected from the group consisting of glycine (Gly) and an empty residue; Bis ...

ANTI-ADRENOMEDULLIN (ADM) ANTIBODY OR ANTI-ADM ANTIBODY FRAGMENT OR ANTI-ADM NON-IG SCAFFOLD FOR PREVENTION OR REDUCTION OF ORGAN DYSFUNCTION OR ORGAN FAILURE IN A PATIENT HAVING A CHRONIC OR ACUTE DISEASE OR ACUTE CONDITION

Subject matter of the present invention is an anti-adrenomedullin (ADM) antibody or an anti-adrenomedullin antibody fragment or an anti-ADM non-Ig scaffold for use in therapy of a chronical or acute disease or acute condition of a patient for prevention or reduction of organ dysfunction or organ failure. In a preferred embodiment subject matter of the invention is an anti-ADM antibody or an anti-adrenomedullin antibody fragment or anti-ADM non-Ig scaffold for use in therapy of a chronical or acute disease or acute condition of a patient for prevention or reduction of kidney dysfunction or kidney failure or liver dysfunction or liver failure. 126.-. (canceled)28. The antibody or fragment thereof of claim 27 , wherein the C-terminal histidine residues of SEQ ID NOs 7-11 are not present.29. The antibody or fragment thereof of claim 27 , wherein (i) CDR1: amino acids 26-33 (SEQ ID NO: 1),', '(ii) CDR2: amino acids 51-58 (SEQ ID NO: 2), and', '(iii) CDR3: amino acids 97-107 (SEQ ID NO: 3), and, 'the invariant CDR sequences in the heavy chain variable regions are located within the heavy chain of SEQ ID NOs 7-11 at the following positions (i) CDR1: amino acids 27-37 (SEQ ID NO: 4),', '(ii) CDR2: amino acids 55-57 (SEQ ID NO: 5), and', '(iii) CDR3: amino acids 94-102 (SEQ ID NO: 6)., 'the invariant CDR sequences in the light chain variable regions are located within the light chain of SEQ ID NOs 12-14 at the following positions30. The antibody or fragment thereof of claim 28 , wherein (i) CDR1: amino acids 26-33 (SEQ ID NO: 1),', '(ii) CDR2: amino acids 51-58 (SEQ ID NO: 2), and', '(iii) CDR3: amino acids 97-107 (SEQ ID NO: 3), and, 'the invariant CDR sequences in the heavy chain variable regions are located within the heavy chain of SEQ ID NOs 7-11 at the following positions (i) CDR1: amino acids 27-37 (SEQ ID NO: 4),', '(ii) CDR2: amino acids 55-57 (SEQ ID NO: 5), and', '(iii) CDR3: amino acids 94-102 (SEQ ID NO: 6)., 'the invariant CDR sequences in the light chain ...

Bispecific binding molecules binding to vegf and ang2

Bispecific binding molecules binding to both VEGF and Ang2, preferably in the form of immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing the same and their use in the treatment of diseases that are associated with VEGF- and/or Ang2-mediated effects on angiogenesis are disclosed. Further, nucleic acids encoding bispecific binding molecules, host cells and methods for preparing same are also described.

COMPOSITIONS AND METHODS FOR DETECTING AND TREATING ESOPHAGEAL CANCER

The present invention relates to methods for the in vitro diagnosis of esophageal cancer, and to compositions and methods for the prevention or the treatment of esophageal cancer, wherein said compositions comprise an antibody binding to progastrin and said methods comprise the use of an antibody binding to progastrin. 1. A method for the in vitro diagnosis of esophageal cancer in a subject , comprising the steps of:a) contacting said biological sample from said subject with at least one progastrin-binding molecule,b) detecting the binding of said progastrin-binding molecule to progastrin in said sample, wherein said binding indicates the presence of esophageal cancer in said subject.2. The method of claim 1 , wherein step b) further comprises determining the concentration of progastrin and wherein a concentration of progastrin at least 10 pM in said biological sample is indicative of the presence of esophageal cancer in said subject.3. The method of claim 2 , comprising the further steps of:c) determining a reference concentration of progastrin in a reference sample,d) comparing the concentration of progastrin in said biological sample with said reference concentration of progastrin,e) determining, from the comparison of step d), the presence of esophageal cancer.4. The method of claim 1 , wherein said progastrin-binding molecule is an antibody claim 1 , or an antigen-binding fragment thereof.5. The method of claim 1 , wherein said antibody claim 1 , or antigen-binding fragment thereof claim 1 , is selected among N-terminal anti-progastrin monoclonal antibodies and C-terminal anti-progastrin monoclonal antibodies.6. The method of claim 1 , wherein said antibody binding to progastrin is a monoclonal antibody chosen from the group consisting of:a monoclonal antibody comprising a heavy chain comprising at least one, preferentially at least two, preferentially three, of CDR-H1, CDR-H2 and CDR-H3 of amino acid sequences SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, ...

COMPOSITIONS AND METHODS FOR DETECTING AND TREATING GASTRIC CANCER

The present invention relates to methods for the in vitro diagnosis of gastric cancer, and to compositions and methods for the prevention or the treatment of gastric cancer, wherein said compositions comprise an antibody binding to progastrin and said methods comprise the use of an antibody binding to progastrin. 1. A method for the in vitro diagnosis of gastric cancer in a subject , comprising the steps of:a) contacting said biological sample from said subject with at least one progastrin-binding molecule,b) detecting the binding of said progastrin-binding molecule to progastrin in said sample, wherein said binding indicates the presence of gastric cancer in said subject.2. The method of claim 1 , wherein step b) further comprises determining the concentration of progastrin and wherein a concentration of progastrin at least 10 pM in said biological sample is indicative of the presence of gastric cancer in said subject.3. The method of claim 2 , comprising the further steps of:c) determining a reference concentration of progastrin in a reference sample,d) comparing the concentration of progastrin in said biological sample with said reference concentration of progastrin,e) determining, from the comparison of step d), the presence of gastric cancer.4. The method of claim 1 , wherein said progastrin-binding molecule is an antibody claim 1 , or an antigen-binding fragment thereof.5. The method of claim 1 , wherein said antibody claim 1 , or antigen-binding fragment thereof claim 1 , is selected among N-terminal anti-progastrin monoclonal antibodies and C-terminal anti-progastrin monoclonal antibodies.6. The method of claim 1 , wherein said antibody binding to progastrin is a monoclonal antibody chosen from the group consisting of:a monoclonal antibody comprising a heavy chain comprising at least one, preferentially at least two, preferentially three, of CDR-H1, CDR-H2 and CDR-H3 of amino acid sequences SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, and a light ...

CANCER ASSOCIATED ANTIBODY COMPOSITIONS AND METHODS OF USE

The disclosure herein relates to novel cancer-associated antibodies that are used in the treatment and diagnosis of a cancer. The complete polypeptide and nucleic acid consensus sequences of the antibodies disclosed herein are reconstructed in silico. 1. An antibody or antigen-binding fragment thereof comprising at least one of:a complementarity-determining region heavy chain 1 (CDR-H1), a CDR-H2 and a CDR-H3, wherein the CDR-H1 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS: 85-98, the CDR-H2 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS: 57-70, and the CDR-H3 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS: 29-42.2. An antibody or antigen-binding fragment thereof that comprising at least one of:a complementarity-determining region light chain 1 (CDR-L1), a CDR-L2 and a CDR-L3, wherein the CDR-L1 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS: 99-112, the CDR-L2 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS: 71-84, and the CDR-L3 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS: 43-56.3. An antibody or antigen-binding fragment thereof comprising:a complementarity-determining region heavy chain 1 (CDR-H1), a CDR-H2 and a CDR-H3, wherein the CDR-H1 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS: 85-98, the CDR-H2 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS: 57-70, and the CDR-H3 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS: 29-42; anda complementarity-determining region light chain 1 (CDR-L1), a CDR-L2 and a CDR-L3, wherein the CDR-L1 comprises a reconstructed polypeptide consensus sequence selected from any one of SEQ ID NOS: 99-112, the CDR-L2 comprises a ...

METHODS OF TREATING OR PREVENTING PRURITIS BY BLOCKING NATRIURETIC POLYPEPTIDE B

Disclosed is a method of treating, reducing, or preventing pruritis in a mammal, the method comprising administering at least one natriuretic polypeptide b (Nppb) blocking agent to a mammal in an amount effective to treat or prevent pruritis in the mammal. An in vitro method of identifying a compound that inhibits Nppb activity is also disclosed. 1. A method of treating , reducing , or preventing pruritis in a mammal , the method comprising administering at least one natriuretic polypeptide b (Nppb) blocking agent to the mammal in an amount effective to treat , reduce , or prevent pruritis in the mammal.2. (canceled)3Trichomonas. The method of claim 1 , wherein the pruritis is associated with a fungal skin infection claim 1 , a skin infection claim 1 , eczema or psoriasis.4. The method of claim 1 , wherein the pruritis is induced by a pruritogen selected from the group consisting of histamine claim 1 , chloroquine claim 1 , endothelin (ET-1) claim 1 , 2-methyl serotonin (5HT) claim 1 , SLIGRL-NH2 (PAR2) claim 1 , and compound 48/80 (48/80).5. The method of claim 1 , wherein the pruritis is associated with a condition selected from the group consisting of acquired immune deficiency syndrome (AIDS) claim 1 , polycythemia vera claim 1 , diabetes claim 1 , hyperthyroidism claim 1 , liver damage claim 1 , liver disease claim 1 , cancer claim 1 , and renal failure.6. The method of claim 1 , wherein the pruritis is associated with kidney dialysis or chemotherapy.7. The method of claim 1 , wherein the pruritis is mediated by interleukin (IL)-31.8. The method of claim 1 , wherein the Nppb blocking agent is an agent that inhibits the binding of Nppb to natriuretic polypeptide receptor A (Npra).9. The method of claim 1 , wherein the Nppb blocking agent is an agent that inhibits Nppb signaling.10. The method of claim 1 , wherein the Nppb blocking agent is an agent that inhibits the production of any one or more of Nppb mRNA claim 1 , Nppb protein claim 1 , Npra mRNA claim 1 , ...

ANTI-ERYTHROPOIETIN ANTIBODIES

The present disclosure provides compositions and methods relating to antibodies that specifically bind to human erythropoietin. The disclosure provides nucleic acids encoding such antibodies and methods of making and using such antibodies. 1. An isolated antibody or fragment of an antibody , wherein the antibody or the fragment specifically binds to human erythropoietin and comprises:a. a variable heavy chain complementarity determining region 1 (VH CDR1) having an amino acid sequence SEQ ID NO: 36;b. a variable heavy chain complementarity determining region 2 (VH CDR2) having an amino acid sequence SEQ ID NO: 37;c. a variable heavy chain complementarity determining region 3 (VH CDR3) having an amino acid sequence SEQ ID NO: 38;d. a variable light chain complementarity determining region 1 (VL CDR1) having an amino acid sequence SEQ ID NO: 6;e. a variable light chain complementarity determining region 2 (VL CDR2) having an amino acid sequence SEQ ID NO: 7; andf. a variable light chain complementarity determining region 3 (VL CDR3) having an amino acid sequence SEQ ID NO: 8.2. An isolated antibody or antibody fragment , wherein the antibody or the fragment specifically binds human erythropoietin and comprises: a heavy chain variable comprising the amino acid of SEQ ID NO: 75; and comprises a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 67.3. An isolated antibody which competes for binding with the antibodies of or .4. The antibody of claim 3 , wherein the antibody is a monoclonal antibody.5. The antibody of claim 3 , wherein the antibody is a chimeric antibody claim 3 , a humanized antibody claim 3 , or a fully human antibody.6. A sterile composition comprising the isolated antibody or antibody fragment of any one of or .7. A kit for detecting antibody-mediated pure red cell aplasia (amPRCA) or predicting the risk or onset of AMPRC comprising the anti-human erythropoietin antibody of or claim 3 , and human erythropoietin. This ...

MEANS AND METHODS OF MEASURING PARATHYROID HORMONE IN PATIENTS SUFFERING FROM OXIDATIVE STRESS

Method for obtaining an antibody or antibody fragment to a conformational epitope specific for oxidized, inactive human parathyroid hormone and fragments thereof; a method for removal of oxidized, inactive human parathyroid hormone from a sample of body fluid; methods of determining the concentration of active parathyroid hormone in a sample, and an in vitro method of diagnosis of renal failure or secondary hyperthyroidism in patients on dialysis. The antibody is obtained by immunizing an animal with an immunogen containing parathyroid hormone or fragment thereof oxidized at methionines at positions 8, 18 or both; and a recovering of antibodies; whereby the complementary determining region of the antibody or antibody fragment or single chain antibody specifically recognizes a conformational epitope (antigenic determinant) which is a tertiary structure and only present on oxidized parathyroid hormone and fragments thereof only but not regular bioactive human parathyroid hormone, while the binding surface to the complementary binding region does not include any one of the oxidized methionines of human parathyroid hormone. 1. A method for obtaining antibody molecules specific for inactive human parathyroid hormone (hPTH) peptide and circulating fragments thereof , comprisinga) obtaining antibodies against human parathyroid hormone peptide by immunizing a non-human animal with an immunogen comprising as hapten oxidized parathyroid hormone or a oxidized fragment of parathyroid hormone, and recovering said antibodies from said non-human animal;b) selecting or purifying said antibodies from antibody molecules that bind to bioactive human parathyroid hormone peptide under physiological conditions to obtain antibodies that specifically recognize oxidized parathyroid hormone or fragments thereof;c) selecting or purifying said antibodies against oxidized parathyroid hormone from antibodies binding to an oxidized hPTH peptide independent from the methionine R-sulfoxide, ...

T cell receptor mimic rl9a

The present invention relates to a methodology of producing antibodies that recognize peptides associated with a tumorigenic or disease state, wherein the peptides are displayed in the context of HLA molecules. These antibodies will mimic the specificity of a T cell receptor (TCR) but will have higher binding affinity such that the molecules may be used as therapeutic, diagnostic and research reagents. The method of producing a T-cell receptor mimic of the present invention includes identifying a peptide of interest, wherein the peptide of interest is capable of being presented by an MHC molecule. Then, an immunogen comprising at least one peptide/MHC complex is formed, wherein the peptide of the peptide/MHC complex is the peptide of interest. An effective amount of the immunogen is then administered to a host for eliciting an immune response, and serum collected from the host is assayed to determine if desired antibodies that recognize a three-dimensional presentation of the peptide in the binding groove of the MHC molecule are being produced. The desired antibodies can differentiate the peptide/MHC complex from the MHC molecule alone, the peptide alone, and a complex of MHC and irrelevant peptide. Finally, the desired antibodies are isolated.

ANTI-HEPCIDIN ANTIBODIES AND USES THEREOF

The present application relates to antibodies that specifically bind to hepcidin and methods of using the antibodies. Another aspect relates to antibodies which bind hepcidin and regulate iron homeostasis. Another aspect relates to the use of humanized antibodies which bind hepcidin for the treatment of a disease or condition associated with hepcidin. 1. An antibody , or antigen-binding fragment thereof , that specifically binds to hepcidin or a hepcidin peptide , comprising a heavy chain variable region and a light chain variable region , (i) a CDR1 having an amino acid sequence of any one of SEQ ID NOS: 55-57,', '(ii) a CDR2 having an amino acid sequence of any one of SEQ ID NOS: 58-60, and', '(iii) a CDR3 having an amino acid sequence of any one of SEQ ID NOS: 61-63;, 'wherein said heavy chain variable region comprises (i) a CDR1 having an amino acid sequence of any one of SEQ ID NOS: 64-66,', '(ii) a CDR2 having an amino acid sequence of any one of SEQ ID NOS: 67-69, and', '(iii) a CDR3 having an amino acid sequence of any one of SEQ ID NOS: 70-72., 'and said light chain variable region comprises2. An antibody claim 2 , or antigen-binding fragment thereof claim 2 , of claim 2 , comprising an IgG1 or IgG4 heavy chain variable region; and an IgG1 or IgG4 light chain variable region.3. An antibody claim 2 , or antigen-binding fragment thereof claim 2 , that specifically binds to hepcidin or a hepcidin peptide claim 2 , prepared by injecting a rodent with a peptide having an amino acid sequence of hepcidin or a hepcidin peptide described herein.4. An antibody claim 2 , or antigen-binding fragment thereof claim 2 , that specifically binds to two or more amino acid residues of an epitope comprising amino acid residues 1-9 of hepcidin.5. An antibody claim 2 , or antigen-binding fragment thereof claim 2 , that specifically binds to an epitope comprising amino acid residues 1-9 of hepcidin.6. The antibody claim 2 , or antigen-binding fragment thereof claim 2 , of or ...

Anti-neurotensin antibodies and uses thereof

The present invention relates to a neutralising antibody which is capable of binding to neurotensin with high affinity. The antibody of the present invention neutralises the activity of neurotensin, in particular the oncogenic activities of neurotensin. In particular, the present invention relates to a neutralising antibody which binds to the human neurotensin long fragment, and having a heavy chain variable region which comprises a H-CDR1 region having at least 90% of identity with SEQ ID NO:2 in the, a H-CDR2 region having at least 90% of identify with SEQ ID NO:3 and a H-CDR3 region having at least 90% of identity with SEQ ID NO:4; and a light chain variable region comprising a L-CDR1 region having at least 90% of identity with SEQ ID NO:6, a L-CDR2 having at least 90% of identity with SEQ ID NO:7 and a L-CDR3 region having at least 90% of identity with SEQ ID NO:8. The present invention also provides the use of such antibodies in the treatment of cancer.

Pac1 antibodies and uses thereof

The present invention relates to neutralizing antibodies of the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the neutralizing antibodies are also described.

IMMUNOASSAY METHOD USING ANTI-HUMAN BNP FRAGMENT (4-32) ANTIBODY

The present invention is intended to enable detection of specific human BNP fragments solely by immunoassay, and, through a ratio measurement of the human BNP fragments, provides a convenient way of providing information useful for diagnosis and prognosis of heart disease. The invention achieves this by providing an assay that uses an antibody specific to human BNP fragment (4-32)—a fragment that has not caught much attention in the past. Provided herein is an immunoassay method for human BNP fragment (4-32) in a sample, and the method uses an antibody that reacts with human BNP fragment (4-32) but does not react with full-length human BNP (1-32), human BNP fragment (3-32), and human BNP fragment (5-32). Also provided herein is an assay in which the antibody is an antibody that reacts with human BNP fragment (4-32) at a site containing the N-terminus, and that reacts with human BNP fragment (4-10). 1. An immunoassay method for human BNP fragment (4-32) in a sample , wherein the method uses an antibody that reacts with human BNP fragment (4-32) but does not react with full-length human BNP (1-32) , human BNP fragment (3-32) , and human BNP fragment (5-32).2. The immunoassay method according to claim 1 , wherein the antibody that reacts with human BNP fragment (4-32) but does not react with full-length human BNP (1-32) claim 1 , human BNP fragment (3-32) claim 1 , and human BNP fragment (5-32) is an antibody that reacts with human BNP fragment (4-32) at a site containing the N-terminus.3. The immunoassay method according to or claim 1 , wherein the antibody that reacts with human BNP fragment (4-32) but does not react with full-length human BNP (1-32) claim 1 , human BNP fragment (3-32) claim 1 , and human BNP fragment (5-32) is an antibody that reacts with human BNP fragment (4-10).4. The immunoassay method according to claim 1 , wherein the antibody that reacts with human BNP fragment (4-32) but does not react with full-length human BNP (1-32) claim 1 , human BNP ...

MULTIVALENT MONO- OR BISPECIFIC RECOMBINANT ANTIBODIES FOR ANALYTIC PURPOSE

The present disclosure relates to novel analyte-specific multivalent recombinant antibodies that are particularly useful in immunoassays. Specifically, hexavalent, octavalent and decavalent antibodies are disclosed, including their construction, production, characterization and use in target antigen detection assays. 1. A non-chimeric or chimeric multivalent recombinant antibody , wherein the antibody comprises p light chain polypeptides Faband a dimer of two heavy chain polypeptides , wherein each heavy chain polypeptide has a structure of Formula I{'br': None, 'sub': N-terminus', 'H', 'n', 'H', 'H', 'H', 'm C-terminus, 'i': 'dd', '[Fab-L-]Fab-L-(Fc)[-L-Fab]\u2003\u2003(Formula I)'}wherein(a) p is a value selected from the group consisting of 6, 8, and 10,the value of p equals (2+2*(n+m)), andeach of m and n is selected independently from an integer of 1 to 3;(b) “-” is a covalent bond within a polypeptide chain;(c) each L is optional and, if present, is an independently selected variable linker amino acid sequence;{'sub': 'H', '(d) each dd(Fc) is a heavy chain dimerization region of a heavy chain of a non-antigen binding immunoglobulin region;'}{'sub': 'H', '(e) in the dimer the two dd(Fc) are aligned with each other in physical proximity;'}{'sub': H', 'H', 'H', 'H', 'H', 'H', 'H, 'claim-text': [{'br': None, 'sub': N-terminus', 'H C-terminus, '[VH-CH1]\u2003\u2003(Formula II),'}, {'br': None, 'sub': N-terminus', 'H C-terminus, '[VH-CL]\u2003\u2003(Formula III),'}, {'br': None, 'sub': N-terminus', 'H C-terminus, '[VL-CL]\u2003\u2003(Formula IV), and'}, {'br': None, 'sub': N-terminus', 'H C-terminus, '[VL-CH1]\u2003\u2003(Formula V),'}], '(f) each Fabis independently selected from Aand B, wherein Aand Bare different, and Aand Bare independently selected from the group consisting of'}whereinVH is a immunoglobulin heavy chain variable domain,VL is a immunoglobulin light chain variable domain,CH1 is a immunoglobulin heavy chain constant domain 1, andCL is a ...

METHODS AND MEANS FOR THE PRODUCTION OF IG-LIKE MOLECULES

The invention provides means and methods for producing one or more Ig-like molecules in a single host cell. Novel CH3 mutations enabling the production of monospecific and/or bispecific Ig-like molecules of interest are also provided. 128-. (canceled)29. A method for producing at least two different antibodies in a single host cell , said method comprising ,providing a host cell comprising{'sup': 'st', 'a first nucleic acid molecule encoding a 1antibody heavy chain comprising at least two substitutions of (i) D399R or D399K and (ii) K409E or K409D in the CH3 domain, and'}{'sup': 'nd', 'a second nucleic acid molecule encoding a 2antibody heavy chain comprising at least one substitution of (i) D399R or D399K and (ii) K409E or K409D in the CH3 domain;'}a third nucleic acid molecule encoding a 3rd antibody heavy chain, anda fourth nucleic acid molecule encoding a 4th antibody heavy chain,{'sup': st', 'nd', 'st', 'nd, 'culturing said host cell and allowing for expression of said antibody heavy chains, wherein the CH3 domain of said 1antibody heavy chain preferentially pairs with the CH3 domain of said 2antibody heavy chain, and the CH3 domain of said 3rd antibody heavy chain preferentially pairs with the CH3 domain of said 4th antibody heavy chain to produce antibodies containing said 1and 2antibody heavy chains and said 3rd and 4th antibody heavy chains; and'}harvesting said at least two different antibodies from the culture.30. The method of claim 29 , wherein said 1antibody heavy chain further comprises the substitution K392D or K392E.31. The method of claim 29 , further comprising providing said host cell with a nucleic acid encoding a common light chain.32. The method of claim 29 , wherein each of the encoded CH3 domain-comprising polypeptide chains further comprises a variable region recognizing an epitope.33. A mixture of at least two different antibodies obtainable by the methods according to .34. A mixture according to claim 33 , wherein said at least two ...

COMPOSITIONS FOR AND METHODS OF DIAGNOSING, PROGNOSING, AND TREATING DIABETES

Among the various aspects of the present disclosure is the provision of compositions for and methods of diagnosing, prognosing, and treating diabetes. 1. A method of detecting insulin peptides comprising:administering glucose to a subject;obtaining a biological sample comprising insulin peptides (e.g., the biological sample comprising circulating blood cells or circulating leukocytes); anddetecting a level of an immunogenic insulin peptide, wherein the immunogenic insulin peptide comprises a pathogenic epitope.2. The method of claim 1 , wherein the biological sample comprises circulating blood cells or circulating leukocytes.3. The method of claim 1 , wherein the immunogenic insulin peptide is a peptide fragment catabolized from insulin released from pancreatic islets into blood.4. The method of claim 1 , wherein the immunogenic insulin peptide is recognized by insulin-specific CD4 T cells.5. The method of claim 4 , wherein the insulin-specific CD4 T cells are segment 12-20 insulin B-chain (B:12-20)-specific CD4 T cells recognizing a B:12-20 epitope.6. The method of claim 5 , wherein the B:12-20-specific T cells have reduced motility when in fluid contact with immunogenic insulin peptides compared to a control in fluid contact with the immunogenic insulin peptides.7. The method of claim 6 , wherein the control is a wild-type CD4 T cell.8. The method of claim 1 , wherein the level of an immunogenic insulin peptide is detected using mass spectrometry.9. The method of claim 8 , wherein peptide components in the biological sample are separated with a gradient: all % Buffer B (0.1% formic acid in ACN): at about 0-40 min claim 8 , at about 2-22%; at about 40-50 min claim 8 , at about 22-35%; at about 50-60 min claim 8 , at about 35-95%; at about 60-70 min claim 8 , isocratic at about 95%; at about 70-71 min claim 8 , at about 95-2%; and at about 71-85 min claim 8 , at about isocratic at 2%.10. The method of claim 1 , further comprising:comparing a level of immunogenic ...

ACTRIIB PROTEINS AND VARIANTS AND USES THEREFORE RELATING TO UTROPHIN INDUCTION FOR MUSCULAR DYSTROPHY THERAPY

In certain aspects, the present invention provides compositions and methods for inducing utrophin expression in muscle with an ActRIIB protein as therapy for muscular dystrophy. The present invention also provides methods of screening compounds that modulate activity of an ActRIIB protein and/or an ActRIIB ligand. 1. A method for increasing sarcolemmal utrophin in a patient in need thereof , the method comprising administering an effective amount of a compound selected from the group consisting of:a. a polypeptide comprising an amino acid sequence that is at least 90% identical to the sequence of amino acids 29-109 of SEQ ID NO: 2; andb. a polypeptide encoded by a nucleic acid that hybridizes under stringent hybridization conditions to the nucleic acid of SEQ ID NO: 3.218-. (canceled)19. A method for increasing sarcolemmal utrophin in a patient in need thereof , the method comprising administering an effective amount of a compound selected from the group consisting of:a. an antagonist of ActRIIB;b. an antagonist of myostatin;c. an antagonist of activin A; andd. an antagonist of activin B.20. The method of claim 19 , wherein the compound is an antagonist of ActRIIB.21. The method of claim 20 , wherein the antagonist of ActRIIB is selected from the group consisting of: an antibody that binds to ActRIIB and a nucleic acid that hybridizes to a nucleic acid encoding ActRIIB and inhibits ActRIIB production.22. The method of claim 19 , wherein the compound is an antagonist of myostatin.23. The method of claim 22 , wherein the antagonist of myostatin is selected from the group consisting of: an antibody that binds to myostatin claim 22 , a nucleic acid that hybridizes to a nucleic acid encoding myostatin and inhibits myostatin production claim 22 , and a polypeptide comprising a myostatin propeptide or variant thereof.24. The method of claim 19 , wherein the compound is an antagonist of activin A.25. The method of claim 24 , wherein the antagonist of activin A is selected ...

Modulation of Activity of Proneurotrophins

The present invention provides agents for inhibiting binding of a pro-neurotrophin to a Vps1 Op-domain receptor, in particular the binding of a pro-NGF or a pro-BDNF to a Sortilin receptor. The invention thus provides agents for the manufacture of a medicament, for treating and/or preventing disease or disorders such as but not limited to neurological, neuropsychiatric and ocular diseases, disorders, and degeneration as well as obesity, diabetes, pain and/or nociception in an individual. 136-. (canceled)38. The method of claim 37 , wherein said agent binds to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:26 and/or SEQ ID NO:27 and/or SEQ ID NO:28.39. The method of claim 37 , wherein said pro-neurotrophin is selected from pro-NGF of SEQ ID NO:6 claim 37 , pro-BDNF of SEQ ID NO:7 claim 37 , pro-NT-3 of SEQ ID NO:8 or proNT-4/5 of SEQ ID NO:9.40. The method of claim 37 , wherein said animal is a human being.41. The method of claim 37 , wherein said agent is selected from proteins claim 37 , peptides claim 37 , polypeptides claim 37 , antibodies claim 37 , antisense RNA claim 37 , antisense DNA claim 37 , organic molecules or SiRNA.42. The method of claim 37 , wherein said agent is an antibody directed against a peptide comprising SEQ ID NO:25 and/or SEQ ID NO:26 and/or SEQ ID NO:27 and/or SEQ ID NO:28 or variant or fragments thereof.43. The method of claim 37 , wherein said agent is an antibody directed against a peptide comprising a sequence at least 70% identical to the prodomain of the pro-neurotrophins of SEQ ID NO:6 and/or SEQ ID NO:7 and/or SEQ ID NO:8 and/or SEQ ID NO:9 or a variant or fragment thereof.44. The method of claim 37 , wherein said agent is a peptide capable of binding to a sequence having at least 70% sequence identity to the prodomain of the pro-neurotrophins of SEQ ID NO:6 and/or SEQ ID NO:7 and/or SEQ ID NO:8 and/or SEQ ID NO:9 or a variant or fragment thereof.45. The method of claim 37 , wherein said agent is a ...

Methods for the Treatment and the Prognostic Assessment of Malignant Pleural Mesothelioma

The present invention relates to methods for the treatment and the prognostic assessment of malignant pleural mesothelioma. 1. A method of determining the prognosis of a subject suffering from malignant pleural mesothelioma , comprising the step of detecting the expression of neurotensin (NTS) in a mesothelioma sample obtained from said subject.2. A method for the treatment of malignant pleural mesothelioma , wherein an inhibitor of the neurotensin activation of neurotensin receptor 1 (NTSR1) is administered to a subject in need thereof.3. The method of claim 2 , wherein said inhibitor of the neurotensin activation of NTSR1 is an agent down-regulating the expression of neurotensin or of NTSR1.4. The method of claim 2 , wherein said inhibitor of the neurotensin activation of NTSR1 is selected from the group consisting of an antibody against neurotensin claim 2 , a fragment thereof which binds to neurotensin claim 2 , an antibody against the neurotensin receptor 1 and a fragment thereof which binds to the neurotensin receptor 1.5. The method of claim 2 , wherein said inhibitor of the neurotensin activation of NTSR1 is an antagonist of NTSR1.6. The method of claim 2 , wherein said inhibitor of the neurotensin activation of NTSR1 is a protease that can degrade neurotensin.7. A method for the treatment of malignant pleural mesothelioma claim 2 , wherein a cytotoxic agent which binds to NTSR1 is administered to a subject in need thereof. The present invention relates to methods for the treatment and the prognostic assessment of malignant pleural mesothelioma.Malignant pleural mesothelioma (MPM) is a relatively infrequent disease, whose incidence is estimated in western countries between less than 1 case/million/year among persons non exposed to asbestos and 100 cases/million/year among individuals professionally exposed to asbestos. The incidence of disease is expected to continue to increase in the next years, with a peak between 2015 and 2020.Prognosis of MPM is ...

MONOCLONAL ANTIBODIES TO PROGASTRIN AND THEIR USES

The present disclosure is directed to progastrin monoclonal antibodies, fragments thereof, compositions comprising progastrin monoclonal antibodies, and methods of making and using progastrin monoclonal antibodies and compositions thereof. The present disclosure is directed to methods of treating colorectal cancer with progastrin monoclonal antibodies and compositions comprising progastrin monoclonal antibodies or fragments thereof. The present disclosure is further directed to methods comprising detection of progastrin, including methods of diagnosing colorectal cancer and methods of monitoring efficacy of anti-cancer therapy in subjects suffering from colorectal cancer. 1. A monoclonal antibody that specifically binds a human progastrin (hPG) polypeptide having an amino acid sequence of SEQ ID NO:20 , but does not detectably bind to an amidated gastrin 17 consisting of SEQ ID NO:103 , a glycine-extended gastrin 17 consisting of SEQ ID NO:104 , or C-terminal Flanking Peptide (CTFP) consisting of SEQ ID NO:105 , wherein said monoclonal antibody is an N-terminal anti-hPG monoclonal antibody that specifically binds an N-terminal region of hPG , wherein:(a) the antibody is obtainable using an immunogen comprising a peptide antigen having an amino acid sequence of SEQ ID NO: 25; and{'sub': H', 'H', 'H', 'H', 'L', 'L', 'L', 'L, '(b) the antibody comprises VCDRs comprising amino acid sequences of VCDR 1.16 (SEQ ID NO:39), VCDR 2.16 (SEQ ID NO:43), VCDR 3.16 (SEQ ID NO:47) and VCDRs comprising amino acid sequences of VCDR 1.16 (SEQ ID NO:50), VCDR 2.16 (SEQ ID NO:53), and VCDR 3.16 (SEQ ID NO:57).'}27.-. (canceled)8. The monoclonal antibody of claim 14 , which comprises Vand Vchains having amino acid sequences of:{'sub': H', 'L, '(i) hV16a (SEQ ID NO:84) and hV16a (SEQ ID NO:85);'}{'sub': H', 'L, '(ii) ii hV16b (SEQ ID NO:86) and hV16b (SEQ ID NO:87); and'}{'sub': H', 'L, '(iii) hV16c (SEQ ID NO:88) and hV16c (SEQ ID NO:89).'}913.-. (canceled)14. The monoclonal antibody of ...

MONOCLONAL ANTIBODY FOR ANALYZING HIGH-MOLECULAR WEIGHT ADIPONECTIN AND UTILIZATION OF SAME

A monoclonal antibody that does not show a crossreactivity with middle-molecular weight (MMW) adiponectin and specifically reacts with high-molecular weight (HMW) adiponectin alone is disclosed. The monoclonal antibody of the present invention can be produced by using HMW adiponectin as an antigen. According to the monoclonal antibody of the present invention, a convenient, high-accurate, and versatile reagent for analyzing HMW adiponectin can be provided. 1. A method for producing a monoclonal antibody which monoclonal antibody specifically reacts with a high-molecular weight adiponectin, the method comprising contacting the monoclonal antibody with a high molecular weight adiponectin as an antigen. The present application is division of U.S. application Ser. No. 13/319,054, filed Nov. 4, 2011, which application is a National Stage application under 35 U.S.C. §371, claiming priority to PCT/JP2010/057747, filed May 6, 2010, which application claims the benefit of priority to Japanese Patent Application No. 2009-112624, filed May 7, 2009, the teachings all of which are incorporated herein by reference in their entirety for all purposes.The present invention relates to a novel monoclonal antibody specific to high-molecular weight adiponectin, and a method for specifically analyzing (in particular, measuring) the high-molecular weight adiponectin using the monoclonal antibody.Adiponectin is a secretory protein that is specifically expressed in adipocytes, and was reported to exhibit an anti-arteriosclerotic effect and an insulin resistance-reducing effect. In recent years, adiponectin has been reported to be involved in cancer, inflammation, and metabolic syndrome, and is considered to function as a defensive factor in the living body. Human adiponectin consists of 244 amino acid residues, and is known to have a molecular weight of approximately 28 kDa as a monomer. It was confirmed that adiponectin is present in blood in forms of a trimer (LMW: Low-molecular weight) ...

ACTRIIB PROTEINS AND VARIANTS AND USES THEREFORE RELATING TO UTROPHIN INDUCTION FOR MUSCULAR DYSTROPHY THERAPY

In certain aspects, the present invention provides compositions and methods for inducing utrophin expression in muscle with an ActRIIB protein as therapy for muscular dystrophy. The present invention also provides methods of screening compounds that modulate activity of an ActRIIB protein and/or an ActRIIB ligand. 152-. (canceled)53. A method for treating a DMD or BMD patient , the method comprising administering to the patient an effective amount of an antibody or antigen-binding fragment thereof that binds to ActRIIB , and wherein the patient has elevated levels of serum CK-MM relative to the norm for patients with the same disease state.54. The method of claim 53 , wherein the patient has DMD55. The method of claim 53 , wherein the patient has BMD.56. The method of claim 53 , wherein administration of the antibody or antigen-binding fragment thereof increases sarcolemmal strength of muscle fibers in the patient.57. The method of claim 56 , wherein utrophin expression is increased in the patient's skeletal or cardiac muscle.58. The method of claim 53 , wherein the method further comprises evaluating a marker for muscle degeneration and selecting a dose level or frequency based on the level of the marker for muscle degeneration claim 53 , wherein the marker for muscle degeneration is serum CK-MM.59. The method of claim 53 , wherein the method comprises administering an effective amount of an antibody that binds to ActRIIB.60. The method of claim 53 , wherein the method comprises administering an effective amount of an antigen-binding fragment that binds to ActRIIB.61. The method of claim 53 , wherein the antibody is humanized.62. The method of claim 53 , wherein the antibody is a monoclonal antibody. This application is a continuation of U.S. application Ser. No. 15/459,338, filed Mar. 15, 2017 (now allowed), which is a continuation of U.S. application Ser. No. 14/254,560, filed Apr. 16, 2014 (now U.S. Pat. No. 9,617,319), which is a continuation of U.S. ...

Dermal patch for transdermal administration of ghrelin pathway blocker

Embodiments of the innovation relate to a dermal patch, comprising a substrate; a set of projections coupled to the substrate and configured to be at least partially insertable into skin, at least a portion of each projection of the set of projections comprising a biodegradable material; and a ghrelin blocker material encapsulated in the plurality of projections. The set of projections are coupled to the substrate via an adhesive that is configured to be dissolved within the skin after the patch is applied to the skin for a predetermined time, thus resulting in separation of the set of projections from the substrate. Once embedded in the skin, the protrusions can degrade and release the anti-ghrelin antibody encapsulated therein. The released anti-ghrelin antibody can find its way into the subject's circulatory system.

HIGHLY SENSITIVE PARTICLE ENHANCED ASSAY FOR THE QUANTIFICATION OF NT-PROBNP

NT-proBNP can be determined in a biological sample using at least one antibody which recognizes an epitope of NT-proBNP in both a glycosylated and non-glycosylated form of NT-proBNP. Said antibody is preferably an isolated polyclonal antibody or a mixture of monoclonal antibodies coated onto a particle, preferably coated onto said particle in a coating ratio of 6-60%, forming a layer or multiple layers of antibodies on said particle. The assay, realized in the form of a nephelometric or turbidimetric assay, can be applied to a wide range of automated clinical analyzers. 2. The method according to claim 1 , wherein said at least one antibody specifically binds to NT-proBNP within the amino acid sequence of SEQ ID NO. 2.3. The method according to claim 1 , wherein said at least one antibody comprises a polyclonal antibody and/or a mixture of monoclonal antibodies.4. The method according to claim 1 , wherein said at least one antibody comprises a polyclonal antibody and/or a mixture of monoclonal antibodies and said polyclonal antibody and/or the mixture of monoclonal antibodies binds specifically to NT-proBNP with a Kto NT-proBNP of less than 10.0E-09 M claim 1 , preferably less than 5.0E-09 M claim 1 , more preferably less than 2.0E-09 M.5. The method according to claim 1 , wherein said at least one antibody comprises a polyclonal antibody and/or a mixture of monoclonal antibodies and said polyclonal antibody and/or the mixture of monoclonal antibodies binds/bind specifically to a peptide having the amino acid sequence of SEQ ID NO. 2 with a Kof less than 5.0E-09 M claim 1 , preferably less than 2.0E-09 M.6. The method according to of claim 1 , wherein said at least one antibody comprises a polyclonal antibody and/or a mixture of monoclonal antibodies and said polyclonal antibody and/or the mixture of monoclonal antibodies binds/bind specifically to a peptide having the amino acid sequence of SEQ ID NO. 3 with a Kof less than 10.0E-09 M claim 1 , preferably less than ...

ANTIGENIC PEPTIDES DERIVING FROM UROCORTIN 3 AND USES THEREOF FOR THE DIAGNOSIS AND TREATMENT OF TYPE 1 DIABETES

Despite the notion that human CD8 T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes (T1D), none of their target epitopes has been demonstrated to be naturally processed and presented by β cells. The inventors therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. Urocortin 3 was identified as a novel β-cell antigen, which was processed into HLA-A2- and HLA-A3-restricted epitopes recognized by circulating naive CD8 T cells in type 1 diabetic and healthy donors. Accordingly, the present invention relates to antigenic peptides derived from urocortin-3 and uses thereof for the diagnosis and treatment of T1D. 1. A peptide derived from urocortin 3 (UCN3) comprising:at least 8 consecutive amino acids in the sequence ranging from the amino acid residue at position 1 to the amino acid residue at position 21 in SEQ ID NO:1 (UCN3), orat least 8 consecutive amino acids in the sequence ranging from the amino acid residue at position 22 to the amino acid residue at position 71 in SEQ ID NO:1 (UCN3), orat least 8 consecutive amino acids in the sequence ranging from the amino acid residue at position 119 to the amino acid residue at position 162 in SEQ ID NO:1 (UCN3).2. The isolated peptide of which consists of the amino acid sequence as set forth in SEQ ID NO: 4 (MLMPVHFLLL) or SEQ ID NO: 34 (SLLSKRSFHY).3. The isolated peptide of which consists of the amino acid sequence as set forth in SEQ ID NO: 2 (MLMPVHFL) claim 1 , SEQ ID NO: 3 (MLMPVHFLL) claim 1 , SEQ ID NO: 4 (MLMPVHFLLL) claim 1 , SEQ ID NO: 5 (MLMPVHFLLLL) claim 1 , SEQ ID NO: 6 (FLLLLLLLL) claim 1 , SEQ ID NO: 7 (LMPVHFLL) claim 1 , SEQ ID NO: 8 (LMPVHFLLL) claim 1 , SEQ ID NO: 9 (LMPVHFLLLL) claim 1 , SEQ ID NO: 10 ( ...

Methods for detecting and quantifying fgf21

The presently disclosed subject matter provides antibodies that bind FGF21 and methods of using the same. In particular, the present disclosure provides immunoassay methods for detecting and quantifying active and total FGF21 levels in a sample and kits for performing such methods.

Antibodies Against Angiopoietins 1 and 2, and Their Use

The present invention relates to antibodies against angiopoietins 1 and 2, and derivatives of these antibodies. More specifically, the present invention relates to therapeutic use of the antibodies and fragment thereof which specifically bind to angiopoietins 1 and 2. 1. An isolated antibody , an antigen-binding portion or a derivative thereof , comprising: (a) a first CDR set , CDR1 , CDR2 and CDR3 , that sequentially together comprises the amino acid sequences of heavy chain CDRs , CDR1 , CDR2 and CDR3 , sequentially together , that are included in the amino acid sequence as set forth in any one of SEQ ID NOs: 2 , 4 , 6 , 8 , 10 , 12 , 14 , 16 , 18 , 20 , 22 , 24 , 26 , 28 , 30 , 32 , 34 , 36 , 38 , 40 , 42 , and 44; (b) a second CDR set , CDR1 , CDR2 and CDR3 , that sequentially together comprises the amino acid sequences of light chain CDRs , CDR1 , CDR2 and CDR3 , sequentially together , that are included in the amino acid sequence as set forth in any one of SEQ ID NOs: 46 , 48 , 50 , 52 , 54 , 56 , 58 , 60 , 62 , 64 , 66 , 68 , 70 , 72 , 74 , 76 , 78 , 80 , 82 , 84 , 86 , 88 , 90 , 92 , and 94; or , (c) a combination of said first CDR set of (a) and said second CDR set of (b).2. The isolated antibody claim 1 , antigen-binding portion or derivative thereof according to claim 1 , comprising a heavy chain claim 1 , a light chain claim 1 , or both of them claim 1 , wherein said heavy chain comprises a heavy chain variable region having the amino acid sequence as set forth in any one of SEQ ID NOs: 2 claim 1 , 4 claim 1 , 6 claim 1 , 8 claim 1 , 10 claim 1 , 12 claim 1 , 14 claim 1 , 16 claim 1 , 18 claim 1 , 20 claim 1 , 22 claim 1 , 24 claim 1 , 26 claim 1 , 28 claim 1 , 30 claim 1 , 32 claim 1 , 34 claim 1 , 36 claim 1 , 38 claim 1 , 40 claim 1 , 42 claim 1 , and 44 claim 1 , or antigen-binding fragments thereof; and said light chain comprises a light chain variable region having the amino acid sequence as set forth in any one of SEQ ID NOs: 46 claim 1 , 48 ...

NON-NATURAL SEMAPHORINS 3 AND THEIR MEDICAL USE

The present invention relates to non-naturally occurring, mutated Semaphorin 3 molecules. Particularly, the invention relates to the mutated Semaphorin 3 or the functional fragment thereof that exhibit improved properties and pharmacologic effects, e.g., in the treatment of angiogenic disease and cancer. In addition, the present invention relates to nucleic acid molecules encoding such polypeptides, and vectors and hosts comprising such nucleic acids. The invention further relates to methods for producing the polypeptides of the invention, and to methods of using them in the treatment of disease, in particular in the medical intervention of angiogenic diseases, tumors and/or cancer. 1. A mutated Semaphorin 3 or a functional fragment thereof wherein said mutated Semaphorin 3 is selected from the group consisting of Semaphorin 3A , Semaphorin 3B , Semaphorin 3C , and Semaphorin 3D and wherein said mutated Semaphorin 3 or said functional fragment thereof comprises an amino acid sequence CXXAGKD , wherein{'sub': '1', 'Xis an amino acid, which is K or N,'}{'sub': '2', 'Xis an amino acid selected from the group of W, M and L,'}{'sub': '3', 'and wherein the alanine (A) is replaced by a hydrophilic amino acid.'}2. The mutated Semaphorin 3 or the functional fragment thereof of claim 1 , wherein said mutated Semaphorin 3 or said functional fragment thereof comprisessaid hydrophilic amino acid in place of the alanine corresponding to position 106 of the wild type Semaphorin 3A as shown in SEQ ID NO: 2;said hydrophilic amino acid in place of the alanine corresponding to position 105 of the wild type Semaphorin 3B as shown in SEQ ID NO: 6;said hydrophilic amino acid in place of the alanine corresponding to position 104 of the wild type Semaphorin 3C as shown in SEQ ID NO: 10; orsaid hydrophilic amino acid in place of the alanine corresponding to position 120 of the wild type Semaphorin 3D as shown in SEQ ID NO: 14.3. The mutated Semaphorin 3 or the functional fragment thereof of ...

COMPOSITIONS AND METHODS FOR TREATING FATTY TISSUE BUILDUP

The present disclosure is directed to the treatment of diseases or conditions involving the buildup of fatty tissues, such as obesity, metabolic syndrome, type II diabetes, etc. A composition containing a monoclonal antibody directed against gastric inhibitory polypeptide is administered. This results in a reduced rate of weight gain and a marked decrease in lipid synthesis and accumulation. 1. A molecular antagonist of gastric inhibitory polypeptide (GIP) , comprising at least one complementarity determining region (CDR) with at least 80% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 20 , SEQ ID NO: 21 , SEQ ID NO: 22 , SEQ ID NO: 23 , SEQ ID NO: 24 , SEQ ID NO: 31 , SEQ ID NO: 32 , and SEQ ID NO: 33.2. The molecular antagonist of claim 1 , comprising a light chain variable domain having a first CDR and a second CDR claim 1 , each CDR having at least 95% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 20 claim 1 , SEQ ID NO: 21 claim 1 , SEQ ID NO: 22 claim 1 , SEQ ID NO: 23 claim 1 , and SEQ ID NO: 24.3. The molecular antagonist of claim 2 , wherein the first CDR and the second CDR are joined to each other by a linking group.4. The molecular antagonist of claim 3 , wherein the linking group is a chain of amino acids.5. The molecular antagonist of claim 1 , comprising a light chain variable domain having a first CDR with at least 80% identity to the amino acid sequence of SEQ ID NO: 20 claim 1 , a second CDR with at least 80% identity to the amino acid sequence of SEQ ID NO: 21 claim 1 , and a third CDR with at least 85% identity to the amino acid sequence of SEQ ID NO: 22.6. The molecular antagonist of claim 5 , wherein the first CDR claim 5 , the second CDR claim 5 , and the third CDR are joined to each other by linking groups.7. The molecular antagonist of claim 6 , wherein the linking groups are independently a chain of amino acids.8. The molecular antagonist of claim 1 , comprising a ...

Parathyroid Hormone Receptor 1 (PTH1R) Antibodies and Uses Thereof

The present disclosure relates, in general, human antibodies against human parathyroid hormone receptor 1 (PTH1R) and methods of use of such antibodies in the treatment of cancer, Humoral Hypercalcemia of Malignancy (HHM), or Primary Hyperparathyroidism (PHPT) and Secondary Hyperparathyroidism (SHPT) and cachexia. 1. An antibody that binds parathyroid hormone receptor 1 (PTH1R) with an affinity Kof 2×10M or less.2. The antibody of wherein the antibody binds the N-terminal portion of PTH1R.3. The antibody of wherein the antibody does not bind parathyroid hormone receptor 2 (PTH2R).4. The antibody of claim 1 , wherein the antibody binds PTH1R on the surface of a cell.5. The antibody of claim 1 , wherein the antibody binds allosterically to PTH1R.6. The antibody of any claim 1 , wherein the antibody is a negative modulator antibody claim 1 , optionally wherein the antibody is capable of weakening the binding affinity between PTH or PTHrP and with PTH1R by at least about 2-fold claim 1 , optionally up to 1000-fold.7. The antibody of claim 1 , wherein the antibody inhibits calcium flux in a cell in response to stimulation of the receptor with parathyroid hormone (PTH) or parathyroid hormone related protein (PTHrP).8. The antibody of claim 1 , wherein the antibody inhibits PTH- or PTHrP-mediated cyclic adenosine mono-phosphate (cAMP) accumulation.9. The antibody of that is a monoclonal antibody.10. An antibody that binds parathyroid hormone receptor 1 (PTH1R) comprising (a) a heavy chain CDR1 amino acid sequence set forth in SEQ ID NOs: 27 claim 1 , 30 claim 1 , 33 claim 1 , 36 claim 1 , 39 claim 1 , 42 claim 1 , 45 claim 1 , 48 claim 1 , 51 claim 1 , 54 claim 1 , 57 claim 1 , 60 claim 1 , 63 claim 1 , 66 claim 1 , 69 claim 1 , 72 claim 1 , 75 claim 1 , 78 claim 1 , 81 claim 1 , 84 claim 1 , 87 claim 1 , 90 claim 1 , 93 claim 1 , 96 claim 1 , 99 claim 1 ,102 claim 1 , or a variant thereof in which one or two amino acids have been changed;(b) a heavy chain CDR2 amino acid ...

PREVENTING, TREATING, AND REDUCING (PERSISTENT) POST-TRAUMATIC HEADACHE

Disclosed herein are methods of treating or reducing incidence of post-traumatic headache and/or at least one secondary symptom associated with post-traumatic headache in a subject comprising administering to the subject a monoclonal antibody that modulates the CGRP pathway. Compositions for use in the disclosed methods are also provided. Antagonist antibody G1 and antibodies derived from G1 directed to CGRP are also described. 120.-. (canceled)21. A method of reducing incidence of a post-traumatic headache in a subject , the method comprising:selecting a subject who has suffered a mild traumatic brain injury; andadministering to the subject a therapeutically effective amount of a humanized monoclonal anti-calcitonin gene-related peptide (CGRP) antagonist antibody comprising the amino acid sequence of the heavy chain variable region set forth in SEQ ID NO: 1 and the amino acid sequence of the light chain variable region set forth in SEQ ID NO: 2.22. The method of claim 21 , wherein the monoclonal antibody is administered to the subject intravenously or subcutaneously.23. The method of claim 21 , wherein the monoclonal antibody is administered to the subject intravenously in an infusion over about one hour.24. The method of claim 21 , further comprising administering one or more additional doses of the monoclonal antibody to the subject.25. The method of claim 21 , wherein the monoclonal antibody is administered at a dose of about 675 mg.26. The method of claim 25 , further comprising administering to the subject the monoclonal antibody at a dose of about 225 mg on the following two months.27. The method of claim 21 , wherein the monoclonal antibody is administered at a dose of about 900 mg.28. The method of claim 27 , wherein the monoclonal antibody is administered at a dose of about 900 mg quarterly.29. The method of claim 21 , wherein the monoclonal antibody is administered immediately after the brain injury.30. The method of claim 21 , wherein the reducing ...

METHOD OF TREATMENT TO PREVENT OR REVERSE AGE-ASSOCIATED INFLAMMATION, COGNITIVE DECLINE, AND NEURODEGENERATION

In aging mice, myeloid cell bioenergetics are suppressed in response to increased signaling by the lipid messenger prostaglandin E2 (PGE2), a major modulator of inflammation. In aging macrophages and microglia, PGE2 signaling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. Inhibition of myeloid EP2 signaling restores youthful energy metabolism in peripheral macrophages and microglia, rejuvenates systemic and brain inflammatory states, and prevents loss of hippocampal synaptic plasticity and spatial memory. Blockade of peripheral myeloid EP2 signaling is sufficient to restore cognition in aged mice. 1. A method for reducing inflammation in a subject , wherein the inflammation is associated with neurological or cognitive decline in the subject , comprising inhibiting an EP2 (Prostaglandin Ereceptor 2)-generated signal in the subject by contacting EP2 with an EP2 antagonist.2. The method of claim 1 , wherein inhibiting the EP2 signal comprises administering to the subject a composition comprising a brain-penetrant EP2 antagonist claim 1 , a peripheral EP2 antagonist claim 1 , or both.3. The method of claim 1 , wherein the EP2 antagonist is a small molecule antagonist.4. The method of claim 1 , wherein the EP2 is in aged human monocyte-derived macrophages.5. The method of claim 4 , wherein the brain-penetrant EP2 antagonist is compound 52.6. The method of claim 4 , wherein the peripheral EP2 antagonist is PF04418948.7. A method for reducing cognitive decline in a subject claim 4 , comprising inhibiting an EP2-generated signal by administering a composition comprising an EP2 antagonist to a subject in need thereof.8. The method of claim 7 , wherein the EP2-generated signal is a myeloid EP2-generated signal.9. The method of claim 8 , wherein the myeloid EP2-generated signal is inhibited in aged mammalian monocyte-derived macrophages.10. The method of claim 7 , wherein the composition is ...

Use of an inhibitor of ntsr1 activation or expression for preventing weight loss, muscle loss, and protein blood level decrease in subjects in need thereof

Cachexia is a potentially lethal syndrome afflicting mammals, frequently complicates the treatment of infection, inflammation and cancer. It is characterized by involuntary weight loss, including muscle loss and decrease in protein blood level content. The inventors now show in 2 animal models (mice fed with normal diet and mice fed with high fat diet) that neutralisation of the long fragment of neurotensin with an inhibitor of NTSR1 activation or expression prevents weight loss, muscle loss and protein blood level decrease. Accordingly, the present invention relates to use of an inhibitor of NTSR1 activation or expression for preventing weight loss, muscle loss, and protein blood level decrease in subjects in need thereof.

Monoclonal antibody of human-derived procalcitonin, and preparation method and application thereof

The present invention provides a monoclonal antibody that specifically binds to human-derived procalcitonin and application thereof. The present invention also provides a hybridoma cell line secreting the monoclonal antibody and having an accession number of CGMCC No. 10417, and a method for preparing an antibody against procalcitonin by using a procalcitonin mutant antigen as the immunogen.

LONG LIFE POLYPEPTIDE BINDING MOLECULES

The present invention relates to a binding molecule comprising at least three domains comprised in at least one polypeptide chain, wherein the first binding domain is a binding domain which is capable of binding to a cell surface molecule on a target cell, the second binding domain is a binding domain which is capable of binding to the T cell CD3 receptor complex, and the third domain is a binding domain which is capable of binding to serum albumin, wherein said third domain is positioned at the C-terminus of said second domain. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule. 1. A binding molecule comprising at least three binding domains comprised in at least one polypeptide chain , wherein(a) the first domain is a binding domain which is capable of binding to a cell surface molecule on a target cell; and(b) the second domain is a binding domain which is capable of binding to the T cell CD3 receptor complex; and(c) the third domain is a binding domain which is capable of binding to serum albumin, wherein said third domain is positioned at the C-terminus of said second domain.2. The binding molecule according to claim 1 , wherein the three domains are on one polypeptide in the order from the N-terminus to the C-terminusthe first binding domain;the second binding domain; andthe third binding domain.3. The binding molecule according to or claim 1 , wherein the third binding of the binding molecule is an scFv or single domain antibody.4. The binding molecule according to any of to claim 1 , wherein(a) the first binding domain is capable of binding to the cell surface molecule on a human and a non-human primate cell;(b) the second binding ...

ANTIBODY AGAINST AFFINITY COMPLEX

The present invention provides a means and a method for specifically measuring a substance such as a small substance with high sensitivity by a sandwich method. Specifically, the present invention provides an antibody capable of specifically binding to an affinity complex and a method of measuring of the affinity complex comprising measuring the affinity complex using the antibody capable of specifically binding to the affinity complex. The antibody of the present invention may be a full-length antibody. The antibody of the present invention may also have a region derived from an immunoglobulin from an animal having an ability of gene conversion (e.g., a complementarity-determining region, a framework region, or a variable region). Examples of at least one factor that constitutes the affinity complex include a small substance or a protein (e.g., antibody). 1. An antibody capable of specifically binding to an affinity complex.2. The antibody according to claim 1 , wherein the antibody is a full-length antibody.3. The antibody according to claim 1 , wherein the antibody has a region derived from an immunoglobulin from an animal having an ability of gene conversion.4. The antibody according to claim 3 , wherein the region derived from the immunoglobulin from the animal having the ability of gene conversion is a complementarity-determining region claim 3 , a framework region claim 3 , or a variable region.5. The antibody according to claim 1 , wherein the affinity complex comprises a small substance as a factor.6. The antibody according to claim 1 , wherein the affinity complex comprises a protein as a factor.7. The antibody according to claim 1 , wherein the affinity complex is a complex comprising a small substance and an antibody thereto.8. The antibody according to claim 7 , wherein the small substance is a steroid compound claim 7 , an amino acid compound claim 7 , or a vitamin.9. The antibody according to claim 8 , whereinthe steroid compound is an estrogen,the ...

Methods for Modulating Angiogenesis of Cancers Refractory to Anti-VEGF Treatment

A method for modulating angiogenesis in a cancer or tumor refractory to anti-VEGF, including identifying a cancer cell as being referactory to anti-VEGF, and then contacting the cancer cell refractory to anti-VEGF with an effective amount of an agent that modulates interaction between Gal1 or a Gal1 fragment and the natural binding partner of Gal1 or the Gal1 fragment to thereby modulate angiogenesis. 1. A method for modulating angiogenesis in a cancer refractory to anti-VEGF , comprising:(a) identifying a cancer cell as refractory to anti-VEGF; and(b) contacting the refractory cancer cell with an effective amount of an agent that modulates interaction between Gal1 or a Gal1 fragment and a natural binding partner of Gal1 or the Gal1 fragment to thereby modulate angiogenesis in the refractory cancer cell.2. The method according to claim 1 , wherein the modulating of angiogenesis inhibits angiogenesis in the refractory cancer cell.3. The method according to claim 2 , wherein the inhibition of angiogenesis decreases angiogenesis in the cancer cell by at least 10% with respect to a level of angiogenesis in a corresponding control refractory cancer cell.4. (canceled)5. (canceled)6. The method according to claim 1 , wherein the agent that modulates interaction between Gal1 or the Gal1 fragment and the natural binding partner of Gal1 or the Gal1 fragment inhibits angiogenesis and is selected from the group consisting of an antibody claim 1 , a nucleic acid claim 1 , a peptide claim 1 , a fusion protein claim 1 , a small molecule claim 1 , and a glycan-related compound.7. (canceled)8. The method according to claim 1 , wherein the agent that modulates interaction between Gal1 or the Gal1 fragment and the natural binding partner of Gal1 or the Gal1 fragment is an anti-Gal1 monoclonal antibody claim 1 , or an antigen-binding fragment thereof.9. (canceled)10. The method according to claim 8 , wherein the monoclonal antibody is selective for Gal1 over other galectins.11. The ...

ANTI-ANGPTL8 ANTIBODIES AND USES THEREOF

The present invention provides antibodies that bind to ANGPTL8 and methods of using the same. According to certain embodiments, the antibodies of the invention bind human ANGPTL8 with high affinity. The antibodies of the invention may be fully human antibodies. The antibodies of the invention are useful for the treatment of various diseases or disorders characterized in part by elevated blood triglyceride levels. 1. An antibody or antigen-binding fragment thereof that binds to the same epitope on ANGPTL8 as a reference antibody , and/or competes for binding to ANGPTL8 with a reference antibody , wherein the reference antibody comprises HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 domains having amino acid sequences of SEQ ID NO: 164/166/168/172/174/176 or 316/318/320/324/326/328 , respectively.2. The antibody of claim 1 , wherein the reference antibody:a) comprises HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 domains having amino acid sequences of SEQ ID NO: 164/166/168/172/174/176 and binds specifically to the epitope as defined by SEQ ID NO: 368; orb) comprises HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 domains having amino acid sequences of SEQ ID NO: 316/318/320/324/326/328 and binds specifically to a linear epitope in the N-terminal region of human ANGPTL8 as defined by SEQ ID NO: 348.3. The antibody of claim 1 , wherein the reference antibody:a) is a fully human monoclonal antibody;b) does not bind to the N-terminal coiled-coil region of human ANGPTL3 peptide of SEQ ID NO: 338, or to the N-terminal coiled-coil region of human ANGPTL4 peptide of SEQ ID NO: 339;{'sub': D', 'D, 'c) binds human ANGPTL8 at 25° C. with a Kof less than about 150 pM and binds monkey ANGPTL3 at 25° C. with a Kof less than about 90 pM as measured by surface plasmon resonance;'}d) lowers triglyceride levels in a mammal by about 68% when administered subcutaneously at a dose of about 10 mg/kg;e) lowers triglyceride levels in a mammal for a period ranging from about 7 days to 21 days, when administered ...

Methods for treating melanoma

The present invention relates to methods for treating melanoma and other indications by inhibiting leptin activity.

METHODS AND ARRAYS FOR USE IN THE SAME

The invention provides a method for determining prostate cancer-associated disease state in an individual comprising or consisting of the steps of: (a) providing a sample to be tested from the individual; and (b) determining a biomarker signature of the test sample by measuring the expression in the test sample of one or more biomarkers selected from the group defined in Table 1; wherein the expression in the test sample of the one or more biomarkers selected from the group defined in Table 1 is indicative of one or more prostate cancer-associated disease state in the individual. The invention also provides arrays and kits for use in the same. 1. A method for determining prostate cancer-associated disease state in an individual comprising or consisting of the steps of:a) providing a sample to be tested from the individual;b) determining a biomarker signature of the test sample by measuring the expression in the test sample of one or more biomarkers selected from the group defined in Table 1;wherein the expression in the test sample of the one or more biomarkers selected from the group defined in Table 1 is indicative of one or more prostate cancer-associated disease state in the individual.2. The method according to further comprising or consisting of the steps of:c) providing one or more control sample from an individual not afflicted with prostate cancer;d) determining a biomarker signature of the control sample by measuring the expression in the control sample of the one or more biomarkers measured in step (b);wherein the one or more prostate cancer-associated disease state is identified in the event that the expression in the test sample of the one or more biomarkers measured in step (b) is different from the expression in the control sample of the one or more biomarkers measured in step (d).3. The method according to or further comprising or consisting of the steps of:e) providing a control sample from an individual afflicted with prostate cancer;f) determining ...

Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide and Methods Using Same

The invention features methods for preventing or treating CGRP associated disorders such as vasomotor symptoms, including headaches (e.g., migraine, cluster headache, and tension headache) and hot flushes, by administering an anti-CGRP antagonist antibody. Antagonist antibody G1 and antibodies derived from G1 directed to CGRP are also described. 1. A method for reducing incidence of or treating cluster headache in an individual , comprising administering to the individual an effective amount of an anti-CGRP antagonist antibody , wherein the anti-CGRP antagonist antibody is a human or humanized antibody that blocks or decreases cyclic adenosine monophosphate (cAMP) activation in cells.2. The method of claim 1 , wherein the anti-CGRP antagonist antibody has a binding affinity (K) to human α-CGRP of 50 nM or less as measured by surface plasmon resonance at 37° C.3. The method of claim 1 , wherein the anti-CGRP antagonist antibody has a binding affinity (K) to human α-CGRP of 10 nM or less as measured by surface plasmon resonance at 37° C.4. The method of claim 1 , wherein the anti-CGRP antagonist antibody has a binding affinity (K) to human α-CGRP of 1 nM or less as measured by surface plasmon resonance at 37° C.5. The method of claim 1 , wherein the anti-CGRP antagonist antibody has a binding affinity (K) to human α-CGRP of 500 pM or less as measured by surface plasmon resonance at 37° C.6. The method of claim 1 , wherein the anti-CGRP antagonist antibody has a binding affinity (K) to human α-CGRP of 100 pM or less as measured by surface plasmon resonance at 37° C.7. The method of claim 1 , wherein the anti-CGRP antagonist antibody has a binding affinity (K) to human α-CGRP of 50 pM or less as measured by surface plasmon resonance at 37° C.8. The method of claim 1 , wherein the anti-CGRP antagonist antibody is a humanized antibody.9. The method of claim 1 , wherein the anti-CGRP antagonist antibody comprises a heavy chain constant region selected from the group ...

MONOCLONAL ANTIBODIES AGAINST ENDOTROPHIN AND THE USE THEREOF

Aspects of the present invention relate to methods and reagents for increasing chemosensitivity to platinum-based chemotherapy. In one aspect, a method of increasing chemosensitivity to platinum-based chemotherapy is provided, comprising administering to a patient in need thereof an effective amount of an endotrophin-neutralizing agent. The agent can be a monoclonal antibody, or fragment thereof, capable of binding to the C5 domain of the alphas chain of collagen VI. In some embodiments, the method can further include administering an effective amount of thiazolidinedione to said patient. 1. A monoclonal antibody or antibody fragment , wherein the antibody or antibody fragment is characterized by clone-paired heavy and light chain CDR sequences from Tables 1 and 2 , respectively.2. The monoclonal antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences according to clone-paired sequences from Table 3.3. The monoclonal antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having at least 70% claim 1 , 80% claim 1 , or 90% identity to clone-paired sequences from Table 3.4. The monoclonal antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having at least 95% identity to clone-paired sequences from Table 3.5. The monoclonal antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences according to clone-paired sequences from Table 4.6. The monoclonal antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having at least 70% claim 1 , 80% claim 1 , or 90% identity to clone-paired variable sequences from Table 4.7. The monoclonal antibody or antibody ...

Method for producing antibody

Disclosed is an antibody in which the 80th amino acid residue in a variable region based on the Kabat method and the 171th amino acid residue in a constant region based on the Kabat method are substituted with cysteine in an antibody in which the 80th amino acid residue in the variable region and the 171th amino acid residue in the constant region are not cysteine.

ION CONCENTRATION-DEPENDENT BINDING MOLECULE LIBRARY

Disclosed is a library consisting essentially of a plurality of antigen-binding molecules differing in sequence from each other, wherein an antigen-binding domain in each of the antigen-binding molecules comprises at least one amino acid residue that changes the antigen-binding activity of the antigen-binding molecule depending on ion concentration conditions. Also disclosed are a composition comprising a plurality of polynucleotide molecules each encoding the antigen-binding molecules, a composition comprising a plurality of vectors each comprising the polynucleotide molecules, a method for selecting the antigen-binding molecules, a method for isolating the polynucleotide molecules, a method for producing the antigen-binding molecules, and a pharmaceutical composition comprising any of the antigen-binding molecules. 122.-. (canceled)23. A library consisting essentially of a plurality of antigen-binding molecules differing in sequence from each other , wherein an antigen-binding domain in each of the antigen-binding molecules comprises at least one amino acid residue that changes the antigen-binding activity of the antigen-binding molecule depending on ion concentration conditions , and wherein the ion concentration conditions are pH conditions.24. The library according to claim 23 , wherein the amino acid residue is contained in the antigen-binding domain in a heavy chain of the antigen-binding molecule.25. The library according to claim 24 , wherein the antigen-binding domain in a heavy chain is a heavy chain variable region.26. The library according to claim 25 , wherein the amino acid residue is located at any one or more of positions 27 claim 25 , 31 claim 25 , 32 claim 25 , 33 claim 25 , 35 claim 25 , 50 claim 25 , 52 claim 25 , 53 claim 25 , 55 claim 25 , 57 claim 25 , 58 claim 25 , 59 claim 25 , 61 claim 25 , 62 claim 25 , 95 claim 25 , 96 claim 25 , 97 claim 25 , 98 claim 25 , 99 claim 25 , 100a claim 25 , 100b claim 25 , 100d claim 25 , 100f claim 25 , ...

Method to screen high affinity antibody

The current invention reports a method for producing an antibody comprising the steps of a) providing a plurality of hybridoma cells each expressing an antibody, b) determining the time dependent amount of said antibody bound to the respective antigen by surface plasmon resonance at different temperatures and different antibody concentrations, c) calculating with the time dependent amount determined in b) based on equations (II) to (XIII) at least the thermodynamic parameters (i) standard association binding entropy (ΔS°‡ass), (ii) standard dissociation binding entropy (ΔS°‡diss), (iii) standard binding entropy (ΔS°), (iv) free standard binding enthalpy (ΔG°), (v) standard dissociation free binding enthalpy (ΔG°‡diss), (vi) standard association free binding enthalpy (ΔG°‡ass), (vii) −TΔS°, (viii) dissociation rate constant kd, (ix) equilibrium binding constant KD, and (x) association rate constant ka, d) selecting a hybridoma cell producing an antibody with at least two of the following: i) a standard association binding entropy of less than 10 J/K*mol, ii) an absolute standard dissociation binding entropy of 100 J/mol*K or more, iii) an absolute standard binding entropy of 100 J/mol*K or more, e) producing an antibody by cultivating said selected cell under conditions suitable for the expression of said antibody and recovering said antibody from the cells or/and the cultivation medium.

IMMUNOASSAY FOR THE DETECTION OF PROCALCITONIN

The present invention relates to an in vitro method for the detection of Procalcitonin or a fragment thereof of at least 20 amino acid residues in length in a biological sample derived from a bodily fluid obtained from a subject, comprising the steps of: (i) contacting said sample with at least two antibodies or functional fragments thereof directed against different epitopes within Procalcitonin, and (ii) qualitatively or quantitatively detecting binding of said at least two antibodies to Procalcitonin or said fragment thereof, wherein binding indicates the presence or concentration of Procalcitonin or said fragment in said sample, wherein at least one antibody or functional fragment thereof is directed against an epitope comprised in the sequence spanning amino acid residues 2 to 52 of Procalcitonin. The invention also pertains to antibodies directed against an N-terminal epitope of Procalcitonin and kits comprising antibodies directed against PCT. 1. In vitro method for the detection of Procalcitonin or a fragment thereof of at least 20 amino acid residues in length in a biological sample derived from a bodily fluid obtained from a subject , comprising the steps of:a. contacting said sample with at least two antibodies or functional fragments thereof directed against different epitopes within Procalcitonin, and 'wherein at least one antibody or functional fragment thereof is directed against an epitope comprised in the sequence spanning amino acid residues 2 to 52 of Procalcitonin.', 'b. qualitatively or quantitatively detecting binding of said at least two antibodies to Procalcitonin or said fragment thereof, wherein binding indicates the presence or concentration of Procalcitonin or said fragment in said sample,'}2. Method according to claim 1 , wherein the antibody or functional fragment thereof claim 1 , which is directed against an epitope comprised in the sequence spanning amino acid residues 2 to 52 of Procalcitonin claim 1 , is a monoclonal antibody.3. ...

ANTI-CGRP COMPOSITIONS AND USE THEREOF

The present invention is directed to antibodies and fragments thereof having binding specificity for CGRP. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the V, Vand CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-CGRP antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-CGRP antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-CGRP antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with CGRP. 1. An anti-human CGRP antibody or antibody fragment which specifically binds to human CGRP , said antibody or antibody fragment comprising the same CDRs as an anti-CGRP antibody selected from Ab1 , Ab2 , Ab3 , Ab4 , Ab5 , Ab6 , Ab7 , Ab , Ab9 , Ab10 , Ab11 , Ab12 , Ab13 or Ab14 , optionally Ab6.2. (canceled)3. The antibody fragment of claim 1 , wherein said fragment is selected from a Fab fragment claim 1 , a Fab′ fragment claim 1 , a F(ab′)2 fragment claim 1 , or a monovalent antibody fragment.46-. (canceled)7. The antibody or antibody fragment of claim 1 , comprising a variable light chain comprising the CDR 1 sequence of SEQ ID NO:55 claim 1 , the CDR 2 sequence of SEQ ID NO:56 claim 1 , and the CDR 3 sequence of SEQ ID NO:57 claim 1 , and/or a variable heavy chain comprising the CDR 1 sequence of SEQ ID NO:58 claim 1 , the CDR 2 sequence of SEQ ID NO:59 claim 1 , and the CDR 3 sequence of SEQ ID NO:60.89-. (canceled)10. The anti-human CGRP antibody or antibody fragment of which:(i) comprises a variable light polypeptide possessing at least 80% sequence identity to SEQ ID NO: 51 and a variable heavy chain polypeptide possessing at least 80% sequence identity to SEQ ID NO: 53;(ii) ...

METHODS FOR TREATING VISCERAL PAIN BY ADMINISTERING ANTAGONIST ANTIBODIES DIRECTED AGAINST CALCITONIN GENE-RELATED PEPTIDE

The invention features methods for preventing or treating visceral pain, including pain associated with functional bowel disorder, inflammatory bowel disease and interstitial cystitis, by administering an anti-CGRP antagonist antibody. 1. A method of treating visceral pain and/or one or more symptoms of visceral pain in an individual , comprising administration of a therapeutically effective amount of an anti-CGRP antagonist antibody to an individual suffering from or at risk for visceral pain.2. The method of claim 1 , wherein the visceral pain is associated with a functional bowel disorder (FBD).3. The method of claim 2 , wherein the FBD is selected from the group consisting of gastro-esophageal reflux claim 2 , dyspepsia claim 2 , irritable bowel syndrome (IBS) and functional abdominal pain syndrome (FAPS).4. The method of claim 1 , wherein the visceral pain is associated with inflammatory bowel disease (IBD).5. The method of claim 4 , wherein the IBD is selected from the group consisting of Crohn's disease claim 4 , ileitis and ulcerative colitis.6. The method of claim 1 , wherein the visceral pain is associated with renal colic claim 1 , dysmenorrhea claim 1 , cystitis claim 1 , menstrual period claim 1 , labor claim 1 , menopause claim 1 , prostatitis or pancreatitis.7. The method of claim 6 , wherein the visceral pain is associated with interstitial cystitis (IC).8. The method of claim 1 , wherein the anti-CGRP antagonist antibody binds CGRP with a Kof 50 nM or less (as measured by surface plasmon resonance at 37° C.); and/or has a half life in-vivo of at least 7 days.9. The method of claim 1 , wherein the anti-CGRP antagonist antibody specifically binds to the C-terminal region of CGRP.10. The method of claim 9 , wherein the anti-CGRP antagonist antibody specifically recognizes the epitope defined by the sequence GSKAF (SEQ ID NO: 39).11. The method of claim 1 , wherein the anti-CGRP antibody comprises a VH domain having the amino acid sequence shown in SEQ ...

ASPROSIN, A FAST-INDUCED GLUCOGENIC PROTEIN HORMONE

Embodiments of the disclosure concern methods and compositions that relate to increasing or decreasing the weight (including, for example, by increasing or decreasing the adipose mass) in individuals in need thereof. Such methods and compositions, in particular embodiments, concern providing an effective amount of the hormone asprosin to increase adipose mass in an individual with insufficient adipose mass and providing an antibody or inhibitor of asprosin in an individual with obesity or diabetes, for example, to reduce adipose mass. 1. An isolated antibody or antibody fragment that specifically binds a peptide consisting of SEQ ID NO:4.2. The antibody or antibody fragment of claim 1 , wherein the antibody is produced by hybridoma cell line deposited with the American Type Culture Collection under accession number ATCC PTA-123085.3. The antibody or antibody fragment of claim 1 , wherein the antibody is a humanized antibody.4. The antibody or antibody fragment of claim 1 , wherein the antibody is a single chain antibody.5. The antibody or antibody fragment of claim 1 , wherein the antibody is a nanobody.6. The antibody or antibody fragment of claim 1 , wherein the antibody is a humanized single chain antibody or nanobody.7. The antibody or antibody fragment of claim 1 , wherein the antibody is a bispecific antibody.8. The antibody or antibody fragment of claim 1 , wherein the antibody is a humanized bispecific antibody.9. The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment is conjugated to a biologically active effector domain.10. A hybridoma cell as deposited with the American Type Culture Collection under accession number ATCC PTA-123085.11. A monoclonal antibody produced by a hybridoma deposited with the American Type Culture Collection under accession number ATCC PTA-123085.12. A composition comprising the antibody of .13. Hybridoma cell line ATCC PTA-123085.14. An antibody produced by the cell line of .15. A method of ...

COMPOSITIONS AND METHODS FOR TREATING FATTY TISSUE BUILDUP

The present disclosure is directed to the treatment of diseases or conditions involving the buildup of fatty tissues, such as obesity, metabolic syndrome, type II diabetes, etc. A composition containing a monoclonal antibody directed against gastric inhibitory polypeptide is administered. This results in a reduced rate of weight gain and a marked decrease in lipid synthesis and accumulation. 1. A method of treating obesity , type II diabetes , food-induced Cushing's syndrome , or metabolic syndrome , or for reducing fatty tissue buildup in the liver or omentum , or for reducing subcutaneous fatty tissue buildup , comprising:administering to a person a composition comprising a pharmaceutically effective amount of a molecular antagonist of gastric inhibitory polypeptide (GIP),wherein the molecular antagonist comprises at least one complementarity determining region (CDR) with at least 80% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 31, SEQ ID NO: 32, and SEQ ID NO: 33.2. The method of claim 1 , wherein the molecular antagonist comprises a light chain variable domain having a first CDR and a second CDR claim 1 , each CDR having at least 95% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 20 claim 1 , SEQ ID NO: 21 claim 1 , SEQ ID NO: 22 claim 1 , SEQ ID NO: 23 claim 1 , and SEQ ID NO: 24.3. The method of claim 2 , wherein the first CDR and the second CDR of the molecular antagonist are joined to each other by a linking group.4. The method of claim 3 , wherein the linking group is a chain of amino acids.5. The method of claim 1 , wherein the molecular antagonist comprises a light chain variable domain having a first CDR with at least 80% identity to the amino acid sequence of SEQ ID NO: 20 claim 1 , a second CDR with at least 80% identity to the amino acid sequence of SEQ ID NO: 21 claim 1 , and a third CDR with at least ...

Antagonist antibodies directed against calcitonin gene-related peptide and methods using same

The invention features methods for preventing or treating CGRP associated disorders such as vasomotor symptoms, including headaches (e.g., migraine, cluster headache, and tension headache) and hot flushes, by administering an anti-CGRP antagonist antibody. Antagonist antibody G1 and antibodies derived from G1 directed to CGRP are also described.

Methods and agents to treat tumor cells and cancer

This disclosure provides cell surface anchoring conjugates that can bind with an exogenous antibody, compositions and formulations comprising said cell surface anchoring conjugates, TLR agonist and methods of using the same for boosting immunity in a subject and treating tumor cell and cancer.

ANTIBODIES AND USE THEREOF

The present invention relates to specific antibodies and use thereof, such as for identifying and/or quantifying liraglutide fibrils and/or semaglutide fibrils.

MELATONIN MONOCLONAL ANTIBODY, DETECTION, METHODS AND USES THEREOF

The invention provides monoclonal antibodies and fragments thereof that specifically bind to melatonin. Also provided are heavy chain variable region (VH) and light chain variable region (VL) sequences of such monoclonal antibodies and fragments thereof. Further provided are melatonin conjugates, and methods and uses, for example, determining, detecting, measuring, screening for, analyzing and monitoring an amount of melatonin in a sample. 1. A monoclonal antibody or fragment thereof that specifically binds to melatonin , wherein the antibody comprises:a heavy chain variable region comprising a CDR-H1 sequence comprising at least 80% sequence identity with the sequence of SEQ ID NO: 7, a CDR-H2 sequence comprising at least 90% sequence identity with the sequence of SEQ ID NO: 8, and a CDR-H3 sequence comprising at least 80% sequence identity with the sequence of SEQ ID NO: 9; anda light chain variable region comprising a CDR-L1 sequence comprising at least 80% sequence identity with the sequence of SEQ ID NO: 17, a CDR-L2 sequence comprising at least 80% sequence identity with the sequence of SEQ ID NO: 18, and a CDR-L3 sequence comprising at least 80% sequence identity with the sequence of SEQ ID NO: 19.2. A monoclonal antibody or fragment thereof that specifically binds to melatonin , wherein the antibody comprises:{'sub': 'H', 'a heavy chain variable region (V) comprising at least 80% sequence identity with the sequence of SEQ ID NO: 6; and'}{'sub': 'L', 'a light chain variable region (V) comprising at least 80% sequence identity with the sequence of SEQ ID NO: 16.'}3. A heavy chain variable region (VH) comprising a CDR-H1 sequence comprising at least 80% sequence identity with the sequence of SEQ ID NO: 7 , a CDR-H2 sequence comprising at least 90% sequence identity with the sequence of SEQ ID NO: 8 , and a CDR-H3 sequence comprising at least 80% sequence identity with the sequence of SEQ ID NO: 9.4. A light chain variable region (VL) comprising a CDR-L1 ...

COMPOSITIONS AND METHODS FOR ANTIBODIES TARGETING EPO

The present invention relates to compositions and methods for the inhibition of EPO. The invention provides antibodies and antigen binding fragments thereof that bind to EPO and are able to inhibit EPO-dependent cell proliferation and/or EPO-dependent cell signaling. 138-. (canceled)39. A method of treating diabetic macular edema comprising administering to a subject in need thereof an effective amount of a composition comprising an antibody , or an antigen binding fragment thereof , that binds erythropoietin (EPO) , wherein the antibody or antigen binding fragment thereof comprises:a) heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 1, 2, and 3, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 4, 5, and 6, respectively;b) heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 21, 22, and 23, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 24, 25, and 26, respectively;c) heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 41, 42, and 43, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 44, 45, and 46, respectively; ord) heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 61, 62, and 63, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 64, 65, and 66, respectively.40. The method of claim 39 , wherein the antibody or antigen binding fragment thereof comprises heavy chain variable region HCDR1 claim 39 , HCDR2 claim 39 , and HCDR3 as set forth in SEQ ID NOs: 1 claim 39 , 2 claim 39 , and 3 claim 39 , respectively claim 39 , and light chain variable region LCDR1 claim 39 , LCDR2 claim 39 , and LCDR3 as set forth in SEQ ID NOs: 4 claim 39 , 5 claim 39 , and 6 claim 39 , respectively claim 39 , and wherein the antibody or antigen binding fragment thereof comprises a ...

METHOD FOR IDENTIFYING BIOACTIVE PROTEIN, AND BIOACTIVE PROTEIN OBTAINED BY SAID METHOD

An object of the present invention is to provide a method for identifying a physiologically active protein translated from an ORF other than mORF present on mRNA. 1. A method for identifying a physiologically active protein , wherein an ORF which encodes a protein having a physiological activity , other than a main open reading frame (ORF) is identified in eukaryotic mRNA , comprising the steps of:(1) introducing an expression vector incorporating a candidate ORF to cells, and culturing the introduced cells, wherein a start codon of the candidate ORF is AUG or non-AUG in which any one base of AUG is different from AUG,(2) detecting a protein bound to a candidate protein translated from the candidate ORF, from the cultured cells, and(3) determining a candidate protein in which another protein bound to the candidate protein is detected as a physiologically active protein.2. The method for identifying a physiologically active protein according to claim 1 , wherein a proteasome inhibitor or a lysosome inhibitor is added to a cell culture medium in the cell culture step (1).3. The method for identifying a physiologically active protein according to claim 1 , further comprising a step of:detecting an expression of the candidate protein translated from a candidate ORF in advance and selecting a candidate ORF having a large amount of expression, before the binding protein detection step (2).4. The method for identifying a physiologically active protein according to claim 1 , wherein the candidate ORF satisfies one or more conditions selected from the group consisting of:(a) the start codon of the candidate ORF is present on the 5′UTR side from the start codon of the main ORF,(b) a protein encoded by a candidate ORF is 10 amino acids or more,(c) a candidate ORF is an ORF other than the main ORF in mRNA of one eukaryotic organism, and an amino acid sequence translated from the candidate ORF has 50% or more identity to an amino acid sequence translated from an ORF other than ...

HUMANIZED ANTI-ACTH ANTIBODIES AND USE THEREOF

The present invention is directed to antibodies and fragments thereof having binding specificity for ACTH. Embodiments of this invention relate to the binding fragments of antibodies described herein, comprising the sequences of the V, Vand/or CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates anti-ACTH antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention further contemplates methods of making said anti-ACTH antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-ACTH antibodies and binding fragments thereof for the diagnosis, assessment, prevention and treatment of diseases and disorders associated with ACTH, such as CAH, FGD, Cushing's Disease, Cushing's Syndrome, Parkinson's disease, obesity, diabetes, sleep disorders, depression, anxiety disorders, cancer, muscle atrophy, hypertension, hyperinsulinemia, cognitive dysfunction, Alzheimer's disease, galactorrhea, stress related conditions, cardiac conditions, metabolic syndrome, hyperaldosteronism, Conn's syndrome and familial hyperaldosteronism. 1. An anti-human adrenocorticotrophic hormone (ACTH) antibody or antibody fragment that specifically binds to at least one linear or conformational epitope bound by an anti-human ACTH antibody selected from the group consisting of Ab13 , Ab15 , Ab17 , Ab1.H , Ab2.H , Ab3.H , Ab4.H , Ab6.H , Ab7.H , Ab7A.H , Ab10.H , Ab11.H , Ab11A.H , Ab12.H , Ab13.H , Ab15.H , and Ab17.H and/or competes for binding to at least one linear or conformational epitope on human ACTH bound by an anti-human ACTH antibody selected from the group consisting of Ab13 , Ab15 , Ab17 , Ab1.H , Ab2.H , Ab3.H , Ab4.H , Ab6.H , Ab7.H , Ab7A.H , Ab10.H , Ab11.H , Ab11A.H , Ab12.H , Ab13.H , Ab15.H , and Ab17.H , wherein optionally said antibody is human , humanized or chimerized.2. An anti-human adrenocorticotrophic hormone (ACTH) antibody or ...

INDUCTION OF ANTIGEN-SPECIFIC TOLERANCE

Described are compositions and methods for the induction of an antigen-specific tolerance in a vertebrate. Also described are compositions and methods for the induction of antigen-specific tolerance using a fusion or a complex of the antigen (e.g., an antibody or an enzyme) against which tolerance is desired with a phosphatidylserine-binding domain derived from a phosphatidylserine-binding protein (including peptides). 1. A tolerance-inducing molecule , said tolerance-inducing molecule comprising:an antigen; anda phosophatidylserine-binding protein associated with the antigen to form an antigen-phosophatidylserine-binding protein fusion (“APBP”) and/or an antigen-phosophatidylserine-binding protein complex (“APBC”).2. The tolerance-inducing molecule of claim 1 , wherein the antigen comprises a therapeutic molecule.3. The tolerance-inducing molecule of claim 2 , wherein the therapeutic molecule comprises a protein.4. The tolerance-inducing molecule of claim 3 , wherein the protein comprises a therapeutic antibody claim 3 , a therapeutic enzyme claim 3 , a blood coagulation factor claim 3 , a therapeutic cofactor claim 3 , an allergen claim 3 , proteins deficient by genetic disease claim 3 , proteins with non-human glycosylation claim 3 , proteins with a glycosylation pattern not present in the relevant species claim 3 , non-human proteins claim 3 , non-native proteins claim 3 , synthetic proteins not normally found in the species of interest claim 3 , human food antigens claim 3 , human transplantation antigens claim 3 , human autoimmune antigens claim 3 , and/or normally-occurring self antigens to which an immune response is initiated in autoimmune disease.5. The tolerance-inducing molecule of claim 4 , wherein the phosophatidylserine-binding protein is covalently linked to the antigen claim 4 , to form an APBP.6. The tolerance-inducing molecule of claim 5 , wherein the phosophatidylserine-binding protein is directly linked to the antigen.7. The tolerance-inducing ...

ANTI-HEPCIDIN ANTIBODIES AND USES THEREOF

The present application relates to antibodies that specifically bind to hepcidin and methods of using the antibodies. Another aspect relates to antibodies which bind hepcidin and regulate iron homeostasis. Another aspect relates to the use of humanized antibodies which bind hepcidin for the treatment of a disease or condition associated with hepcidin. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. (canceled)17. (canceled)18. (canceled)19. (canceled)20. (canceled)21. (canceled)22. (canceled)23. (canceled)24. (canceled)25. (canceled)26. A method of treating a disorder of iron homeostasis in a subject in need thereof comprising administering to the subject a composition that comprises an antibody , or antigen-binding fragment thereof , that specifically binds to hepcidin (Hep) or a hepcidin peptide , wherein the antibody , or antigen-binding fragment thereof , comprises a heavy chain CDR1 encoded by SEQ ID NO: 57 , a heavy CDR2 encoded by SEQ ID NO: 60 , a heavy chain CDR3 encoded by SEQ ID NO: 63 , a light chain CDR1 encoded by SEQ ID NO: 66 , a light CDR2 encoded by SEQ ID NO: 69 , and a light chain CDR3 encoded by SEQ ID NO: 72 , and an acceptable carrier or excipient.27. A method of reducing hepcidin activity in a subject in need thereof , comprising administering to the subject a composition that comprises an antibody , or antigen-binding fragment thereof , that specifically binds to hepcidin (Hep) or a hepcidin peptide , wherein the antibody , or antigen-binding fragment thereof , comprises a heavy chain CDR1 encoded by SEQ ID NO: 57 , a heavy CDR2 encoded by SEQ ID NO: 60 , a heavy chain CDR3 encoded by SEQ ID NO: 63 , a light chain CDR1 encoded by SEQ ID NO: 66 , a light CDR2 encoded by SEQ ID NO: 69 , and a light chain CDR3 encoded by SEQ ID NO: 72 , and an acceptable carrier or excipient.28. The method ...

HEPCIDIN ANTAGONISTS FOR USE IN THE TREATMENT OF INFLAMMATION

The present invention relates to a hepcidin antagonist for use in the treatment of inflammatory diseases. 1. A method for treating an inflammatory disease , said method comprising a step of administering a hepcidin antagonist to a patient in need thereof.2. The method according to claim 1 , wherein said inflammatory disease is selected from the group consisting of: SIRS claim 1 , sepsis claim 1 , peritonitis claim 1 , inflammatory bowel diseases (IBD) claim 1 , eczema claim 1 , psoriasis claim 1 , dermatitis claim 1 , contact allergies claim 1 , uveitis claim 1 , keratitis claim 1 , pancreatitis claim 1 , nephritis claim 1 , myocarditis claim 1 , atherosclerosis claim 1 , obesity claim 1 , asthma claim 1 , chronic obstructive pulmonary disease claim 1 , chronic bronchitis claim 1 , encephalitis claim 1 , multiple sclerosis and rheumatoid arthritis.3. The method according to claim 1 , wherein said inflammatory disease is an acute inflammatory disease.4. The method according to claim 3 , wherein said acute inflammatory disease is selected from the group consisting of SIRS claim 3 , sepsis and peritonitis.5. The method according to claim 1 , wherein said inflammatory disease is a chronic inflammatory disease.6. The method according to claim 5 , wherein said chronic inflammatory disease is an Inflammatory Bowel Disease (IBD).7. The method according to claim 6 , wherein said IBD is selected from Crohn's disease and ulcerative colitis.8. The method according to claim 1 , wherein said antagonist is administered orally or rectally to a subject in need thereof.9. The method according to claim 1 , wherein said antagonist is an inhibitor of the hepcidin expression selected from the group consisting of an erythropoiesis stimulating agent and an oligonucleotide sequence targeting the hepcidin gene as an antisense oligonucleotide claim 1 , siRNA claim 1 , shRNA or a ribozyme.10. The method according to claim 1 , wherein said antagonist is an inhibitor of the hepcidin activity ...

ASSAYS FOR B-TYPE NATRIURETIC PEPTIDE ANALOGUES RESISTANT TO PROLYL-SPECIFIC DIPEPTIDYL DEGRADATION

The present invention describes compositions and methods for treating cardiovascular disease and myocardial infarction using dipeptidyl peptidase inhibitors. Also provided are methods for increasing natriuretic peptide function by administering one or more analogues of B type natriuretic peptide that provide increased stability in the presence of prolyl-specific dipeptidyl peptidases. 1. A method for the treatment of cardiovascular disease comprisinga) contacting a sample from a subject with a first antibody selected to bind biologically active forms of the natriuretic peptide of interest contacting the sample with a second antibody selected to bind all biologically active and biologically inactive forms of the natriuretic peptide of interest and performing an assay in which the signal depends upon the selected antibody specifically binding to a biologically active form of the natriuretic peptide of interest, but not specifically binding to a biologically inactive form of the natriuretic peptide of interest; andb) administering a therapeutically effective amount of a dipeptidyl peptidase inhibitor to said subject when the presence of said biologically active form of said natriuretic peptide is present, and wherein said administration preserves the presence of said biologically active form of said natriuretic peptide.217.-. (canceled)18. The method of claim 1 , wherein said biologically active natriuretic peptide of interest is BNP-32.19. The method of claim 1 , wherein the first and/or second antibodies are each conjugated to a detectable label.20. The method of claim 19 , wherein the label is a fluorescent or luminescent tag claim 19 , a metal claim 19 , a dye claim 19 , a radionuclide claim 19 , or an enzyme.21. The method of claim 1 , wherein the first and/or second antibodies are immobilized onto a solid support.22. The method of claim 21 , wherein the solid support is a magnetic particle claim 21 , a chromatographic matrix particle claim 21 , the surface of an ...

BI-SPECIFIC ANTIBODIES AND USES THEREOF

Disclosed herein is a bi-specific antibody that specifically directs a therapeutic agent to a cancer cell by targeting a tumor antigen of the cancer cell, and thereby suppressing the growth of the cancer or blocking the invasion or metastasis of the cancer. The bi-specific antibody of the present disclosure includes a first antigen binding site that binds to polyethylene glycol (PEG); and a second antigen binding site that binds to a target ligand, such as a tumor antigen. 1. A humanized bi-specific antibody against the terminal methoxy or hydroxyl group of polyethylene glycol (PEG) and a target ligand on a cancer cell , comprising ,a first antigen binding site that binds to the PEG, wherein the first antigen binding site comprises a first VL-Cκ domain and a first VH-CH1 domain; anda second antigen binding site that binds to the target ligand on the cancer cell, wherein,the first VL-Cκ domain comprises a CDR1 having the sequence of SEQ ID NO: 221; a CDR2 having the sequence of SEQ ID NO: 222; and a CDR3 having the sequence of SEQ ID NO: 223; andthe first VH-CH1 domain comprises a CDR1 having the sequence of SEQ ID NO: 224; a CDR2 having the sequence of SEQ ID NO: 225; and a CDR3 having the sequence of SEQ ID NO: 226.2. The humanized bi-specific antibody of claim 1 , wherein the first VL-Cκ domain has the sequence of SEQ ID NO: 12 claim 1 , and the first VH-CH1 domain has the sequence of SEQ ID NO: 13.3. The humanized bi-specific antibody of claim 1 , wherein the first antigen binding site further comprises a Knob Hinge CH2-CH3 domain connecting to the first VH-CH1 domain claim 1 , wherein the Knob Hinge CH2-CH3 domain has the sequence of SEQ ID NO: 22.4. The humanized bi-specific antibody of claim 1 , wherein the first antigen binding site and the second antigen binding site are Fab or single chain variable fragment (scFv).5. The humanized bi-specific antibody of claim 1 , wherein the target ligand is EGFR claim 1 , HER2 claim 1 , TAG-72 claim 1 , CD19 or CD20.6. A ...

Methods for Detecting 1,25-dihydroxyvitamin D and Related Antibodies

There is disclosed an assay method for selectively detecting 1,25-dihydroxy-vitamin D in a biological fluid sample. According to the method, the pH of the test sample is adjusted to 6-9 and a receptor protein comprising the Ligand Binding Domain of Vitamin D Receptor (VDR-LBD) is added to the test sample, thereby obtaining the formation of a VDR-LBD/1,25-dihydroxyvitamin D complex in which the VDR-LBD portion is conformationally changed with respect to unbound VDR-LBD. The VDR-LBD/1,25-dihydroxyvitamin D complex is then detected by means of a capture moiety which is capable of specifically binding to VDR-LBD bound to 1,25-dihydroxyvitamin D. Also disclosed are an assay kit and an antibody for carrying out the method. The assay is preferably a sandwich immunoassay. 1. A method for detecting 1 ,25-dihydroxyvitamin D (1 ,25(OH)D) or analog thereof in a biological fluid sample , the method comprising the steps of:(i) adjusting the pH of the biological fluid sample to a value comprised between 6 and 9 and simultaneously or subsequently adding to the biological fluid sample a receptor protein comprising the Ligand Binding Domain of Vitamin D Receptor (VDR-LBD), thereby obtaining binding of 1,25-dihydroxyvitamin D or analog thereof to the VDR-LBD of the receptor protein;(ii) capturing the receptor protein comprising the Ligand Binding Domain of Vitamin D Receptor (VDR-LBD) bound to 1,25-dihydroxyvitamin D or analog thereof by means of a capture moiety which is capable of specifically binding the Ligand Binding Domain of Vitamin D Receptor (VDR-LBD) bound to 1,25-dihydroxy-vitamin D or analog thereof without cross-reacting with uncomplexed VDR-LBD; and(iii) detecting the captured receptor protein comprising the Ligand Binding Domain of Vitamin D Receptor (VDR-LBD) bound to 1,25-dihydroxyvitamin D or analog thereof.2. The method according to claim 1 , wherein the receptor protein is the whole Vitamin D Receptor protein or the Ligand Binding Domain (LBD) thereof in an ...

BISPECIFIC ANTI-HAPTEN/ANTI-BLOOD BRAIN BARRIER RECEPTOR ANTIBODIES, COMPLEXES THEREOF AND THEIR USE AS BLOOD BRAIN BARRIER SHUTTLES

Herein is reported a bispecific antibody comprising a first binding specificity that specifically binds to a haptenylated payload and a second binding specificity that specifically binds to a blood brain barrier receptor. 120-. (canceled)21. A method for delivering a haptenylated payload across the blood brain barrier , i) a bispecific antibody, which has a first binding specificity, which specifically binds to a haptenylated payload, and a second binding specificity, which specifically binds to a blood brain barrier receptor, and', 'ii) a haptenylated payload,, 'wherein the haptenylated payload is comprised in a covalent conjugate comprising'}wherein the haptenylated payload is specifically bound by the first binding specificity,wherein the covalent conjugate has a covalent bond between the haptenylated payload and the first binding specificity that specifically binds to the haptenylated payload, andwherein the haptenylated payload is selected from the group consisting of biotinylated payloads, theophyllinylated payloads, digoxigenylated payloads, carboranylated payloads, fluoresceinylated payloads, helicarylated payloads and bromodeoxyuridinylated payloads, andwherein the payload of the haptenylated payload is selected from the group consisting of a label, a chemotherapeutic agent, an anti-angiogenic agent, a cytotoxin, a cytokine, a prodrug, an enzyme, a growth factor, a transcription factor, a drug, a radionuclide, a ligand, an antibody or fragment thereof, a lipsosome, a nanoparticle, and a viral particle.22. A method for targeted delivery of a haptenylated payload across the blood brain barrier by a bispecific antibody , i) a first binding specificity, which specifically binds to the haptenylated payload, and', 'ii) a second binding specificity, which specifically binds to a blood brain barrier receptor,, 'wherein the bispecific antibody comprises'}wherein the haptenylated payload is selected from the group consisting of biotinylated payloads, ...

PROPHYLAXIS OF COLORECTAL AND GASTROINTESTINAL CANCER

The present disclosure provides methods and compositions useful for preventing gastrointestinal and/or colorectal cancer in animals, including humans, having pre-cancerous adenomatous polyps. The present disclosure provides compositions comprising anti-PG antibodies suitable for use in the methods of the disclosure. The present disclosure also provides methods and compositions useful for monitoring the efficacy of anti-PG treatment in subjects with pre-cancerous polyps. 1. A method of preventing gastrointestinal cancer in a human subject , comprising ministering to a human subject predisposed to develop adenomatous polyps an amount of an anti-PG antibody sufficient to provide a therapeutic benefit.2. The method of claim 1 , in which the anti-PG antibody is an anti-hPG monoclonal antibody.3. The method of in which the anti-hPG monoclonal antibody is a humanized anti-hPG monoclonal antibody.4. The method of in which the anti-hPG monoclonal antibody is an N-terminal anti-hPG monoclonal antibody.5. The method of in which the N-terminal anti-hPG monoclonal antibody binds an epitope comprising a sequence selected from the group consisting of DAPLG (SEQ ID NO:28) claim 4 , PDAPLG (SEQ ID NO:29) claim 4 , PRSQQPD (SEQ ID NO:30) claim 4 , WKPRSQQPD (SEQ ID NO:31) and WKPRSQQPDAPLG (SEQ ID NO:32).6. The method of in which the N-terminal anti-hPG monoclonal antibody is raised against an immunogen comprising a peptide having the sequence SWKPRSQQPDAPLG (SEQ ID NO:25).7. The method of in which the N-terminal anti-hPG monoclonal antibody comprises three VCDRs corresponding in sequence to the VCDRs of MAb3 claim 4 , MAb4 claim 4 , MAb15 claim 4 , MAb16 or MAb19 and three VCDRs corresponding in sequence to the VCDRs of MAb3 claim 4 , Mab4 claim 4 , MAb15 claim 4 , MAb16 or MAb19.8. The method of in which the N-terminal anti-hPG monoclonal antibody comprises CDRs corresponding in sequence to the CDRs of MAb3 claim 4 , MAb4 claim 4 , MAb15 claim 4 , MAb16 or MAb 19.9. The method of ...

Methods of treating vasomotor symptoms using antibodies

The invention features methods for preventing or treating CGRP associated disorders such as vasomotor symptoms, including headaches (e.g., migraine, cluster headache, and tension headache) and hot flushes, by administering an anti-CGRP antagonist antibody. Antagonist antibody G1 and antibodies derived from G1 directed to CGRP are also described.

METHODS AND MEANS FOR THE PRODUCTION OF IG-LIKE MOLECULES

The invention provides means and methods for producing one or more Ig-like molecules in a single host cell. Novel CH3 mutations enabling the production of monospecific and/or bispecific Ig-like molecules of interest are also provided. 1. A heterodimeric Ig-like molecule comprising two CH3 domains , wherein one of said two CH3 domains comprises at least one substitution of a neutral amino acid residue by a positively charged amino acid residue and wherein the other of said two CH3 domains comprises at least one substitution of a neutral amino acid residue by a negatively charged amino acid residue , wherein the at least one positively charged amino acid residue substituted in the first CH3 domain interacts with the at least one negatively charged amino acid residue substituted in the second CH3 domain.2. A heterodimeric Ig-like molecule according to claim 1 , wherein one of said two CH3 domains comprises a substitution of the amino acid residue at position 366 by a positively charged amino acid residue claim 1 , and wherein the other of said two CH3 domains comprises a substitution of the amino acid residue at position 351 by a negatively charged amino acid residue.3. A heterodimeric Ig-like molecule according to claim 1 , wherein a first CH3 domain comprises a substitution of the amino acid residue at position 366 by a lysine (K) residue claim 1 , and wherein a second CH3 domain comprises a substitution of the amino acid residue at position 351 by an aspartic acid (D) residue.4. A heterodimeric Ig-like molecule according to claim 3 , wherein the 1CH3 domain further comprises a substitution of the amino acid residue at position 351 by a lysine (K) residue.5. A heterodimeric Ig-like molecule according to claim 3 , wherein the 2CH3 domain further comprises amino acid substitution(s) selected from the group consisting of(i) a substitution of the amino acid residue at position 349 by a glutamic acid (E) residue;(ii) a substitution of the amino acid residue at position ...