СПОСОБ ОБНАРУЖЕНИЯ НЕЙТРАЛИЗУЮЩИХ АНТИТЕЛ ПРОТИВ РЕКОМБИНАНТНОГО ЧЕЛОВЕЧЕСКОГО ИНСУЛИНА В СЫВОРОТКЕ КРОВИ ЧЕЛОВЕКА

Настоящее изобретение относится к высокоспецифичному и селективному способудля выявления присутствия нейтрализующих антител против рекомбинантного человеческого инсулина (rHI) посредством анализа образца сыворотки. Предложенный способ включает стадии (а)-(в). На стадии (а) осуществляется предобработка образца сыворотки, включающая: кислотную диссоциацию и обработку углем, нейтрализацию и обработку полиэтиленгликолем (PEG), а также ресуспендирование осадка. На стадии (б) производят анализ на основе клеток, который включает посев клеток, имеющих рецептор рекомбинантного человеческого инсулина (rHI), голодание клеток в течение 18-22 ч в среде, не содержащей глюкозу, приведение в контакт популяции клеток с rHI и предобработанным образцом сыворотки, лизирование клеток и получение прозрачного лизата, а также оценку лизата в отношении фосфорилирования инсулинового рецептора. На стадии (в) производят выявление присутствия нейтрализующих антител против rHI посредством сравнения выявленного количества ...

ТРАНСГЕННОЕ ЖИВОТНОЕ, ОТЛИЧНОЕ ОТ ЧЕЛОВЕКА, И ЕГО ПРИМЕНЕНИЯ

Группа изобретений относится к области генной инженерии, в целом к трансгенным конструкциям, трансгенным животным, отличным от человека, способам количественного анализа активации GPCR лигандов неинвазивно в интактных животных, тканевых срезах или в нативных клетках, используя трансгенную модель, содержащую систему биолюминесцентного трансгена-репортера, которая является чувствительной к модуляции путей после связывания лиганда с рецепторами GPCR. Трансгенное животное, отличное от человека, для оценки функции рецептора, сопряженного с G-белком (GPCR), имеющее геном, содержащий индуцируемый циклическим АМФ (цАМФ), трансген, содержащий, в направлении от 5′-конца к 3′-концу, первый инсуляторный элемент, ответный элемент цАМФ, промотор, биолюминесцентный репортер, миниген человеческого гормона роста (hGH) и второй инсуляторный элемент. Использование трансгенной конструкции приводит к повышению мышиных линий, продуцирующих мРНК и белок, а также к увеличению уровня экспрессии репортерного гена ...

ТВЕРДОФАЗНЫЙ ИММУНОФЕРМЕНТНЫЙ АНАЛИЗ (ELISA) ДЛЯ ФАКТОРА РОСТА ЭНДОТЕЛИЯ СОСУДОВ (VEGF)

Изобретение относится к области иммунологии, а именно к иммуноферментному анализу, конкретнее к способу детекции форм фактора роста эндотелия сосудов (VEGF) c размером более чем 110 аминокислот в биологическом образце. Способ включает следующие стадии: контактирования и инкубации биологического образца с реагентом захвата, иммобилизованным на твердой подложке, где реагент захвата содержит моноклональное антитело, которое распознает и специфично связывается с остатками, в количестве более чем 110, из VEGF человека; отделение биологического образца от иммобилизованных реагентов захвата; контактирование иммобилизованного молекулярного комплекса реагента захвата-мишени с детектируемым антителом, которое связывается с доменами VEGF, ответственными за связывание с рецептором KDR и/или FLT1, или которое связывается с эпитопом в VEGF; измерение уровня VEGF, связанного с реагентами захвата, с использованием средства детекции для детектируемого антитела. Набор реагентов иммуноанализа для детекции ...

ГИСТОНЫ И/ИЛИ PROADM В КАЧЕСТВЕ МАРКЕРОВ, СВИДЕТЕЛЬСТВУЮЩИХ ОБ ОРГАННОЙ ДИСФУНКЦИИ

Группа изобретений относится к диагностике органной дисфункции у субъекта. Раскрыт способ диагностики полиорганной дисфункции у субъекта, причем указанный способ включает (i) определение уровня по меньшей мере одного гистона в образце от указанного субъекта; (i1) сравнение указанного уровня по меньшей мере одного гистона с контрольным уровнем этого по меньшей мере одного гистона; (ii) определение уровня проадреномедуллина (proADM) в образце от указанного субъекта; и (ii1) сравнение указанного уровня proADM с контрольным уровнем proADM; (iii) при этом у указанного субъекта выявляют полиорганную дисфункцию на основании сравнения на этапе (i1) и (ii1) соответственно. Также раскрыты набор для реализации указанного способа и применение указанного набора. Группа изобретений обеспечивает улучшенную диагностику органной дисфункции за счет использования двух маркеров по сравнению с определением только одного маркера. 3 н. и 12 з.п. ф-лы, 6 ил., 5 табл., 1 пр.

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Изобретение относится к области биохимии. Способ идентификации клеток, которые показывают восприимчивость к ингибированию передачи сигнала, в которую вовлечены рецептор фактора роста фибробластов (FGF-R) или его вариант, включающий определение статуса фосфорилирования субстрата 2 рецептора FGF-R (FRS-2), его варианта или его фрагмента, содержащего тирозин, в биологическом образце, в качестве биомаркера такой чувствительности к ингибированию, где в отношении клеток, которые показывают фосфорилирование тирозина FRS-2, можно ожидать, что они покажут восприимчивость к ингибированию передачи сигнала с участием FGF-R. Способ идентификации фосфорилирования в FRS-2, его варианта или его фрагмента, содержащих тирозин, в качестве биомаркера для клеток, тканей или органов. Применение идентификации фосфорилирования в FRS-2, его варианта или его фрагмента, содержащего тирозин, в качестве биомаркера для клеток, тканей или органов, которые показывают гиперактивную передачу сигнала с участием FGF-R. Применение ...

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.

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Изобретение относится к пептидным производным общей формулы (I), их стереоизомерам, их смесям и/или их фармацевтически приемлемым солям, к способам их получения, к фармацевтическим композициям, содержащим их, и к применению их для лечения, предупреждения и/или диагностики тех состояний, расстройств и/патологий, при которых экспрессируются соматостатиновые рецепторы sstr1, sstr2, sstr3, sstr4 и/или sstr5. 3 н. и 11 з.п. ф-лы, 5 табл., 33 пр.

АНАЛИЗ СВЯЗЫВАНИЯ С ЛИГАНДОМ ДЛЯ ОБНАРУЖЕНИЯ ГИББЕРЕЛЛИНОВ

Изобретение относится к области биохимии, в частности к тест-системе связывания с лигандом для обнаружения присутствия гиббереллинов в образце. Изобретение позволяет эффективно обнаружить присутствие гиббереллинов в образце. 9 з.п. ф-лы, 1 табл., 1 пр., 16 ил.

СПОСОБ ОЦЕНКИ ФУНКЦИИ ПОЧЕК У КОШЕК ПУТЕМ ИЗМЕРЕНИЯ УРОВНЕЙ ГОРМОНА ГРЕЛИНА

Изобретение относится к ветеринарии. Способ оценки функции почек у кошки включает определение наблюдаемого уровня грелина в ткани или биожидкости кошки и установление прямой зависимости наблюдаемого уровня грелина от функции почек путем сравнения наблюдаемого уровня грелина с референтным уровнем грелина, характеризующим нормальную функцию почек. Способ диагностики заболевания почек у кошки включает определение наблюдаемого уровня грелина в ткани или биожидкости кошки и сравнение наблюдаемого уровня грелина с референтным уровнем грелина, характеризующим нормальную функцию почек, где наблюдаемый уровень ниже, чем референтный уровень, является свидетельством заболевания почек или предрасположенности к нему. Способ определения начала заболевания почек у кошки включает мониторинг уровня грелина в ткани или биожидкости кошки в течение некоторого периода времени, где начало определяют, если в любой момент времени отмечается понижение уровня грелина по сравнению с начальным уровнем, характеризующим ...

Способ прогнозирования течения невротических, связанных со стрессом расстройств

Изобретение относится к медицине, а именно к психиатрии, и может быть использовано для прогноза формирования затяжного течения невротических, связанных со стрессом расстройств на раннем этапе заболевания. Сущность изобретения заключается в том, что больным с расстройствами приспособительных реакций проводится гормональное обследование. При одновременном содержании в крови концентрации кортизола более 717 нмоль/л, концентрации пролактина более 818 мМЕ/л, концентрации тиреотропного гормона менее 1,05 мкМЕ/мл прогнозируют затяжное течение невротических, связанных со стрессом расстройств с формированием стойкого изменения личности. Изобретение обеспечивает расширение арсенала биомаркеров прогнозирования течения невротических, связанных со стрессом расстройств на более ранних этапах заболевания и позволяет целенаправленно проводить психофармакологические мероприятия. Способ прост в осуществлении. 2 пр.

СПОСОБ ПРОГНОЗИРОВАНИЯ РАЗВИТИЯ И ПРОГРЕССИРОВАНИЯ ПЛОСКО-ВАЛЬГУСНОЙ ДЕФОРМАЦИИ СТОП И ПЛОСКОСТОПИЯ ПО УРОВНЮ СЕРОТОНИНА В СЫВОРОТКЕ КРОВИ ДЕТЕЙ И ПОДРОСТКОВ

Изобретение относится к медицине, а именно ортопедии, педиатрии, и может быть использовано для прогнозирования развития и прогрессирования плоско-вальгусной деформации стоп и плоскостопия у детей и подростков с помощью иммуноферментного анализа крови. У ребенка в возрасте от 3 лет до 15 лет в сыворотке крови определяют серотонин. При его значении у детей до 270 нг/мл формирование сводов стопы считают благоприятным. При значении показателя серотонина выше 270 нг/мл риск прогрессирования плоско-вальгусной деформации стоп и плоскостопия считают высоким. Способ обеспечивает возможность прогнозирования развития и прогрессирования плоско-вальгусной деформации стоп и плоскостопия у детей и подростков в возрасте от 3 до 15 лет на ранних стадиях с высокой точностью за счет определения серотонина в сыворотке крови детей и подростков. 3 пр.

СПОСОБ ПРОГНОЗИРОВАНИЯ ПРЕЖДЕВРЕМЕННОГО СТАРЕНИЯ У МУЖЧИН МОЛОДОГО И СРЕДНЕГО ВОЗРАСТА, АССОЦИИРОВАННОГО С ПОЛИМОРБИДНОЙ СЕРДЕЧНО-СОСУДИСТОЙ ПАТОЛОГИЕЙ

Изобретение относится к медицине, а именно к геронтологии, и может быть использовано для прогнозирования преждевременного старения (ПС) у мужчин молодого и среднего возраста, ассоциированного с полиморбидной сердечно-сосудистой патологией. Проводят оценку значения фактора роста фибробластов. Производят определение концентрации фактора роста фибробластов 21 в сыворотке крови методом иммуноферментного анализа в нг/л, затем производят определение концентрации белка р53 в сыворотке крови методом твердофазного иммуноферментного анализа в U/мл; затем производят определение концентрации СРБ в сыворотке крови в мг/л; затем производят определение концентрации β-эндорфина в сыворотке крови методом иммуноферментного анализа в нг/мл; затем производят определение концентрации 6-СОМТ день и 6-СОМТ ночь в моче методом иммуноферментного анализа в нг/мл. Суточную мочу собирают не позднее третьего дня от момента госпитализации, а пробы, собранные с 23.00 до 7.00 принимают за одну, измеряют общий объем мочи ...

Способ прогнозирования результатов хирургического лечения морбидного ожирения при рестриктивном типе бариатрической операции

Изобретение относится к медицине, а именно к хирургии, и может быть использовано для прогнозирования результатов хирургического лечения морбидного ожирения при рестриктивном типебариатрической операции. Проводят определение исходной концентрации показателя в сыворотке крови. В качестве показателя определяют концентрацию грелина. При ее значении 350 пкг/мл и более прогнозируют благоприятное течение послеоперационного периода при рестриктивном типе операции. При ее значении менее 350 пкг/мл прогнозируют рецидив ожирения при рестриктивном типе, бариатрическую операцию дополняют шунтирующим компонентом. Способ обеспечивает возможность повышения точности и упрощения прогнозирования результатов хирургического лечения морбидного ожирения при рестриктивном типебариатрической операции за счет определения концентрации грелина в крови. 1 табл., 4 пр.

СПОСОБ ВЫЯВЛЕНИЯ САХАРНОГО ДИАБЕТА ПЕРВОГО ТИПА

Изобретение относится к медицине, а именно к клинической диагностике, и может быть использовано для выявления сахарного диабета первого типа у беременных. Осуществляют забор образца крови пациента; пробоподготовку образца крови пациента с получением аналита; определение содержания в качестве маркера сахарного диабета первого типа в аналите белка Angiotensinogen и/или Apolipoprotein С-III и/или Vitronectin. При значении относительного содержания Angiotensinogen не менее 1,29% от общего содержания белков в аналите и/или при значении Apolipoprotein С-III не менее 2,91% от общего содержания белков в аналите и/или при отсутствии у пациента диагноза «ожирение» при значении Vitronectin не более 0,71% от общего содержания белков в аналите выявляют сахарный диабет первого типа. Определение содержания маркера сахарного диабета первого типа в аналите проводят методом иммуноферментного анализа или методом хромато-масс-спектрометрии. Способ обеспечивает повышение точности анализа в диагностике сахарного ...

Способ оценки степени тяжести овариальной дисфункции у девочек с пубертатной гиперандрогенией

Изобретение относится к области медицины, а именно гинекологии и эндокринологии, и может быть использовано для определения тяжести овариальной дисфункции у девочек-подростков, страдающих нарушениями менструального цикла. Для этого у девочек с пубертатной гиперандрогенией при нарушениях менструального цикла на 4-5 день цикла в сыворотке крови проводят определение АМГ и фоллистатина, при этом при повышении уровня АМГ до 10 нг/мл и фоллистатина до 1000 пг/мл диагностируют овариальную дисфункцию легкой степени, при повышении уровня АМГ более 10 нг/мл и фоллистатина более 1000 пг/мл диагностируют овариальную дисфункцию тяжелой степени. Способ позволяет с высокой точностью определить ту или иную форму овариальной дисфункции с целью прогноза и оптимизации подходов к лечению для каждой пациентки. 3 пр.

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 ...

ТВЕРДОФАЗНЫЙ ИММУНОФЕРМЕНТНЫЙ АНАЛИЗ (ELISA) ДЛЯ ФАКТОРА РОСТА ЭНДОТЕЛИЯ СОСУДОВ (VEGF)

... 1. Способ детекции селективных форм (VEGF110+) фактора роста эндотелия сосудов (VEGF) в биологическом образце, включающий стадии ! (a) контактирования и инкубации биологического образца с реагентом захвата, иммобилизованным на твердой подложке, где реагент захвата представляет собой антитело, которое распознает тот же эпитоп, что и антитело 5C3 против VEGF человека, причем указанное моноклональное антитело специфично связывается с остатками, в количестве более чем 110, из VEGF человека; ! (b) отделение биологического образца от иммобилизованных реагентов захвата; ! (c) контактирование иммобилизованного молекулярного комплекса реагента захвата-мишени с детектируемым антителом, которое связывается с доменами VEGF, ответственными за связывание с рецептором KDR и/или FLT1, или которое связывается с эпитопом в VEGF1-110; и ! (d) измерение уровня VEGF110+, связанного с реагентами захвата, с использованием средства детекции для детектируемого антитела. ! 2. Способ по п.1, где биологический образец ...

СПОСОБ ОЦЕНКИ ФУНКЦИИ ПОЧЕК У КОШЕК ПУТЕМ ИЗМЕРЕНИЯ УРОВНЕЙ ГОРМОНА ГРЕЛИНА

... 1. Способ оценки функции почек у кошки, включающий определение уровня грелина в ткани или биожидкости кошки и прямой зависимости уровня грелина от функции почек. ! 2. Способ по п.1, в котором кошкой является домашняя кошка. ! 3. Способ по п.1, в котором ткань или биожидкость включает биообразец, взятый у кошки. ! 4. Способ по п.3, в котором биообразец включает цельную кровь, плазму крови или сыворотку крови. ! 5. Способ по п.3, в котором биообразец получают, когда кошка находится в голодном состоянии (натощак). ! 6. Способ по п.3, в котором уровень грелина в биообразце определяют с использованием одного или более методов иммуноферментного анализа, иммуносорбентного анализа с ферментной меткой, иммунофлюоресцентного анализа, радиоиммуноанализа, вестерн-блот анализа, биохимического анализа, ферментного анализа или колориметрического анализа. ! 7. Способ диагностики заболевания почек у кошки, включающий определение наблюдаемого уровня грелина в ткани или биожидкости кошки и сравнение наблюдаемого ...

AGTR1 В КАЧЕСТВЕ МАРКЕРА ДЛЯ КОМБИНИРОВАННЫХ ТЕРАПИЙ С ИСПОЛЬЗОВАНИЕМ БЕВАЦИЗУМАБА

... 1. Способ идентификации пациента, реагирующего на лечение бевацизумабом или чувствительного к такому лечению, где у указанного пациента предполагается наличие пролиферативного нарушения или который предрасположен к нему, где способ заключается в том, что осуществляют стадию, на которой определяют уровень экспрессии рецептора ангиотензина II типа 1 (AGTR1) в биологическом образце, взятом из организма указанного пациента,при этом повышенный уровень экспрессии AGTR1 по сравнению с контрольным уровнем, определенным у пациентов, страдающих раком, свидетельствует о том, что указанный пациент должен реагирует на лечение бевацизумабом или является чувствительным к такому лечению.2. Способ по п.1, в котором указанное пролиферативное нарушение выбирают из группы, состоящей из рака молочной железы; местно-распространенного, рецидивирующего или метастатического HER2-негативного рака молочной железы, колоректального рака (CRC), немелкоклеточного рака легкого (NSCLC), рака почки; почечно-клеточной карциномы ...

СПОСОБ БИОХИМИЧЕСКОЙ ДИАГНОСТИКИ ПЕРВИЧНОГО ГИПЕРПАРАТИРЕОЗА

Изобретение относится к медицине, а именно к лабораторной диагностике, и может быть использовано для биохимической диагностики первичного гиперпаратиреоза. Проводят определение в периферической крови фосфора, кальция. Определяют уровень ионизированного кальция и паратгормона. Рассчитывают показатель первичного гиперпаратиреоза Кпгпт по формуле:Са- уровень ионизированного кальция в плазме крови, ммоль/л; Р - уровень фосфора в плазме крови, ммоль/л; ПТГ - уровень паратгормона в плазме крови, пг/мл. При значении Кпгпт меньше или равно 1,95 подтверждают первичный гиперпаратиреоз. При значении Кпгпт больше 1,95 судят об отсутствии заболевания. Способ обеспечивает возможность биохимической диагностики первичного гиперпаратиреоза за счет определения уровня ионизированного кальция, фосфора, паратгормона в периферической крови и расчета показателя первичного гиперпаратиреоза. 2 пр.

СПОСОБ ДИАГНОСТИКИ ПЕРВИЧНОГО ГИПЕРПАРАТИРЕОЗА

Изобретение относится к медицине, а именно к лабораторной диагностике, и может быть использовано для диагностики первичного гиперпаратиреоза. Проводят определение общего кальция, фосфора в периферической крови. Дополнительно в ней определяют содержание паратгормона. Рассчитывают индекс первичного гиперпаратиреоза Iпгпт по формуле:Са- уровень общего кальция в плазме крови, ммоль/л; Р - уровень фосфора в плазме крови, ммоль/л; ПТГ - уровень паратгормона в плазме крови, пг/мл. При значении Iпгпт меньше или равно 2,46 судят о наличии первичного гиперпаратиреоза. При Iбольше 2,46 - об отсутствии заболевания. Способ обеспечивает возможность биохимической диагностики первичного гиперпаратиреоза за счет определения фосфорно-кальциевого отношения и определения единого интегрального показателя, отражающего соотношение общего кальция и фосфора к паратгормону. 2 пр.

СПОСОБЫ ИДЕНТИФИКАЦИИ МОДУЛЯТОРОВ GPR92

ПРИМЕНЕНИЕ СЕРЕЛАКСИНА ДЛЯ СНИЖЕНИЯ GDF-15

КОМБИНИРОВАННЫЕ ВИДЫ ЛЕЧЕНИЯ, СОДЕРЖАЩИЕ АНТАГОНИСТЫ С-МЕТ И АНТАГОНИСТЫ B-RAF

... 1. Способ лечения пациента со злокачественной опухолью, предусматривающий введение эффективного количества антагониста B-raf и антагониста c-met.2. Способ лечения пациента со злокачественной опухолью, которая характеризуется повышенной вероятностью развития устойчивости к антагонисту B-raf, предусматривающий введение эффективного количества антагониста B-raf и антагониста c-met.3. Способ увеличения и/или восстановления чувствительности к антагонисту B-raf, предусматривающий введение пациенту со злокачественной опухолью эффективного количества антагониста B-raf и антагониста c-met.4. Способ увеличения периода чувствительности к антагонисту B-raf, предусматривающий введение пациенту со злокачественной опухолью эффективного количества антагониста B-raf и антагониста c-met.5. Способ лечения пациента с устойчивой к антагонисту B-raf злокачественной опухолью, предусматривающий введение эффективного количества антагониста B-raf и антагониста c-met.6. Способ увеличения длительности ответа на антагонист ...

КОАГОНИСТЫ РЕЦЕПТОРОВ ГЛЮКАГОНА/GLP-1

... 1. Пептид, содержащий аминокислотную последовательность SEQ ID NO: 37, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 47 или SEQ ID NO: 35.2. Пептид, содержащий аминокислотную последовательность, выбранную из (i) группы, состоящей из: SEQ ID NO: 13-16, 19-25, 27-29 и 31-33, (ii) группы, состоящей из SEQ ID NO: 26 и 30, (iii) группы, состоящей из: SEQ ID NO: 35-37.3. Пептид, содержащий аминокислотную последовательность, выбранную из (i) группы, состоящей из: SEQ ID NO: 38-49 и 54, или (ii) группы, состоящей из: SEQ ID NO: 50-52 и 55, где аналог проявляет по меньшей мере в 100 раз более высокую селективность в отношении рецептора GLP-1 человека относительно рецептора GIP, и необязательно эффективность GLP-1 по меньшей мере 1%.4. Вариант пептида, содержащий (i) аминокислотную последовательность, которая по меньшей мере на 85%, 90% или 95% идентична аминокислотной последовательности пептида по любому из пп.1-3, где вариант пептида проявляет увеличенную активность в отношении рецептора GLP-1 рецептор ...

УСОВЕРШЕНСТВОВАННОЕ УСТРОЙСТВО И СПОСОБ ТЕСТИРОВАНИЯ НА БЕРЕМЕННОСТЬ

СОЕДИНЕНИЯ ПЕПТИДНО-ОЛИГОМОЧЕВИННЫХ ФОЛДАМЕРОВ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

Способы лечения бесплодия

АНТИТЕЛА ПРОТИВ РЕЦЕПТОРА 2 ФАКТОРА РОСТА ЭНДОТЕЛИЯ СОСУДОВ (VEGFR2)

ИММУНОГЛОБУЛИН С ДВУМЯ ВАРИАБЕЛЬНЫМИ ДОМЕНАМИ И ЕГО ПРИМЕНЕНИЕ

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

МАРКЕРЫ ДЛЯ ПРОГНОЗИРОВАНИЯ И ОЦЕНКИ РИСКА РАЗВИТИЯ ОБУСЛОВЛЕННЫХ БЕРЕМЕННОСТЬЮ ГИПЕРТЕНЗИИ И ПРЕЭКЛАМПСИИ

... 1. Способ прогнозирования развития обусловленных беременностью гипертензии и/или преэклампсии или оценки риска развития у беременных женщин обусловленных беременностью гипертензии и/или преэклампсии, заключающийся в том, что осуществляют стадии, на которых:(I) получают образец общей воды организма индивидуума,(II) определяют уровни про-ADM или его фрагментов и/или про-ЕТ-1 или его фрагментов в указанном образце,(III) устанавливают корреляцию между уровнем про-ADM или его фрагментов и/или про-ЕТ-1 или его фрагментов с прогнозом или оценкой риска для беременной женщины,где указанные фрагменты состоят по меньшей мере из 6 аминокислотных остатков.2. Способ по п.1, в котором определение уровней про-ADM или его фрагментов и/или про-ЕТ-1 или его фрагментов осуществляют в первый-второй триместр (с 8-ой по 26-ую неделю беременности), более предпочтительно, в период с первого по начало второго триместра (с 8-ой по 20-ую неделю беременности), еще более предпочтительно в первый триместр (с 8-ой по ...

ПРОКАЛЬЦИТОНИН ДЛЯ ДИАГНОСТИКИ БАКТЕРИАЛЬНЫХ ИНФЕКЦИЙ И КОНТРОЛЯ ЛЕЧЕНИЯ АНТИБИОТИКАМИ ДЛЯ ПАЦИЕНТОВ С НЕСПЕЦИФИЧЕСКИМИ ЖАЛОБАМИ

... 1. Способ диагностирования бактериальной инфекции у пациента, поступившего в отделение неотложной помощи с неспецифическими жалобами, включающий следующие этапы:(i) обеспечение образца из организма пациента, поступившего с неспецифическими жалобами;(ii) определение уровня прокальцитонина (РСТ) или его фрагмента длиной как минимум 12 аминокислот в вышеупомянутом образце; и(iii) определение у вышеупомянутого пациента наличия или отсутствия бактериальной инфекции путем сравнения вышеупомянутого определенного уровня РСТ с заданным пороговым уровнем,причем заданный пороговый уровень составляет от 0,02 нг/мл до 0,25 нг/мл.2. Способ по п.1, отличающийся тем, что вышеупомянутый образец представляет собой жидкость организма, в частности, кровь, сыворотку, плазму, спинномозговую жидкость, мочу, слюну или плевральный выпот.3. Способ по пп.1 и 2, отличающийся тем, что фрагмент РСТ или фрагмент предшественника РСТ имеет длину как минимум 12 аминокислотных остатков.4. Способ по п.1, отличающийся тем, ...

КОМПОЗИЦИИ RON И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

ELISA ДЛЯ VEGF

... 1. Способ детекции селективных форм (VEGF) фактора роста эндотелия сосудов (VEGF) в биологическом образце, включающий стадии:(a) контактирования и инкубации биологического образца с реагентом захвата, иммобилизованным на твердой подложке, где реагент захвата представляет собой антитело, которое распознает тот же эпитоп, что и антитело 5C3 против VEGF человека, причем указанное моноклональное антитело специфично связывается с остатками, в количестве более чем 110, из VEGF человека;(b) отделение биологического образца от иммобилизованных реагентов захвата;(c) контактирование иммобилизованного молекулярного комплекса реагента захвата-мишени с детектируемым антителом, которое связывается с доменами VEGF, ответственными за связывание с рецептором KDR и/или FLT1, или которое связывается с эпитопом в VEGF1-110; и(d) измерение уровня VEGF, связанного с реагентами захвата, с использованием средства детекции для детектируемого антитела.2. Способ по п. 1, где биологический образец отобран у человека ...

ДЛИННЫЕ ЖЕСТКИЕ СПЕЙСЕРЫ ДЛЯ УЛУЧШЕНИЯ КИНЕТИКИ СВЯЗЫВАНИЯ В ИММУНОАНАЛИЗАХ

... 1. Устройство для детектирования молекулы-мишени в образце, содержащее:(a) контейнер для образцов для количественного определения молекулы-мишени в образце,(b) первую частицу, где указанная первая частица функционализирована первой связывающей молекулой, способной к специфическому связыванию с указанной молекулой-мишенью, и(c) поверхностную структуру, содержащую вторую связывающую молекулу, где указанная поверхностная структура покрывает плоский сенсор или присутствует на второй частице,где указанная первая частица способна к связыванию указанной второй связывающей молекулы поверхностной структуры напрямую или ненапрямую; где указанная первая и/или вторая связывающая молекула присоединена к поверхности частицы указанной первой и/или второй частицы и/или поверхности плоского сенсора посредством длинной и жесткой линкерной молекулы; где длина и консистенция указанной линкерной молекулы выбраны так, чтобы в результате была получена средняя протяженность удлинения указанного линкера более 60 ...

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 ...

Insulinstandardlösung

VERFAHREN ZUR GENETISCHEN PRÜFUNG

VERFAHREN ZUR FREISETZUNG BINDENDER PROTEINE VON LIGANDEN

VERFAHREN ZUR BESTIMMUNG DES SCHWANGERSCHAFTSSTADIUMS

OSTEOGENISCHE PROTEINE IN DER BEHANDLUNG VON METABOLISCHEN KNOCHENKRANKHEITEN

METHOD FOR QUANTITATIVE ANALYSIS OF LOW MOLECULAR WEIGHT COMPONENTS CONTAINED IN PROTEIN-CONTAINING LIQUID SAMPLE

Immunchemisches Verfahren und Reagenz zur Bestimmung eines polyvalenten Antigens in einer flüssigen Probe.

IMIDAZOLDERIVATE ALS HISTAMIN-H3-MODULATOREN

REZEPTOREN FÜR FIBROBLASTEN-WACHSTUMSFAKTOREN

Verfahren zum Nachweis von endogenen und exogenen Stoffen im Organismus

The invention relates to a method for simultaneously identifying and/or differentiating endogenic and exogenic substances, in particular substances comprising at least one peptide bond in an organism. According to the invention, endogenic and exogenic substances present in collected endogenic material that is collected in particular from a human or animal organism are accumulated on a support material and said substances are subsequently identified and/or differentiated by means of their differing masses.

NMR-VERFAHREN ZUR BESTIMMUNG DES RISIKOS ZUR ENTWICKLUNG VON DIABETES TYPE 2

DIAGNOSE VON PRE-ECLAMPSIA

VERWENDUNG VON LONG PENTRAXIN PTX3 FÜR DIE BEHANDLUNG VON INFERTILITÄT BEI FRAUEN

ERFINDUNG BETREFFEND GLP-1 UND EXENDIN

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

Verfahren zur Prognose und Diagnose von Herzinsuffizienz

Die Erfindung betrifft ein Verfahren zur Diagnose oder Prognose von Herzversagen oder Herzinsuffizienz und gegebenenfalls des Bedarfs einer vorbeugenden Behandlung, welches sich dadurch auszeichnet, dass die Menge an Relaxinpeptiden oder Fragmenten oder Isoformen hiervon in einer Probe der Körperflüssigkeit bestimmt wird. Es wird ein Verfahren bereitgestellt unter Verwendung von polyklonalen oder monoklonalen Antikörpern, die Peptide oder Fragmente oder Isoformen von Relaxin binden.

SCREENING-VERFAHREN

MENSCHLICHER G-PROTEIN-GEKOPPELTER REZEPTOR UND MODULATOREN DAVON ZUR BEHANDLUNG VON HERZKREISLAUFERKRANKUNGEN

Verfahren zur Identifizierung von Verbindungen zur Therapie von Alterungsprozessen des Herz-Kreislauf Systems

The invention relates to a method for identifying a compound that modifies the activity of the urotensin II receptors by influencing those genes or gene products that are associated with the composition, formation or degradation of the extracellular matrix.

Verfahren zum Nachweis entspannungsfördernder Wirkungen von Testsubstanzen beim Menschen

Therapeutic and diagnostic peptides

ENZYME IMMUNOASSAY

Hormone replacement therapy involving human growth hormone (somatotropin)

There is described a multi-component hormone supplement therapy comprising human growth hormone (HGH/somatotropin) and at least two other hormones selected from a sex hormone, an adrenal hormone, a thyroid hormone, a thymic hormone or melatonin. Preferably the androgens are testosterone, oestrogen, pregnenolone, progesterone or dehydroepiandrosterone (DHEA). Insulin-like growth factor IGF-I is preferably also included. In the preferred method all of the aforementioned hormones are used.

Sandwich assay

An assay for detecting a detectable species comprising forming a complex between an analyte and a capture species, wherein said capture species is immobilized on a magnetic particle; contacting said complex with a detectable species which specifically binds to said analyte thereby forming an immobilized complex; transferring said immobilized complex to another vessel free of said detectable species; eluting said detectable species from said immobilized complex and detecting said detectable species. Also claimed is a dataset from an assay comprising at least one data point corresponding to a signal from an analyte collected from an assay.

Improvements in diagnostic test sheets

Diagnostic sheets indicative of ovulatory function are prepared by applying female saliva, or nasal or verical mucous to a sheet impregnated or coated with a substance reacting to chloride ion with colour change. The body liquid may be withdrawn by means of an alginate swab, at daily intervals during a menstrual cycle and the samples applied to separate sheets or different areas of a single filter paper sheet. The preferred reagent is silver chromate or dichromate containing excess silver ions. Preparations of suitable reagent sheets falling with the disclosures of Specification 1103402 and 1103403 are disclosed.

Diagnostic test material for determination of ovulatory function

A chloride ion indicator comprises a sheet form base carrying a compound including silver ions that will react with colour change with chloride ions, and an excess of silver ions over that present in said compound, the said compound and the said excess having been obtained by reaction of materials that provide an excess of silver ions of at least 10.2% by weight (as Ag NO3) based on said compound. The excess may be up to 58.5%. The silver compound may be silver chromate or dichromate; the excess silver may be present as nitrate, acetate or chlorate. The sheet form base may be paper, woven or non-woven cellulosic sheets, or fabric. The indicator may be made by dipping the sheet form base into aqueous solutions of a silver salt and a chromate or dichromate sequentially in either order; or by incorporating a preformed silver compound plus excess silver ion composition into the beater stage of a paper making process. The indicators may be used to in testing ovulatory function as described in ...

Screening Systems Utilizing RTP801

RTP801 represents a unique gene target for hypoxia-inducible factor 1 (HIF-I). Down regulation of the mTOR pathway activity by hypoxia requires de novo mRNA synthesis and correlates with increased expression of RTP801. The present invention relates to screening systems utilizing RTP801 and/or RTP801 interactors and/or RTP801 biological activity, to drag candidates identified by such screening systems, and to the use of such drug candidates in the treatment of various disorders.

Magnetic assay reagents

The invention provides a method of assaying a ligand in a sample by means of contacting the sample with homogeneous colloidal magnetic particles having a reagent immobilised thereon, forming an immobilised complex on the said colloidal magnetic particles, and subsequently separating the colloidal magnetic particles and immobilised complex from the assay medium. Mechanical agitation of the assay medium is unnecessary.

Screening Systems Utilizing RTP801

Screening

Screening method and anti-tumor drug candidate obtained therefrom

Endocrine disruption

Assay

METHOD OF IMMUNOASSAY

Airways contraction assay

METHOD OF ASSAY

IMPROVEMENTS IN THE MANAGEMENT OF INFERTILITY

Inositol phosphoglycans for therapeutic use in the treatment of diabetes and obesity

Use of a milk protein hydrolysate in the treatment of diabetes

IMMUNOASSAY

INTERMEDIATES USEFUL IN THE SYNTHESIS OF CHEMILUMINESCENT NAPHTHALENE-1,2-DICARBOXYLIC ACID HYDRAZIDE-LABELLED CONJUGATES

BIOLOGICAL ANALYSIS

Therapy

Antibody to leptin receptor

The present technology relates generally to compositions and methods of preventing or treating diseases associated with mutantleptin receptors, leptin deficiency or leptin dysfunction. The present technology also relates to administering the anti-leptin receptor antibodies in effective amounts to treat a subject suffering from, or predisposed to, a disease associated with mutant leptin receptors, obesity, leptin deficiency, leptin resistance, and/or hypoleptinemia.

Diagnostic test panel for the diagnostic of malaria and severe bacterial infections.

Portable fertility tester.

A portable fertility tester (1) for identifying the days during the menstrual cycle when a woman is most likely to conceive. The tester has a circular disk (19) with transparent regions (23) indexed to each day of the month.

Diagnostic test panel for the diagnostic of malaria and severe bacterial infections

Portable fertility tester

Methods of diagnosing and treating pre-eclampsia or eclampsia.

Diagnostic test panel for the diagnostic of malaria and severe bacterial infections.

Portable fertility tester

Methods of diagnosing and treating pre-eclampsia or eclampsia.

Methods of diagnosing and treating pre-eclampsia or eclampsia.

Portable fertility tester

Methods of diagnosing and treating pre-eclampsia or eclampsia.

Diagnostic test panel for the diagnostic of malaria and severe bacterial infections.

POLYKLONALE ANTIBODIES AGAINST THE HUMAN ALPHA PDGF RECEPTOR AND ITS USE

MORE AGAIN GALANINREZEPTOR

IMMUNOREAKTIVE AND IMMUNOTHERAPEUTI MOLECULES WHICH IN INDIVIDUALS WITH INSULIN-DEPENDENT DIABETES MELLITUS INTERACTION

Method of treatment or prophylaxis

The present invention is directed to methods and agents that are useful in the prevention and amelioration of signs and symptoms associated with neuropathic conditions. More particularly, the present invention discloses the use of angiotensin II receptor 2 (AT 2 receptor) antagonists for the treatment, prophylaxis, reversal and/or symptomatic relief of neuropathic pain, including mechanical hyperalgesia, thermal or mechanical allodynia, diabetic pain and entrapment pain, in vertebrate animals and particularly in human subjects. The AT 2 receptor antagonists may be provided alone or in combination with other compounds such as those that are useful in the control of neuropathic conditions.

Estrogen receptors and methods of use

The present invention provides isolated polypeptides having an amino acid sequence having at least 70% identity to SEQ ID NO:20, wherein the polypeptide has ER-α36 activity. The invention further provides methods for identifying agents that bind to such polypeptides, methods for detecting such polypeptides, and methods for altering the activity of such polypeptides. Also provided are antibodies that specifically bind to an amino acid sequence depicted at SEQ ID NO:1, or an immunogenic fragment thereof, and methods for making and using such antibodies.

Methods and kits for diagnosing osteoarthritis and predicting progression

This disclosure relates to methods and kits for diagnosing osteoarthritis and for determining the progression of osteoarthritis in a subject.

Predicting risk of major adverse cardiac events

Measurement of circulating ST2 and natriuretic peptide (e.g., NT-proBNP) concentrations is useful for the prognostic evaluation of subjects, in particular for the prediction of adverse clinical outcomes, e.g., mortality, transplantation, and heart failure.

Myostatin binding agents

The present invention provides binding agents comprising peptides capable of binding myostatin and inhibiting its activity. In one embodiment the binding agent comprises at least one myostatin-binding peptide attached directly or indirectly to at least one vehicle such as a polymer or an Fc domain. The binding agents of the present invention produced increased lean muscle mass when administered to animals and decreased fat to muscle ratios. Therapeutic compositions containing the binding agents of the present invention are useful for treating muscle-wasting disorders and metabolic disorders including diabetes and obesity.

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.

Diagnostic agent for ischemic heart disease risk group

The present invention relates to a diagnostic agent for an ischemic heart disease risk group comprising an anti-brain-derived neurotrophic factor antibody as an effective ingredient, to an assay method for an ischemic heart disease risk group performed by measuring a brain-derived neurotrophic factor concentration in blood, and to a suppressive/preventive drug for ischemic heart disease, particularly for post-infarction myocardial remodeling, comprising a brain-derived neurotrophic factor.

Methods for detecting dihydrotestosterone by mass spectrometry

Provided are methods for determining the amount of dihydrotestosterone (DHT) in a sample using mass spectrometry. The methods generally involve ionizing DHT in a sample and detecting and quantifying the amount of the ion to determine the amount of DHT in the sample.

Human domain antibodies against components of the human insulin-like growth factor (igf) system

The invention provides antibodies or antibody fragments that bind to insulin-like growth factor (IGF) 1 receptor (IGF-1R) or IGF-2, as well as method of using the antibodies for inhibiting the IGF-mediated signaling pathway, inhibiting IGF-1R signaling, and treating cancer. The invention also provides a method of detecting the presence of IGF-1R or IGF-2 in a sample using the inventive antibodies and antibody fragments.

Immunoassay for determining the release of neurotensin into the circulation

The invention relates to an immunodiagnostic determination method for determining the release of neurotensin into the circulation of mammals during which an immunoreactivity of the N-terminal portion of a mammal proneurotensin (PNT immunoreactivity) is selectively determined in a serum sample or plasma sample of a test mammal, this immunoreactivity not being a neurotensin or neuromedin immunoreactivity.

Materials and methods for the differential diagnosis of pacreatic lesions

Levels of VEGF-A, VEGF-C and PGE 2 were measured in patient groups presenting with different types of pancreatic lesions. Pancreatic fluids that exhibited high levels of VEGF-A and relative low levels of VEGF-C correlated well with a diagnosis of serous cystadenoma. Pancreatic fluids collected from cysts in patients that did not have a clinical diagnosis of pancreatic cancer and that exhibited relatively low levels of VEGF-A correlated with a diagnosis of intraductal papillary mucinous neo-plasms (IPMN). Furthermore, the level of PGE 2 increased with dysplastic stage. Contacting pancreatic fluid with reagents that selectively bind to VEGF-A, VEGF-C and PGE 2 provide a useful diagnostic tool for identifying patients with these benign, pre-malignant or malignant lesions of the pancreas.

Method for detection of basic peptide and reagent for detection of basic peptide

The present invention provides a method for detection of a basic peptide by mixing a sample suspected to contain the basic peptide and a reagent containing denatured albumin and detecting turbidness due to a complex of the basic peptide and denatured albumin.

Simultaneous detection of mutational status and gene copy number

The present invention provides compositions and methods for simultaneously detecting mutational status and gene copy number. In particular, the present invention provides simultaneous measurement of gene copy number and detection of the L858R and Exon 19 del mutations in a tissue sample.

Small molecules that covalently modify transthyretin

A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and reacts chemoselectively with one or two of four Lys-15 ε-amino groups within the transthyretin tetramer. The crystal structure confirms the binding orientation of the compound substructure and the conjugating amide bond. A covalent transthyretin kinetic stabilizer exhibits superior amyloid inhibition potency, compared to a non-covalent counterpart, and inhibits cytotoxicity associated with amyloidogenesis.

Use of tyrosine kinase inhibitors for treatment of cushing's disease and hypercortisolism

The invention relates to methods and kits for the treatment of, prevention of, and lowering the chances of developing Cushing's Disease and/or hypercortisolism by the administration of a tyrosine kinase inhibitor, such as gefitinib.

Methods and compositions for diagnosis and prognosis of renal injury and renal failure

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a one or more assays configured to detect a kidney injury marker selected from the group consisting of Endothelin-1, Somatotropin, and Interleukin-13 as diagnostic and prognostic biomarkers in renal injuries.

Arrays Of Biological Membranes And Methods And Use Thereof

The present invention overcomes the problems and disadvantages associated with prior art arrays by providing an array comprising a plurality of biological membrane microspots associated with a surface of a substrate that can be produced, used and stored, not in an aqueous environment, but in an environment exposed to air under ambient or controlled humidities. Preferably, the biological membrane microspots comprise a membrane bound protein. Most preferably, the membrane bound protein is a G-protein coupled receptor, an ion channel, a receptor serine/threonine kinase or a receptor tyrosine kinase.

Methods of identifying modulators of gpr17

The present invention is related to a method of determining a test compound's ability to modify the biological activity of a GPR17. Said method comprises, among others, the step of contacting the test compound with a GPR17, or a functional GPR17 fragment in the presence of a suitable amount of a GPR17 agonist of formula I.

COMBINATION TREATMENTS COMPRISING C-MET ANTAGONISTS AND B-RAF ANTAGONISTS

The present invention relates generally to the fields of molecular biology and growth factor regulation. More specifically, the invention relates to therapies for the treatment of pathological conditions, such as cancer. 1. A method for treating a patient with cancer comprising administering an effective amount of B-raf antagonist and c-met antagonist.2. A method for treating a cancer patient who has increased likelihood of developing resistance to B-raf antagonist comprising administering an effective amount of B-raf antagonist and c-met antagonist.3. A method for increasing and/or restoring sensitivity to B-raf antagonist comprising administering to a cancer patient an effective amount of B-raf antagonist and c-met antagonist.4. A method for extending period of B-raf antagonist sensitivity comprising administering to a cancer patient an effective amount of B-raf antagonist and c-met antagonist.5. A method for treating a patient with B-raf antagonist resistant cancer comprising administering an effective amount of B-raf antagonist and c-met antagonist.6. A method for extending duration of response to B-raf antagonist comprising administering an effect amount of B-raf antagonist and c-met antagonist.7. A method for delaying or preventing development of HGF-mediated B-raf antagonist resistant cancer in a patient comprising administering an effective amount of B-raf antagonist and c-met antagonist.87. The method of any of - claims 1 , wherein the patient's cancer has been shown to express B-raf biomarker.9. The method of claim 8 , wherein the B-raf biomarker is B-raf V600.10. The method of claim 8 , wherein B-raf biomarker is B-raf V600E.1110. The method of any of - claims 8 , wherein mutant B-raf biomarker expression in the patient's cancer is determined using a method comprising (a) performing one or more of gene expression profiling claims 8 , PCR hybridization assay claims 8 , in situ hybridization claims 8 , 5′ nuclease assay mutation detection assay claims 8 , ...

Cortisol immunoassay using fluorescent particles

Provided are a base plate and a method for cortisol immunoassay, which enable immunoassay of cortisol with high sensitivity particularly in a clinically significant cortisol concentration range (that is, 1 μg/dL to 30 μg/dL). A base plate for cortisol immunoassay which has a cortisol albumin conjugate having a cortisol/albumin ratio of from 12 to 20 immobilized thereon is disclosed.

Phoshorylation of Estrogen Receptor Alpha Serine 282 as a Marker for Endocrine Therapies in Breast Cancer

The present invention provides diagnostic methods and markers based on the phosphorylation state of certain amino acid residues of estrogen receptor α. The invention relates to the phosphorylation of specific estrogen receptor alpha residues as a marker for susceptibility to chemotherapy. The invention specifically discloses the phosphorylation of serine 282 of the ER-alpha, as a diagnostic marker for breast cancer cells which are more responsive to hormone therapy than cells without the said phosphorylation. 1. A diagnostic marker composition which detects cancerous cells susceptible to endocrine therapy , said composition comprising an agent which detects the phosphorylation status of serine 282 of estrogen receptor α.2. A diagnostic marker composition which detects cancerous cells resistant to endocrine therapy , said composition comprising an agent which detects the phosphorylation status of threonine 311 of estrogen receptor α.3. A diagnostic marker composition which detects cancerous cells resistant to endocrine therapy , said composition comprising an agent which detects the phosphorylation status of serine 559 of estrogen receptor α.4. A diagnostic method for cancerous cells resistant to endocrine therapy said method comprising:(a) obtaining a sample from a subject; and(b) detecting the phosphorylation status of one or more residues of estrogen receptor α, said residues being selected from threonine 311 and serine 559.5. A diagnostic method for cancerous cells susceptible to endocrine therapy said method comprising:(a) obtaining a sample from a subject; and(b) detecting the phosphorylation status of one or more residues of estrogen receptor α, said residues being selected from serine 282 and serine 294.6. A diagnostic method for cancerous cells susceptible to endocrine therapy said method comprising:(a) obtaining a sample from a subject; and(b) detecting the phosphorylation status of the serine 282 residue of estrogen receptor α.76. The method of , , or ...

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.

PEPTIDE DERIVATIVES OF EXENDIN-4

In the current invention peptides, which are derived from GLP-1 (glucagon-like peptide-1) and exendin-3 and/or exendin-4, are provided which bond to the GLP-1 receptor and can be used, labeled or unlabeled, for the production of an agent for diagnostic and therapy of benign and malignant diseases, in which GLP-1 receptor expression plays a role. 1. Peptide derivatives of GLP-1 and exendin-3 , wherein their C-terminus is modified by an amine and wherein their N-terminus binds to the GLP-1 receptor.3. Peptide derivatives of GLP-1 and exendin-3 according to claim 1 , wherein they are based on GLP1(x-y)Aor exendin-3 (z-k)Awithx representing the amino acids 1-36 of the GLP-1 amino acid sequence,y representing the amino acids 2-37 of the GLP-1 amino acid sequence,z representing the amino acids 1-38 of the exendin-3 amino acid sequence,k representing the amino acids 2-39 of the exendin 3 amino acid sequenceand A being an attachment group comprising of one or more amino acids or its derivatives as a signal molecule, or to bond signal molecules or to stabilize them, whereby the exponent indicates at which position the attachment group can be found within the amino acid sequence.4. Peptide derivatives from GLP-1 and exendin-3 according to claim 3 , wherein the attachment group A is preferably located at the C-Terminus and represents an amine.5. Peptide derivatives from GLP-1 and exendin-3 according to claim 3 , wherein the attachment group A is preferably lysine.6. Peptide derivatives from GLP-1 and exendin-3 according to claim 3 , wherein the attachment group A is an amino acid claim 3 , such as ornithine claim 3 , or an organic group comprising free amine.7. Peptide derivatives from GLP-1 and exendin-3 according to claim 3 , wherein a chelator is coupled with attachment group A for the labeling with radionuclides or a MRI contrast agent claim 3 , fluorescent pigments or a chemotherapeutic agent.8. Peptide derivatives from GLP-1 and exendin-3 according to claim 7 , wherein ...

METHODS AND SYSTEMS FOR IDENTIFYING AND TREATING ANTI-PROGESTIN SENSITIVE TUMORS

Methods and systems for identifying and treating a patient suspected of having a tumor susceptible to growth inhibition by anti-progestins are provided. The degree of focal distribution of the progesterone receptor can be used to identify tumors susceptible to treatment with anti-progestin therapy. 1. A method of inhibiting the growth of a tumor susceptible to growth inhibition by anti-progestins , comprising:a) obtaining a tissue sample suspected of being tumorigenic or cancerous from a patient;b) identifying progesterone receptor positive cells in the tissue sample;c) determining the degree of focal distribution of the progesterone receptor in nuclei of the progesterone positive cells from the tissue sample; andd) administering an anti-progestin to the patient if the degree of focal distribution in the tissue sample is greater than about 5% of the progesterone receptor positive cells.2. The method of claim 1 , further comprising determining the degree of focal distribution in nuclei in cells from the tissue by exposing the tissue to anti-progesterone receptor antibodies.3. The method of claim 1 , wherein the tumor is selected from the group consisting of breast claim 1 , brain claim 1 , meningiomas claim 1 , prostate claim 1 , ovarian claim 1 , endometrial claim 1 , uterine leiomyoma claim 1 , lung claim 1 , and uterine tissue.4. The method of claim 1 , wherein the anti-progestin is selected from the group consisting of onapristone claim 1 , lonaprisan claim 1 , mifepristone claim 1 , PP-02413873 claim 1 , telapristone claim 1 , lilopristone claim 1 , ORG2058 claim 1 , apoprisnil claim 1 , and ulipristal.5. The method of claim 1 , wherein the degree of focal distribution is determined by identifying the binding pattern of the progesterone receptor in the progesterone positive cells of the tissue.6. The method of claim 5 , wherein the binding pattern is selected from group consisting of diffuse (D) claim 5 , active (A) claim 5 , and active/diffuse (AD).7. The ...

Procalcitonin for the diagnosis of bacterial infections and guidance of antibiotic treatment in patients with non-specific complaints

The present invention relates to the determination of the level of marker peptides in a sample derived from a bodily fluid of a subject presenting with non-specific complaints.

PREDICTION AND RECOGNITION OF ACUTE KIDNEY INJURY AFTER SURGERY

Systems, kits, and methods for predicting the risk of an adverse event related to acute kidney injury AKI as a consequence of a surgical intervention in a subject. Embodiments of the system and methods include means and steps for determining an amount of liver-type fatty acid binding protein (L-FABP) in a sample, such as a urine-sample of a subject; comparing the amounts of the L-FABP with a reference amount, and predicting the risk of an adverse event related to acute kidney injury as a consequence of surgical intervention in the subject. 1. A method for diagnosing acute kidney injury in a subject , comprising:determining an amount of liver-type fatty acid binding protein, or a variant thereof, in a portion of a sample of a subject;comparing the amount of liver-type fatty acid binding protein, or variant thereof, determined in said step of determining to a liver-type fatty acid binding protein reference amount; andproviding a diagnosis of acute kidney injury in the subject if the amount of liver-type fatty acid binding protein, or the variant thereof, determined in said step of determining is greater than the liver-type fatty acid binding protein reference amount.2. The method of claim 1 , wherein the sample is a urine sample.3. The method of claim 1 , wherein the sample is procured from the subject prior to a surgical intervention.4. The method of claim 1 , wherein said step of determining comprises contacting claim 1 , in vitro claim 1 , the portion of the sample with an antibody having specific binding affinity for liver-type fatty acid binding protein claim 1 , or a variant thereof.5. The method of claim 1 , wherein the liver-type fatty acid binding protein reference amount is 10.7 μg/g creatinine.6. A method of diagnosing a subject as at increased risk of for an adverse event related to acute kidney injury after a surgical intervention claim 1 , comprising the steps of:a) determining an amount of liver-type fatty acid binding protein, or a variant thereof, in ...

Phoshorylation of Estrogen Receptor Alpha

The present invention provides use and methods markers based on the phosphorylation state of certain amino acid residues of estrogen receptor α. 1. An antibody which binds to one or more phosphorylated residues of estrogen receptor α wherein said residues are selected from serine 282; serine 294; threonine 311; and serine 559.2. A method of diagnosis said method comprising:(a) isolating a sample from a subject having, thought to have, or at risk of developing breast cancer;(b) exposing the sample to an antibody which binds to one or more phosphorylated residues of estrogen receptor α; and(c) determining if the residue(s) is/are positive for phosphorylation;wherein the residues are selected from serine 282; serine 294; threonine 311; and serine 559.3. The method of wherein the phosphorylation state of one or more of serine 104/106; serine 118; serine 167 of estrogen receptor α is determined using an antibody which binds to the phosphorylated form of said residues.4. A kit comprising antibodies which bind to one or more phosphorylated residues of estrogen receptor α claim 2 , wherein said residues are selected from serine 282; serine 294; threonine 311; and serine 559.5. A kit comprising antibodies which bind to four or more phosphorylated residues of estrogen receptor α claim 2 , wherein said residues are selected from serine 104/106; serine 118; serine 167; serine 282; serine 294; threonine 311; and serine 559. The present invention relates to the phosphorylation state of a number of residues on estrogen receptor α. The present invention provides methods, uses, kits, and antibodies relating to the phosphorylated estrogen receptor.The hormone-dependent nature of breast cancer is well known and was first described by Beatson in 1896. Since then numerous agents have been introduced designed to either modulate estrogen receptor (ER) function or to affect the levels of circulating estrogens. Among these agents are the selective estrogen receptor modulators (e.g. ...

Islet Amyloid Polypeptide Toxic Oligomer is a Biomarker of Heart or Kidney Failure in Type-2 Diabetes Mellitus

Methods for predicting a propensity for heart or kidney failure in a diabetic or pre-diabetic individual by determining the amount and/or molecular weight of islet amyloid polypeptide present in a sample from the individual are provided. 1. A method for predicting a propensity for failure of an organ selected from heart and kidney in an individual who has type 2 diabetes or is pre-diabetic , the method comprisingdetermining the amount of islet amyloid polypeptide (IAPP) oligomer in a sample from the individual; andpredicting the propensity for heart failure in the individual based on the determined amount of IAPP oligomer, wherein an elevated amount of IAPP oligomer compared to normal levels indicates an increased propensity for heart failure.2. The method of claim 1 , wherein the sample is a blood sample extracted from said individual.3. (canceled)4. (canceled)5. The method of claim 1 , wherein the determining step comprisescontacting an antibody reagent that specifically binds IAPP oligomers to the sample; anddetecting the amount of IAPP oligomers bound by the reagent, said detecting comprising:contacting a detectably labeled detection antibody that binds IAPP oligomers to the IAPP oligomers bound to the antibody reagent; andquantifying the binding of the detection antibody to the bound IAPP oligomers.6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. The method of claim 1 , wherein it is determined that the individual has a propensity for heart failure or kidney failure claim 1 , the method further comprising designing a treatment plan to reduce the propensity for heart failure or kidney failure claim 1 , respectively in the individual.11. A kit for predicting a propensity for failure of an organ selected from heart and kidney in an individual who has type 2 diabetes or is pre-diabetic claim 1 , the kit comprising a solid support operably linked to a reagent that specifically binds IAPP oligomers.12. The kit of claim 11 , wherein the reagent is an antibody. ...

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.

TISSUE STAINING METHOD, TISSUE EVALUATION METHOD AND BIOSUBSTANCE DETECTION METHOD

A tissue staining method which comprises: staining a tissue with a staining reagent wherein a biosubstance recognition site is bonded to particles carrying multiple fluorescent substances accumulated therein; in the stained tissue, counting fluorescent points or measuring fluorescent brightness; and evaluating the expression level of a biosubstance, which matches the biosubstance recognition site, in the aforesaid tissue on the basis of the number of the fluorescent points or fluorescent brightness that was measured. 1. A tissue staining method comprising:staining a tissue with a staining reagent comprising a particle holding plural phosphors, wherein a biosubstance-recognizing body is bound to the particle.2. The tissue staining method according to claim 1 , wherein.the particle holding plural phosphors contains the plural phosphors therein.3. The tissue staining method according to claim 1 , whereinthe phosphor is a fluorescent dye, a semiconductor particle, or a rare-earth element particle.4. The tissue staining method according claim 1 , whereinthe particle holding the plural phosphors has a particle diameter of 40 to 500 nm.5. A tissue evaluation method claim 1 , comprising:staining a tissue section with a staining reagent comprising a phosphor-holding particle which holds plural phosphors, wherein a biosubstance-recognizing body is hound to the phosphor-holding particle;counting the number of bright spots of fluorescence in the stained tissue section; andevaluating an expression level of a biosubstance corresponding to the biosubstance-recognizing body in the stained tissue section on the basis of the number of the counted bright spots.6. The tissue evaluation method according to claim 5 , comprising:measuring brightness of each bright spot in the stained tissue section;determining a brightness distribution on the basis of the number of the counted bright spots and the be of each bright spot;calculating the brightness per phosphor-holding particle on the basis ...

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) ...

SMALL MOLECULE-DEPENDENT SPLIT APTAMER LIGATION

Methods, assays, and products for the detection of small molecules are provided. In one aspect, for example, a method of detecting a small molecule in a sample can include reacting together a first half of a DNA split aptamer having a first reactive group coupled thereto, a second half of a DNA split aptamer having a second reactive group coupled thereto, where the DNA split aptamer is selective for the small molecule, and a sample containing the small molecule. The first half and the second half bind to the small molecule and the first reactive group and the second reactive group react to form an aptamer ligation product of the first half and the second half. The method can also include assaying for the aptamer ligation product in order to detect the small molecule presence in the sample. 1. A method of detecting a small molecule in a sample , comprising: a first half of a DNA split aptamer having a first reactive group coupled thereto;', 'a second half of a DNA split aptamer having a second reactive group coupled thereto, wherein the DNA split aptamer is selective for the small molecule;', 'a sample containing the small molecule;, 'reacting togetherwherein the first half and the second half bind to the small molecule and the first reactive group and the second reactive group react to form an aptamer ligation product of the first half and the second half; andassaying for the aptamer ligation product to detect the small molecule presence in the sample.2. The method of claim 1 , wherein the small molecule is a controlled substance.3. The method of claim 1 , wherein the small molecule is an opioid.4. The method of claim 1 , wherein the small molecule is a steroid.5. The method of claim 1 , wherein the small molecule is cocaine.6. The method of claim 1 , wherein the first reactive group is an azide and the second reactive group is a cyclooctyne carboxylic acid and the ligation product is a result of a strain-promoted azide-alkyne cycloaddition reaction.7. The method of ...

ASSAYS FOR HUMAN NT-PRO B-TYPE NATRIURETIC PEPTIDE, HUMAN PRO B-TYPE NATRIURETIC PEPTIDE AND HUMAN B-TYPE NATRIURETIC PEPTIDE

The present disclosure relates to assays for detecting and/or quantifying the amount of human NT-pro B-type natriuretic peptide, human pro B-type natriuretic peptide and human B-type natriuretic peptide in a test sample. 1. Immunodiagnostic reagents comprising:(a) a first capture antibody specific for human NT-pro B-type natriuretic peptide (“human NT-proBNP”);(b) a second capture antibody which is specific to each of human pro B-type natriuretic peptide (“human proBNP”) and human brain natriuretic peptide (“hBNP”);(c) a first detection antibody which is specific to each of human NT-proBNP and human proBNP; and(d) a second detection antibody which is specific to hBNP.2. The immunodiagnostic reagents of claim 1 , wherein the first capture antibody is antibody 15F11.3. The immunodiagnostic reagents of claim 1 , wherein the second capture antibody is antibody 8.1.4. The immunodiagnostic reagents of claim 1 , wherein the first detection antibody is antibody 15C4.5. The immunodiagnostic reagents of claim 1 , wherein the second detection antibody is antibody 201.3.6. A kit for detecting the amount of human NT-pro B-type natriuretic peptide (“human NT-proBNP”) claim 1 , human pro B-type natriuretic peptide (“human proBNP”) and human brain natriuretic peptide (“hBNP”) in a test sample claim 1 , said kit comprising:(a) instructions for conducting the assay of the test sample; and (i) a first capture antibody specific for human NT-proBNP;', '(ii) a second capture antibody which is specific to each of human proBNP and hBNP;', '(iii) a first detection antibody which is specific to each of human NT-proBNP and human proBNP; and', '(iv) a second detection antibody which is specific to hBNP., '(b) immunodiagnostic reagents comprising7. The kit of claim 6 , wherein the first capture antibody is antibody 15F11.8. The kit of claim 6 , wherein the second capture antibody is antibody 8.1.9. The kit of claim 6 , wherein the first detection antibody is antibody 15C4.10. The kit of claim 6 ...

METHODS AND COMPOSITIONS FOR DIAGNOSIS AND PROGNOSIS OF RENAL INJURY AND RENAL FAILURE

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a one or more assays configured to detect a kidney injury marker selected from the group consisting of Cancer antigen CA 15-3, C-C Motif chemokine 18, C-C Motif chemokine 24, Cathepsin D, C-X-C Motif chemokine 13, C-C motif chemokine 8, Interleukin-2 receptor alpha chain, Insulin-like growth factor-binding protein 3, Interleukin-11, Matrix Metalloproteinase-8, Transforming growth factor alpha, IgG1, and IgG2 as diagnostic and prognostic biomarkers in renal injuries. 1. A method for evaluating renal status in a subject , comprising:obtaining a urine sample from a subject selected for evaluation based on a determination that the subject is at risk of a future or current acute renal injury;performing one or more assays configured to detect one or more biomarkers selected from the group consisting of Cancer antigen CA 15-3, C-C Motif chemokine 18, C-C Motif chemokine 24, Cathepsin D, C-X-C Motif chemokine 13, C-C motif chemokine 8, Interleukin-2 receptor alpha chain, Insulin-like growth factor-binding protein 3, Interleukin-11, Matrix Metalloproteinase-8, Transforming growth factor alpha, IgG1, and IgG2 by introducing the urine sample obtained from the subject into an assay instrument which (i) for each analyte binding assay performed, contacts all or a portion of the urine sample with a binding reagent which specifically binds for detection the kidney injury marker which is assayed, and (ii) generates one or more assay results indicative of binding of each biomarker which is assayed to its respective binding reagent and displays the assay results generated in human readable form; andcorrelating the assay result(s) generated by the assay instrument to the renal status of the subject.2. A method according to claim 1 , wherein ...

Antibodies Directed to the Unprocessed Receptor Tyrosine Kinase c-Met

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

METHOD TO IDENTIFY A PATIENT WITH AN INCREASED LIKELIHOOD OF RESPONDING TO AN ANTI-CANCER THERAPY

The invention provides methods for identifying patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist. The invention also provides methods for monitoring a patients' response to the anti-cancer therapy. The invention also provides kits and articles of manufacture for use in the methods. 1. A method of identifying a patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist , the method comprising:determining an expression level of unmodified VEGF in a sample obtained from the patient, wherein a level of unmodified VEGF in the sample obtained from the patient at or above a reference level indicates that the patient may benefit from treatment with the anti-cancer therapy.2. A method of predicting responsiveness of a patient suffering from cancer to treatment with an anti-cancer therapy comprising a VEGF-A antagonist , the method comprising:determining an expression level of unmodified VEGF in a sample obtained from the patient, wherein a level of unmodified VEGF in the sample obtained from the patient at or above a reference level indicates that the patient is more likely to be responsive to treatment with the anti-cancer therapy.3. A method for determining the likelihood that a patient with cancer will exhibit benefit from anti-cancer therapy comprising a VEGF-A antagonist , the method comprising:determining an expression level of unmodified VEGF in a sample obtained from the patient, wherein a level of unmodified VEGF in the sample obtained from the patient at or above a reference level indicates that the patient has increased likelihood of benefit from the anti-cancer therapy.4. A method for optimizing the therapeutic efficacy of an anti-cancer therapy comprising a VEGF-A antagonist , the method comprising:determining an expression level of unmodified VEGF in a sample obtained from the patient, wherein a level of unmodified VEGF in the sample obtained from the patient at or above a ...

MARKERS FOR THE PROGNOSIS AND RISK ASSESSMENT OF PREGNANCY-INDUCED HYPERTENSION AND PREECLAMPSIA

The present invention relates to the prognosis and risk assessment in pregnant women to develop pregnancy-induced hypertension and/or preeclampsia by the determination of marker levels. 1. A method for the prognosis of development of pregnancy-induced hypertension and/or preeclampsia or risk assessment in pregnant women to develop pregnancy-induced hypertension and/or preeclampsia comprising the steps of:(i) providing a sample of a bodily fluid of a subject,(ii) determining the level of pro-ADM or fragments thereof and/or pro-ET-1 or fragments thereof in said sample,(iii) correlating the level of pro-ADM or fragments thereof and/or pro-ET-1 or fragments thereof with the prognosis or risk assessment for a pregnant woman,wherein said fragments have a lengths of at least 6 amino acid residues.2. The method of claim 1 , wherein the determination of the level pro-ADM or fragments thereof and/or pro-ET-1 or fragments thereof is carried out within the first to second trimester (8to 26week of pregnancy) claim 1 , more preferred within the first to early second trimester (8to 20week of pregnancy) claim 1 , even more preferred within the first trimester (8to 14week of pregnancy) claim 1 , mostly preferred within the early first trimester (8to 10week of pregnancy).3. The method of claim 1 , wherein the prognosis or risk assessment is related to an early onset (between 20 to 34 weeks of gestation) or a late onset (after 34 weeks of gestation) of preeclampsia.4. The method of claim 1 , wherein at least one further marker selected from the group sflt-1 claim 1 , sEng claim 1 , PIGF claim 1 , VEGF claim 1 , PP-13 claim 1 , ADAM12 claim 1 , P-Selectin claim 1 , cell-free fetal DNA claim 1 , PTX3 claim 1 , PAPP-A claim 1 , Visfatin claim 1 , inhibin A claim 1 , activin A claim 1 , human chorionic gonadotropin (hCG) claim 1 , alpha-fetoprotein (AFP) claim 1 , metalloproteinase-9 (MMP-9) claim 1 , ultrasound markers (uterine artery pulsatility index and/or diastolic notching) claim 1 ...

NORMALIZATION OF PLATELET BIOMARKERS

Described herein are methods useful for normalizing any biomarker in platelets. This has application in any method in which one wishes to ascertain or compare the level of a biomarker, e.g., for diagnostic or prognostic methods relating to a biomarker of interest. Using such an approach can permit the assessment of disease status (e.g., angiogenic status) of an individual with less error than an expression value that is not normalized or that is normalized to total protein levels. Also provided are methods for selecting a normalizing protein for normalizing biomarkers in a sample, e.g., a platelet sample. 1. An assay for determining the level of a biomarker in a platelet preparation comprising:(a) determining the level of a surrogate marker in a platelet preparation sample, wherein the surrogate marker corresponds to platelet number, platelet concentration or platelet volume;(b) determining the level of a biomarker in the sample,(c) normalizing the level of the biomarker in the sample to the level of the surrogate marker, whereby a normalized biomarker level for the sample is determined.2. The assay of claim 1 , wherein the normalizing step comprises dividing the value obtained for the level of the biomarker in the sample by the value obtained for the level of the surrogate marker.3. The assay of claim 1 , wherein the surrogate marker is polymerized or monomeric actin.4. The assay of claim 1 , wherein step (a) comprises placing the sample obtained from an individual under conditions that induce actin polymerization claim 1 , such that actin in the sample is substantially polymerized.5. (canceled)6. The assay of claim 1 , wherein the biomarker is an angiogenic regulator.7. A method for identifying a surrogate marker for platelet number claim 1 , platelet concentration claim 1 , or platelet volume claim 1 , the method comprising:(a) assaying the amount of a plurality of candidate markers in each sample of a series of samples prepared from a single platelet preparation ...

METHOD TO IDENTIFY A PATIENT WITH AN INCREASED LIKELIHOOD OF RESPONDING TO AN ANTI-CANCER THERAPY

The invention provides methods for identifying patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist. The invention also provides methods for monitoring a patients' response to the anti-cancer therapy. The invention also provides kits and articles of manufacture for use in the methods. 1. A method of identifying a patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist , the method comprising:(a) determining an expression level of unmodified VEGF in a sample obtained from the patient, wherein a level of unmodified VEGF in the sample obtained from the patient at or above a reference level identifies that the patient may benefit from treatment with the anti-cancer therapy; and(b) informing the patient that they may benefit from anti-cancer therapy comprising a VEGF antagonist.2. A method of predicting responsiveness of a patient suffering from cancer to treatment with an anti-cancer therapy comprising a VEGF antagonist , the method comprising:(a) determining an expression level of unmodified VEGF in a sample obtained from the patient, wherein a level of unmodified VEGF in the sample obtained from the patient at or above a reference level indicates that the patient is more likely to be responsive to treatment with the anti-cancer therapy; and(b) informing the patient that they have an increased likelihood of being responsive to anti-cancer therapy comprising a VEGF antagonist.3. A method for determining the likelihood that a patient with cancer will exhibit benefit from anti-cancer therapy comprising a VEGF antagonist , the method comprising:(a) determining an expression level of unmodified VEGF in a sample obtained from the patient, wherein a level of unmodified VEGF in the sample obtained from the patient at or above a reference level indicates that the patient has increased likelihood of benefit from the anti-cancer therapy; and(b) informing the patient that they have an increased ...

METHODS OF DIAGNOSING ACUTE CARDIAC DISORDERS USING BNP-SP

The invention provides methods for predicting, diagnosing or monitoring acute cardiac disorders, cardiac transplant rejection, or distinguishing acute cardiac disorders from pulmonary disorders, by measuring BNP signal peptide levels in a sample taken from a subject shortly after onset of, or presentation with the disorder or transplant rejection. 1. An assay method for diagnosing an acute cardiac disorder in a subject , the method comprising:a. obtaining a biological sample from the subject;b. contacting the sample with a BNP-SP fragment binding agent;c. determining the level of a BNP-SP fragment in the biological sample obtained from the subject; andd. comparing the level of said BNP-SP fragment in the sample with the level of said BNP-SP fragment in a control or reference value,wherein a level of BNP-SP fragment in the sample that is higher than the control level is diagnostic of an acute cardiac disorder.2. A method according to claim 1 , wherein said method is used to evaluate or monitor a response to treatment of an acute cardiac disorder claim 1 , wherein said assay method is carried out on one or more biological samples from said subject and a change in the measured level of BNP-SP fragment from said control or reference value is determined claim 1 , said method further comprising the step of determining whether to adjust treatment for said acute cardiac disorder based on a change in the measured level of BNP-SP fragment from the control or reference value and claim 1 , optionally claim 1 , adjusting said treatment.3. A method according to claim 1 , which further comprises the step of providing therapy to the subject for treatment of an acute cardiac disorder.4. A method according to that further comprises the step of evaluating one more risk factors and/or test results in conjunction with determining the level of BNP-SP fragment in the sample.5. A method according to claim 1 , wherein the control is an individual or group from which BNP-SP fragment samples ...

Method for detecting adrenocorticotropic hormone and adsorbent

A method for detecting adrenocorticotropic hormone comprising: bringing a liquid sample containing adrenocorticotropic hormone into contact with gelled casein to adsorb adrenocorticotropic hormone to the gelled casein; and detecting the adrenocorticotropic hormone adsorbed to the gelled casein is disclosed. An adsorbent of adrenocorticotropic hormone comprising gelled casein is also disclosed.

SENSITIVITY AND SPECIFICITY FOR OVARIAN CANCER

Improved ovarian cancer assays are provided. 1. A method of detecting the presence or absence of ovarian cancer in an individual human , the method comprising ,detecting the level of the following agents in a biological sample from the individual:a. CA-125; andb. IGFBP-2 or prolactin or osteopontin; andcorrelating the level of the agents to the presence, absence, or stage of ovarian cancer in the individual wherein the correlating comprises using the IGFBP-2 or prolactin or osteopontin levels as a confirmatory criterion for higher than normal levels of CA-125.2. The method of claim 1 , further detecting in a biological sample from the individual the level of:at least one autoantibody specific for a target antigen protein, wherein an elevated level of the autoantibody specific for the target antigen protein is indicative of cancer.3. The method of claim 1 , wherein the correlating comprises determining whether the level of CA-125 is below about 30 IU/mL serum claim 1 , between about 30 and 100 IU/mL serum claim 1 , or over about 100 IU/mL serum claim 1 , and whether IGFBP-2 or prolactin or osteopontin levels are above normal levels claim 1 , wherein the presence of ovarian cancer is indicated by:a CA-125 level over about 100 IU/mL; ora CA-125 level between about 30 and 100 IU/mL and an IGFBP-2 or prolactin or osteopontin level are above the normal level.4. The method of claim 2 , wherein autoantibodies specific for the target antigen protein are separately captured by:the target antigen protein; andthe immunogenic fragment thereof; andthe detecting comprises separately detecting binding of the autoantibodies to the target antigen protein and to the immunogenic fragment thereof.5. The method of claim 2 , wherein more than one target antigen protein for more than one different autoantibodies are linked to the solid support claim 2 , thereby detecting the level of more than one autoantibody in the sample.6. The method of claim 2 , wherein the autoantibody target antigen ...

ANTI-VEGF ANTIBODIES AND USES THEREOF

Provided are monoclonal antibodies and antigen binding fragments thereof that specifically bind vascular endothelial growth factor (VEGF). The anti-VEGF monoclonal antibodies block VEGF binding to its receptors (e.g., VEGFR1 and/or VEGFR2) and prevent phosphorylation of VEGFR2 by VEGF. Also provided are methods of using the monoclonal anti-VEGF antibodies for treatment of disease, including cancer. 1. An isolated antibody or antigen binding fragment thereof that specifically binds to VEGF , wherein the VH of said antibody or fragment thereof comprises a Kabat heavy chain complementarity determining region-3 (VH-CDR3) amino acid sequence identical to SEQ ID NO:5 and said isolated antibody or antigen binding fragment thereof comprises at least one CDR selected from the group consisting of: a Chothia-Kabat heavy chain complementarity determining region-1 (VH-CDR1) amino acid sequence identical to SEQ ID NO:3 , a Kabat heavy chain complementarity determining region-2 (VH-CDR2) amino acid sequence identical to SEQ ID NO:4 , a Kabat light chain complementarity determining region-1 (VL-CDR1) amino acid sequence identical to SEQ ID NO:6 , a Kabat light chain complementarity determining region-2 (VL-CDR2) amino acid sequence identical to SEQ ID NO:7 , a Kabat light chain complementarity determining region-3 (VL-CDR3) amino acid sequence identical to SEQ ID NO:8 , and a combination of 2 or more of said CDRs.26-. (canceled)7. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the VH of said antibody or fragment thereof comprises VH-CDR1 claim 1 , VH-CDR2 claim 1 , and VH-CDR3 amino acid sequences comprising SEQ ID NOs: 3 claim 1 , 4 claim 1 , and 5 claim 1 , respectively.8. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the VL of said antibody or fragment thereof comprises VL-CDR1 claim 1 , VL-CDR2 claim 1 , and VL-CDR3 amino acid sequences comprising SEQ ID NOs: 6 claim 1 , 7 claim 1 , and 8 claim 1 , respectively.9. ...

Methods and compositions for diagnosis and prognosis of renal injury and renal failure

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a one or more assays configured to detect a kidney injury marker selected from the group consisting of Tumor necrosis factor receptor superfamily member 8, Alpha-Fetoprotein, Thyroxine-binding globulin, Prostate-specific antigen (free form), Apolipoprotein A Apolipoprotein E, Thyrotropin subunit beta, Platelet-derived growth factor B/B dimer, C-C motif chemokine 7, C-C motif chemokine 26, Complement C4-B, Corticotropin, Interferon alpha-2, Interleukin-4 receptor alpha chain, Insulin-like growth factor-binding protein 4, Insulin-like growth factor-binding protein 5, Interleukin 21, Interleukin 23 alpha subunit, Interleukin-28A, Interleukin-33, Lutropin subunit beta, Matrix Metalloproteinase-1, Neural cell adhesion molecule 1, Pigment epithelium-derived factor, Vascular endothelial growth factor receptor 2, Vascular endothelial growth factor receptor 3, and IgG4 as diagnostic and prognostic biomarkers in renal injuries.

Glycoprotein Analysis Kit and Use Thereof

Disclosed are a glycoprotein analysis kit and use thereof. The glycoprotein analysis kit comprises a fluorescently labeled antibody, a fluorescently labeled biomaterial, and a support, and is used in a dual probing method for analyzing the content of a glycoprotein and profiling the oligosaccharide chain, simultaneously, and a method for selecting a single cell producing the glycoprotein having a desired glycosylation pattern. Also, a single cell producing the glycoprotein having a desired glycosylation pattern is provided. 1. A glycoprotein analysis kit comprising:(A) a fluorescently labeled antibody selectively binding to a protein moiety of a glycoprotein of interest;(B) a fluorescently labeled biomaterial selectively binding to a carbohydrate moiety of the glycoprotein of interest; and(C) a support for immobilizing the glycoprotein of interest thereto.2. The glycoprotein analysis kit of claim 1 , wherein the biomaterial selectively binds to a specific carbohydrate structure and is selected from the group consisting of a lectin claim 1 , an antibody claim 1 , an aptamer and a peptide.3. The glycoprotein analysis kit of claim 1 , wherein the antibody and the biomaterial are labeled with respective fluorescent dyes which are different in absorption and emission wavelengths from each other.4. The glycoprotein analysis kit of claim 1 , wherein the glycoprotein is a purified glycoprotein or a glycoprotein isolated from single cells.5. The glycoprotein analysis kit of claim 1 , wherein the support is coated with an another antibody capable of binding to the glycoprotein of interest.6. A method for quantitating a glycoprotein of interest claim 1 , comprising:(A) reacting a glycoprotein of interest immobilized onto a support with a fluorescently labeled antibody binding selectively to a protein moiety of the glycoprotein of interest and a fluorescently labeled biomaterial binding selectively to a carbohydrate moiety of the glycoprotein of interest; and(B) measuring ...

MASS SPECTROMETRY ASSAY FOR CONGENITAL ADRENAL HYPERPLASIA

Methods are provided for detecting the amount of one or more CAH panel analytes (i.e., pregnenolone, 17-OH pregnenolone, progesterone, 17-OH progesterone, dehydroepiandrosterone (DHEA), androstenedione, testosterone, deoxycorticosterone, 11-deoxycortisol, and cortisol) in a sample by mass spectrometry. The methods generally involve ionizing one or more CAH panel analytes in a sample and quantifying the generated ions to determine the amount of one or more CAH panel analytes in the sample. In methods where amounts of multiple CAH panel analytes are detected, the amounts of multiple analytes are detected in the same sample injection. 1. A method for determining in a sample , by mass spectrometry , the amounts of at least three analytes selected from the group consisting of pregnenolone , 17-OH pregnenolone , progesterone , 17-OH progesterone , dehydroepiandrosterone (DHEA) , androstenedione , testosterone , 11-deoxycortisol , deoxycorticosterone , and cortisol , the method comprising:subjecting the sample to an ionization source under conditions suitable to produce one or more ions detectable by mass spectrometry from each of the analytes, wherein the analytes are not derivatized prior to ionization;determining, by tandem mass spectrometry, the amounts of the one or more ions from each of the analytes; andusing the determined amounts of the one or more ions to determine the amount of each of the analytes in the sample.2. The method of claim 1 , wherein the analytes comprise cortisol claim 1 , androstenedione and 17-OH progesterone.3. The method of claim 1 , wherein the analytes comprise cortisol claim 1 , androstenedione and progesterone.4. The method of claim 1 , wherein the analytes comprise cortisol claim 1 , deoxycorticosterone and 17-OH progesterone.5. The method of claim 1 , wherein the analytes comprise testosterone claim 1 , androstenedione and dehydroepiandrosterone (DHEA).6. The method of claim 1 , wherein the analytes comprise four or more analytes.7. The ...

WISE/SOST NUCLEIC ACID SEQUENCES AND AMINO ACID SEQUENCES

The present invention relates to nucleic acid sequences and amino acid sequences which influence bone deposition, the Wnt pathway, ocular development, tooth development, and may bind to LRP. The nucleic acid sequence and polypeptides include Wise and Sost as well as a family of molecules which express a cysteine knot polypeptide. Additionally, the present invention relates to various molecular tools derived from the nucleic acids and polypeptides including vectors, transfected host cells, monochronal antibodies, Fab fragments, and methods for impacting the pathways. 1235-. (canceled)236. A method for preventing a Sost polypeptide from binding to an LRP selected from the group consisting of LRP5 and LRP6 comprising:(a) isolating a Sost nucleic acid sequence selected from a group consisting of SEQ ID No. 6-7, 9-11, 13-14, 101-102, 110, and 111;(b) forming a plasmid vector with a Sost nucleic acid sequence from (a) and transfecting a host cell with the plasmid vector whereby the host cell expresses the Sost nucleic acid sequence to produce a Sost polypeptide;(c) immunizing a host organism with the Sost polypeptide;(d) isolating an antibody to the Sost polypeptide from the host;(e) contacting the antibody with the Sost polypeptide that is encoded by the Sost nucleic acid, wherein the antibody prevents the Sost polypeptide from binding to an LRP selected from LRP5 and LRP6.237. The method according to claim 236 , wherein the antibody is monoclonal.238. The method according to claim 236 , wherein the antibody is polyclonal.239. The method according to claim 236 , wherein the antibody is recombinant.240. The method according to claim 236 , wherein the antibody was treated to produce an antibody fragment prior to contacting with the Sost polypeptide in step (e).241. The method according to claim 240 , wherein the antibody fragment is selected from the group consisting of a Fab claim 240 , a F(ab) claim 240 , a Fv claim 240 , and an antibody combining region.242. The method ...

ErbB3 ANTIBODIES

Antibodies are disclosed which bind to ErbB3 protein and further possess any one or more of the following properties: an ability to reduce heregulin-induced formation of an ErbB2-ErbB3 protein complex in a cell which expresses ErbB2 and ErbB3; the ability to increase the binding affinity of heregulin for ErbB3 protein; and the characteristic of reducing heregulin-induced ErbB2 activation in a cell which expresses ErbB2 and ErbB3. 1. An antibody which binds to ErbB3 protein and reduces heregulin-induced formation of an ErbB2-ErbB3 protein complex in a cell which expresses ErbB2 and ErbB3 , wherein the antibody is conjugated to a cytotoxic agent.2. The antibody of which further increases the binding affinity of heregulin for ErbB3 protein.3. The antibody of which further reduces heregulin-induced ErbB2 activation in the cell.4. The antibody of which is a monoclonal antibody.5. The antibody of which is humanized.6. The antibody of which is human.7. The antibody of which is an antibody fragment.8. The antibody fragment of which is a Fab.9. The antibody of which is labelled.10. The antibody of which is immobilized on a solid phase.11. (canceled)12. An antibody which binds to ErbB3 protein and reduces heregulin-induced ErbB2 activation in a cell which expresses ErbB2 and ErbB3.13. An antibody which binds to ErbB3 protein and reduces heregulin binding thereto.14. The antibody of which further reduces heregulin-induced ErbB2 activation in a cell which expresses ErbB2 and ErbB315. The antibody of which binds to the epitope bound by the 8B8 antibody.16. The antibody of which has the complementarity determining regions of the 8B8 antibody.17. A composition comprising the antibody of and a pharmaceutically acceptable carrier.18. A cell line which produces the antibody of .19. The cell line of which is a hybridoma cell line producing the 8B8 antibody.20. A method for determining the presence of ErbB3 protein comprising exposing a cell suspected of containing the ErbB3 protein to ...

Egfr-related polypeptides and methods of use

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

Method and kit for the diagnosis and/or prognosis of tolerance in liver transplantation

The invention refers to a method and kit for the in vitro diagnosis and/or prognosis of the tolerant state of a patient to be submitted to liver transplantation, which comprises assessing the level of systemic and/or intra-hepatic iron stores in a biological sample obtained from the patient under investigation, and comparing it either with the level of iron stores of a reference sample, or with a pre-determined threshold.

Biomarkers for Cardiodiabetes

The invention provides compositions and methods for determining cardiodiabetes status in a subject. The invention also provides compositions and methods for treating a subject experiencing cardiodiabetes.

PFKs as Modifiers of the IGFR Pathway and Methods of Use

Human PFK genes are identified as modulators of the IGFR pathway, and thus are therapeutic targets for disorders associated with defective IGFR function. Methods for identifying modulators of IGFR, comprising screening for agents that modulate the activity of PFK are provided. 1. A method of identifying a candidate IGFR pathway modulating agent , said method comprising the steps of:(a) providing an assay system comprising a PFK polypeptide or nucleic acid;(b) contacting the assay system with a test agent under conditions whereby, but for the presence of the test agent, the system provides a reference activity; and(c) detecting a test agent-biased activity of the assay system, wherein a difference between the test agent-biased activity and the reference activity identifies the test agent as a candidate IGFR pathway modulating agent.2. The method of wherein the assay system comprises cultured cells that express the PFK polypeptide.3. The method of wherein the cultured cells additionally have defective IGFR function.4. The method of wherein the assay system includes a screening assay comprising a PFK polypeptide claim 1 , and the candidate test agent is a small molecule modulator.5. The method of wherein the assay is a kinase assay.6. The method of wherein the assay system is selected from the group consisting of an apoptosis assay system claim 1 , a cell proliferation assay system claim 1 , an angiogenesis assay system claim 1 , and a hypoxic induction assay system.7. The method of wherein the assay system includes a binding assay comprising a PFK polypeptide and the candidate test agent is an antibody.8. The method of wherein the assay system includes an expression assay comprising a PFK nucleic acid and the candidate test agent is a nucleic acid modulator.9. The method of wherein the nucleic acid modulator is an antisense oligomer.10. The method of wherein the nucleic acid modulator is a PMO.11. The method of additionally comprising:(d) administering the candidate ...

PARATHYROID HORMONE VARIANTS AND ASSAYS RELATED TO DISEASE

The invention relates to PTH variants and uses thereof in the detection, diagnosis, and treatment of various disease states. 1. A method of detecting a parathyroid hormone(PTH)-related disease in a patient , comprising detecting the presence of one or more PTH variants in a biological sample from the patient , wherein the one or more PTH variants is selected from the group consisting of PTH 48-84 (SEQ ID NO: 1) , 28-84 (SEQ ID NO: 6) , 34-77 (SEQ ID NO: 7) , 37-77 (SEQ ID NO: 8) , 38-77 (SEQ ID NO:9), 34-79 (SEQ ID NO: 10), 38-76 (SEQ ID NO: 11), 38-79 (SEQ ID NO: 12), 44-84 (SEQ ID NO: 13), 38-80 (SEQ ID NO: 14), 41-84 (SEQ ID NO: 15), 30-78 (SEQ ID NO: 16), 27-75 (SEQ ID NO: 17), 26-77 (SEQ ID NO: 18), 19-70 (SEQ ID NO: 19), 9-75 (SEQ ID NO: 20), 4-82 (SEQ ID NO: 21), 44-77 (SEQ ID NO:30), and 23-84 (SEQ ID NO: 22), and wherein the presence of one or more variants in the biological sample is indicative of a PTH-related disease in the patient.2. The method of claim 1 , wherein the one or more PTH variants is selected from the group consisting of PTH (48-84)(SEQ ID NO: 1) claim 1 , (28-84)(SEQ ID NO: 6) claim 1 , (34-77)(SEQ ID NO: 7) claim 1 , (37-77)(SEQ ID NO: 8) claim 1 , (38-77)(SEQ ID NO: 9) claim 1 , (34-79) (SEQ ID NO: 10) claim 1 , (41-84) (SEQ ID NO: 15) claim 1 , and 44-77 (SEQ ID NO: 30).3. The method of claim 1 , wherein the detecting the presence of one or more PTH variants in the biological sample comprises:(a) capturing the one or more PTH variants using PTH affinity capture; and(b) identifying specific PTH variants using a polypeptide separation assay.4. The method of claim 1 , wherein the detecting the presence of the one or more PTH variants in the biological sample comprises identifying the one or more PTH variants using binding molecules specific for each individual PTH variant to be detected.5. The method of claim 1 , wherein the method further comprises determining the quantity of the one or more PTH variants.6. The method of claim 1 , wherein ...

Selective Androgen Receptor Modulators

This invention provides compounds of formula I, pharmaceutical compositions comprising a compound of formula I and a pharmaceutically acceptable excipient, methods of modulating the androgen receptor, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type 2 diabetes related disorders or diseases, anemia, depression, and renal disease) and processes for making compounds and intermediates useful in the preparation of same.

METHODS AND COMPOSITIONS FOR DIAGNOSTIC USE IN CANCER PATIENTS

Disclosed herein are methods and compositions useful for identifying therapies likely to confer optimal clinical benefit for patients with cancer. 1. A method of identifying a patient suffering from breast cancer who may benefit from anti-cancer therapy other than , or in addition to , anti-angiogenic therapy comprising an anti-VEGF antibody , the method comprising:(a) determining an expression level of placental growth factor (PlGF) in a sample obtained from the patient, wherein an increased expression level of PlGF in the sample obtained from the patient as compared to a reference sample identifies the patient as one who may benefit from anti-cancer therapy other than, or in addition to, anti-angiogenic therapy comprising an anti-VEGF antibody; and(b) informing the identified patient that they may benefit from anti-cancer therapy other than, or in addition to, anti-angiogenic therapy comprising an anti-VEGF antibody.2. A method of predicting responsiveness of a patient suffering from breast cancer to anti-angiogenic therapy comprising an anti-VEGF antibody , the method comprising:(a) determining an expression level of PlGF in a sample obtained from the patient, wherein an increased expression level of PlGF in the sample obtained from the patient as compared to a reference sample predicts that the patient is less likely to be respond favorably to anti-angiogenic therapy comprising an anti-VEGF antibody alone; and(b) informing the patient that they may benefit from anti-cancer therapy other than, or in addition to, anti-angiogenic therapy comprising an anti-VEGF antibody.3. A method of monitoring effectiveness of an anti-angiogenic therapy comprising an anti-VEGF antibody in a patient suffering from breast cancer , the method comprising:(a) determining an expression level of PlGF in a sample obtained from the patient, wherein increased expression level of PlGF in the sample obtained from the patient as compared to a reference sample indicates that the patient is ...

METHODS AND COMPOSITIONS FOR DIAGNOSTIC USE IN CANCER PATIENTS

Disclosed herein are methods and compositions useful for identifying therapies likely to confer optimal clinical benefit for patients with cancer. 1. A method of selecting a cancer treatment for a patient suffering from breast cancer , the method comprising:(a) determining that a sample obtained from the patient has an increased expression level of placental growth factor (PlGF) as compared to a reference sample; and(b) providing a recommendation that the cancer treatment selected for the patient be an anti-cancer therapy other than, or in addition to, anti-angiogenic therapy comprising an anti-VEGF antibody.2. A method of monitoring patient response to a cancer treatment for a patient suffering from breast cancer , the method comprising:(a) determining that a sample obtained from the patient has an increased expression level of PlGF as compared to a reference sample; and(b) providing a recommendation that the cancer treatment for the patient be an anti-cancer therapy other than, or in addition to, anti-angiogenic therapy comprising an anti-VEGF antibody.3. A method for treating cancer in a patient suffering from breast cancer , the method comprising:(a) determining that a sample obtained from the patient has an increased expression level of PlGF as compared to a reference sample; and(b) administering an effective amount of an anti-cancer therapy other than, or in addition to, anti-angiogenic therapy comprising an anti-VEGF antibody.43. The method of any one of - claims 1 , wherein the breast cancer is metastatic breast cancer.5. The method of claim 1 , wherein the sample obtained from the patient is selected from the group consisting of: whole blood claim 1 , plasma claim 1 , serum claim 1 , and combinations thereof.6. The method of claim 1 , wherein the sample is obtained from the patient prior to anti-angiogenic therapy comprising an anti-VEGF antibody.7. The method of claim 1 , wherein the sample is obtained from the patient after commencement of anti-angiogenic ...

ANTI-MULLERIAN HORMONE DETECTION IN WHOLE BLOOD

The present invention provides methods, kits, compositions, and devices for detecting Anti-Mullerian hormone (AMH) in whole blood samples. In certain embodiments, the methods, kits, compositions, and devices employ immunoassays that generate a colorimetric or fluorescent signal (e.g., using antibodies conjugated to gold nanoparticles or fluorescent particles) where the signal generated is proportional to the approximate concentration of AMH in a whole blood sample. In particular embodiments, the present invention provides quantitative or semi-quantitative lateral flow immunoassay devices and kits for detecting AMH at home (e.g., in order for women to estimate their ovarian age or diagnose polycystic ovarian syndrome). 1. A method of determining the approximate concentration of Anti-Mullerian hormone (AMH) in a whole blood sample comprising:a) contacting a whole blood sample from a subject with first antibodies specific for AMH under conditions such that a signal is generated that is proportional to the approximate concentration of AMH in said whole blood sample; andb) detecting the approximate level of said signal, thereby determining said approximate concentration of AMH in said whole blood sample.2. The method of claim 1 , wherein said first antibodies are labeled with first nanoparticles that produce a colorimetric or fluorescent signal when aggregated.3. The method of claim 1 , wherein said first nanoparticles comprise gold nanoparticles or fluorescent particles.4. The method of claim 1 , further comprising contacting said whole blood sample with a second antibodies specific for a non-AMH protein in whole blood.5. The method of claim 1 , wherein said second antibodies are labeled with first nanoparticles that produce a colorimetric or fluorescent signal when aggregated.6. The method of claim 1 , wherein said contacting is conducted on a membrane claim 1 , wherein said membrane comprises: at least one test capture region which comprises third antibodies specific ...

Diagnosis and treatment of brain tumors

The present invention relates to methods for the localisation, diagnosis, prognosis and/or prediction of therapeutic outcome of cancer, as well as methods for treating or preventing cancer. In particular, the present invention relates to methods for the localisation, diagnosis, prognosis and/or prediction of therapeutic outcome of brain tumors expressing calcitonin receptor, as well as the treatment and prevention of brain tumors by targeting calcitonin receptor expressing brain tumour cells.

BIOMARKERS FOR RESPONSE TO TYROSINE KINASE PATHWAY INHIBITORS IN CANCER

Copy number gains detected in tumors and associated with drug sensitivity and resistance in vivo and in vitro can be used as biomarkers to select, predict and monitor drug treatment outcomes in cancer patients treated with tyrosine kinase inhibitors. Methods to identify patients with NSCLC or other malignancies who are more likely to benefit from tyrosine kinase inhibitors such as VEGF or VEGFR inhibitors when used either as monotherapy or in combination with other therapies such as chemotherapy or EGFR inhibitors, and who are in the advanced stages of disease and/or who have undergone adjuvant therapy are also provided herein. 1. A method of treating a cancer patient comprising:(a) selecting a patient determined to have a cancer with an elevated KDR, PDGFR, or KIT level; and(b) treating the patient with a VEGF/VEGFR, PDGFR, or KIT pathway inhibitor.2. The method of claim 1 , wherein the elevated KDR claim 1 , PDGFR claim 1 , or KIT level is further defined as a gain in gene copy number claim 1 , increased mRNA expression claim 1 , or increased protein expression.3. The method of claim 1 , wherein the elevated KDR level is further defined as an increased mRNA or protein level of a KDR-regulated gene.4. The method of claim 3 , wherein the KDR-regulated gene is HIF-1α.5. The method of claim 1 , wherein the cancer patient has a NSCLC or glioblastoma.6. The method of claim 1 , wherein the cancer is metastatic.7. The method of claim 1 , wherein the patient is treated with a VEGF/VEGFR pathway inhibitor.8. The method of claim 1 , wherein the patient is treated with a combination of two or more VEGF/VEGFR claim 1 , PDGFR claim 1 , or KIT pathway inhibitors.9. The method of claim 1 , further comprising treating the patient with a second anti-cancer therapy.10. The method of claim 9 , wherein the second anti-cancer therapy is not a platinum-based chemotherapeutic agent or an EGFR inhibitor.11. The method of claim 1 , wherein the patient has undergone surgery or radiotherapy ...

Myostatin binding agents

The present invention provides binding agents comprising peptides capable of binding myostatin and inhibiting its activity. In one embodiment the binding agent comprises at least one myostatin-binding peptide attached directly or indirectly to at least one vehicle such as a polymer or an Fc domain. The binding agents of the present invention produced increased lean muscle mass when administered to animals and decreased fat to muscle ratios. Therapeutic compositions containing the binding agents of the present invention are useful for treating muscle-wasting disorders and metabolic disorders including diabetes and obesity.

CHIMERIC FGF21 PROTEINS WITH ENHANCED BINDING AFFINITY FOR BETA-KLOTHO FOR THE TREATMENT OF TYPE II DIABETES, OBESITY, AND RELATED METABOLIC DISORDERS

The present invention relates to chimeric proteins that include an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion of fibroblast growth factor 21 (“FGF21”) and the C-terminus includes a C-terminal portion of fibroblast growth factor 19 (“FGF19”). The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, as well as methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, methods of treating a subject in need of increased FGF21-βKlotho-FGF receptor complex formation, methods of causing increased FGF21 receptor agonist-βKlotho-FGF receptor complex formation, and methods of screening for compounds with enhanced binding affinity for the βKlotho-FGF receptor complex involving the use of chimeric proteins of the present invention. 1. An isolated chimeric protein comprising:an N-terminus coupled to a C-terminus, wherein the N-terminus comprises an N-terminal portion of fibroblast growth factor 21 (“FGF21”) having a core domain and the C-terminus comprises a C-terminal portion of fibroblast growth factor 19 (“FGF19”), wherein either (i) the N-terminal portion of FGF21 comprises at least one amino acid residue substitution to increase stability of the FGF21 core domain compared to the wild type FGF21; (ii) the C-terminal portion of FGF19 begins at a residue corresponding to any one of residues 169 to 204 of SEQ ID NO: 1 and comprises amino acid residues TGLEAV(R/N)SPSFEK (SEQ ID NO: 49); or (iii) both (i) and (ii).2. The chimeric protein according to claim 1 , wherein the C-terminal portion of FGF19 of (ii) does not include any of amino acid residues 1 to 168 of SEQ ID NO: 1.3. The chimeric protein according to claim 1 , wherein the C-terminal portion of FGF19 begins at a residue corresponding to any one of residues 169 claim 1 , 197 claim 1 , or 204 of SEQ ID NO: 1.4. The chimeric protein according to claim 1 , wherein the C-terminal ...

COMPOSITIONS AND METHODS FOR PLASMA PEPTIDE ANALYSIS

Provided herein are composition, methods and kits for peptide analysis in blood by mass spectroscopy. Isotopic peptides are also provided that facilitate quantification of peptide levels, e.g., hepcidin levels, in blood by mass spectroscopy. Further disclosed are methods and compositions for quantifying blood hepcidin levels and evaluating iron-associated disorders. 1. A method for detecting a peptide in a subject , the method comprising: (i.) combining the blood sample with a denaturation buffer comprising a volatile organic acid, wherein the concentration of the volatile organic acid in the combination is between 1% and 50%; and', '(ii.) separating a soluble fraction from an insoluble fraction of the combination; and, '(a) processing a blood sample obtained from a subject by(b) performing MALDI-TOF mass spectrometry on the soluble fraction to detect the peptide.2. The method of claim 1 , wherein the concentration of the volatile organic acid in the combination is 1%.3. The method of claim 1 , wherein the concentration of the volatile organic acid in the combination is 4%.4. (canceled)5. The method of claim 1 , wherein the volatile organic acid is trifluoroacetic acid (TFA).6. The method of claim 1 , wherein the denaturation buffer further comprises an organic solvent.710-. (canceled)11. The method of claim 1 , wherein processing the test sample further comprises adding a pre-treatment solution comprising a surfactant to the blood sample prior to step (i.).1217-. (canceled)18. The method of claim 1 , wherein the peptide has a molecular weight in a range of 0.3 kDa to 10 kDa.19. The method of claim 1 , wherein the peptide is hepcidin.2026-. (canceled)27. A method for detecting a peptide in a plurality of subjects claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'implementing the method of in a multiplex format to detect the peptide in blood samples obtained from a plurality of subjects.'}28. A method for monitoring peptide levels in ...

PREDICTING RISK OF MAJOR ADVERSE CARDIAC EVENTS

Measurement of circulating ST2 and natriuretic peptide (e.g., NT-proBNP) concentrations is useful for the prognostic evaluation of subjects, in particular for the prediction of adverse clinical outcomes, e.g., mortality, transplantation, and heart failure. 1. A method for evaluating the risk of a major adverse cardiac event (MACE) for a subject within one year , the method comprising:performing an assay to determine a first level of soluble ST2 in a biological sample obtained from a subject at a first time point (ST2 T0);performing an assay to determine a second level of soluble ST2 in a biological sample obtained from the subject at a second time point (ST2 T1);performing an assay to determine a level of a natriuretic peptide (NP) in a biological sample obtained from the subject at the second time point (NP T1);determining a MACE risk score (MACERS) for a subject based upon, at least in part, the ratio of ST2 T1 to ST2 T0, in combination with a weighted logarithm of NP T1;comparing the MACERS determined for the subject to a reference MACERS; andidentifying a subject having an elevated MACERS as compared to the reference MACERS as having an increased risk of a MACE within one year or identifying a subject having a decreased MACERS as compared to the reference MACERS as not having an increased risk of a MACE within one year.2. (canceled)3. The method of claim 1 , wherein the logarithm of NP T1 includes a natural logarithm.4. The method of claim 1 , wherein the MACERS is determined using the following formula:{'br': None, 'MACERS=(ST2 T1/ST2 T0)+α ln(NP T1),'}wherein the coefficient α is a weighting factor for the variable it acts on.5. The method of claim 4 , wherein the coefficient α is about 0.33.6. The method of claim 1 , wherein the NP is N-terminal pro-brain natriuretic peptide (NT-proBNP).7. The method of claim 1 , wherein the first time point is within 1-7 days of the onset of symptoms in the subject.8. The method of claim 1 , wherein the second time point is ...

FISH SEXUAL CHARACTERISTIC DETERMINATION USING PEPTIDE HORMONES

Fish sexual characteristics are determined by measuring the concentration in fish serum, plasma or whole blood of one or more peptide hormones of the transforming growth factor-beta superfamily (TGF-β superfamily). The disclosed method and an accompanying field test kit may be used in sturgeon aquaculture to cull out young male fish so that increased time and resources may be devoted to the further rearing of female fish for caviar production. The method and test kit may also be used for wild fish life history studies. 1. A method for fish sexual characteristic determination , which method comprises collecting blood from fish; optionally separating serum or plasma from such blood; measuring the concentration in such serum , plasma or blood of one or more peptide hormones of the transforming growth factor-beta superfamily (TGF-β superfamily); and determining a desired fish sexual characteristic based on such peptide hormone concentration.2. A method according to claim 1 , wherein the fish are from the family Acipenseridae.3. A method according to claim 1 , wherein the fish are sturgeon.4. A method according to claim 1 , wherein the fish are aquaculture-reared and are three years of age or less.56-. (canceled)7. A method according to claim 1 , wherein the fish are 1.5 years of age or less.8. A method according to claim 1 , wherein the peptide hormone comprises Inhibin A.9. A method according to claim 1 , wherein the peptide hormone comprises Inhibin B or AMH.10. A method according to claim 1 , wherein the desired fish sexual characteristic is determined based on the peptide hormone concentrations of more than one peptide hormone of the TGF-β superfamily.11. A method according to claim 1 , comprising measuring peptide hormone concentration in whole blood samples.12. A method according to claim 1 , comprising measuring peptide hormone concentration in serum or plasma samples.13. A method according to claim 1 , comprising determining fish gender.14. A method according to ...

Method for screening compounds for treating sepsis targeting nod2 signalling pathway and composition for treating sepsis comprising nod2 signalling pathway inhibitors

Methods for screening compounds for treating sepsis are disclosed. The present methods and compositions are targeting NOD2 mediated signaling pathway and the agents identified by the present methods are qualified as drug candidates for clinical development. Further Methods and composition for treating sepsis are disclosed.

Procalcitonin gene expression as a precise biomarker of aging process

The invention relates to a method for diagnosis and/or complications and/or risk assessment of aging, in particular of aging process, wherein a determination of the marker procalcitonin (PCT: SEQ ID No. 1) or a partial peptide or fragment thereof or if contained in a marker combination (Panel, Cluster) is carried out on a patient within normal value ranges of leucocytes under investigation. The invention further relates to invent new drugs, a diagnostic device and a kit for carrying out said method.

Targeting mtor substrates in treating proliferative diseases

Provided are over 300 mTOR kinase targets identified by a comprehensive phosphoproteomics assay. Methods of targeting mTOR kinase targets, methods to determine the level of mTOR activity by measuring the level of phosphorylation of an mTOR targeted phosphorylation site, methods for distinguishing different classes of mTOR activity in a cell based on phosphoproteomic analysis of mTOR-targeted proteins are also provided. Also provided is the classification of a hyperproliferative disease based on phosphoproteomic analysis of mTOR-targeted proteins, as well as the personalization of therapeutic methods for the treatment of hyperproliferative disease based on phosphoproteomics. Also provided are therapeutic methods including administering to a subject an mTOR inhibitor, an mTOR inhibitor and an additional kinase inhibitor, or a dual inhibitor of mTOR and an additional kinase based on the phosphorylation levels of mTOR targets determined in the subject. Some aspects of this invention relate to the discovery that GrblO is an mTOR-targeted tumor suppressor gene.

Signature for Predicting Clinical Outcome in Human HER2+ Breast Cancer

A method of predicting outcome in a subject with for example Her2+ (ERα) breast cancer comprising: 1. A method of predicting outcome and/or anti-Her2 treatment response and/or diagnosing a high risk HER2+ ERα negative breast cancer in a subject afflicted with breast cancer comprising:a. determining HTICs expression signature comprising determining an expression level of 2 or more HTICS biomarkers selected from Aurkb, Ccna2, Scrn1, Npy, Atp7b, Chaf1b, Ccnb1 Cldn8, Nrp1, Ccr2, C1qb, Cd74, Vcam1, Cd180, Itgb2, Cd72 and St8sia4 in a test sample from the subject; andb. comparing the expression level of the 2 or more biomarkers with a control;c. identifying the subject as having an increased likelihood of poor outcome or a good outcome, and/or predicting a response or lack of response to an anti-Her2 treatment and/or diagnosing the subject with high risk HER2+ ERα negative breast cancer or low risk Her2+ ERα negative breast cancer according to a difference or a similarity in the expression level of the 2 or more biomarkers between the test sample and the control.2. The method of claim 1 , whereina. an increase in the expression level of 2 or more HTICS markers selected from Aurkb, Ccna2, Scrn1, Npy, Atp7b, Chaf1b, Ccnb1 and/or Cldn8 and/or a decrease in the expression level of 2 or more HTICS markers selected from Nrp1, Ccr2, C1qb, Cd74, Vcam1, Cd180, Itgb2, Cd72 and/or St8sia4 identifies a subject with poor outcome and/or response to anti-Her2 treatment and/or diagnosing the subject with high risk HER2+ERα negative breast cancer, orb. a decrease in the expression level of 2 or more HTICS markers selected from Aurkb, Ccna2, Scrn1, Npy, Atp7b, Chaf1b, Ccnb1 and/or Cldn8 and/or an increase in the expression level of 2 or more HTICS markers selected from Nrp1, Ccr2, C1qb, Cd74, Vcam1, Cd180, Itgb2, Cd72 and/or St8sia4 identifies a subject with a good outcome and/or lack of response to an anti-Her2 treatment and/or or low risk Her2+ ERα negative breast cancer.3. The method of ...

Methods and Compositions for Highly Sensitive Detection of Molecules

The present invention discloses methods for the detection and monitoring of a condition in a subject using highly sensitive detection of molecules. The invention provides a method for detecting or monitoring a condition in a subject, comprising detecting a first marker in a first sample from the subject and detecting a second marker, wherein the first marker comprises a biomarker, e.g., Cardiac Troponin-I (cTnI) or Vascular Endothelial Growth Factor (VEGF), and wherein the limit of detection of the first marker is less than about 10 pg/ml. The second marker can be a biomarker, physiological marker, a molecular marker or a genetic marker. 1. A method for detecting or monitoring a condition in a subject, comprising detecting a first marker in a first sample from the subject and detecting a second marker, wherein the first marker comprises Cardiac Troponin-I (cTnI) or Vascular Endothelial Growth Factor (VEGF), and wherein the limit of detection of the first marker is less than about 20 pg/ml. This application is a continuation of U.S. patent application Ser. No. 12/398,175 filed Mar. 4, 2009, which claims the benefit of priority under 35 U.S.C. §119 to U.S. Provisional Application No. 61/033,897, filed Mar. 5, 2008 and entitled “Methods and Compositions for Highly Sensitive Detection of Molecules” and U.S. Provisional Application No. 61/038,714, filed Mar. 21, 2008 and entitled “Ultrasensitive Assays and Methods of Use for the Detection of VEGF”; both of which applications are incorporated herein by reference in their entirety.Advances in biomedical research, medical diagnosis, prognosis, monitoring and treatment selection, bioterrorism detection, and other fields involving the analysis of multiple samples of low volume and concentration of analytes have led to development of sample analysis systems capable of sensitively detecting particles in a sample at ever-decreasing concentrations. U.S. Pat. Nos. 4,793,705 and 5,209,834 describe previous systems in which ...

Compositions and Methods for the Diagnosis and Treatment of Primary Insulin-Like Growth Factor Deficiency (PIGFD) and Idiopathic Short Stature (ISS)

Compositions and methods for identifying patients at increased risk for PIGFD and ISS are disclosed. 1. A method for identifying a subject with an increased risk of primary insulin-like growth factor deficiency , comprisinga) obtaining a sample from said patient and determining whether GRP94 is altered relative to the wild type sequence and exhibits altered GRP94 function, wherein altered GRP94 is correlated with reduced insulin-like growth factor secretion, thereby conferring an increased risk of PIGD.2. The method of claim 1 , wherein said alteration is selected from the alterations shown in Table 1 or Table 2 and excludes N636H.3. The method of claim 1 , wherein said alteration is K513N mutation.4. A method for identifying a subject with an increased risk of idiopathic short stature claim 1 , comprisinga) obtaining a sample from said patient and determining whether GRP94 is altered relative to the wild type sequence, wherein altered GRP94 is correlated with reduced insulin-like growth factor secretion, thereby conferring an increased risk of idiopathic short stature.5. The method of claim 4 , wherein said alteration is selected from the alterations shown in Table 1 and excludes N636H.6. The method of claim 4 , wherein said alteration is K513N mutation.7. A method for identifying agents which modulate GRP94 regulation of IGF secretion comprising claim 4 ,a) providing cells expressing a single nucleotide polymorphism selected from the group consisting of those set forth in Table 1 or Table 2;b) providing cells which express the cognate sequences which lack the polymorphisms of step a);c) contacting the cells of steps a) and b) with a test agent andd) analyzing whether said agent alters an IGF secretion in cells contacted in step a) relative to those of step b), thereby identifying agents which modulate GRP94 regulation of IGF secretion, with the proviso that GRP94 variations which do not alter GRP94 function are excluded from said method.8. The method of claim 7 , ...

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 ...

Single Molecule Assays

The present invention provides single molecule analyses of species of use in analytical, diagnostic or prognostic assays. In exemplary embodiments, the assays utilize samples prepared by novel methods, affording assays of unexpected sensitivity and robustness. The method is described in a non-limiting manner by reference to cytokine assays. 140-. (canceled)41. A method of performing an assay detecting a single molecule of a detectable antibody correlating to a single molecule of an analyte to which said detectable antibody specifically binds , said method comprising: (i) forming a hapten-antibody complex between said analyte and a capture antibody specifically binding said analyte, wherein said capture antibody comprises biotin and is immobilized on a magnetic particle comprising streptavidin through interaction between said biotin and said streptavidin; and', '(ii) following (i), contacting said complex with said detectable antibody which specifically binds to said analyte thereby forming an immobilized complex of said detectable antibody;, '(a) in a first vessel,'}(b) transferring said immobilized complex to a second vessel free of said detectable antibody;(c) eluting said detectable antibody from said immobilized complex; and(d) detecting said single molecule of said detectable antibody.42. The method of wherein claim 41 , prior to (a)(i) claim 41 , said single molecule of said analyte is removed from a middle layer of a three-layered plasma sample comprising an upper lipid layer claim 41 , said middle layer comprising said single molecule of said analyte claim 41 , and a lower fibrin clot layer; said single molecule of said analyte removed in an aliquot from said middle layer of said sample.43. The method of wherein said biotin is bound to said capture antibody at a site which is a member selected from an amine moiety and a hinge saccharyl moiety.44. A method of performing an assay of a sample detecting a single molecule of a detectable species correlating to a ...

Screening Method for Candidate Agonist Compounds for Adiponectin Receptor I

A method of screening for candidate compounds for adiponectin receptor 1 agonist including a step of bringing test compounds into contact with cells to determine whether they cause intracellular influx of extracellular calcium ions and selecting, from the test compounds, compounds causing the intracellular influx of extracellular calcium ions as the candidate compounds for adiponectin receptor 1 agonist.

Method for Assaying Fibroblast Growth Factor-23 and Assay Reagent

A method for measuring fibroblast growth factor-23 (FGF-23) in a sample, which comprise the following steps: 1. A method for measuring fibroblast growth factor-23 FGF-23) in a sample , comprising:(1) reacting, in an aqueous medium, FGF-23 in a sample with a magnetic particle, a first antibody or a fragment thereof which binds to FGF-23, and a second antibody or a fragment thereof which binds to FGF-23, to form on the magnetic particle an immunocomplex comprising the first antibody or a fragment thereof which binds to FGF-23, FGF-23, and the second antibody or a fragment thereof which binds to FGF-23;(2) collecting the magnetic particle in the reaction mixture after step (1) by magnetic force, and separating the magnetic particle collected by magnetic force from the other components; and(3) measuring the immunocomplex on the magnetic particle separated in step (2).2. The method of claim 1 , wherein the second antibody is a labeled antibody.3. The method of claim 2 , wherein the labeled antibody is an alkaline phosphatase-labeled antibody.4. The method of claim 1 , wherein measurement of the immunocomplex on the magnetic particle in step (3) is carried out by measurement of chemiluminescence.5. The method of claim 1 , wherein the sample is serum or plasma.6. A reagent for measuring FGF-23 in a sample claim 1 , which comprises a magnetic particle claim 1 , a first antibody or a fragment thereof which binds to FGF-23 claim 1 , and a second antibody or a fragment thereof which binds to FGF-23.7. The reagent of claim 6 , wherein the second antibody is a labeled antibody.8. The reagent of claim 7 , wherein the labeled antibody is an alkaline phosphatase-labeled antibody.9. The reagent of claim 6 , further comprising a reagent for measuring chemiluminescence.10. The reagent of claim 6 , wherein the sample is serum or plasma. The present invention relates to a method for measuring fibroblast growth factor-23 (hereinafter indicated as FGF-23) in a sample, and a reagent for ...

PARATHYROID HORMONE RECEPTOR ACTIVATION AND STEM AND PROGENITOR CELL EXPANSION

The invention relates to methods for manipulating hematopoietic stem or progenitor cells, mesenchymal stem cells, epithelial stem cells, neural stem cells and related products through activation of the PTH/PTHrP receptor in neighboring cells. 158-. (canceled)59. A method for preparing a population of cells for enhancing the growth or maintenance of stem cells selected from the group consisting of mesenchymal stem cells , epithelial stem cells and neural stem cells , the method comprising:contacting a cell expressing a PTH/PTHrP receptor with an agent that activates the PTH/PTHrP receptor in an amount effective to support the growth or maintenance of mesenchymal stem cells, epithelial stem cells or neural stem cells.60. The method of claim 59 , wherein the cell expressing a PTH/PTHrP receptor is present in the immediate vicinity of a mesenchymal stem cell claim 59 , an epithelial stem cell or a neural stem cell.61. The method of claim 59 , wherein the cell expressing a PTH/PTHrP receptor is chosen from a bone claim 59 , breast claim 59 , skin claim 59 , epithelial claim 59 , lung claim 59 , urogenital and gastrointestinal cell.62. The method of claim 59 , wherein said contacting the cell expressing a PTH/PTHrP receptor with an agent that activates the PTH/PTHrP receptor occurs in vitro or in vivo.63. (canceled)64. The method of claim 59 , wherein the agent that activates the PTH/PTHrP receptor is PTH claim 59 , a PTH analogue claim 59 , or a PTH/PTHrP receptor agonist.65. The method of claim 59 , wherein the growth and maintenance of mesenchymal stem cells claim 59 , epithelial stem cells or neural stem cells occurs in vitro or in vivo.6676-. (canceled)77. The method of claim 60 , wherein the cell expressing a PTH/PTHrP receptor is present in the immediate vicinity of a neural stem cell and is selected from the group consisting of a astrocyte claim 60 , oligodendrocyte claim 60 , glial cell claim 60 , GABAergic neuron dopaminergic neuron and a cell of the cerebellum ...

METHODS OF ADMINISTERING AN EGFR INHIBITOR

Disclosed are methods of treating a patient having cancer with an EGFR inhibitor requiring an active step of avoiding or modifying the co-administration of such drugs with P-gp modulators. This invention also relates to a medicament for treating a patient having cancer, comprising an EGFR inhibitor as the active product ingredient, customized for avoiding co-administration with P-gp inducers and/or inhibitors by an instruction added to the medicament or the package containing said medicament. 1. A method of treatment with an EGRF inhibitor , the method comprising(a) identifying a patient in need of treatment with an EGRF inhibitor;(b) determining that the patient is receiving therapy with a P-gp modulator;(c) causing the patient's therapy with the P-gp modulator to cease for the duration of treatment with the EGRF inhibitor; and(d) administering the EGRF inhibitor to the patient.2. A method of treatment with an EGRF inhibitor , the method comprising(a) identifying a patient in need of treatment with an EGRF inhibitor;(b) determining that the patient is receiving therapy with a P-gp modulator;(c) modifying the administering of said P-gp modulator before starting of administering the EGFR inhibitor; and(d) administering the EGRF inhibitor to the patient.3. The method of claim 1 , wherein the P-gp modulator is a P-gp inhibitor.4. The method of claim 1 , wherein the P-gp modulator is a P-gp inducer.5. The method of claim 1 , wherein the EGFR inhibitor is a reversible EGFR inhibitor.6. The method of wherein the EGFR inhibitor is an irreversible EGFR inhibitor.7. The method of wherein the EGFR inhibitor is BIBW2992 or a pharmaceutically acceptable salt thereof.8. A method of treatment with BIBW 2992 claim 2 , the method comprising(a) administering BIBW 2992 to a patient who is receiving therapy with a P-gp modulator;(b) detecting symptoms of BIBW 2992 adverse events in the patient; and(c) reducing or ceasing therapy with the P-gp modulator, while continuing therapy with ...

NGAL FOR DIAGNOSIS OF RENAL CONDITIONS

Use of serum neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker, alone or in conjunction with creatinine to aid in the diagnosis of renal conditions such as acute tubular necrosis and acute renal failure, and a method and a kit for assigning a diagnosis of acute tubular necrosis or acute renal failure to a subject based on the correlation between the levels of NGAL and optionally creatinine in a sample obtained from a subject when compared to a sample obtained from a normal subject not experiencing acute tubular necrosis or acute renal failure. 1. A method of assigning a diagnosis of acute tubular necrosis to a subject , comprising;a) measuring a level of NGAL in a sample obtained from said subject,b) comparing the level of NGAL in the sample from said subject with the level of NGAL in a sample from a normal subject, and; assigning a diagnosis of acute tubular necrosis when the level of NGAL in a sample obtained from said subject is greater than said normal subject.2. The method of wherein the level of NGAL in said subject is at least about 7 fold greater than said normal subject.3. The method of wherein the level of NGAL in a sample from a normal subject is about 20 ng/mL.4. A method of diagnosing whether a subject is experiencing acute renal failure or chronic renal failure claim 1 , comprising;a) measuring the level of NGAL in a sample obtained from the subject;b) measuring the level of creatinine in a sample obtained from the subject;c) correlating the level of NGAL with the level of creatinine, and assigning a diagnosis of acute renal failure or chronic renal failure based on said correlation.5. The method of wherein when there is a high correlation between the measured level of NGAL and creatinine claim 4 , assigning a diagnosis of acute renal failure to said subject.6. The method of wherein when there is no correlation between the measured level of NGAL and creatinine claim 4 , assigning a diagnosis of chronic renal failure to said subject.7. ...

METHOD FOR DETECTION OF BASIC PEPTIDE AND REAGENT FOR DETECTION OF BASIC PEPTIDE

The present invention provides a method for detection of a basic peptide by mixing a sample suspected to contain the basic peptide and a reagent containing denatured albumin and detecting turbidness due to a complex of the basic peptide and denatured albumin. 110-. (canceled)11. A method for diagnosing a disease comprising:obtaining a sample from a biological specimen suspected of having a disease, wherein said disease is identifiable by detecting a basic peptide;mixing the sample and a reagent comprising a heat-denatured albumin;forming a complex comprising the basic peptide and the heat-denatured albumin;obtaining optical information by irradiating the mixed sample and reagent with light;detecting the basic peptide using said optical information.12. The method of claim 11 , wherein the basic peptide is one or more of a adrenocorticotrophic hormone (ACTH) claim 11 , a brain natriuretic peptide (BNP) claim 11 , a atrial natriuretic peptide (ANP) claim 11 , a fibrinogen α claim 11 , a ghrelin claim 11 , a inter-α-trypsin inhibitor heavy chain subunit 4 (ITIH4) claim 11 , a prothrombin claim 11 , kininogen claim 11 , a proto-oncogene protein L-myc-1 claim 11 , a transcription factor SOX-3 or a α2-HS-glycoprotein.13. The method according to claim 11 , wherein the basic peptide is a ACTH claim 11 , and the disease is adrenal tumor claim 11 , hyperadrenocorticism claim 11 , panhypopituitarism or depression.14. The method according to claim 11 , wherein the basic peptide is a BNP and the disease is heart failure.15. The method according to claim 11 , wherein the basic peptide is a ANP and the disease is heart failure claim 11 , renal failure or primary aldosteronism.16. The method according to claim 11 , wherein the optical information is an optical density.17. The method according to claim 16 , wherein the optical density is obtained from one or more of a refractive index claim 16 , a reflected light intensity claim 16 , a diffracted light intensity claim 16 , an ...

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.

TRUNCATED HER2 SRM/MRM ASSAY

This disclosure provides ten (10) specific peptides, and particular peptide characteristics, from the cell membrane-bound Her2 protein and a diagnostic assay useful for determining the presence and amount of full length and truncated versions of the full-length Her2 protein in cells derived from formalin fixed paraffin embedded tissue. 1. A method for detecting the presence and measuring the level of the Her2 protein and the degree of truncated versions of the Her2 protein in a protein digest prepared from a biological sample , comprising detecting specific peptides from the Her2 protein in a protein digest prepared from said biological sample using mass spectrometry; and calculating the level of these 2 versions of the Her2 protein in said sample wherein said level is an absolute level of both versions of the Her2 protein.2. The method of claim 1 , further comprising the step of fractionating said protein digest prior to detecting said peptides.3. The method of claim 2 , wherein said fractionating step is selected from the group consisting of gel electrophoresis claim 2 , liquid chromatography claim 2 , capillary electrophoresis claim 2 , nano-reversed phase liquid chromatography claim 2 , high performance liquid chromatography claim 2 , or reverse phase high performance liquid chromatography.4. The method of claim 1 , wherein said protein digest of said biological sample is prepared by the Liquid Tissue protocol.5. The method of claim 1 , wherein said protein digest comprises a protease digest.6. The method of claim 5 , wherein said protein digest comprises a trypsin digest.7. The method of claim 1 , wherein mass spectrometry comprises tandem mass spectrometry claim 1 , ion trap mass spectrometry claim 1 , triple quadrupole mass spectrometry claim 1 , MALDI-TOF mass spectrometry claim 1 , MALDI mass spectrometry claim 1 , and/or time of flight mass spectrometry.8. The method of claim 7 , wherein the mode of mass spectrometry used is Selected Reaction Monitoring ( ...

METHOD FOR CONTROL OF INVASION AND USE OF ADIPONECTIN

Physical condition under stress can be controlled by using adiponectin in blood as a stress marker and measuring a level thereof. Moreover, endotoxin activity can be inhibited by using adiponectin. 124-. (canceled)25. A method for control of invasion , wherein the control of invasion is control of post-operative infection , comprising: (a) measuring adiponectin level in the blood before and after operation to calculate a ratio of the adiponectin level after operation to the adiponectin level before operation and (b) predicting post-operative infection from the ratio.26. The method for prediction of post-operative infection according to claim 25 , wherein the operation is a transplantation treatment.27. The method for prediction of post-operative infection according to claim 25 , wherein the infection is involved in sepsis claim 25 , hypercytokinemia claim 25 , or multiple organ failure.28. A method for prediction of post-operative infection in a patient claim 25 , comprising: measuring adiponectin level in blood before and after a patient's operation and predicting the patient is more susceptible to infection if the adiponectin level in blood after the operation is decreased as compared to the adiponectin level in blood before the operation.29. The method for prediction of post-operative infection according to claim 28 , wherein the patient is predicted to be more susceptible to infection if the adiponectin level in blood after the operation is at least 10% less than the adiponectin level in blood before the operation.30. The method for prediction of post-operative infection according to claim 28 , wherein the patient is predicted to be more susceptible to infection if the adiponectin level in blood after the operation is at least 20% less than the adiponectin level in blood before the operation.31. The method for prediction of post-operative infection according to claim 28 , wherein the patient is predicted to be more susceptible to infection if the adiponectin ...

ASSESSMENT OF IGF-1 LEVELS IN HIV-INFECTED SUBJECTS AND USES THEREOF

Improved methods for determining normal IGF-1 levels in HIV infected subjects, based on a determination of the log of IGF-1 values obtained in blood-derived samples from a population of HIV-infected subjects, are disclosed. Also disclosed are methods of determining whether a given HIV-infected subject exhibits a normal IGF-1 level, based on a comparison of either the IGF-1 value or the log of the IGF-1 value obtained from a blood-derived sample of the subject with a normative IGF-1 range determined using the exponentiation of the log of IGF-1 values or the log of IGF-values obtained in blood-derived samples from a population of age- and gender-matched HIV-infected subjects. Such methods are useful for example to monitor GH stimulation therapy in HIV-infected subjects. 1. (canceled)3. (canceled)4. The method of claim 2 , wherein said log is log.5. The method of claim 2 , wherein z is 1.645 claim 2 , 1.96 claim 2 , 2.0 claim 2 , 2.5 claim 2 , 2.576 or 3.0.610-. (canceled)11. The method of claim 2 , wherein said IGF-1 level is a serum IGF-1 level and said blood-derived sample is a serum sample.12. (canceled)14. (canceled)16. (canceled)17. The method of claim 15 , wherein A is e.18. The method of claim 13 , wherein z is 1.645 claim 13 , 1.96 claim 13 , 2.0 claim 13 , 2.5 claim 13 , 2.576 or 3.0.1923-. (canceled)24. The method of claim 13 , wherein said IGF-1 level is serum IGF-1 level and said blood-derived sample is a serum sample.25. The method of claim 2 , wherein said HIV-infected subject suffers from lipodystrophy.26. The method of claim 2 , wherein said HIV-infected subject is undergoing a growth hormone stimulation therapy.27. A method for determining a normative range for the monitoring of insulin-like growth factor 1 (IGF-1) levels in HIV-infected subjects claim 2 , said method comprising:(a) obtaining IGF-1 values from blood-derived samples from a population of HIV-infected subjects; {'br': None, 'i': A', 'Z, 'normative range=(μ±(α·σ))'}, '(b) calculating said ...

Vegf-a121 assay

The invention provides a method for determining the level of VEGF-A 121 isoform in a sample by selectively removing the VEGF-A 165 isoform from the sample using a neuropilin-1 pull-down procedure, then determining the total amount of VEGF-A remaining afterward. The invention provides methods of treating a patient suffering from a disease which may benefit from the administration of a VEGF antagonist by determining the level of VEGF-A 121 in the patient's circulation. Methods of diagnosis, prognosis, monitoring, and patient stratification are also provided.

Methods of Diagnosing and Treating an Inflammatory Response

The present invention relates to the discovery that VEGF, PlGF, and sFlt-1 levels are increased in inflammatory response such as in sepsis, severe sepsis, or septic shock. Additionally, the invention provides methods of identifying treatments as well as providing treatments for such an inflammatory response, which include decreasing VEGF or PlGF levels, or increasing sFlt-1 or PlGF levels. 1. A method of diagnosing an inflammatory response in a test subject , said method comprising analyzing the level of sFlt-1 expression in a sample isolated from said test subject , wherein an increased level of sFlt-1 expression in said sample relative to the level found in an unaffected subject indicates that said test subject has said inflammatory response.2. The method of claim 1 , wherein said method further comprises analyzing the level of at least one of VEGF claim 1 , PlGF claim 1 , TNF-a claim 1 , IL-6 claim 1 , D-dimer claim 1 , E-selectin claim 1 , P-selectin claim 1 , ICAM-1 claim 1 , VCAM-1 claim 1 , Cox-2 claim 1 , or PAI-1.3. The method of claim 1 , wherein said subject is a human.4. The method of claim 1 , wherein said inflammatory response to be diagnosed is sepsis claim 1 , severe sepsis or septic shock.5. A method of diagnosing an inflammatory response in a test subject claim 1 , said method comprising analyzing the level of sFlt-1 activity in a sample isolated from said test subject claim 1 , wherein an increased level of sFlt-1 activity in said sample relative to the level found in an unaffected subject indicates that said test subject has said inflammatory response.6. The method of claim 5 , wherein said method further comprises analyzing the level of at least one of VEGF claim 5 , PlGF claim 5 , TNF-a claim 5 , IL-6 claim 5 , D-dimer claim 5 , E-selectin claim 5 , P-selectin claim 5 , ICAM-1 claim 5 , VCAM-1 claim 5 , Cox-2 claim 5 , or PAI-1.7. The method of claim 5 , wherein said subject is a human.8. The method of claim 5 , wherein said inflammatory ...

Breast cancer diagnostics

The present invention relates to methods and means for detecting cancer or of predicting a patient developing cancer or of determining the rate of progression of cancer in a patient suffering from cancer, comprising determining RANKL activity and/or the amount of OPG in a sample of said patient.

HOMOGENOUS AND FULLY GLYCOSYLATED HUMAN ERYTHROPOIETIN

The present invention provides homogenous, fully-glycosylated, full length erythropoietin and the methods of producing the same. 2. (canceled)3. The composition of claim 1 , wherein Argis deleted.4. The composition of claim 1 , wherein the primary amino acid sequence of the erythropoietin SEQ ID NO: 1 has 1-10 amino acid substitutions claim 1 , addition claim 1 , and/or deletions claim 1 , wherein Asn claim 1 , Asn claim 1 , Asnand Serare not mutated.5. The composition of claim 1 , wherein the erythropoietin has one or more disulfide bond formed between cysteine residues.6. The composition of claim 5 , wherein the erythropoietin has a disulfide bond formed between Cysand Cys.7. The composition of claim 1 , wherein the erythropoietin is folded.1112-. (canceled)16. A fragment of erythropoietin selected from EPO (1-28) claim 1 , EPO (1-29) claim 1 , EPO (29-78) claim 1 , EPO (30-78) claim 1 , EPO (79-124) claim 1 , EPO (125-166) claim 1 , EPO (128-166) claim 1 , EPO (79-166) and EPO (29-166) claim 1 , wherein the fragment is optionally protected and optionally homogeneously glycosylated.18. A fragment of claim 16 , having 1-10 amino acid substitutions claim 16 , additions claim 16 , and/or deletions.19. A method of preparing a composition of claim 1 , comprising the step of ligating one or more EPO fragments.20. The method of claim 1 , wherein the EPO fragments are selected from those of .2126-. (canceled)27. The use of one or more of pseudoproline dipeptides at SS claim 1 ,VS claim 1 , LTand ISfor the synthesis of erythropoietin or its fragments.2830-. (canceled)31. A method for studying the structure-function relationships of glycosylated erythropoietin claim 1 , comprising the use of a composition of .32. A method for improving properties of glycosylated erythropoietin claim 1 , comprising the use of a composition of .33. (canceled) The present application claims priority to U.S. Provisional Application Ser. No. 61/640,640, filed Apr. 30, 2012, the entirety of which ...

BIOMARKER FOR PROSTATE CANCER AND METHOD OF USING THE SAME

The present invention relates to a biomarker for characterizing prostate cancer and method of using the same. More particularly, the invention relates to method of using a membrane-associated C family G protein-coupled receptor GPRC6A as biomarker of characterizing prostate cancer progression. The present invention also provides a kit for detecting prostate cancer in a subject. 1. A method of characterizing a disease in a subject , comprising the steps of:determining the level of GPRC6A in a biological sample from the subject; andcomparing the level of GPRC6A in the biological sample to a reference, wherein the disease is characterized based on a measurable difference in the level of GPRC6A in the biological sample as compared to the reference.2. The method of claim 1 , further comprising determining the amount of cyclic AMP in the biological sample from the subject and comparing the amount of cyclic AMP in the biological sample to a reference claim 1 , wherein the disease is characterized based on a measurable difference in the amount of cyclic AMP in the biological sample as compared to the reference.3. The method of claim 1 , wherein the disease is prostate cancer.4. The method of claim 3 , wherein the prostate cancer is treatment-resistant prostate cancer.5. The method of claim 1 , wherein the determining and comparing said expression levels comprises isolating the GPRC6A from the biological sample of the subject.6. The method of claim 1 , wherein the determining and comparing said expression levels comprises performing an in vitro assay on the protein biomarker gene or gene products claim 1 , said assay selected from the group consisting of immunoassay claim 1 , histological or cytological assay claim 1 , quantitative real-time PCR claim 1 , and mRNA expression level assay.7. The method of claim 1 , wherein the determining and comparing said expression levels compriseisolating the GPRC6A from the biological sample of the subject; andperforming an in vitro assay ...

METHODS AND COMPOSITIONS FOR DIAGNOSIS AND PROGNOSIS OF RENAL INJURY AND RENAL FAILURE

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a one or more assays configured to detect a kidney injury marker selected from the group consisting of Angiopoietin-related protein 3, Soluble Lymphatic vessel endothelial hyaluronic acid receptor 1, and Vascular endothelial growth factor D as diagnostic and prognostic biomarkers in renal injuries. 1. A method for evaluating renal status in a subject , comprising:obtaining a urine sample from a subject selected for evaluation based on a determination that the subject is at risk of a future or current acute renal injury;performing one or more assays configured to detect one or more biomarkers selected from the group consisting of Angiopoietin-related protein 3, Soluble Lymphatic vessel endothelial hyaluronic acid receptor 1, and Vascular endothelial growth factor D by introducing the urine sample obtained from the subject into an assay instrument which (i) for each analyte binding assay performed, contacts all or a portion of the urine sample with a binding reagent which specifically binds for detection the kidney injury marker which is assayed, (ii) generates one or more assay results indicative of binding of each biomarker which is assayed to its respective binding reagent; andcorrelating the assay result(s) to the renal status of the subject generated by the assay instrument to the renal status of the subject by using the one or more assay results to assign the patient to a predetermined subpopulation of individuals having a known predisposition of a future or current acute renal injury.2. A method according to claim 1 , wherein said correlation step comprises correlating the assay result(s) to one or more of risk stratification claim 1 , diagnosis claim 1 , staging claim 1 , prognosis claim 1 , classifying and ...

Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy

The invention provides methods for identifying patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist. The invention also provides methods for monitoring a patients' response to the anti-cancer therapy. The invention also provides kits and articles of manufacture for use in the methods.

RISK STRATIFICATION FOR ACUTE CORONARY SYNDROME BY MEANS OF FRAGMENTS/PARTIAL PEPTIDES OF PROVASOPRESSIN, ESPECIALLY COPEPTIN OR NEUROPHYSIN II

The invention relates to a method for risk stratification for acute coronary syndrome (ACS), in particular acute myocardial infarction (AMI) and angina pectoris (AP), wherein provasopressin (proAVP) or fragments and partial peptides thereof, in particular copeptin or neurophysin II, is determined by an in vitro diagnosis. 1. Method for risk stratification for acute coronary syndrome , wherein provasopressin (proAVP) or fragments and partial peptides thereof , in particular copeptin or neurophysin II , is determined by an in vitro diagnosis.2. Method for risk stratification for acute coronary syndrome according to for identification of patients with elevated risk and/or unfavorable prognosis of acute coronary syndrome claim 1 , in particular myocardial infarction and angina pectoris.3. Method for risk stratification for acute coronary syndrome according to claim 1 , wherein the patient is a symptomatic and/or asymptomatic patient claim 1 , in particular an emergency care patient.4. Method for risk stratification for acute coronary syndrome according to for therapeutic control of acute coronary syndrome claim 1 , in particular myocardial infarction (AMI) and angina pectoris (AP) claim 1 , in particular in intensive or emergency medical care.5. Method for risk stratification for acute coronary syndrome according to for making clinical decisions claim 1 , in particular for further treatment and therapy with medicaments claim 1 , in particular in intensive or emergency medical care.6. Method for in vitro diagnostics for early or differential diagnosis or prognosis of myocardial infarction or angina pectoris claim 1 , wherein the marker provasopressin (proAVP) or fragments and partial peptides thereof claim 1 , in particular copeptin or neurophysin II claim 1 , is determined in a patient to be studied.7. Method for in vitro diagnostics and/or early or differential diagnosis and/or prognosis for acute coronary syndrome claim 6 , in particular myocardial infarction or ...

IGFBP-3 DERIVATIVES AND USES THEREOF

The present invention provides polypeptide derivatives of IGFBP-3 that are resistant to proteolytic cleavage. These IGFBP-3 derivatives are useful in a variety of therapeutic and diagnostic applications. Also provided are pharmaceutical compositions and kits comprising such IGFBP-3 derivatives and methods for using these derivatives for the treatment of a variety of disorders. 1. An IGFBP-3 polypeptide derivative comprising an N-terminal domain , an intermediary domain and a C-terminal domain , wherein:the N-terminal domain comprises the amino acid sequence of the N-terminal domain of wild-type IGFBP-3, of a biologically active variant thereof or of a biologically active fragment thereof;the intermediary domain comprises a linker resistant to proteolytic cleavage; andthe C-terminal domain comprises the amino acid sequence of the C-terminal domain of wild-type IGFBP-3, of a biologically active variant thereof or of a biologically active fragment thereof.2. The IGFBP-3 polypeptide derivative according to claim 1 , wherein:the intermediary domain of the IGFBP-3 polypeptide derivative comprises the amino acid sequence of the intermediary domain of wild-type IGFBP-3, wherein a portion of said amino acid sequence is replaced by the linker resistant to proteolytic cleavage.3. The IGFBP-3 polypeptide derivative according to claim 1 , wherein IGFBP-3 is human IGFBP-3 and wherein:the amino acid sequence of the N-terminal domain of wild-type IGFBP-3 is as set forth in SEQ ID NO: 1;the amino acid sequence of the intermediary domain of wild-type IGFBP-3 is as set forth in SEQ ID NO: 2; andthe amino acid sequence of the C-terminal domain of wild-type IGFBP-3 is as set forth in SEQ ID NO: 3.4. The IGFBP-3 polypeptide derivative according to claim 1 , wherein the linker has the sequence set forth in SEQ ID NO: 4 or any variant thereof that is resistant to proteolytic cleavage.5. The IGFBP-3 polypeptide derivative according to claim 3 , wherein amino acid residues 43 to 47 in SEQ ID ...

Chimeric gene constructs for generation of fluorescent transgenic ornamental fish

Four zebrafish gene promoters, which are skin specific, muscle specific, skeletal muscle specific and ubiquitously expressed respectively, were isolated and ligated to the 5′ end of the EGFP gene. When the resulting chimeric gene constructs were introduced into zebrafish, the transgenic zebrafish emit green fluorescence under a blue light or ultraviolet light according to the specificity of the promoters used. Thus, new varieties of ornamental fish of different fluorescence patterns, e.g., skin fluorescence, muscle fluorescence, skeletal muscle-specific and/or ubiquitous fluorescence, are developed.

Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy

The invention provides methods for identifying patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist. The invention also provides methods for monitoring a patients' response to the anti-cancer therapy. The invention also provides kits and articles of manufacture for use in the methods.

METHOD TO IDENTIFY A PATIENT WITH AN INCREASED LIKELIHOOD OF RESPONDING TO AN ANTI-CANCER THERAPY

The invention provides methods for identifying patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist. The invention also provides methods for monitoring a patients' response to the anti-cancer therapy. The invention also provides kits and articles of manufacture for use in the methods. 133-. (canceled)34. A method of selecting a cancer treatment for a patient , the method comprising{'sub': 121', '110', '110', '121, 'determining that a sample obtained from the patient has a level of VEGFand VEGFat or above the level of VEGFand VEGFin a reference sample; and'}providing a recommendation that the cancer treatment selected for the patient comprise an effective amount of a VEGF-A antagonist.35. A method of monitoring patient response to a cancer treatment , the method comprising{'sub': 121', '110', '121', '110, 'determining that a sample obtained from the patient has a level of VEGFand VEGFat or above the level of VEGFand VEGFin a reference sample; and'}providing a recommendation that the cancer treatment for the patient comprise an effective amount of a VEGF-A antagonist.36. A method of identifying a patient responsive to or sensitive to treatment with an anti-cancer therapy comprising a VEGF antagonist , the method comprising:{'sub': 121', '110', '121', '110, 'determining an expression level of VEGFand VEGFin a sample obtained from the patient, said sample being contacted with EDTA, whereby a level of VEGFand VEGFin the sample obtained from the patient at or above a reference level identifies the patient as being responsive or sensitive to treatment with the anti-cancer therapy.'}37. A method of predicting the response to or sensitivity to treatment with an anti-cancer therapy comprising a VEGF-A antagonist of a patient suffering from cancer , the method comprising:{'sub': 121', '110', '121', '110, 'determining an expression level of VEGFand VEGFin a sample obtained from the patient, said sample being contacted with EDTA, ...

METHOD TO IDENTIFY A PATIENT WITH AN INCREASED LIKELIHOOD OF RESPONDING TO AN ANTI-CANCER THERAPY

The invention provides methods for identifying patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist. The invention also provides methods for monitoring a patients' response to the anti-cancer therapy. The invention also provides kits and articles of manufacture for use in the methods. 1. A method of identifying a patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist , the method comprising:{'sub': 121', '110', '121', '110, 'determining an expression level of VEGFand VEGFin a sample obtained from the patient, wherein a level of VEGFand VEGFin the sample obtained from the patient at or above a reference level indicates that the patient may benefit from treatment with the anti-cancer therapy, and;'}informing the identified patient that they may benefit from anti-cancer therapy comprising a VEGF antagonist.2. A method of predicting responsiveness of a patient suffering from cancer to treatment with an anti-cancer therapy comprising a VEGF-A antagonist , the method comprising:{'sub': 121', '110', '121', '110, 'determining an expression level of VEGFand VEGFin a sample obtained from the patient, wherein a level of VEGFand VEGFin the sample obtained from the patient at or above a reference level indicates that the patient is more likely to be responsive to treatment with the anti-cancer therapy, and;'}informing the patient that they have an increased likelihood of being responsive to anti-cancer therapy comprising a VEGF-A antagonist.3. A method for determining the likelihood that a patient with cancer will exhibit benefit from anti-cancer therapy comprising a VEGF-A antagonist , the method comprising:{'sub': 121', '110', '121', '110, 'determining an expression level of VEGFand VEGFin a sample obtained from the patient, wherein a level of VEGFand VEGFin the sample obtained from the patient at or above a reference level indicates that the patient has increased likelihood of benefit from the ...

HUMANIZED FORMS OF MONOCLONAL ANTIBODIES TO HUMAN GnRH RECEPTOR

Humanized forms of murine GHR106 monoclonal antibodies and methods of using them are described. Humanized GHR106 monoclonal antibodies have high affinity and specificity to the corresponding tumor-associated antigen, gonadotropin-releasing hormone (GnRH) receptor comparable to murine GHR106. 1. A humanized monoclonal antibody (mAb) or fragment thereof that reacts specifically with an epitope present in amino acid residues 1-29 of the extracellular domain of the human GnRH receptor , and{'sub': 'D', 'sup': '−7', 'that binds to the GnRH receptor with a dissociation constant (K) of less than or equal to 10M, and'}that competes with GnRH for binding to the receptor.2. The mAb of that is a complete antibody.3. The fragment of which is a F(ab') claim 1 , Fab claim 1 , Fv claim 1 , or scFv fragment.4. The mAb or fragment which comprises the CDR regions inherent in one of the heavy chain and/or one of the light chain variable regions shown in according to the numbering system of either Kabat or Clothia.5. The monoclonal antibody (mAb) or fragment of any claim 1 , wherein:a) the CDR1 region of the heavy chain is of the sequence RYSVH (SEQ ID NO:1);b) the CDR2 region of the heavy chain is of the sequence MIWGGGSTDYNSPSLKS (SEQ ID NO:2) or MIWGGGSTDYNSSLQS (SEQ ID NO:3) or MIWGGSTDYNSSLQS (SEQ ID NO:4); andc) the CDR3 region of the heavy chain is of the sequence GNDGYYSFAY (SEQ ID NO:5); andd) the CDR1 region of the light chain is of the sequence KSSQSLLNSRTRKNYLA (SEQ ID NO:6);e) the CDR2 region of the light chain is of the sequence WASTRES (SEQ ID NO:7); andf) the CDR3 region of light chain is of the sequence KQSYNLYT (SEQ ID NO:8).6. The mAb or fragment of claim 1 , wherein the heavy chain comprises the variable region of H65 claim 1 , H66 or H64.7. The mAb or fragment of claim 1 , wherein the light chain comprises the variable region of L41 claim 1 , L42 or L43.8. The mAb or fragment of claim 6 , wherein the light chain comprises the variable region of L41 claim 6 , L42 or ...

AGTR1 AS A MARKER FOR BEVACIZUMAB COMBINATION THERAPIES

The present invention provides methods for assessing the responsiveness or sensitivity of a patient to bevacizumab, compositions comprising bevacizumab and methods of treating patients with bevacizumab. 1. A method for identifying a locally advanced , Her2 negative breast cancer patient responsive or sensitive to bevacizumab treatment ,the method comprising determining the expression level of angiotensin II type receptor 1 (AGTR1) in a biological sample of the patient,identifying the patient as responsive to or sensitive to bevacizumab treatment when an increased expression level of AGTR1 compared to a control level is detected in the sample of the patient, andadministering said bevacizumab treatment to the patient.2. The method of claim 1 , wherein said treatment further comprises chemotherapy.3. The method of claim 2 , wherein said bevacizumab treatment is administered before or after said chemotherapy.4. The method of claim 2 , wherein said chemotherapy comprises docetaxel.5. The method of claim 2 , wherein said chemotherapy comprises doxorubicin and cyclophosphamide.6. The method of claim 1 , wherein said expression level of AGTR1 is determined by detecting protein or mRNA.7. The method of claim 6 , wherein said expression level of AGTR1 is measured by an immunohistochemical (IHC) method or a PCR method.8. The method of claim 7 , wherein said biological sample is a breast tissue biopsy sample or breast tissue resection sample.9. The method of claim 2 , wherein said treatment further comprises one or more anti-cancer therapies.10. The method of claim 9 , wherein said anti-cancer therapy is radiation.11. The method of claim 1 , wherein said biological sample was obtained before neoadjuvant or adjuvant therapy.12. A method for treating locally advanced claim 1 , Her2 negative breast cancer claim 1 , the method comprising administering an effective amount of bevacizumab to a patient identified as responsive or sensitive to bevacizumab therapy claim 1 , wherein the ...

Protein Detection Using Three-Dimensional Carbon Microarrays

The potential of aptamers as ligand binding molecule have opened new avenues in the development of biosensors for proteins, such as cancer oncoproteins. Disclosed herein is a label-free detection strategy using signaling aptamer/protein binding complex for proteins, such as platelet-derived growth factor (PDGF-BB) oncoprotein. The detection mechanism is based on the release of a fluorophore (e.g., TOTO intercalating dye) from the target binding aptamer's stem structure when it captures the protein, e.g., PDGF. Amino-terminated three-dimensional carbon microarrays fabricated by pyrolyzing patterned photoresist are used as a detection platform. The sensor showed near linear relationship between the relative fluorescence difference and protein concentration even in the sub-nanomolar range with an excellent detection limit of 5 pmol. This detection strategy is promising in a wide range of applications in the detection of cancer biomarkers and other proteins. 1. A method for detection of a biomarker in a biological sample , comprisingcontacting the biological sample with sensor that comprises an aptamer immobilized on a substrate, wherein the aptamer that selectively binds to the biomarker; and wherein the substrate comprises a three dimension (3D) carbon microarray; and wherein the substrate is not a diamond substrate; anddetecting the biomarker in the biological sample by detecting biomarker bound to the sensor.2. The method of claim 1 , wherein the aptamer further comprises a intercalating dye.3. The method of claim 2 , wherein the dye is TOTO.4. The method of claim 1 , that further comprises measuring the biomarker in the biological sample by measuring the amount of biomarker bound to the sensor.5. The method of claim 4 , wherein the measuring of the biomarker comprises measuring a fluorescence signal from the dye claim 4 , indicative of the amount of the biomarker bound to the aptamer.6. The method of claim 1 , wherein the carbon in the substrate comprises pyrolyzed ...

HIGH-MOLECULAR-WEIGHT ADIPONECTIN MEASUREMENT METHOD

Provided is a method of separating and measuring highly active HMW adiponectin in adiponectin multimers. A method of measuring high-molecular-weight adiponectin in a sample, wherein adiponectin multimers are separated by use of a protease and measured immunologically, the method comprising reacting a sample containing adiponectin multimers with chymotrypsin. 1. A method of measuring high-molecular-weight adiponectin in a sample , wherein adiponectin multimers are separated by use of a protease and measured immunologically , the method comprising reacting a sample containing adiponectin multimers with chymotrypsin.2. The method according to claim 1 , wherein the sample is human serum or plasma claim 1 , mouse serum or plasma claim 1 , or rat serum or plasma. This application is a continuation of Ser. No. 13/596,695 filed Aug. 28, 2012, which is a continuation of Ser. No. 12/920,190 filed Aug. 30, 2010, which is a Nation Stage of PCT/JP09/000,903 filed Feb. 27, 2009, the entire content of which is incorporated herein by reference.The present invention relates to a method of separating and immunologically measuring a high-molecular-weight (HMW) fraction in adiponectin multimers contained in a biological sample.Adiponectin is a hormone which is produced and secreted specifically in fatty tissue and having anti-diabetes and anti-arteriosclerosis activity, and is present in blood at a relatively high level. In recent years, hypoadiponectinemia associated with obesity, particularly caused by accumulation of visceral fat, is thought to trigger onset of diabetes, arteriosclerotic diseases or hypertension.Structurally, adiponectin belongs to the C1q (Complement 1q) family and has a collagen-like domain which is intrinsic to the C1q family. A study has reported that adiponectin forms a multimer mainly composed of trimers. Recently, the present inventors have revealed the structure of adiponectin multimers present in human blood (trimer including albumin-bound trimer, hexamer, ...

Human monoclonal antibodies that bind insulin-like growth factor (igf) i and ii

Disclosed herein are human monoclonal antibodies that specifically bind both IGF-I and IGF-II with picomolar affinity and potently inhibit the IGF-IR signal transduction function. These antibodies are active in both an IgG and a scFv format. Bispecific forms of these antibodies are also disclosed. Nucleic acids encoding these antibodies, vectors including these nucleic acids, and host cells transformed with these vectors are also disclosed herein. Also disclosed are pharmaceutical compositions including these antibodies. Methods are provided for treating a subject with cancer and for inhibiting phosphorylation of the insulin-like growth factor-I receptor. Methods are also provided for diagnosing cancer.