ОДНОДОМЕННОЕ АНТИТЕЛО И ЕГО ПРОИЗВОДНЫЕ БЕЛКИ К ЛИГАНДУ-1 БЕЛКА ПРОГРАММИРУЕМОЙ СМЕРТИ КЛЕТОК (PDLI)

Изобретение относится к области биотехнологии. Предложена молекула, специфически связывающая лиганд-1 белка программируемой смерти (PDL1) и ее применение, например, в составе фармацевтической композиции для лечения или предупреждения рака. Также изобретение раскрывает молекулу нуклеиновой кислоты, кодирующую указанную PDL1-связывающую молекулу, экспрессирующий вектор и клетку-хозяина, предназначенные для получения PDL1-связывающей молекулы. Изобретение обеспечивает связывание с PDL1 с высокой аффинностью и специфичностью, которое приводит к блокированию связывания PDL1 с PD-1. 8 н. и 12 з.п. ф-лы, 24 ил., 7 табл., 6 пр.

ФОСФОСПЕЦИФИЧНЫЕ АНТИТЕЛА, РАСПОЗНАЮЩИЕ ТАУ

Настоящее изобретение относится к иммунологии. Предложены антитело и его фрагмент, которые связываются с фосфо-эпитопом на белке Тау, а также кодирующие их полинуклеотиды; линии клеток, продуцирующие антитела; вектор, содержащая его клетка-хозяин и способ получения антитела и его функционального фрагмента. Кроме того, предложены фармацевтический состав, способ лечения, облегчения или защиты от таупатии; способ индукции пассивной иммунной реакции у животного; способ диагностики связанного с белком тау заболевания, расстройства или состояния или предрасположенности к связанному с белком тау заболеванию; способ мониторинга минимального остаточного заболевания у пациента после лечения антителом против тау; способ прогнозирования ответа больного на лечение антителом против тау; способы обнаружения мультимеров фосфо-Тау (pTau) в образце мозга, в том числе посмертного обнаружения; диагностический набор. Данное изобретение может найти дальнейшее применение в диагностике и терапии заболеваний, связанных ...

ГУМАНИЗИРОВАННЫЕ АНТИТЕЛА ПРОТИВ AXL

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

КОНЪЮГАТ АНТИТЕЛО-ЛЕКАРСТВЕННОЕ СРЕДСТВО

Изобретение относится к области биохимии. Описана группа изобретений, включающая конъюгат антитело-лекарственное средство для лечения опухоли и/или рака, лекарственное средство, противоопухолевое лекарственное средство и/или противораковое лекарственное средство, содержащие вышеуказанный конъюгат антитело-лекарственное средство, фармацевтическую композицию, способ лечения опухоли и/или рака, промежуточное соединение лекарственное средство-линкер, линкер для получения вышеуказанного конъюгата антитело-лекарственное средство. Конъюгат антитело-лекарственное средство содержит в себе противоопухолевое соединение, конъюгированное с антителом через линкер, имеющий структуру, представленную следующей формулой: -L-L-L-NH-(CH)n-L-L-L-, где антитело присоединено к концу L, а противоопухолевое соединение присоединено к концу Lс помощью атома азота аминогруппы в положение 1 в качестве положения для соединения. Предложенное изобретение расширяет арсенал средств с противоопухолевой активностью. 7 н.

ГУМАНИЗИРОВАННОЕ АНТИТЕЛО К АМИЛОИДУ БЕТА

Настоящее изобретение относится к иммунологии. Предложены варианты антитела, содержащие две различные пары тяжелых/легких цепей, одна из которых распознает и связывает β-амилоидный белок. Для получения антитела предложены молекула нуклеиновой кислоты, экспрессионный вектор и клетка. Кроме того, описано применение антитела для получения лекарственного средства, фармацевтическая композиция и способы предупреждения, лечения или облегчения эффектов амилоидоза, а также способ нарушения агрегации ранее сформированных бета-амилоидных волокон и способ предупреждения деградации нейронов. Рассмотрен способ диагностирования амилоидоза у пациента, способ определения степени нагрузки амилоидогенными бляшками и набор для определения и диагностирования ассоциированных с амилоидами заболеваний и состояний. Антитела по настоящему изобретению могут найти применение в терапии и диагностике болезни Альцгеймера и других заболеваний, ассоциированных с амилоидозом. 21 н. и 40 з.п. ф-лы, 18 ил., 9 табл., 16 пр ...

АНТИТЕЛА ПРОТИВ БЕЛКА РЕЦЕПТОРА С-МЕТ

Изобретение относится к биохимии. Описано антитело или его антигенсвязывающий фрагмент, которое специфически связывается с белком c-Met человека. Также описан выделенный полинуклеотид, кодирующий данное антитело, вектор экспрессии, содержащий данный полинуклеотид, клетка-хозяин, содержащая данный вектор. Представлен способ получения рекомбинантного антитела путём культивирования описанной клетки-хозяина. Представлена фармацевтическая композиция для лечения рака и иммуноконъюгат, содержащие описанное антитело. Представлен способ лечения рака, включающий введение описанного антитела. Изобретение расширяет арсенал средств лечения рака. 9 н. и 6 з.п. ф-лы, 25 ил., 16 табл., 26 пр.

АНТИТЕЛА, СПЕЦИФИЧЕСКИЕ К РЕЦЕПТОРУ ПОЛИОВИРУСА (PVR) ЧЕЛОВЕКА

Изобретение относится к области биотехнологии, в частности к выделенному моноклональному антителу, которое специфически связывается с рецептором полиовируса (PVR) человека, или к его фрагменту, а также к содержащей его композиции. Также раскрыт полинуклеотид, кодирующий последовательность вариабельной области легкой или тяжелой цепи указанного антитела, а также плазмида и клетка, его содержащие. Изобретение позволяет эффективно осуществлять диагностирование или лечение рака у субъекта. 8 н. и 23 з.п. ф-лы, 16 ил., 4 табл., 13 пр.

АНТИТЕЛА ЧЕЛОВЕКА К ДЕЛЬТА-ПОДОБНОМУ ЛИГАНДУ-4 ЧЕЛОВЕКА

Изобретение относится к биохимии. Описано выделенное антитело человека или фрагмент антитела, которые специфическим образом связывают дельта-подобный лиганд-4 человека (hDII4), указанное антитело человека или фрагмент антитела содержит вариабельную область тяжелой цепи (HCVR), содержащую три определяющие комплементарность области (CDR) тяжелой цепи, и вариабельную область легкой цепи (LCVR), содержащую три CDR легкой цепи, где указанные три CDR тяжелой цепи содержат CDR1, CDR2 и CDR3 последовательности SEQ ID NO:429 или SEQ ID NO:901, а указанные три CDR легкой цепи содержат CDR1, CDR2 и CDR3 последовательности SEQ ID NO:437 или SEQ ID NO:903, и где указанное антитело или его фрагмент связывается с эпитопом в пределах N-концевого-DSL домена hDII4. Описана выделенная молекула нуклеиновой кислоты, кодирующая описанное антитело или его антигенсвязывающий фрагмент. Представлены вектор экспрессии, содержащий описанную молекулу нуклеиновой кислоты, и система «хозяин-вектор» для получения описанного ...

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ДЛЯ ЛЕЧЕНИЯ ПРОФИЛАКТИКИ РАКА

... 1. Антитело или его фрагмент, который обладает иммунологической реактивностью по отношению к неполному полипептиду CAPRIN-1, состоящему из аминокислотной последовательности, указанной в SEQ ID NO: 5, или аминокислотной последовательности, имеющей 80% или более высокую идентичность последовательности с данной аминокислотной последовательностью.2. Антитело или его фрагмент по п. 1, в котором антитело или его фрагмент обладает цитотоксической активностью, направленной против раковой клетки, экспрессирующей белок CAPRIN-1.3. Антитело или его фрагмент по п. 1 или 2, в котором антитело представляет собой моноклональное антитело или поликлональное антитело.4. Антитело или его фрагмент по п. 1, в котором антитело представляет собой человеческое антитело, гуманизированное антитело, химерное антитело, одноцепочечное антитело или полиспецифичное антитело.5. Антитело или его фрагмент по п. 1, в котором антитело или его фрагмент содержит вариабельную область тяжелой цепи, содержащую определяющие комплементарность ...

АНТИТЕЛО ПРОТИВ SIGLEC-15

... 1. Антитело или функциональный фрагмент антитела, которое связывается с полипептидом, состоящим из аминокислотных остатков 39-165 аминокислотной последовательности SEQ ID NO:2, и ингибирует образование остеокластов и, необязательно, остеокластную резорбцию кости, где антитело получают с помощью полипептида, содержащего аминокислотные остатки от 39 до 165 аминокислотной последовательности SEQ ID NO:2.2. Антитело или функциональный фрагмент антитела по п. 1, отличающееся тем, что:последовательность тяжелой цепи содержит вариабельную область с CDRH1, CDRH2 и CDRH3, и CDRH1 содержит аминокислотную последовательность SEQ ID NO:44, CDRH2 содержит любую аминокислотную последовательность из последовательностей SEQ ID NO:45 и SEQ ID NO:97, и CDRH3 содержит аминокислотную последовательность SEQ ID NO:46; ипоследовательность легкой цепи содержит вариабельную область с CDRL1, CDRL2 и CDRL3, и CDRL1 содержит аминокислотную последовательность SEQ ID NO:47, CDRL2 содержит аминокислотную последовательность ...

НОВОЕ АНТИТЕЛО К CXCR4 И ЕГО ПРИМЕНЕНИЕ ДЛЯ ВЫЯВЛЕНИЯ И ДИАГНОСТИКИ РАКА

... 1. Антитело, его антигенсвязывающий фрагмент или производное, включающее:i) тяжелую цепь, включающую следующие три региона, определяющих комплементарность (CDR), соответственно: CDR-H1, имеющий последовательность SEQ ID No.1, CDR-H2, имеющий последовательность SEQ ID No.2, и CDR-H3, имеющий последовательность SEQ ID No.3; иii) легкую цепь, включающую следующие три региона, определяющих комплементарность, соответственно: CDR-L1, имеющий последовательность SEQ ID No.4, CDR-L2, имеющий последовательность SEQ ID No.5, и CDR-L3, имеющий последовательность SEQ ID No.6.2. Антитело по п. 1, его антигенсвязывающий фрагмент или производное, где указанное антитело выбрано из:а. антитела с тяжелой цепью, включающей следующие три региона, определяющих комплементарность, соответственно: CDR-H1, имеющий последовательность SEQ ID No.1, CDR-H2, имеющий последовательность SEQ ID No.2, и CDR-H3, имеющий последовательность SEQ ID No.3; и вариабельный домен легкой цепи, включающий последовательность SEQ ID ...

СПОСОБ ИНГИБИРОВАНИЯ КЛЕТОЧНОЙ АКТИВАЦИИ, ВЫЗЫВАЕМОЙ ИНСУЛИНОПОДОБНЫМ ФАКТОРОМ РОСТА 1

... 1. Моноклональное антитело, которое специфически связывает эпитоп, состоящий из аминокислот 71-80 белка IAP человека, и является антагонистом связывания IAP с SHPS-1.2. Антитело по п.1, связанное с детектируемой группой.3. Антитело по п.1, связанное с терапевтической группой.4. Антитело по п.1, отличающееся тем, что антитело не разрушает связывание IAP с белком β.5. Фармацевтическая композиция, содержащая антитело по п.1 в фармацевтически приемлемом носителе.6. Антитело по п.1, отличающееся тем, что антитело выбирают из группы, состоящей из (a) моноклонального антитела, продуцируемого гибридомой NPG-1, и (b) моноклонального антитела, которое конкурирует за связывание с тем же эпитопом, что и эпитоп, связываемый моноклональным антителом, продуцируемым гибридомой NPG-1.7. Антитело по п.6, связанное с детектируемой группой.8. Антитело по п.6, связанное с терапевтической группой.9. Фармацевтическая композиция, содержащая антитело по п.6 в фармацевтически приемлемом носителе.10. Способ ингибирования ...

АНТИТЕЛА ПРОТИВ ЧЕЛОВЕЧЕСКОГО HER3, ИМЕЮЩИЕ НИЗКОЕ СОДЕРЖАНИЕ ФУКОЗЫ, И ОБЛАСТИ ИХ ПРИМЕНЕНИЯ

ДИЗАЙН УСТОЙЧИВОГО ГЕТЕРОДИМЕРНОГО АНТИТЕЛА С МУТАЦИЯМИ В FC ДОМЕНЕ

... 1. Выделенный гетеромультимер, содержащий гетеродимерную Fc область, которая включает вариантный СН3 домен, содержащий аминокислотные мутации, стимулирующее образование гетеродимерная Fc области с повышенной устойчивостью по сравнению с СН2 доменом, который не содержит аминокислотные мутации, и где вариантный СН3 домен имеет температуру плавления (Tm) около 70°С или выше.2. Выделенный гетеромультимер по п.1, где гетеродимерная Fc область дополнительно включает вариантный СН2 домен, содержащий асимметричные аминокислотные модификации, для стимулирующее селективное связывание Fc гамма рецептора.3. Выделенный гетеромультимер по п.2, в котором вариантный СН2 домен селективно связывает Fc гамма IIIa рецептор по сравнению с СН2 доменом дикого типа.4. Выделенный гетеромультимер по любому из пп.1-3, в котором гетеродимерная область Fc не содержит дополнительную дисульфидную связь в СН3 домене по сравнению с Fc областью дикого типа.5. Выделенный гетеромультимер по любому из пп.1-3, в котором гетеродимерная ...

КОНЪЮГАТЫ АНТИТЕЛА К CCR7 И ЛЕКАРСТВЕННОГО СРЕДСТВА

ИММУНОТЕРАПЕВТИЧЕСКОЕ ЛЕЧЕНИЕ

... 1. Применение иммунотерапии против окисленных липопротеидов низкой плотности (ЛПНП) для индуцирования обратного развития атеросклеротических бляшек у особи. ! 2. Применение по п.1, где иммунотерапия направлена против эпитопа, присутствующего на окисленном ЛПНП, но отсутствующего на нативном ЛПНП. ! 3. Применение по п.1 или 2, где иммунотерапия направлена против, по меньшей мере, одного окисленного эпитопа АроВ-100. ! 4. Применение по п.3, где эпитоп АроВ-100 выбирается из пептидов, перечисленных в Таблице 1, или фрагмента, содержащего, по меньшей мере, 6 последовательных аминокислотных остатков пептида, перечисленного в Таблице 1. ! 5. Применение по п.1 или 2, где иммунотерапия направлена против, по меньшей мере, одного окисленного липидного эпитопа, присутствующего на окисленном ЛПНП. ! 6. Способ индуцирования обратного развития атеросклеротических бляшек у особи, которая в этом нуждается, включающий введение особи: ! (a) по меньшей мере, одного антитела, которое селективно связывается ...

МОЛЕКУЛЫ АНТИТЕЛ ЧЕЛОВЕКА К IL-13

... 1. Способ получения антигенсвязывающего домена антитела, специфичного в отношении IL-13 человека, при этом способ включает в себя получение посредством присоединения, делеции, замены или инсерции одной или нескольких аминокислот в аминокислотной последовательности исходного домена VH, содержащего HCDR 1, HCDR2 и HCDR3, где HCDR1, HCDR2 и HCDR3 исходного домена VH представляют собой набор HCDR BAK167A11, в котором, согласно определению, HCDR1 имеет аминокислотную последовательность SEQ ID NO: 55, HCDR2 имеет аминокислотную последовательность SEQ ID NO: 56, HCDR3 имеет аминокислотную последовательность SEQ ID NO: 57, набор HCDR BAK615E3, в котором, согласно определению, HCDR1 имеет аминокислотную последовательность SEQ ID NO: 153, HCDR2 имеет аминокислотную последовательность SEQ ID NO: 154, HCDR3 имеет аминокислотную последовательность SEQ ID NO: 155, набор HCDR BAK582F7, в котором, согласно определению, HCDR1 имеет аминокислотную последовательность SEQ ID NO: 141, HCDR2 имеет аминокислотную ...

АНТИТЕЛА ПРОТИВ ТОФАЦИТИНИБА И ИХ ПРИМЕНЕНИЕ ДЛЯ ЛЕКАРСТВЕННОГО МОНИТОРИНГА

... 1. Иммуногенный конъюгат тофацитиниба, содержащий тофацитиниб, связанный с иммуногенным носителем, представляющим собой белок, выбранный из группы, состоящей из гемоцианина лимфы улитки и бычьего сывороточного альбумина, где:(a) иммуногенный конъюгат тофацитиниба имеет структуругде BSA представляет собой бычий сывороточный альбумин; или(b) иммуногенный конъюгат тофацитиниба имеет структуругде KLH представляет собой гемоцианин лимфы улитки.2. Способ оценки концентрации тофацитиниба в образце, включающий:(a) предоставление образца, предположительно содержащего тофацитиниб;(b) приведение образца или экстракта образца в контакт с антителом, специфичным к тофацитинибу, в условиях, подходящих для связывания антитела с тофацитинибом, с образованием смеси для анализа; и(c) выявление связывания антитела с тофацитинибом.3. Выделенное антитело, имеющее более высокую аффинность связывания с тофацитинибом, чем с метаболитом 1 тофацитиниба Формулы II и метаболитом 2 тофацитиниба Формулы III4. Выделенное ...

ЛИГАНДЫ, СВЯЗЫВАЮЩИЕ КОМПЛЕКС АКТИВАТОРА ПЛАЗМИНОГЕНА УРОКИНАЗНОГО ТИПА (UPA) И ЕГО РЕЦЕПТОРА (UPAR), КОТОРЫЕ ИНГИБИРУЮТ ПОСЛЕДУЮЩИЕ ВЗАИМОДЕЙСТВИЯ UPAR: ИДЕНТИФИКАЦИЯ И ИСПОЛЬЗОВАНИЕ В ДИАГНОСТИКЕ ИЛИ ТЕРАПИИ

... 1. Лиганд, который связывается с бинарным комплексом uPA-uPAR, но который по существу не связывается с (i) свободным uPA или (ii) участком uPAR, который распознает и связывается с uPA, так что лиганд не ингибирует связывание uPA-uPAR. 2. Лиганд, который связывается с тройным комплексом uPA-uPAR и дополнительной молекулой Х, где лиганд (а) связывается с комплексом uPA-uPAR-Х; (b) по существу не связывается с одним из следующих компонентов: (i) комплексом uPA-uPAR, (ii) комплексом uPA-Х, (iii) uPA-распознающим и uPA-связывающим участком uPAR, (iv) uPA-распознающим и uPA-связывающим участком Х, (v) свободным uPA, или (vi) свободным Х; и (с) по существу не ингибирует связывание uPA-uPAR или связывание uPA-Х. 3. Лиганд по п.2, отличающийся тем, что Х представляет собой белок PAI-1. 4. Лиганд по любому из пп.1-3, который по существу не связывается со свободным uPAR. 5. Лиганд по любому из пп.1-3, который представляет собой полипептид. 6. Лиганд по п.4, который представляет собой полипептид. 7 ...

ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ДЛЯ ЛЕЧЕНИЯ И/ИЛИ ПРОФИЛАКТИКИ РАКА

... 1. Антитело или его фрагмент, который обладает иммунологической реактивностью по отношению к неполному полипептиду CAPRIN-1, состоящему из аминокислотной последовательности, указанной в SEQ ID NO: 5, или аминокислотной последовательности, имеющей 80% или более высокую идентичность последовательности с данной аминокислотной последовательностью.2. Антитело или его фрагмент по п. 1, в котором антитело или его фрагмент обладает цитотоксической активностью, направленной против раковой клетки, экспрессирующей белок CAPRIN-1.3. Антитело или его фрагмент по п. 1 или 2, в котором антитело представляет собой моноклональное антитело или поликлональное антитело.4. Антитело или его фрагмент по п. 1, в котором антитело представляет собой человеческое антитело, гуманизированное антитело, химерное антитело, одноцепочечное антитело или полиспецифичное антитело.5. Антитело или его фрагмент по п. 1, в котором антитело или его фрагмент содержит вариабельную область тяжелой цепи, содержащую определяющие комплементарность ...

Humaner Endothelinrezeptor bindender Antikörper und dessen Verwendung

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

ANTIKÖRPER GEGEN NICHTFUNKTIONELLE P 2 X 7 REZEPTOREN, DIAGNOSE UND BEHANDLUNG VON KREBS UND ANDEREN LEIDEN

Immunoassay for compounds of the NBOMe family

Antibodies to ADP-ribosyl cyclase 2

CX3CR1-binding polypeptides

Antibody drug conjugates

CX3CR1-binding polypeptides

Compositions and methods for antibodies targeting factor P

Antibodies to ADP-ribosyl cyclase 2

Compositions and methods for antibodies targeting factor P

CX3CR1-binding polypeptides

Antibodies to ADP-ribosyl cyclase 2

Antibody drug conjugates

MONOCLONAL ANTIBODIES AGAINST DETERGENZIEN AND YOUR DEGRADATION PRODUCTS, AND THEIR USE IN IMMUNE TESTS

HUMANISIERTE ANTIBODY AGAINST THE RESPIRATORY SYNCYTIALVIRUS

Novel TNFR agonists and uses thereof

The present invention relates to a new class of TNFR agonist comprising multiple binding portions to two different parts of the same TNFR. The present invention also relates to methods of activating components of the immune system in a patient via the administration of a TNFR agonist according to the present invention as well as the use of such materials for further therapeutic and other purposes.

Monoclonal antibodies against the beta chain region of human TRBV9

The invention relates to a monoclonal humanized antibody or an antigen-binding fragment thereof which bind specifically to the TRBV9 family of human Т-cell receptors. The invention also relates to a nucleic acid which codes for said antibody or for an antigen-binding fragment thereof, an expression vector, a method for producing the antibody, and the use of said antibody for treating diseases or disorders associated with said family of human T-cell receptors. The invention is directed towards producing antibodies which can be used, in particular, for treating ankylosing spondylitis (AS or Bekhterev's disease), coeliac disease and blood cancers, the pathogenesis of which involves T-cell receptors of the TRBV9 family.

CD38-directed chimeric antigen receptor constructs

There is disclosed compositions and methods relating to or derived from anti-CD38 antibodies. More specifically, there is disclosed fully human antibodies that bind CD38, CD38-antibody binding fragments and derivatives of such antibodies, and CD38-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating a disease.

Anti-human PD-L1 antibodies and their uses

An anti-PD-L1 antibody, or an antigen-binding fragment thereof, comprising: a heavy chain variable region comprising the three CDRs with the sequences of SEQ ID NOs: 2-4, 6-8, 10-12, 14-16, or 18-20; and/or a light chain variable region comprising the three CDRs with the sequences of SEQ ID NOs: 22-24, 26-28, 30-32, 34-36, or 38-40, wherein the antibody is a chimeric, humanized, composite, or human antibody.

Antibodies against carcinoembryonic antigen for cancer therapy and diagnosis

The invention relates to antibodies against carcinoembryonic antigen (CEA) which have a direct cell growth inhibition activity on tumor cells expressing CEA and to their use for the treatment and diagnosis of cancer.

Novel cancer-associated antigen

Anti-CepsilonmX antibodies capable of binding to human mIgE on B lymphocytes

The invention pertains to the generation and utility of antibodies that can bind effectively to CmX domain on membrane-bound IgE (mIgE) expressed on the surface of human B lymphocytes. The CmX domain of 52 amino acid residues, located between the CH4 domain and the C-terminal membrane-anchor peptide on human membrane-bound epsilon chain, had been suggested as an antigenic site for immunological targeting of B cells expressing mlgE. Previous reported monoclonal antibodies, including a20, which bind to RADWPGPP peptide at the C-terminal of CmX, have now been found to bind poorly to mlgE on human B cells. We have discovered that only monoclonal antibodies specific for certain segments, such as GLAGGSAQSQRAPDRVL and HSGQQQGLPRAAGGSVPHPR, of CmX can bind effectively to mlgE on human B cells and hence have the utility for targeting those B cells for the treatment of diseases mediated by IgE.

Methods and compositions for modulating notch activity

Provided herein are polypeptides and derivatives thereof that contain sequences of a Serrate protein and that inhibit Notch pathway function. Also provided herein are nucleic acids that encode the polypeptides, vectors and cells for producing the polypeptides, and related pharmaceutical compositions and kits. Additionally provided are antibodies which bind to the Notch inhibitory region of a Serrate protein. Therapeutic methods are also provided.

Compositions and methods for treating and preventing Staphylococcus aureus infections

Antibodies having Fab regions that specifically bind to ...

CD20 ANTIBODIES AND USES THEREOF

CD20 is a transmembrane protein of the tetra-spanin family expressed on the surface of B-cells and has been found on B-cells from peripheral blood as well as lymphoid tissues. CD20 expression persists from the early pre-B cell stage until the plasma cell differentiation stage. Conversely, it is not found on hematopoietic stem cells, pro-B cells, differentiated plasma cells or non-lymphoid tissues. In addition to expression in normal B-cells, CD20 is expressed in B-cell derived malignancies such as non-Hodgkins lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). CD20 expressing cells are known to play a role in other diseases and disorders, including inflammation. The present invention includes anti-CD20 antibodies, forms and fragments, having superior physical and functional properties; immunoconjugates, compositions, diagnostic reagents, methods for inhibiting growth, therapeutic methods, improved antibodies and cell lines; and polynucleotides, vectors and genetic constructs ...

BCMA-BINDING ANTIBODIES AND USES THEREOF

Antibody species that bind B-Cell Maturation Antigen (BCMA) are provided as well as methods of depleting BCMA-expressing cells in a patient in need thereof, comprising administering a therapeutically effective amount of the antibody species or an entity comprising a BCMA binding fragment thereof. Methods of treating B cell-related disorders associated with BCMA expression in a patient in need thereof are provided, comprising administering to the patient a therapeutically effective amount of the antibody species or an entity comprising a BCMA binding fragment thereof.

NOVEL TNFR AGONISTS AND USES THEREOF

The present invention relates to a new class of TNFR agonist comprising multiple binding portions to two different parts of the same TNFR. The present invention also relates to methods of activating components of the immune system in a patient via the administration of a TNFR agonist according to the present invention as well as the use of such materials for further therapeutic and other purposes.

GENETIC PRODUCTS DIFFERENTIALLY EXPRESSED IN TUMORS AND THE USE THEREOF

... ² The invention relates to the identification of genetic ²products expressed in association with tumors and to ²coding nucleic acids for said products. Said invention ²also relates to the therapy and diagnosis of disease in ²which the genetic products are aberrantly expressed in ²association with tumors, proteins, polypeptides and ²peptides which are expressed in association with ²tumors,and to the nucleic coding acids for said ²polypeptides, peptides and proteins. ² ...

MULTIMERIC OX40 BINDING MOLECULES AND USES THEREOF

This disclosure provides dimeric, pentameric, and hexameric OX40 agonist binding molecules and methods of using such binding molecules to induce anti-tumor immunity.

CONFORMATION-INDEPENDENT ANTIBODIES AGAINST NEUROTOXIC TAU PROTEINS

An antibody or fragment thereof capable of binding to a neurotoxic tau protein. The neurotoxic tau protein includes a phosphorylation site at threonine residue 231 in AT180 domain of tau proteins and an amino acid substitution of proline residue 232 to glycine (P232G) in AT180 domain of tau proteins.

ANTI-IL1-RAP ANTIBODIES

Provided herein are antibodies specific for IL1-RAP.

ANTI-MET ANTIBODIES AND COMPOSITIONS

The present invention relates to novel recombinant antibodies directed against human MET (c-MET), as well as compositions comprising mixtures of at least two of said antibodies and use of the antibodies and antibody compositions for treatment of MET-mediated disorders such as cancer.

HUMAN ANTIBODIES TO NAV1.7

The present invention provides antibodies that bind to the human voltage gated sodium channel designated Nav1.7 and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human Nav1.7 (hNav1.7). The antibodies of the invention are useful for the treatment of diseases and disorders associated with one or more Nav1.7 biological activities, including the treatment of acute or chronic pain conditions, or inflammatory conditions.

COMPOSITIONS AND METHODS FOR TREATING AND PREVENTING STAPHYLOCOCCUS AUREUS INFECTIONS

Antibodies having Fab regions that specifically bind to Staphylococcus aureus protein A are capable of mediating opsinization of Staphylococcus aureus bacteria despite their expression of antibody-neutralizing protein A. These antibodies and antigen-binding fragments thereof can be used in methods of treating and/or preventing Staphylococcus aureus infections.

ANTI-COMPLEMENT C1S ANTIBODIES AND USES THEREOF

The present disclosure provides antibodies that bind complement C1s protein; and nucleic acid molecules that encode such antibodies. In some embodiments, such anti- complement C1s antibodies inhibit proteolytic activity of C1s. The present disclosure also provides compositions comprising such antibodies, and methods to produce and use such antibodies, nucleic acid molecules, and compositions.

USE OF SEMAPHORIN-4D BINDING MOLECULES FOR TREATING NEURODEGENERATIVE DISORDERS

Provided are methods for alleviating symptoms in a subject having a neurodegenerative disorder, comprising administering to the subject an effective amount of an isolated binding molecule which specifically binds to semaphorin-4D (SEMA4D) or to its Plexin-B1 or Plexin-B2 receptors. Further provided is an isolated binding molecule which specifically binds to the same SEMA4D epitope as a reference monoclonal antibody selected from the group consisting of VX15/2503 and 67.

HUMAN ANTIBODIES THAT BIND HUMAN IL-12 AND METHODS FOR PRODUCING

Human antibodies, preferably recombinant human antibodies, that specifica lly bind to human interleukin-12 (hIL-12) are disclosed. Preferred antibodie s have high affinity for hIL-12 and neutralize hIL-12 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an an tigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and for inhibiting hIL-12 activity , e.g., in a human subject suffering from a disorder in which hIL-12 activit y is detrimental. Nucleic acids, vectors and host cells for expressing the r ecombinant human antibodies of the invention, and methods of synthesizing th e recombinant human antibodies, are also encompassed by the invention. ...

TREATMENT METHOD USING EGFR ANTIBODIES AND SRC INHIBITORS AND RELATED FORMULATIONS

The present invention relates to the treatment of EGFR-mediated disease, particularly cancer by inhibiting or blocking EGFR and src in combination or simultaneously. The invention relates to treatment, prevention, or modulation of cancer, particularly EGFR- mediated disease, with one or more EGFR modulator and src inhibitor in combination. The invention further relates to the treatment of cancer with anti-EGFR antibodies and src inhibitors. Methods and compositions for treatment of cancer with the antibody anti- EGFR mAb806 in combination or series with a src inhibitor or src inhibitors are described.

ANTIBODY COMPOSITIONS AND METHODS OF USE

The invention provides compositions comprising anti-gH antibodies and anti-Complex I antibodies as well as methods of using the same.

ANTI-HUMAN IGG1 ANTIBODY

Herein are reported a monoclonal antibody specifically binding to a human IgG1 antibody and not specifically binding to the immunoglobulin of an experimental animal and the use of the antibody in immunoassays.

HUMAN ANTI-SOD1 ANTIBODIES

Provided are novel human copper-zinc superoxide dismutase, also known as superoxide dismutase 1 or SOD1, specific antibodies as well as fragments, derivatives and variants thereof as well as methods related thereto. Assays, kits, and solid supports related to antibodies specific for SOD1 are also disclosed. The antibody, immunoglobulin chain(s), as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for SOD1 targeted immunotherapy and diagnosis, respectively.

METHODS AND COMPOSITIONS FOR MODULATING NOTCH ACTIVITY

Provided herein are polypeptides and derivatives thereof that contain sequences of a Serrate protein and that inhibit Notch pathway function. Also provided herein are nucleic acids that encode the polypeptides, vectors and cells for producing the polypeptides, and related pharmaceutical compositions and kits. Additionally provided are antibodies which bind to the Notch inhibitory region of a Serrate protein. Therapeutic methods are also provided.

PHARMACEUTICAL COMPOSITION FOR TREATMENT AND/OR PREVENTION OF CANCER

The present invention provides an antibody targeting a cancer antigen protein that is specifically expressed on the surface of a cancer cell, and the use of the antibody as a therapeutic and/or prophylactic agent for cancer. More specifically, the present invention provides: an antibody, or a fragment thereof, that has an immunological reactivity with a CAPRIN-1 partial polypeptide comprising an amino acid sequence represented by SEQ ID NO:5 or an amino acid sequence having a sequence identity of 80% or greater with said amino acid sequence; and a medicinal composition for treating and/or preventing cancer, said medicinal composition being characterized by comprising the aforesaid antibody or a fragment thereof as the active ingredient.

ANTIBODY SPECIFIC FOR TRANS-RESVERATROL AND USE THEREOF

The present invention provides a method of detecting or measuring trans-Resveratrol (tRV) in a sample, comprising: contacting a sample to be tested with an antibody against tRV, or an antigen binding fragment of such an antibody; and detecting or measuring any tRV bound by the antibody or antibody fragment. The invention also provides an antibody against trans-Resveratrol.

MONOCLONAL ANTIBODIES AGAISNT ACTIVATED PROTEIN C (APC)

Provided herein are antibodies, antigen-binding antibody fragments (Fabs), and other protein scaffolds, directed against human activated Protein C (aPC) with minimal binding to its zymogen Protein C (PC). Moreover, these aPC binding proteins could potentially block the anti-coagulant activity of aPC to induce coagulation. Therapeutic uses of these binders are described herein as are methods of panning and screening specific antibodies.

MESOTHELIN ANTIBODIES AND METHODS FOR ELICITING POTENT ANTITUMOR ACTIVITY

Described herein is the use of phage display antibody engineering technology and synthetic peptide screening to identify SDl and SD2, human single-domain antibodies to mesothelin. SDl recognizes a conformational epitope at the C-terminal end (residues 539-588) of human mesothelin close to the cell surface. SD2 binds full-length mesothelin. To investigate SDl as a potential therapeutic agent, a recombinant human Fc (SDl-hFc) fusion protein was generated. The SDl-hFc protein exhibits strong complement-dependent cytotoxicity (CDC), in addition to antibody- dependent cellular cytotoxicity (ADCC), against mesothelin-expressing tumor cells. Furthermore, the SDl-hFc protein causes significant tumor growth inhibition of tumor xenografts in nude mice. SDl and SD2 are the first human single-domain antibodies targeting mesothelin-expressing tumors.

ANTIBODIES AND ANTIGEN-BINDING FRAGMENTS, WHICH SPECIFICALLY BIND WITH PROTEIN TAU, ASSOCIATED WITH MICROTUBULES

ANTI - PSF - TAU - ANTIBODIES AND METHODS OF THEIR APPLICATION

CONJUGATES OF ANTIBODIES TO CCR7 IS AND A MEDICINAL AGENT

ANTIBODIES

POLYPEPTIDES

NEW T CELL RECEPTORS AND IMMUNOTHERAPY WITH THEIR USING

ANTIBODIES, SPECIFIC TO OF TGF-BETA

APPLICATION OF SEMAPHORIN-4D-BINDING MOLECULES FOR TREATMENT OF NEURODEGENERATIVE DISORDERS

MAKROPINOTsITOZIRUYuShchIE HUMAN ANTI-CD46 ANTIBODIES AND TARGETNAYa CANCER THERAPY

ANTIBODIES TO MSAM AND METHODS OF THEIR APPLICATION

COMPOSITIONS OF ANTIBODIES AND METHODS OF APPLICATION

HUMAN ANTI-- TAU ANTIBODIES

HUMAN ANTIBODIES TO SPAIK - PROTEIN RELIEF CORONAVIRUS RESPIRATORY SYNDROME

MEDICINAL CONJUGATES OF ANTIBODIES

НОВЫЕ АНТИТЕЛА К CD38 ДЛЯ ЛЕЧЕНИЯ РАКА

Антитела, гуманизированные антитела, антитела с реструктурированной поверхностью, фрагменты антител, дериватизированные антитела и их конъюгаты с цитотоксическими агентами, которые специфически связываются с CD38, способны вызывать цитолиз клеток CD38+ путем апоптоза, антитело-обусловленной клеточнозависимой цитотоксичности (ADCC) и комплементзависимой цитотоксичности (CDC). Указанные антитела и их фрагменты можно применять при лечении опухолей, которые экспрессируют белок CD38, таких как множественная миелома, хронический лимфолейкоз, хронический миелолейкоз, острый миелолейкоз или острый лимфолейкоз, или лечении аутоиммунных и воспалительных заболеваний, таких как системная красная волчанка, ревматоидный артрит, рассеянный склероз, эритематоз и астма. Указанные дериватизированные антитела можно применять при диагностике и визуализации опухолей, которые экспрессируют повышенные уровни CD38. Предоставляются также цитотоксические конъюгаты, включающие связывающийся с клеткой агент и цитотоксический ...

ANTIBODIES TO ADP-RIBOSYL CYCLASE 2

CX3CR1-BINDING POLYPEPTIDES

ANTIBODIES TO ADP-RIBOSYL CYCLASE 2

CX3CR1-BINDING POLYPEPTIDES

ANTIGEN-BINDING PROTEINS AGAINST NEIROPILINA AND METHODS OF THEIR APPLICATION

ANTIBODIES, THAT BIND WITH CCR6, AND VERSIONS OF APPLICATION SAID ANTIBODIES

ANTIBODIES, SPECIFIC TO OF TGF-BETA

스타필로코커스 아우레우스 감염의 치료 및 예방을 위한 조성물 및 방법

... 스타필로코커스 아우레우스 단백질 A에 특이적으로 결합하는 Fab 영역을 갖는 항체는 스타필로코커스 아우레우스 박테리아의 항체-중화 단백질 A의 발현에도 불구하고, 스타필로코커스 아우레우스 박테리아의 옵소닌화를 매개할 수 있다. 이들 항체 및 그의 항원-결합 단편은 스타필로코커스 아우레우스 감염의 치료 및/또는 예방 방법에 사용될 수 있다.

GENETIC PRODUCTS DIFFERENTIALLY EXPRESSED IN TUMORS AND THE USE THEREOF

항-헵신 항체 및 그의 용도

... 본 출원은 항-헵신 항체의 제조 방법, 항-헵신 항체, 항-헵신 항체의 활성을 스크리닝하는 방법, 항-헵신 항체의 약제학적 조성물, 항-헵신 항체를 포함하는 키트, 및 암을 진단하기 위해 항-헵신 항체를 사용하는 방법을 개시한다.

Antibodies specific for hyperphosphorylated tau and methods of use thereof

The present invention relates to a class of monoclonal antibody that specifically binds the phosphorylated serine 396 residue on pathological hyperphosphorylated (PHF) tau (pS396) with improved affinity, as well as to methods of using these molecules and their tau binding fragments in the treatment of Alzheimer's disease and other tauopathies.

Methods of controlling the formation of disulfide bonds in protein solutions

Disclosed herein are methods that have been developed to control the formation of disulfide bonds between polypeptides of a multimeric protein produced by a bioprocess. Also disclosed are protein solution parameters that allow for controlling the formation of disulfide bonds. In one example, the methods disclosed herein can be used to control the proportion of half antibody molecules in an antibody solution.

ANTIBODIES SPECIFIC FOR TGF-BETA

The present disclosure relates, in general, to materials and methods for antibodies specific for transforming growth factor beta (TGFP), including TGF1, TGF2 and TGF3, and uses of these antibodies in the treatment of subjects having cancer, an eye disease, condition or disorder, fibrosis, including ophthalmic fibrosis or fibrosis of the eye, and other conditions or disorders related to TGF expression.

Stable Heterodimeric Antibody Design with Mutations in the Fc Domain

The provided scaffolds have heavy chains that are asymmetric in the various domains (e.g. CH2 and CH3) to accomplish selectivity between the various Fc receptors involved in modulating effector function, beyond those achievable with a natural homodimeric (symmetric) Fc molecule, and increased stability and purity of the resulting variant Fc heterodimers. These novel molecules comprise complexes of heterogeneous components designed to alter the natural way antibodies behave and that find use in therapeutics.

Methods and Compositions for the Treatment of Immune Disorders

The present invention provides a method of treating an immune-related disorder in a subject, comprising administering to the subject an effective amount of an inhibitor of plexin-A4 activity, which results in reducing the plexin-A4 activity in the subject, and thereby treating the immune-related disorder Inhibitors of plexin-A4 activity include, for example, plexin-A4 antibodies and plexin-A4 fusion proteins. The present invention further provides a method of treating an immune-related disorder in a subject, comprising administering to the subject an effective amount of an inhibitor of semaphorin-3A (Sema3A) activity, which results in reducing the Sema3A activity in the subject, thereby treating the immune-related disorder. Inhibitors of Sema3A activity include, for example, Sema3A antibodies and Sema3A fusion proteins.

Antiviral agent, abzyme, primer set, method for producing polynucleotide, and method for producing polypeptide

The present invention provides: a novel antiviral agent containing a human antibody κ light chain, a novel human abzyme containing a human antibody κ light chain; a polynucleotide, a vector, and a transformant, each of which relating to the containing a human antibody κ light chain of the above; a primer set for effectively obtaining a human antibody κ light chain having a function as an antiviral agent or abzyme; and a method for producing a polynucleotide and a method for producing a polypeptide, each of which method utilizes the primer set.

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

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

Method of Providing Disease-Specific Binding Molecules and Targets

Provided are novel specific binding molecules, particularly human antibodies as well as fragments, derivatives and variants thereof that recognize neoepitopes of disease-associated proteins which derive from native endogenous proteins but are prevalent in the body of a patient in a variant form and/or out of their normal physiological context. In addition, pharmaceutical compositions comprising such binding molecules, antibodies and mimics thereof and methods of screening for novel binding molecules, which may or may not be antibodies as well as targets in the treatment of neurological disorders such as Alzheimer's disease are described.

Anti-c epsilon mx antibodies capable of binding to human mige on b lymphocytes

The invention pertains to the generation and utility of antibodies that can bind effectively to CεmX domain on membrane-bound IgE (mIgE) expressed on the surface of human B lymphocytes. The CεmX domain of 52 amino acid residues, located between the CH4 domain and the C-terminal membrane-anchor peptide on human membrane-bound epsilon chain, had been suggested as an antigenic site for immunological targeting of B cells expressing mIgE. Previous reported monoclonal antibodies, including a20, which bind to RADWPGPP (SEQ ID NO:1) peptide at the C-terminal of CεmX, have now been found to bind poorly to mIgE on human B cells. We have discovered that only monoclonal antibodies specific for certain segments, such as GLAGGSAQSQRAPDRVL (SEQ ID NO:2) and HSGQQQGLPRAAGGSVPHPR (SEQ ID NO:3), of CεmX can bind effectively to mIgE on human B cells and hence have the utility for targeting those B cells for the treatment of diseases mediated by IgE.

Lox and loxl2 inhibitors and uses thereof

The present application relates to anti-LOX and anti-LOXL2 antibodies and their use in purification, diagnostic and therapeutic methods. Antibodies include monoclonal antibodies, humanized antibodies and functional fragments thereof. Anti-LOX and anti-LOXL2 antibodies can be used to identify and treat conditions such as a fibrotic condition, angiogenesis, or to prevent a transition from an epithelial cell state to a mesenchymal cell state.

Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery

Herein is reported a polypeptide-polynucleotide-complex as therapeutic agent and its use as tool for the targeted delivery of an effector moiety. The polynucleotide part of the complex is essentially resistant to proteolytic and enzymatic degradation in vivo. Additionally the polypeptide part specifically binds to a compound or structure such as a tissue or organ, a process or a disease. Thus, one aspect as reported herein is a polypeptide-polynucleotide-complex comprising a) a polypeptide specifically binding to a target and conjugated to a first member of a binding pair, b) a polynucleotide linker conjugated at its first terminus to the second member of the binding pair, and c) an effector moiety conjugated to a polynucleotide that is complementary to at least a part of the polynucleotide linker.

Human antibodies to the glucagon receptor

The present invention provides antibodies that bind to the human glucagon receptor, designated GCGR and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human GCGR. The antibodies of the invention are useful for lowering blood glucose levels and blood ketone levels and are also useful for the treatment of diseases and disorders associated with one or more GCGR biological activities, including the treatment of diabetes, diabetic ketoacidosis and long-term complications associated with diabetes, or other metabolic disorders characterized in part by elevated blood glucose levels.

Cd8 imaging constructs and methods of use thereof

Antigen binding constructs that bind to CD8, as well as formulations and methods of using them, are described herein.

COMPOSITIONS AND METHODS TO EXPEDITE ANTIBODY-BASED EXCHANGE IMAGING

A method for exchange imaging of at least two targets in a sample includes (a) incubating a sample with at least two or more target-recognizing antibodies, each bound to a corresponding monovalent tight antibody binder-docketing moiety (MTAB-DM) reagent capable of binding monovalently to the target-recognizing antibodies, (b) applying at least two imager moieties corresponding to the MTAB-DM, either in series, in batches, or in parallel, and (d) imaging the at least two imager moieties either in series, in batches, or in parallel. 1. A method for exchange imaging of at least two targets in a sample comprising:a. incubating a sample with at least two or more target-recognizing antibodies, each bound to a corresponding monovalent tight antibody binder-docketing moiety (MTAB-DM) reagent capable of binding monovalently to the target-recognizing antibodies,b. applying at least two imager moieties corresponding to the MTAB-DM, either in series, in batches, or in parallel,c. imaging the at least two imager moieties either in series, in batches, or in parallel.2. The method of claim 1 , wherein the MTAB comprises Protein A claim 1 , Protein G claim 1 , Protein A/G claim 1 , Protein L claim 1 , or a monovalent antibody fragment.3. The method of claim 1 , wherein all of the target-recognizing antibodies each bound to a corresponding MTAB-DM reagent are incubated with the sample simultaneously.4. The method of claim 1 , wherein the imager moieties are applied in batches with at least one batch having two or more imager moieties and the method having at least two batches and wherein the imaging occurs in at least two batches.5. The method of claim 1 , wherein before incubating the target-recognizing antibodies with the sample claim 1 , an excess of MTAB-DM is employed to prevent an excess of free target-recognizing antibody.6. The method of claim 1 , wherein before incubating the target-recognizing antibodies with the sample claim 1 , free MTAB-DM is removed using ...

Polypeptides

There is provided inter alia a polypeptide comprising an immunoglobulin chain variable domain which binds to TNF-alpha, wherein the immunoglobulin chain variable domain comprises three complementarity determining regions (CDR1-CDR3) and four framework regions (FR1-FR4), wherein CDR1-CDR3 and FR1-FR4 are as defined in the specification.

Antibody Constructs For CDH19 and CD3

The present invention provides to a bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 114-. (canceled)15. A method for treating or ameliorating a melanoma disease , comprising the step of administering to a subject in need thereof a bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell ,wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:(a)(i) CDR-H1 as set forth in SEQ ID NO: 14, CDR-H2 as set forth in SEQ ID NO: 15, CDR-H3 as set forth in SEQ ID NO: 16, CDR-L1 as set forth in SEQ ID NO: 17, CDR-L2 as set forth in SEQ ID NO: 18 and CDR-L3 as set forth in SEQ ID NO: 19;(a)(ii) CDR-H1 as set forth in SEQ ID NO: 27, CDR-H2 as set forth in SEQ ID NO: 28, CDR-H3 as set forth in SEQ ID NO: 29, CDR-L1 as set forth in SEQ ID NO: 30, CDR-L2 as set forth in SEQ ID NO: 31 and CDR-L3 as set forth in SEQ ID NO: 32;(a)(iii) CDR-H1 as set forth in SEQ ID NO: 40, CDR-H2 as set forth in SEQ ID NO: 41, CDR-H3 as set forth in SEQ ID NO: 42, CDR-L1 as set forth in SEQ ID NO: 43, CDR-L2 as set forth in SEQ ID NO: 44 and CDR-L3 as set forth in SEQ ID NO: 45;(a)(iv) CDR-H1 as set forth in SEQ ID NO: 53, CDR-H2 as set forth in SEQ ID NO: 54, CDR-H3 as set ...

Novel t cell receptors and immune therapy using the same

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

Multivalent binding molecules

The present invention relates to a modular multivalent antigen-binding protein complex, use of the antigen-binding protein complex in medicine and use of the antigen-binding protein complex in the prophylaxis, treatment or diagnosis of a disorder or disease.

MONOCLONAL ANTIBODIES AGAINST CD32B

Isolated monoclonal antibodies which bind to human CD32b and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies, and therapeutic and diagnostic methods for using the antibodies. 1. An anti-CD32b antibody which competes for CD32b binding , or binds to the same epitope on CD32b , with a reference anti-CD32b antibody comprising:a) a VH region comprising the sequence of SEQ ID NO:1 and a VL region comprising the sequence of SEQ ID NO: 5,b) a VH region comprising the sequence of SEQ ID NO:9 and a VL region comprising the sequence of SEQ ID NO:13,c) a VH region comprising the sequence of SEQ ID NO:17 and a VL region comprising the sequence of SEQ ID NO:21,d) a VH region comprising the sequence of SEQ ID NO:25 and a VL region comprising the sequence of SEQ ID NO:29,e) a VH region comprising the sequence of SEQ ID NO:33 and a VL region comprising the sequence of SEQ ID NO:37,f) a VH region comprising the sequence of SEQ ID NO:41 and a VL region comprising the sequence of SEQ ID NO:21,g) a VH region comprising the sequence of SEQ ID NO:45 and a VL region comprising the sequence of SEQ ID NO:49,h) a VH region comprising the sequence of SEQ ID NO:61 and a VL region comprising the sequence of SEQ ID NO:65, ori) a VH region comprising the sequence of SEQ ID NO:69 and a VL region comprising the sequence of SEQ ID NO:73.2. A monoclonal anti-CD32b antibody comprising a variable region which allows the antibody to compete with ligand binding to the extracellular domain of CD32b , but wherein a Fab fragment of said antibody does not completely inhibit ligand binding even in the presence of large excess of Fab fragment relative to the amount of ligand.3. The antibody of claim 2 , wherein the antibody induces between 20 and 90% claim 2 , such as between 25 and 80% claim 2 , e.g. between 40 and 80% inhibition of ligand binding at antibody concentrations in the range of 0.1-1 μg/ml in the assay ...

Rspo binding agents and uses thereof

The present invention relates to RSPO-binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human RSPO proteins and modulate β-catenin activity. The present invention further provides methods of using agents that modulate the activity of RSPO proteins, such as antibodies that specifically bind RSPO1, RSPO2, and/or RSPO3 and inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

Antibody-drug conjugate

As an antitumor drug which is excellent in terms of antitumor effect and safety, there is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an antibody via a linker having a structure represented by the following formula: -L1-L2-LP-NH—(CH2)n1-La-Lb-Lc- wherein the antibody is connected to the terminal of L1, and the antitumor compound is connected to the terminal of Lc with the nitrogen atom of the amino group at position 1 as a connecting position.

Anti-igf-i receptor humanized antibody

Provided is a humanized antibody that, through IGF-I receptor, increases muscle mass but does not lower the blood glucose level. This humanized antibody: is an anti-IGF-I receptor humanized antibody, a fragment thereof, or a derivative thereof; has a specific amino acid sequence such as SEQ ID NOs: 1 to 6 serving as a CDR sequence; and specifically binds to IGF-I receptor extracellular domain.

PHARMACEUTICAL COMPOSITION FOR TREATMENT AND/OR PREVENTION OF CANCER

This invention provides an antibody targeting a cancer antigenic protein specifically expressed on the surface of cancer cells and use thereof in a therapeutic and/or preventive agent for cancer. Specifically, this invention provides an antibody or a fragment thereof which has immunological reactivity with a partial CAPRIN-1 polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 5 or an amino acid sequence having 80% or higher sequence identity to the amino acid sequence, and a pharmaceutical composition for treatment and/or prevention of cancer, comprising the antibody or fragment thereof as an active ingredient. 1. An antibody or a fragment thereof which has immunological reactivity with a partial CAPRIN-1 polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 5 or an amino acid sequence having 80% or higher sequence identity to the amino acid sequence.2. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof has cytotoxic activity against a cancer cell expressing a CAPRIN-1 protein.3. The antibody or fragment thereof according to claim 1 , wherein the antibody is a monoclonal antibody or a polyclonal antibody.4. The antibody or fragment thereof according to claim 1 , wherein the antibody is a human antibody claim 1 , a humanized antibody claim 1 , a chimeric antibody claim 1 , a single-chain antibody claim 1 , or a multispecific antibody.5. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof comprises a heavy chain variable region comprising complementarity determining regions of SEQ ID NOs: 8 claim 1 , 9 claim 1 , and 10 (CDR1 claim 1 , CDR2 claim 1 , and CDR3 claim 1 , respectively) and a light chain variable region comprising complementarity determining regions of SEQ ID NOs: 12 claim 1 , 13 claim 1 , and 14 (CDR1 claim 1 , CDR2 claim 1 , and CDR3 claim 1 , respectively) and has immunological reactivity with the CAPRIN-1 protein.6. The ...

Composition comprising material for regulating oct4 modification to repress stemness

The present invention relates to a composition for repressing the sternness of stem cells, which comprises a material for regulating OCT4 modification. The material for regulating OCT4 modification according to the present invention may regulate the phosphorylation or methylation of OCT4 and inhibit Wnt signaling, thereby effectively reducing the sternness of various stem cells. Therefore, since it can be effectively used in inhibition of proliferation, recurrence and metastasis of cancer, and inhibition of resistance to an anticancer agent, and can reduce sternness even in normal stem cells, it is expected that the time for differentiation of embryonic stem cells into specific cells is shortened, and efficiency is increased.

T cell receptor mimic rl9a

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

CONJUGATED ANTI-CD38 ANTIBODIES

Isolated antibodies that bind to human CD38 and cynomolgus CD38 are disclosed. Also disclosed are pharmaceutical compositions comprising the disclosed antibodies, and therapeutic and diagnostic methods for using the disclosed antibodies. 121.-. (canceled)23. An isolated antibody according to wherein said heavy chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:9 and said light chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:10.24. An isolated antibody according to further comprising an Fc domain.25. An isolated antibody according to wherein said Fc domain is human Fc domain.26. An isolated antibody according to wherein said Fc domain is a variant Fc domain.27. An isolated antibody according to wherein said drug moiety is attached to said antibody using a linker.28. An isolated antibody according to wherein said drug moiety is selected from the group consisting of an auristatin claim 27 , a maytansinoid claim 27 , and calicheamicin claim 27 , a dolastatin claim 27 , and a trichothecene.30. An isolated antibody according to wherein said heavy chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:11 and said light chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:12.31. An isolated antibody according to further comprising an Fc domain.32. An isolated antibody according to wherein said Fc domain is human Fc domain.33. An isolated antibody according to wherein said Fc domain is a variant Fc domain.34. An isolated antibody according to wherein said drug moiety is attached to said antibody using a linker.35. An isolated antibody according to wherein said drug moiety is selected from the group consisting of an auristatin claim 34 , a maytansinoid claim 34 , and calicheamicin claim 34 , a dolastatin claim 34 , and a trichothecene.39. A method of treating a cancer ...

HUMAN ANTIBODIES TO NAV1.7

The present invention provides antibodies that bind to the human voltage gated sodium channel designated Na1.7 and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human Na1.7 (hNa1.7). The antibodies of the invention are useful for the treatment of diseases and disorders associated with one or more Na1.7 biological activities, including the treatment of acute or chronic pain conditions, or inflammatory conditions. 1. An isolated human antibody or antigen-binding fragment of a human antibody that specifically binds to at least one extracellular (EC) loop , or a fragment thereof , or to the paddle region , or a fragment thereof , of human Na1.7.2. The isolated antibody of claim 1 , wherein the antibody or an antigen-binding fragment thereof binds to an EC loop selected from EC1 claim 1 , EC2 and EC3 within any one of domains 1 claim 1 , 2 claim 1 , 3 or 4.3. The isolated antibody of claim 2 , wherein the antibody binds to EC3 within domain 1 claim 2 , which domain comprises amino acid residues ranging from about residue number 269 to about residue 338 of SEQ ID NO: 670.4. The isolated antibody of claim 2 , wherein the antibody binds to EC3 within domain 3 claim 2 , which domain comprises amino acid residues ranging from about residue number 1333 to about residue 1382 of SEQ ID NO: 670.5. The isolated antibody of claim 1 , wherein the antibody binds to the paddle region of Nav1.7 claim 1 , which paddle region comprises amino acid residues ranging from about residue number 202 to about residue 232 of SEQ ID NO: 670.65. The isolated human antibody or antigen-binding fragment thereof of any of - claims 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region (HCVR) having an amino acid sequence selected from the group consisting of SEQ ID NO: 2 claims 1 , 6 claims 1 , 10 claims 1 , 14 claims 1 , 18 claims 1 , 22 claims 1 , 26 claims 1 , 30 claims 1 , 34 ...

ANTI-NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE ANTIBODY GENES AND METHODS OF USE THEREOF

The present disclosure provides anti-NAMPT cDNA clones and the amino acid sequences encoded by the clones. Such clones and amino acid sequences are combinable in several variations and can be used to decrease NAD synthesis in a targeted cell population. 1. A method of inhibition of nicotinamide phosphoribosyltransferase (NAMPT) in a targeted cell , said method comprising: [{'sub': H', 'L, 'a variable region of heavy (V) chain of immunoglobulin and a variable region of light (V) chain of immunoglobulin; and'}, {'sub': 'H', 'a peptide linker disposed between and connecting the and Vvariable regions,'}], 'administering to a human or animal a cDNA sequence encoding a recombinant single-chain variable fragment antibody that recognizes and binds to NAMPT comprisingwherein said antibody is specifically expressed and inhibits said NAMPT in a targeted cell of said human or animal.211.-. (canceled)12. The method of claim 1 , wherein said single-chain variable fragment antibody comprises an amino acid sequence having at least 96% sequence homology with SEQ ID NO. 2 or SEQ ID NO. 4.13. The method of claim 1 , wherein said single-chain variable fragment antibody comprises six portions claim 1 , wherein the first portion is an amino acid sequence having at least 96% sequence homology with SEQ ID NO. 10 claim 1 , the second portion is an amino acid sequence having at least 96% sequence homology with SEQ ID NO. 12 or SEQ ID NO. 14 claim 1 , the third portion is an amino acid sequence having at least 96% sequence homology with SEQ ID NO. 16 or SEQ ID NO. 18 claim 1 , the fourth portion is an amino acid sequence having at least 96% sequence homology with SEQ ID NO. 20 claim 1 , the fifth portion is an amino acid sequence having at least 96% sequence homology with SEQ ID NO. 22 or SEQ ID NO. 24 claim 1 , and the sixth portion is an amino acid sequence having at least 96% sequence homology with a sequence SEQ ID NO. 26 or SEQ ID NO. 28.14. (canceled)15. The method of claim 1 , wherein ...

ANTI OLIGOSACCHARIDE ANTIBODY

An antigen-binding protein, or an antigen-binding fragment thereof that binds to a Lewis X type glycan on SLAMF7, comprising () a heavy chain variable domain comprising a VHCDR1 having the amino acid sequence GYTFTSYWIH; a VHCDR2 having the amino acid sequence EINPSNGRTNFNEKFKN and a VHCDR3 having the amino acid sequence VDYDEAY; and (ii) a light chain variable domain comprising a VLCDR1 having the amino acid sequence RSSKSLLHSNGITYLY, a VLCDR2 having the amino acid sequence QMSNLAS, and a VLCDR3 having the amino acid sequence AQNLELWT is provided. Methods of using the antibody for detecting or treating cancer, and a kit comprising the antibody are also provided. 1. An antigen-binding protein , or an antigen-binding fragment thereof , comprising (i) a heavy chain variable domain comprising a VHCDR1 having the amino acid sequence GYTFTSYWIH (SEQ ID NO:1); a VHCDR2 having the amino acid sequence EINPSNGRTNFNEKFKN (SEQ ID NO:2) and a VHCDR3 having the amino acid sequence VDYDEAY (SEQ ID NO:3); and (ii) a light chain variable domain comprising a VLCDR1 having the amino acid sequence RSSKSLLHSNGITYLY (SEQ ID NO:4) , a VLCDR2 having the amino acid sequence QMSNLAS (SEQ ID NO:5) , and a VLCDR3 having the amino acid sequence AQNLELWT (SEQ ID NO:6).2. The antigen-binding protein claim 1 , or antigen-binding fragment thereof claim 1 , as claimed in claim 1 , comprising heavy and light chain CDR regions that are about 80% claim 1 , about 85% claim 1 , about 90% claim 1 , about 95% claim 1 , about 96% claim 1 , about 97% claim 1 , about 98% or about 99% identical to the heavy and light chain CDR regions of (i) and (ii).4. The antigen-binding protein claim 3 , or antigen-binding fragment thereof claim 3 , as claimed in claim 3 , comprising a heavy chain variable region which comprises an amino acid sequence having about 80% claim 3 , about 85% claim 3 , about 90% claim 3 , about 95% claim 3 , about 96% claim 3 , about 97% claim 3 , about 98% or about 99% identity to the amino ...

Tau Imaging Ligands and Their Uses in the Diagnosis and Treatment of Tauopathy

The present invention relates to antibody-based probes (including single domain antibody fragment, scFv molecules, antibodies, antibody fragments, diabodies, and the epitope-binding domains thereof) that are capable of immunospecifically and selectively binding to a phosphoserine-containing epitope of Tau, such as, for example, Tau-phospho-serine 396/404 peptide. Such imaging ligands are useful to detect pathological Tau protein conformer if present in a biological sample, especially in conjunction with the diagnosis of Alzheimer's disease or other tauopathy, and thus provide a diagnostic for Alzheimer's disease and other Tau pathologies. The scFv molecules of the present invention have utility as diagnostic markers for, Alzheimer's disease and related tauopathies and as pharmaceutical compositions for the treatment of such conditions. 1. A. A pharmaceutical composition comprising: wherein said antibody and said epitope-binding portion thereof comprise 6 CDRs, wherein said CDRs are independently selected from, or are independently derived from, the group consisting of:', '(1) a Light Chain CDR1 having the amino acid sequence of SEQ ID NO:12;', '(2) a Light Chain CDR2 having the amino acid sequence of SEQ ID NO:13;', '(3) a Light Chain CDR3 having the amino acid sequence of SEQ ID NO:14;', '(4) a Heavy Chain CDR1 having the amino acid sequence of SEQ ID NO:15;', '(5) a Heavy Chain CDR2 having the amino acid sequence of SEQ ID NO:16; and', '(6) a Heavy Chain CDR3 having the amino acid sequence of SEQ ID NO:17; and', '(B) a pharmaceutically acceptable carrier, diluent and/or stabilizer., '(A) a molecule capable of immunospecifically binding to phosphorylated Tau with greater selectivity than to non-phosphorylated Tau, wherein said molecule is a humanized antibody, or comprises an epitope-binding portion thereof;'}2. The pharmaceutical composition of claim 1 , wherein said molecule is capable of immunospecifically binding to phosphorylated Tau and to a phosphorylated ...

Methods for reducing an adverse immune response to a foreign antigen in a human subject with anti-cd4 antibodies or cd4-binding fragments thereof or cd4-binding molecules

Provided herein are methods of inducing tolerance or reducing an immune response to a foreign antigen in a human subject. The methods include administering anti-CD4 antibodies or CD4-binding fragments thereof or CD4-binding molecules, and the foreign antigen to the human subject.

METHODS OF IDENTIFYING BACTERIA COMPRISING BINDING POLYPEPTIDES

The invention provides methods of identifying bacteria comprising binding polypeptides. The invention also provides methods of identifying bacteria with improved expression of binding polypeptides. The invention also provides methods of identifying binding polypeptides with improved expression. The invention also provides engineered bacteria suitable for use in the methods of the invention. The invention also provides compositions that can be obtained using the methods, for example, anti-interleukin-13 (IL-13) antibodies with improved expression and/or stability. The invention also provides libraries comprising binding polypeptide (e.g., antibody) variants. 1. A method for identifying a bacterium comprising a binding polypeptide that specifically binds a target molecule , the method comprising the steps of:(a) providing a bacterium having an outer membrane permeable to a molecule having a molecular weight greater than 10 kDa, the bacterium expressing a nucleic acid encoding a candidate binding polypeptide, wherein the candidate binding polypeptide is present within the periplasm of the bacterium;(b) contacting the bacterium with a detectably labeled target molecule; and(c) identifying the bacterium as comprising a binding polypeptide by the presence of the labeled target molecule within the periplasm, wherein the bacterium remains viable following step (c).2. A method for identifying a bacterium with improved expression of a binding polypeptide that specifically binds a target molecule , the method comprising the steps of:(a) providing a bacterium having an outer membrane permeable to a molecule having a molecular weight greater than 10 kDa, the bacterium expressing a nucleic acid encoding a binding polypeptide, wherein the binding polypeptide is present within the periplasm of the bacterium;(b) contacting the bacterium with a detectably labeled target molecule; and(c) identifying the bacterium as having improved expression of the binding polypeptide by the presence ...

DIAGNOSIS OF CHRONIC KIDNEY DISEASE BY QUANTITATIVE ANALYSIS OF POST-TRANSLATIONAL MODIFICATIONS OF PLASMA PROTEINS

The present invention relates to methods for diagnosing and/or monitoring the onset or progression of chronic kidney disease (CKD) in a patient by the analysis of post-translational modification of plasma proteins. The present invention provides improved means for diagnosing chronic kidney disease (CKD), and especially for the early recognition of CKD. 1. A method for diagnosing or monitoring pre-disease state or early stage chronic kidney disease (CKD) in an individual , the method comprising:(a) analyzing in vitro the pattern of posttranslational modifications of a plasma protein of an individual to be diagnosed, wherein, if the plasma protein is LDL, the posttranslational modification is not carbamylation, and wherein, if the plasma protein is haemoglobin, the posttranslational modification is not carbamylation or oxidation;(b) comparing the posttranslational modification pattern of the plasma protein of the individual to be diagnosed with the posttranslational modification pattern of the plasma protein of an individual not suffering from CKD; and(c) detecting a difference in the posttranslational modification pattern of the plasma protein of the individual to be diagnosed as compared to the posttranslational modification pattern of the plasma protein from the individual not suffering from CKD.2. The method of claim 1 , further comprising:(d) diagnosing CKD, if the plasma protein of the individual to be diagnosed exhibits at least one posttranslational modification that is absent in the plasma protein of the individual not suffering from CKD.3. The method of claim 1 , wherein the individual to be diagnosed does not exhibit an elevated level of creatinine or albuminurea claim 1 , wherein optionally the individual to be diagnosed exhibits a glomerular filtration rate (GFR) of >90 mL/min.4. The method of claim 1 , wherein the plasma protein is selected from the group consisting of albumin claim 1 , beta-2 microglobulin (β2MG) claim 1 , cystatin C claim 1 , ...

Conjugated anti-cd38 antibodies

Isolated antibodies that bind to human CD38 and cynomolgus CD38 are disclosed. Also disclosed are pharmaceutical compositions comprising the disclosed antibodies, and therapeutic and diagnostic methods for using the disclosed antibodies.

HUMANIZED AXL ANTIBODIES

The present invention refers to monoclonal humanized antibodies, which bind to the extracellular domain of the AXL receptor tyrosine kinase and which at least partially inhibit AXL activity.

Methods for treating melanoma

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

ASSAY REAGENTS FOR A NEUROGRANIN DIAGNOSTIC KIT

The present invention relates to the field of biomarkers. More specifically, the present invention relates to assay reagents useful in detecting neurogranin. In a specific embodiment, the present invention provides an isolated antibody or fragment thereof that specifically binds to neurogranin. In another embodiment, the present invention provides a polynucleotide aptamer that specifically binds neurogranin. 1. An isolated antibody or fragment thereof that specifically binds to neurogranin.2. An isolated antibody or fragment thereof that specifically binds to amino acids 1-78 of SEQ ID NO:4.3. An isolated antibody or fragment thereof that specifically binds to amino acids 55-78 of SEQ ID NO:4.4. The isolated antibody or fragment thereof according to any of - , wherein the antibody or fragment thereof is polyclonal.5. The isolated antibody or fragment thereof according to any of - , wherein the antibody or fragment thereof is monoclonal.6. The isolated antibody or fragment thereof according to any of - , wherein the antibody or fragment thereof is mammalian.7. The isolated antibody or fragment thereof according to any of - , wherein the antibody or fragment thereof is human.8. A hybridoma cell which produces the antibody or fragment thereof according to .9. The isolated antibody or fragment thereof according to any of - claim 5 , wherein the fragment is selected from the group consisting of a Fab fragment; a F(ab′) 2 fragment; a Fv fragment; and a single chain fragment.10. The isolated antibody or fragment thereof according to any of - claim 5 , further comprising a detectable substance coupled to the antibody.11. The isolated antibody or fragment thereof of claim 10 , wherein the detectable substance is selected from the group consisting of an enzyme; a fluorescent label; a radioisotope; and chemiluminescent label.12. The isolated antibody or fragment thereof of claim 10 , which specifically binds to neurogranin in an ELISA.13. The isolated antibody or fragment ...

Anti-IL-23 Antibodies, Compositions, Methods and Uses

An anti-IL-23 antibody, including isolated nucleic acids that encode at least one anti-IL-23 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices. 1. An article of manufacture for human pharmaceutical or diagnostic use , comprising packaging material and a container comprising a solution or a lyophilized form of an IL-23p19 antibody comprising a light chain variable region and a heavy chain variable region , said light chain variable region comprising a complementarity determining region light chain 1 (CDRL1) amino acid sequence selected from the group consisting of SEQ ID NOS:9 , 19 , 29 , and 39; a CDRL2 amino acid sequence selected from the group consisting of SEQ ID NOS:10 , 20 , 30 , and 40; and a CDRL3 amino acid sequence selected from the group consisting of SEQ ID NOS:11 , 21 , 31 , and 41 , said heavy chain variable region comprising a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence selected from the group consisting of SEQ ID NOS:4 , 14 , 24 , and 34; a CDRH2 amino acid sequence selected from the group consisting of SEQ ID NOS:5 , 15 , 25 , and 35; and a CDRH3 amino acid sequence selected from the group consisting of SEQ ID NOS:6 , 16 , 26 , and 36.2. The article of manufacture of claim 1 , wherein said container is a component of a parenteral claim 1 , subcutaneous claim 1 , intramuscular claim 1 , intravenous claim 1 , intrarticular claim 1 , intrabronchial claim 1 , intraabdominal claim 1 , intracapsular claim 1 , intracartilaginous claim 1 , intracavitary claim 1 , intracelial claim 1 , intracerebellar claim 1 , intracerebroventricular claim 1 , intracolic claim 1 , intracervical claim 1 , intragastric claim 1 , intrahepatic claim 1 , intramyocardial claim 1 , intraosteal claim 1 , intrapelvic claim 1 , intrapericardiac claim 1 , intraperitoneal claim 1 , intrapleural claim 1 , intraprostatic ...

Anti-CD112R Compositions and Methods

The invention provides anti-CD112R antibody compositions and their use in treating cancer.

ANTIBODIES SPECIFIC TO HUMAN POLIOVIRUS RECEPTOR (PVR)

The present invention provides monoclonal antibodies that recognize polio virus receptor (PVR) and inhibit its binding to T cell immunoreceptor with Ig and ITIM domains (TIGIT). The present invention further provides pharmaceutical compositions comprising the antibodies and methods for their use in cancer immunotherapy, treating infections and in diagnosis. 1. An isolated monoclonal antibody which binds to human poliovirus receptor (PVR) , or an antibody fragment thereof comprising at least the antigen binding portion , wherein the isolated antibody or antibody fragment comprises:(i) three complementarity determining regions (CDRs) of a heavy-chain (HC) variable region comprising SEQ ID NO: 77 and three CDRs of a light-chain (LC) variable region comprising SEQ ID NO: 79, or an analog or derivative thereof having at least 90% sequence identity with said antibody or fragment sequence; or(ii) three CDRs of a heavy-chain variable region comprising SEQ ID NO: 69 and three CDRs of a light-chain variable region comprising SEQ ID NO: 71, or an analog or derivative thereof having at least 90% sequence identity with said antibody or fragment sequence; or(iii) three CDRs of a heavy-chain variable region comprising SEQ ID NO: 73 and three CDRs of a light-chain variable region comprising SEQ ID NO: 75, or an analog or derivative thereof having at least 90% sequence identity with said antibody or fragment sequence.2. The isolated monoclonal antibody or the antibody fragment according to claim 1 , comprising a CDR set selected from the group consisting of:i. a CDR set of six CDRs wherein: HC CDR1 is selected from GYTFSNYWIE (SEQ ID NO: 36) and SNYWIE (SEQ ID NO: 84); HC CDR2 is EIFPGSGRINFNEKFKG (SEQ ID NO: 38); HC CDR3 is TKIYGNSFDY (SEQ ID NO: 40); LC CDR1 is selected from KASQDVGTAVV (SEQ ID NO: 44) and KASQDVGTAV (SEQ ID NO: 85); LC CDR2 is selected from the group consisting of: WASSRHN (SEQ ID NO: 46), WASSRHA (SEQ ID NO: 56), WASSRHR (SEQ ID NO: 57), WASSRHD (SEQ ID NO: 58), ...

METHODS OF USING BUTYROPHILIN ANTIBODIES FOR TREATING HIV INFECTION

The present invention relates to methods for treating individuals infected with the human immunodeficiency virus (HIV) comprising administering to the subject with an antibody to Butyrophilin that reactivates HIV from latency and/or activates CD4+ T cells.

IMMUNOLOGICAL TREATMENT OF CEREBRAL AUTOSOMAL DOMINANT ARTERIOPATHY WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY

The present invention relates to an anti-Notch 3 antibody therapy useful for treatment of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. In particular, the invention relates to an anti-Notch3 antibody or a fragment thereof having a 2 fold, 4 fold or 10 fold higher affinity to Notch 3 than to Notch 1 or Notch 2 for use in therapy. 1. A method of preventing or treating inward remodelling and reduced myogenic tone of brain arteries in a subject in need thereof comprisingadministering to the subject an effective amount of an anti-Notch3 antibody or a fragment thereof having a 2 fold, 4 fold or 10 fold higher affinity to Notch 3 than to Notch 1 or Notch 2.2. The method according to claim 1 , wherein said anti-Notch3 antibody or fragment thereof is binds to a Notch3ECD deposit and/or Wild Type Notch3ECD.3. The method according to claim 1 , wherein said anti-Notch3 antibody or fragment thereof does not bind Notch 1 or Notch 2.4. The method according to claim 1 , wherein said anti-Notch3 antibody or fragment thereof binds to an epitope comprising amino acids 40-1643 of human Notch3 (SEQ ID NO: 3).5. The method according to wherein said anti-Notch3 antibody or fragment thereof binds to an epitope comprised in amino acids 657-846 of human Notch3 (SEQ ID NO 7).6. The method according to . claim 1 , wherein said anti-Notch3 antibody or fragment thereof is isolated.7. (canceled)8. The method according to claim 1 , wherein the anti-Notch3 antibody or fragment thereof comprises all ofa heavy chain variable region H-CDR1 comprising SEQ ID NO: 8a heavy chain variable region H-CDR2 comprising SEQ ID NO: 9a heavy chain variable region H-CDR3 comprising SEQ ID NO: 10a light chain variable region L-CDR1 comprising SEQ ID NO:12a light chain variable region L-CDR2 comprising SEQ ID NO: 13 anda light chain variable region L-CDR3 comprising SEQ ID NO:14.910-. (canceled)11. The method according to claim 1 , wherein said anti-Notch3 ...

Uses and Compositions for Treatment of Rheumatoid Arthritis

The invention provides methods, uses and compositions for the treatment of rheumatoid arthritis. The invention describes methods and uses for treating rheumatoid arthritis wherein a TNFα inhibitor, such as a human TNFα antibody, or antigen-binding portion thereof. Also described are methods for determining the efficacy of a TNFα inhibitor for treatment of rheumatoid arthritis in a subject.

BINDING PROTEINS AND METHODS OF USE THEREOF

The present disclosure provides binding proteins, such as antibodies, that bind to a GDNF Family Receptor Alpha Like (GFRAL) protein, including human GFRAL protein, and methods of their use. 1106.-. (canceled)107. An antibody or antigen-binding fragment thereof that binds to a GDNF Family Receptor Alpha-Like (GFRAL) protein , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL) , wherein:(a) the VH comprises a VH complementarity determining region (CDR)1, a VH CDR2, and a VH CDR3 from the amino acid sequence set forth in SEQ ID NO:7, and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 from the amino acid sequence set forth in SEQ ID NO:8;(b) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 from the amino acid sequence set forth in SEQ ID NO:15, and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 from the amino acid sequence set forth in SEQ ID NO:16;(c) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 from the amino acid sequence set forth in SEQ ID NO:1, and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 from the amino acid sequence set forth in SEQ ID NO:2;(d) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 from the amino acid sequence set forth in SEQ ID NO:11, and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 from the amino acid sequence set forth in SEQ ID NO:12;(e) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 from the amino acid sequence set forth in SEQ ID NO:21, and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 from the amino acid sequence set forth in SEQ ID NO:22;(f) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 from the amino acid sequence set forth in SEQ ID NO:23, and the VL comprises a VL CDR1, a VL CDR2, and a VL CDR3 from the amino acid sequence set forth in SEQ ID NO:24;(g) the VH comprises a VH CDR1, a VH CDR2, and a VH CDR3 from the amino acid sequence set forth in SEQ ID NO:25, and the VL comprises a VL ...

Novel agonistic anti tnfr2 antibody molecules

Described are novel antagonistic antibody molecules that specifically bind to TNFR2 on a target cell and thereby block TNF-α binding to TNFR2 and block TNFR2 signaling, wherein the antibody molecules also bind to Fc receptors via the Fc region. Also described is the use of such antibody molecules in treatment of cancer or infections caused by intracellular pathogens.

EBV ANTIGEN SPECIFIC T-CELL RECEPTOR AND USE THEREOF

The present invention relates to an EBV antigen specific T-cell receptor and the use thereof. Specifically, the present invention provides T cells specific for LMP1 of EBV using a T-cell receptor which is highly specific for specific epitopes derived from an EBV antigen, LMP1. In addition, the EBV antigen specific T-cell can be used in the prevention or treatment of EBV-associated diseases. 1. A T-cell receptor capable of binding to a peptide derived from a latent membrane protein 1 (LMP1) of an Epstein-Barr Virus (EBV) on being presented by a major histocompatibility complex (MHC) , wherein the peptide is represented by an amino acid sequence set forth in SEQ ID NO: 1.2. The T-cell receptor of claim 1 , wherein the T-cell receptor comprises a α-chain and a β-chain claim 1 , and each chains includes three complementarity determining regions (CDRs) represented by the following amino acid sequences:CDR1α—SEQ ID NO: 3CDR2α—SEQ ID NO: 4CDR3α—SEQ ID NO: 5CDR1β—SEQ ID NO: 7CDR2β—SEQ ID NO: 8CDR3β—SEQ ID NO: 93. The T-cell receptor of claim 2 , wherein the α-chain of the T-cell receptor is represented by the amino acid sequence set forth in SEQ ID NO: 2.4. The T-cell receptor of claim 1 , wherein the β-chain of the T-cell receptor is represented by the amino acid sequence set forth in SEQ ID NO: 6.5. A nucleotide sequence encoding the T-cell receptor of .6. The nucleotide sequence of claim 5 , wherein the nucleotide sequence comprises a nucleotide sequence encoding an α-chain of the T-cell receptor represented by a base sequence set forth in SEQ ID NO: 10 and a nucleotide sequence encoding an β-chain of the T-cell receptor represented by a base sequence set forth in SEQ ID NO: 14.7. A vector comprising the nucleotide sequence of .8. A host cell transformed with the vector of .9. The host cell of claim 8 , wherein the host cell comprises T cells.10. A composition for prevention or treatment of EBV-associated diseases claim 7 , comprising the vector of .11. The composition ...

Methods for Determining the Likelihood of Survival and for Predicting Likelihood of Metastasis in Cancer Patients

The present invention relates generally to methods of accurately quantifying HER2 and/or p95 expression in subjects with a HER2 positive cancer and indicating the risk of brain relapse in such patients. 139-. (canceled)40. A method of treating a subject with a HER2-positive cancer , comprising:(a) obtaining a sample of a HER2 positive tumor from a subject diagnosed with a HER2 positive cancer, wherein the subject does not have a detectable brain metastasis;(b) providing a p95-HER2 monoclonal antibody that specifically binds to p95-HER2 protein having a first amino acid corresponding to methionine 611 of HER2 protein, wherein the p95-HER2 monoclonal antibody does not bind to full length HER2;(c) providing a binding compound that binds to the p95-HER2 monoclonal antibody, wherein the binding compound comprises a molecular tag covalently attached thereto via a cleavable linkage;(d) quantifying the amount of p95-HER2 in the sample by the steps of (i) incubating the sample with the p95-HER2 monoclonal antibody and the binding compound, (ii) treating the sample with a cleaving agent to release the molecular tag from the binding compound, and (iii) measuring the amount of released molecular tag as indicative of p95-HER2 levels in the sample to determine the amount of p95-HER2 protein in the sample; and(e) monitoring the subject by performing imaging on the subject's brain at different times after initial diagnosis of the HER2 positive cancer to detect brain metastasis if the amount of p95-HER2 protein in the sample is above a predetermined cutoff amount of p95-HER2 determined in a reference population of subjects having the HER2-positive cancer.41. The method of claim 40 , wherein the subject's cancer has been characterized as HER2-positive based on at least one of an elevated level of HER2 gene expression claim 40 , an elevated level of HER2 protein level claim 40 , or HER2 gene amplification.42. The method of claim 40 , wherein the subject's cancer comprises breast ...

Antibodies Specific for TGF-Beta

The present disclosure relates, in general, to materials and methods for antibodies specific for transforming growth factor beta (TGFβ), including TGFβ1, TGFβ2 and TGFβ3, and uses of these antibodies in the treatment of subjects having cancer, an eye disease, condition or disorder, fibrosis, including ophthalmic fibrosis or fibrosis of the eye, and other conditions or disorders related to TGFβ expression. 1. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes an antibody that binds transforming growth factor beta (TGFβ)1 , TGFβ2 and TGFβ3 comprising:(a) a heavy chain CDR1 amino acid sequence set forth in Table 1 or SEQ ID NOs: 13, 19 and 25, or a variant thereof in which one or two amino acids have been changed;(b) a heavy chain CDR2 amino acid sequence set forth in Table 1 or SEQ ID NOs: 14, 20 and 26 that is from the same heavy chain variable region as (a), or a variant thereof in which one or two amino acids have been changed; and(c) a heavy chain CDR3 amino acid sequence set forth in Table 1 or SEQ ID NOs: 15, 21 and 27 that is from the same heavy chain variable region as (a), or a variant thereof in which one or two amino acids have been changed.2. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes an antibody that binds transforming growth factor beta (TGFβ)1 , TGFβ2 and TGFβ3 comprising:(a) a heavy chain CDR1 amino acid sequence set forth in Table 1 or SEQ ID NOs: 13, 19 and 25, or a variant thereof having at least 70% identity thereto;(b) a heavy chain CDR2 amino acid sequence set forth in Table 1 or SEQ ID NOs: 14, 20 and 26 that is from the same heavy chain variable region as (a), or a variant thereof having at least 70% identity thereto; and(c) a heavy chain CDR3 amino acid sequence set forth in Table 1 or SEQ ID NOs: 15, 21 and 27 that is from the same heavy chain variable region as (a), or a variant thereof having at least 70% identity thereto.3. An isolated nucleic acid molecule comprising a ...

Antibodies Against Carcinoembryonic Antigen for Cancer Therapy and Diagnosis

The invention relates to antibodies against carcinoembryonic antigen (CEA) which have a direct cell growth inhibition activity on tumor cells expressing CEA and to their use for the treatment and diagnosis of cancer. 1. An antibody against carcinoembryonic antigen (CEA) which has a direct tumor cell growth inhibition activity on tumor cells expressing CEA and which comprises light-chain (VL) and heavy-chain (VH) variable domains complementarity-determining region (CDR) sequences selected from the group consisting of:(a) the VL-CDR1 sequence of SEQ ID NO: 1; the VL-CDR2 sequence AAT; the VL-CDR3 sequence of SEQ ID NO: 2; the VH-CDR1 sequence of SEQ ID NO: 3; the VH-CDR2 sequence of SEQ ID NO: 4; the VH-CDR3 sequence of SEQ ID NO: 5;(b) the VL-CDR1 sequence of SEQ ID NO: 6; the VL-CDR2 sequence YAS; the VL-CDR3 sequence of SEQ ID NO: 7; the VH-CDR1 sequence of SEQ ID NO: 8; the VH-CDR2 sequence of SEQ ID NO: 9; the VH-CDR3 sequence SEQ ID NO: 10; and(c) VL-CDR1, VL-CDR2, VL-CDR3, VH-CDR1, VH-CDR2 and VH-CDR3 sequences which differ from the sequences AAT, YAS and SEQ ID NO: 1 to 10 by 1 or 2 amino acid differences, and wherein the antibody comprising said sequence variants specifically recognizes CEA and has a direct tumor cell growth inhibition activity on tumor cells expressing CEA.2. The antibody according to claim 1 , which has a variable region formed by the association of a VL domain of SEQ ID NO: 11 and a VH domain of SEQ ID NO: 12 or a VL domain of SEQ ID NO: 13 and a VH domain of SEQ ID NO: 14.3. The antibody according to claim 1 , which binds to the epitope bound by the antibody having a variable region formed by the association of a VL domain of SEQ ID NO: 11 and a VH domain of SEQ ID NO: 12 or a VL domain of SEQ ID NO: 13 and a VH domain of SEQ ID NO: 14.4. The antibody according to claim 1 , which is a human/mouse chimeric antibody.5. (canceled)6. The antibody according to claim 1 , which is an IgA.7. The antibody according to claim 1 , which is a ...

MONOCLONAL ANTIBODY RECOGNIZING SIALYLATED SUGAR CHAINS

The purpose of the present invention is to provide a novel monoclonal antibody having high affinity and that strictly recognizes, as a sugar chain epitope, only a “Siaα2,6Galβ1,4GlcNAc (6′-Sialyl-LacNAc): CDw75” sugar chain structure, being a molecular target for diagnosis of the malignancy of tumors. An anti-CDw75 monoclonal antibody is provided that recognizes “CDw75” sugar chain structures but does not recognize similar sugar chain structures indicated by “Galβ1,4GlcNAc”, “Siaα2,3Galβ1,4GlcNAc”, or “Siaα2,6Galβ1,4Glc”, by using a glycolipid antigen bonding a carrier lipid compound “HOCHCH (NH—CO—(CH)—CH)—(CH)—CH(C12L)” developed by the inventors to a “CDw75” sugar chain. The obtained anti-CDw75 monoclonal antibody is an excellent detection drug for B-cell lymphoma, gastric cancer, or colorectal cancer, an excellent diagnostic agent for tumor malignancy, etc., an excellent treatment agent for B-cell lymphoma, gastric cancer, or colorectal cancer, and an excellent prevention/treatment drug for influenza. 1. An anti-CDw75 monoclonal antibody or a fragment thereof , characterized in that recognizes sugar chain structure CDw75 represented by Siaα2 ,6Galβ1 ,4GlcNAc but not a sugar chain structure represented by Galβ1 ,4GlcNAc ,; Siaα2 ,3Galβ1 ,4GlcNAc; or 6′-Sialyllactose (Siaα2 ,6Galβ1 ,4Glc).3. The anti-CDw75 monoclonal antibody or a fragment thereof according to claim 1 , the antibody being produced by hybridoma FR9 (deposit number: NITE BP-01516).4. A composition comprising the anti-CDw75 monoclonal antibody or a fragment thereof according to claim 1 , and a pharmaceutically acceptable carrier.5. The pharmaceutical composition according to claim 4 , the composition being used for inhibition and/or treatment of B-cell lymphoma claim 4 , gastric cancer claim 4 , or colorectal cancer.6. The pharmaceutical composition according to claim 4 , the composition being used for prevention and/or treatment of influenza.7. The composition according to claim 4 , the composition ...

Anti-cd38 antibodies

Isolated antibodies that bind to human CD38 and cynomolgus CD38 are disclosed. Also disclosed are pharmaceutical compositions comprising the disclosed antibodies, and therapeutic and diagnostic methods for using the disclosed antibodies.

Isoform specific anti-her4 antibodies

Compositions and methods useful for detecting and treating cancers which express the HER4 JM-a isoform are disclosed.

ANTI-HUMAN PD-1 HUMANIZED MONOCLONAL ANTIBODY AND APPLICATION THEREOF

The present invention relates to the biomedicine field, in particular to an anti-human PD-1 humanized monoclonal antibody and its applications. The invention obtains an anti-human PD-1 humanized monoclonal antibody with good specificity, high affinity and stability by screening, and the antibody can specifically bind to human PD-1 instead of binding to other members of CD28 family, block the binding of PD-L1 and PD-1 with CD80 and partially restore functions of T-cells, so it can significantly inhibit the growth of tumor. 1. An anti-human PD-1 humanized monoclonal antibody or an antigen binding part thereof is characterized in: it comprises a CDR region selected from a group of the following: The sequences of heavy chains CDR1 , CDR2 and CDR3 are shown as SEQ ID NO: 17-19 , respectively. The sequences of light chains CDR1 , CDR2 and CDR3 are shown as SEQ ID NO: 35-37 , respectively , or includes sequences that bind antigenic epitopes same to above sequences.2. The anti-human PD-1 humanized monoclonal antibody or its antigen binding part thereof as described in is characterized in that it also includes sequences selected from the following framework regions of heavy chain variable region: FR1 claim 1 , FR2 claim 1 , FR3 and FR4 claim 1 , as shown in SEQ ID NO: 20-23 claim 1 , respectively claim 1 , or other sequences that having greater than 70% claim 1 , 80% claim 1 , 85% claim 1 , 90% claim 1 , 95% claim 1 , 99% identity to them claim 1 , respectively.3. The anti-human PD-1 humanized monoclonal antibody or its antigen binding part thereof as described in is characterized in that claim 2 , the sequence of heavy chain is as shown in SEQ ID NO: 8.4. The anti-human PD-1 humanized monoclonal antibody or its antigen binding part thereof as described in is characterized in that it also includes sequences selected from the following framework regions of light chain variable region: FR1 claim 1 , FR2 claim 1 , FR3 and FR4 claim 1 , as shown in SEQ ID NO: 38-41 claim 1 , ...

Methods And Compositions For Treating And Preventing Disease Associated With Alpha 8 Beta 1 Integrin

Provided herein are monoclonal antibodies that recognize, bind to, and block interactions of other molecules with integrin α8β1. Also provided herein are methods of using said antibodies to treat gastrointestinal motility disorders. 1. An isolated monoclonal antibody , wherein the antibody specifically binds to an integrin α8β1 receptor and wherein the antibody competes for binding of the receptor with Milk fat Globule Epidermal Growth Factor like 8 (Mfge8).2. The isolated antibody of any one of claim 1 , wherein the antibody is recombinant.3. The isolated antibody of claim 1 , wherein the antibody is an IgG claim 1 , IgM claim 1 , IgA or an antigen binding fragment thereof.4. The isolated antibody of claim 1 , wherein the antibody is a Fab′ claim 1 , a F(ab′)2 claim 1 , a F(ab′)3 claim 1 , a monovalent scFv claim 1 , a bivalent scFv claim 1 , or a single domain antibody.5. The isolated antibody of claim 1 , wherein the antibody is a human claim 1 , humanized claim 1 , or de-immunized antibody.6. The isolated antibody of claim 1 , wherein the antibody binds with a high affinity to a protein having at least a 90% sequence identity to SEQ ID NO: 1.7. The isolated antibody of claim 6 , wherein the antibody binds with a high affinity to a protein having the sequence of SEQ ID NO: 1.8. A composition comprising an antibody of in a pharmaceutically acceptable carrier.9. An isolated polynucleotide molecule comprising a nucleic acid sequence encoding a protein incorporated into an antibody of .10. A method for treating a gastrointestinal motility disorder in a patient comprising administering to the patient an antibody that disrupts the α8β1/Mfge8 interaction in an amount effective to treat the gastrointestinal motility disorder.11. A method for treating a subject having a gastrointestinal motility disorder comprising administering an effective amount of an antibody of to the subject.12. The method of claim 11 , wherein the gastrointestinal motility disorder is diabetic ...

PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF ADAM17 SUBSTRATE DEPENDENT CANCERS

The present disclosure relates to the treatment of cancers and, more particularly, to the treatment of ADAM17 substrate dependant cancers which are refractory. The pharmaceutical composition contains an ADAM17 antibody (it recognizes an epitope within the membrane proximal domain of ADAM17 localized between the residues 564 and 642) characterized by the sequences of its variable chains. 119.-. (canceled)20. A method of treating ADAM17 substrate dependent tumors , comprising administering to a patient in need thereof a pharmaceutical composition comprising an effective amount of an ADAM17 antibody , or an antigen-binding fragment thereof , said ADAM17 antibody having the following properties:a) it binds to ADAM17 with a Kd of 3 nM or less;b) it recognizes an epitope within the membrane proximal domain (MPD) of ADAM17, said MPD being localized between the residues 564 and 642;c) it does not bind to ADAM10;{'sub': '50', 'd) it inhibits the cellular shedding of at least one ADAM17 substrate with an ICof 200 pM or less;'}{'sub': 'off', 'sup': '−4', 'e) it has an off rate for ADAM17 of Kof 3×10or smaller;'}f) it inhibits the growth and/or proliferation in vivo of at least one tumor cell expressing ADAM17;g) it does not bind to the murine ADAM17; andh) it binds to the cynomolgus ADAM17.21. The method of claim 20 , wherein said ADAM17 substrate dependent tumors are:(i) tumors characterized by an elevated level of at least one ADAM17 substrate compared to the basal level of said at least one substrate, or(ii) tumors that are resistant or refractory to treatment with an ErbB therapy.22. The method of claim 20 , wherein said ADAM17 antibody inhibits the shedding of at least one substrate selected from TNF-α claim 20 , TGF-α claim 20 , AREG claim 20 , HB-EGF with an ICof 500 pM or less.23. The method of claim 20 , wherein 7 said ADAM17 antibody inhibits the shedding of the substrates TNF-α claim 20 , TGF-α claim 20 , AREG and HB-EGF with an ICof 500 pM or less.24. The method of ...

Anti-gm-csf antibodies and uses thereof

Provided are anti-GM-CSF antibodies or fragments thereof including humanized antibodies and fragments. Also provided are uses of the antibodies and fragments for therapeutic, diagnostic and prognostic purposes. Therapeutic uses of the antibodies and fragments, for example include the treatment of inflammatory and autoimmune diseases and disorders.

BASEHIT, a high-throughput assay to identify proteins involved in host-microbe interaction

The invention provides a BASEHIT screening method for identifying proteins that are involved in host-microbe interactions which may function as therapeutic targets. 1. A method of detecting molecules involved in microbial interactions , the method comprising the steps of:a) contacting a first population of cells comprising one or more display molecules with a second population of cells comprising cells from at least one microbial species;b) selecting at least one bound display molecule:microbe complex; andc) detecting the identity of at least one of a bound display molecule.2. The method of claim 1 , wherein the first population of cells comprises a population of yeast cells.3. The method of claim 1 , wherein the display molecule comprises at least one of a protein claim 1 , a peptide claim 1 , a fusion protein claim 1 , an antibody claim 1 , a nanobody claim 1 , an affibody claim 1 , an anticalin claim 1 , and a monobody.4. The method of claim 3 , wherein the display molecule comprises a nanobody comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1 claim 3 , SEQ ID NO:2 claim 3 , SEQ ID NO:3 claim 3 , SEQ ID NO:4 claim 3 , SEQ ID NO:5 claim 3 , SEQ ID NO:6 claim 3 , SEQ ID NO:7 claim 3 , SEQ ID NO:8 claim 3 , SEQ ID NO:9 and SEQ ID NO:10.5. The method of claim 1 , wherein the at least one display molecule comprises a library of host protein sequences.6. The method of claim 1 , wherein the microbial species is selected from the group consisting of a commensal microbe of the host species and a pathogenic microbe of the host species.7. (canceled)8. The method of claim 1 , further comprising identifying the at least one bound display molecule as a therapeutic target.9. A method of detecting a microbe that can interact with at least one target sequence claim 1 , the method comprising the steps of:a) contacting a first population of cells comprising at least one display molecule comprising at least one target sequence, with a second ...

Altered april binding antibodies

The invention relates to APRIL-binding antibodies, which bind the same epitope of human APRIL as an antibody having an antigen binding site of hAPRIL.01A. The antibodies of the present invention comprise specific selections of framework sequences of the V H and V L domains and have unexpected features in comparison to hAPRIL.01A. The invention further relates to compositions comprising an antibody of the invention and to the medical and diagnostic uses of the antibodies and compositions.

Anti-complement c1s antibodies and uses thereof

The present disclosure provides antibodies that bind complement C1s protein; and nucleic acid molecules that encode such antibodies. In some embodiments, such anti-complement C1s antibodies inhibit proteolytic activity of C1s. The present disclosure also provides compositions comprising such antibodies, and methods to produce and use such antibodies, nucleic acid molecules, and compositions.

Antibodies that bind to ccr6 and their uses

The present invention relates to antibodies or fragments thereof that bind to CCR6. More specifically, the present invention relates to an antibody or fragment thereof that binds to CCR6 comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 31, and/or a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 32, SEQ ID NO: 190, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 254 or SEQ ID NO: 255 and/or a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 33; and/or comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 34, SEQ ID NO: 191, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO: 246 or SEQ ID NO: 256, and/or a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 35, SEQ ID NO: 247, SEQ ID NO: 248 or SEQ ID NO:257 and/or a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 36 or SEQ ID NO: 192 or SEQ ID NO: 193.

ANTIBODY BASED REAGENTS THAT SPECIFICALLY RECOGNIZE TOXIC OLIGOMERIC FORMS OF TAU

The invention relates to antibodies, antibody fragments and binding agents that specifically recognize oligomeric tau but do not bind to monomelic tau, fibrillar tau or non-disease associated forms of tau. 1. An antibody or antibody fragment that specifically recognizes oligomeric tau but does not bind monomeric tau , fibrillar tau or non-disease associated forms of tau.2. The antibody or antibody fragment of claim 1 , wherein the oligomeric tau is dimeric tau or trimeric tau.3. The antibody or antibody fragment of claim 2 , wherein the oligomeric tau is trimeric tau.4. The antibody or antibody fragment of claim 1 , wherein the oligomeric tau is soluble.5. The antibody or antibody fragment of claim 1 , wherein said antibody fragment is isolated according to a method comprising the steps of: (i) a generic protein; and', '(ii) mononeric forms of tau;, 'a. a negative panning of a scFV phage library wherein said negative panning eliminates phage that bind to non-desired antigens wherein said negative panning comprises serially contacting phage withand monitoring the binding of said phage to the generic protein and monomeric forms of tau using Atomic Force Microscope (AFM) Imaging and repeating steps (i) and (ii) until no phage is observed binding to antigen by said AFM imaging to produce an aliquot of phage;b. contacting the aliquot of phage with tau oligomers and incubating for time sufficient to allow binding of phage to said oligomers; andc. eluting the bound phage particles from step (b).6. An antibody or antibody fragment isolated according to a method comprising the steps of: (i) a generic protein; and', '(ii) mononeric forms of tau;', 'and until less than 5% of the phage is observed binding to antigen, which produces an aliquot of phage;, '(a) negative panning a scFV phage library comprising serially contacting phage with(b) positive panning of the aliquot from step (a) comprising contacting the aliquot of phage from step (a) with tau oligomers, and incubating ...

Co-Therapy Comprising A Small Molecule CSF-1R Inhibitor And An Agonistic Antibody That Specifically Binds CD40 For The Treatment Of Cancer

The present invention is directed to methods for treating cancer, preferably a solid tumor or hematological malignancy, including for example pancreatic cancer, lung cancer (including but not limited to non-small cell lung cancer (NSCLC)), prostate cancer, colorectal cancer, breast cancer, melanoma or non-Hodgkin's lymphoma, comprising administering to a subject in need thereof a therapeutically effective amount of co-therapy comprising, consisting or consisting essentially of (a) a small molecule CSF-1R inhibitor and (b) an agonistic antibody that binds CD40.

Antibodies Directed Against Lymphocyte Activation Gene 3 (LAG-3)

The invention relates to an isolated immunoglobulin heavy chain polypeptide and an isolated immunoglobulin light chain polypeptide that bind to a protein encoded by the Lymphocyte Activation Gene-3 (LAG-3). The invention provides a LAG-3-binding agent that comprises the aforementioned immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide. The invention also provides related vectors, compositions, and methods of using, the LAG-3-binding, agent to treat a disorder or disease that is responsive to LAG-3 inhibition, such as cancer or an infectious disease.

AMYLOID-BETA BINDING PROTEINS

The present invention relates to amyloid-beta (Aβ) binding proteins. Antibodies of the invention have high affinity to Aβ(20-42) globulomer or any Aβ form that comprises the globulomer epitope. Method of making and method of using the antibodies of the invention are also provided. 117-. (canceled)18. A method for treating a subject for a disease or a disorder selected from the group consisting of Systemic AL amyloidosis , Nodular AL amyloidosis , Systemic AA amyloidosis , Prostatic amyloidosis , Hemodialysis amyloidosis , Familial visceral amyloidosis , Senile systemic amyloidosis , Familial cardiac amyloidosis and Down syndrome by administering to the subject an effective amount of an anti-Aβ(20-42) globulomer antibody comprising:a first amino acid sequence which is at least 90% identical to SEQ ID NO:2 or SEQ ID NO:3; and a second amino acid sequence which is at least 90% identical to SEQ ID NO: 1,wherein the first amino acid sequence comprises three complementary determining regions consisting of amino acids 31-35, 50-65 and 98-101, respectively, of SEQ ID NO:2 or SEQ ID NO:3; and the second amino acid sequence comprises three complementary determining regions consisting of amino acids 24-39, 55-61 and 94-102, respectively, of SEQ ID NO: 1.19. The method of claim 18 , wherein the first amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:4 claim 18 , SEQ ID NO:5 claim 18 , SEQ ID NO:6 claim 18 , SEQ ID NO:7 claim 18 , SEQ ID NO:8 claim 18 , SEQ ID NO:9 claim 18 , SEQ ID NO:10 claim 18 , and SEQ ID NO:11.20. The method of claim 18 , wherein the second amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:12 claim 18 , SEQ ID NO:13 claim 18 , SEQ ID NO:14 claim 18 , SEQ ID NO:15 claim 18 , and SEQ ID NO:16.21. The method of claim 18 , wherein the first amino acid sequence is at least 90% identical to an amino acid sequence selected ...

Method for the treatment of myasthenia gravis

The disclosure relates to a method of treating or preventing Myasthenia Gravis (MG) in a human in need thereof using an anti-FcRn antibody or antigen binding fragment thereof. In particular, the method provides suitable dosage regimens for such treatment.

Binding proteins and methods of use thereof

The present disclosure provides binding proteins, such as antibodies, that bind to a GDNF Family Receptor Alpha Like (GFRAL) protein, including human GFRAL protein, and methods of their use.

ANTI-IL1RAP ANTIBODIES AND METHODS OF USE THEREOF

The present invention provides binding proteins, such as antibodies and antigen-binding fragments, which specifically bind to human interleukin-1 receptor accessory protein (hu-IL1RAP) and fully block the IL-1, IL-33, and IL-36 intracellular signaling pathways. Compositions comprising such binding proteins and methods of making and using such binding proteins are also provided. 1. An anti-IL1RAP antibody comprising: (i) a first light chain hypervariable region (HVR-L1) , a second light chain hypervariable region (HVR-L2) , and a third light chain hypervariable region (HVR-L3) , and/or (ii) a first heavy chain hypervariable region (HVR-H1) , a second heavy chain hypervariable region (HVR-H2) , and a third heavy chain hypervariable region (HVR-H3); wherein:(a) HVR-L1 comprises an amino acid sequence RASENIXXNXX (SEQ ID NO: 10), wherein X at position 7 is Y or W, X at position 8 is S, H, K, L, M, N, Q, R, or Y, X at position 10 is L, A, G, I, M, N, Q, S, T, V, or Y, and X at position 11 is A, G, N, S, or T;(b) HVR-L2 comprises an amino acid sequence GXXNXAD (SEQ ID NO: 36), wherein X at position 2 is A, D, E, F, G, H, I, K, L, M, N, Q, R, S, T, V, W, or Y, X at position 3 is K, G, or N, and X at position 5 is L, F, H, W, or Y;(c) HVR-L3 comprises an amino acid sequence XXFXTXPRT (SEQ ID NO: 62), wherein X at position 1 is Q or S, X at position 2 is H or S, X at position 4 is W, A, F, G, H, I, K, L, M, V, or Y, and X at position 6 is T, I, or V;(d) HVR-H1 comprises an amino acid sequence XXXXXXX (SEQ ID NO: 77), wherein X at position 1 is F, A, D, E, G, H, I, K, M, N, P, Q, R, S, T, W, or Y, X at position 2 is S, E, G, K, P, Q, R, or T, X at position 3 is N, D, E, G, K, Q, or R, X at position 4 is Y, A, D, E, H, S, or V, X at position 5 is A, N, or S, X at position 6 is M, V, or W, and X at position 7 is S, or G;(e) HVR-H2 comprises an amino acid sequence TXXXXXXXXYXLXDVKG (SEQ ID NO: 140), wherein X at position 2 is V, A, N, or S, X at position 3 is T or S, X at ...

Anti-cxcr5 antibodies and compositions and uses thereof

The invention provides antibodies, and antigen-binding fragments thereof, that specifically bind to CXCR5. The antibodies can be afucosylated and exhibit increased ADCC compared with the otherwise identical fucosylated antibodies. The invention includes uses, and associated methods of using the antibodies.

Anti-Polyubiquitin Antibodies and Methods of Use

The invention provides anti-polyubiquitin antibodies and methods of using the same. 145-. (canceled)46. A method of separating K11-linked polyubiquitinated protein from non-K11-linked polyubiquitinated protein in a sample , comprising contacting the sample with an antibody that binds K11-linked polyubiquitin , wherein the antibody comprises an HVR-L1 sequence selected from SEQ ID NOs: 2 and 57 to 60 , an HVR-L2 sequence selected from SEQ ID NOs: 3 and 61 , an HVR-L3 sequence of SEQ ID NO: 4 , an HVR-H1 sequence selected from SEQ ID NOs: 6 to 11 , an HVR-H2 sequence selected from SEQ ID NOs: 12 to 17 and 67 , and an HVR-H3 sequence selected from SEQ ID NOs: 18 to 23 , 68 and 69.47. The method of claim 46 , wherein the antibody comprises an HVR-L1 sequence selected from SEQ ID NOs: 2 and 57 to 60 claim 46 , an HVR-L2 sequence selected from SEQ ID NOs: 3 and 61 claim 46 , an HVR-L3 sequence of SEQ ID NO: 4 claim 46 , an HVR-H1 sequence of SEQ ID NO: 11 claim 46 , an HVR-H2 sequence selected from SEQ ID NOs: 17 and 67 claim 46 , and an HVR-H3 sequence selected from SEQ ID NOs: 23 claim 46 , 68 and 69.48. The method of claim 46 , wherein the antibody comprises an HVR-L1 sequence selected from SEQ ID NOs: 58 and 59 claim 46 , an HVR-L2 sequence of SEQ ID NO: 3 claim 46 , an HVR-L3 sequence of SEQ ID NO: 4 claim 46 , an HVR-H1 sequence of SEQ ID NO: 11 claim 46 , an HVR-H2 sequence of SEQ ID NO: 67 claim 46 , and an HVR-H3 sequence of SEQ ID NO: 23.49. The method of claim 46 , wherein the antibody comprises comprising an HVR-L1 sequence of SEQ ID NO: 59 claim 46 , an HVR-L2 sequence of SEQ ID NO: 3 claim 46 , an HVR-L3 sequence of SEQ ID NO: 4 claim 46 , an HVR-H1 sequence of SEQ ID NO: 11 claim 46 , an HVR-H2 sequence of SEQ ID NO: 67 claim 46 , and an HVR-H3 sequence of SEQ ID NO: 23.50. The method of claim 46 , wherein the antibody comprises a heavy chain variable region comprising a sequence with at least 95% sequence identity to SEQ ID NO: 72 and a light chain ...

ANTI-KIT ANTIBODIES AND USES THEREOF

Provided herein, in one aspect, are antibodies that immunospecifically bind to a human KIT antigen comprising the fourth and/or fifth extracellular Ig-like domains (that is, D4 and/or D5 domains), polynucleotides comprising nucleotide sequences encoding such antibodies, and expression vectors and host cells for producing such antibodies. The antibodies can inhibit KIT activity, such as ligand-induced receptor phosphorylation. Also provided herein are kits and pharmaceutical compositions comprising antibodies that specifically bind to a KIT antigen, as well as methods of treating or managing a KIT-mediated disorder or disease and methods of diagnosing a KIT-mediated disorder or disease using the antibodies described herein. 1. An antibody , which immunospecifically binds to a D4/D5 region of human KIT (SEQ ID NO: 15) , comprising:(i) a variable light (“VL”) chain region comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 22, respectively; and(ii) a variable heavy (“VH”) chain region comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 23, SEQ ID NO: 24, and SEQ ID NO: 25, respectively.2. The antibody of claim 1 , which immunospecifically binds to a D4/D5 region of human KIT (SEQ ID NO: 15) claim 1 , comprising:(A) a VL chain region comprising the amino acid sequence of SEQ ID NO: 2, and a VH chain region comprising the amino acid sequence of SEQ ID NO: 3; or(B) a VL chain region comprising the amino acid sequence of SEQ ID NO: 2 and a VH chain region comprising the amino acid sequence of SEQ ID NO: 5.3. The antibody of claim 1 , which immunospecifically binds to a D4/D5 region of human KIT (SEQ ID NO: 15) claim 1 , comprising:a VL chain region comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 22, respectively; and a VH chain region comprising the amino acid sequence of SEQ ID NO: 3 or 5.4. ...

Use of Semaphorin-4D Binding Molecules for Treating Neurodegenerative Disorders

Provided herein are methods for alleviating symptoms in a subject having a neurodegenerative disorder, comprising administering to the subject an effective amount of an isolated binding molecule which specifically binds to semaphorin-4D (SEMA4D) or to its Plexin-B1 or Plexin-B2 receptors.

Genetic Products Differentially Expressed In Tumors And The Use Thereof

The present technology relates to the identification of genetic products expressed in association with tumors and to coding nucleic acids for the expressed products. An embodiment of the present technology also relates to the therapy and diagnosis of disease in which the genetic products are aberrantly expressed in association with tumors, proteins, polypeptides and peptides which are expressed in association with tumors, and to the nucleic acids coding for the polypeptides, peptides and proteins.

Immunotherapeutic molecules and uses

The invention provides molecule comprising: (i) a targeting moiety capable of directly or indirectly targeting to unwanted cells, and (ii) a further moiety that has a masked immune cell binding region so as to prevent binding of the further moiety to an immune cell, wherein the masked immune cell binding region is capable of being selectively unmasked when the molecule is in the vicinity of the unwanted cells so as to allow binding of the further moiety to an immune cell.

Anti-MCAM Antibodies And Associated Methods Of Use

Described herein are anti-MCAM antibodies and antigen binding fragments thereof that are capable of inhibiting the interaction between MCAM and its ligand, a protein comprising a laminin α-4 chain. These anti-MCAM antibodies and antigen binding fragments thereof may be useful for, for example, treating inflammatory conditions characterized by the infiltration of MCAM-expressing cells into a site of inflammation in the body. 110-. (canceled)11. An isolated anti-MCAM antibody , or antigen binding fragment thereof , said antibody or antigen binding fragment thereof comprising a light chain variable region and a heavy chain variable region , wherein:(a) the light chain variable region comprises the amino acid sequence of SEQ ID NO:30 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:35;(b) the light chain variable region comprises the amino acid sequence of SEQ ID NO:40 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:45;(c) the light chain variable region comprises the amino acid sequence of SEQ ID NO:50 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:55;(d) the light chain variable region comprises the amino acid sequence of SEQ ID NO:60 or 98 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:65 or 95;(e) the light chain variable region comprises the amino acid sequence of any one of SEQ ID NOS:70, 71, or 72 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:77;(f) the light chain variable region comprises the amino acid sequence of any one of SEQ ID NOS:83 or 84 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:89, or(g) the light variable region comprises the amino acid sequence of SEQ ID NO:2 and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:7.12. The isolated anti-MCAM antibody claim 11 , or antigen binding fragment thereof claim 11 , ...

Anti-lilrb antibodies and uses thereof

Disclosed herein are specific and pan antibodies that interact with one or more members of the LILRB receptor family. In some instances, also described herein are pharmaceutical compositions that comprise one or more anti-LILRB antibodies and methods of modulating inflammatory macrophage activation, lymphocyte activation, and phagocytosis.

MeCP2 ISOFORM-SPECIFIC ANTIBODY FOR DETECTION OF ENDOGENOUS EXPRESSION OF MeCP2E1

An antibody that binds a MeCP2E1 isoform of MeCP2 protein, wherein the antibody comprises a region comprising the amino acid sequence of SEQ ID NO:4. A method for detecting and/or monitoring a disease or a disorder caused by an over-expression or an under-expression of a MeCP2E1 isoform of MeCP2 protein, comprising the steps of: (i) obtaining a first sample from a mammalian subject; (ii) contacting the first sample with the anti-MeCP2E1antibody; (iii) removing unbound antibody from the sample; (iv) conducting an immunoassay on the first sample to determine a first value for expression of the MeCP2E1 isoform; (v) comparing the first value to a reference value for expression of the MeCP2E1 isoform in healthy mammalian subjects; wherein a deviation of the first value from the reference value indicates the presence of a disease or a disorder caused by an over-expression or an under-expression of the MeCP2E1 isoform. 1. An antibody that binds a MeCP2E1 isoform of Methyl CpG Binding Protein 2 , wherein said antibody comprises a region comprising the amino acid sequence set forth in SEQ ID NO:4 or SEQ ID NO:5.2. The antibody of claim 1 , wherein said antibody does not bind a MeCP2E2 isoform of Methyl CpG Binding Protein 2.3. The antibody of claim 1 , wherein said antibody is a polyclonal antibody.4. The antibody of claim 1 , wherein said antibody is a monoclonal antibody.5. The antibody of claim 1 , wherein the antibody is conjugated to a detectable label.6. The antibody of claim 5 , wherein the label is a fluorescent label claim 5 , an enzymatic label claim 5 , a luminescent label claim 5 , or a chromaphore label.7. A composition comprising an antibody that binds a MeCP2E1 isoform of Methyl CpG Binding Protein 2 claim 5 , wherein said antibody comprises a region comprising the amino acid sequence set forth in SEQ ID NO:4.8. The composition of claim 7 , wherein said antibody does not bind a MeCP2E2 isoform of Methyl CpG Binding Protein 2.9. The composition of claim 7 , ...

ANTIBODIES SPECIFIC FOR HYPERPHOSPHORYLATED TAU AND METHODS OF USE THEREOF

The present invention relates to a class of monoclonal antibody that specifically binds the phosphorylated serine 396 residue on pathological hyperphosphorylated (PH F) tau (pS396) with improved affinity, as well as to methods of using these molecules and their tau binding fragments in the treatment of Alzheimer's disease and other tauopathies. 1. A monoclonal antibody , or an epitope-binding fragment thereof , comprising:(a) a Light Chain CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:31; SEQ ID NO:32; SEQ ID NO:33; SEQ ID NO:34; SEQ ID NO:35; SEQ ID NO:36; SEQ ID NO:37; SEQ ID NO:38; SEQ ID NO:40; and SEQ ID NO:46;(b) a Light Chain CDR2 comprising the amino acid sequence of SEQ ID NO:4; SEQ ID NO:41; and SEQ ID NO:47;(c) a Light Chain CDR3 comprising the amino acid sequence of SEQ ID NO:5; SEQ ID NO:42; and SEQ ID NO:48;(d) a Heavy Chain CDR1 comprising the amino acid sequence of SEQ ID NO:6; SEQ ID NO:43; SEQ ID NO:49; SEQ ID NO:52; and SEQ ID NO:55; 'and', '(e) a Heavy Chain CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7; SEQ ID NO:28; SEQ ID NO:29; SEQ ID NO:30; SEQ ID NO:44; SEQ ID NO:50; SEQ ID NO:53; and SEQ ID NO:56;'}(f) a Heavy Chain CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:39; SEQ ID NO:45; SEQ ID NO:51; SEQ ID NO:54; and SEQ ID NO:57.2. A monoclonal antibody , or an epitope-binding fragment thereof , comprising:(a) a Light Chain selected from the group consisting of SEQ ID NO:12; SEQ ID NO:16; SEQ ID NO:17; SEQ ID NO:18; SEQ ID NO:19; SEQ ID NO:20; SEQ ID NO:21; SEQ ID NO:22 and SEQ ID NO:23; and(b) a Heavy Chain selected from the group consisting of SEQ ID NO:11; SEQ ID NO:13; SEQ ID NO:14; SEQ ID NO:15; SEQ ID NO:24; SEQ ID NO:25; SEQ ID NO:26; and SEQ ID NO:27.3. The monoclonal antibody claim 1 , or epitope-binding fragment thereof claim 1 , according to claim 1 , wherein:(a) the Light Chain is SEQ ...

ANTAGONISTIC CD40 MONOCLONAL ANTIBODIES AND USES THEREOF

The disclosure provides for antibodies that bind CD40, including a humanized antibody and a chimeric antibody with different Fc domains. The antibodies bind CD40 and do not exhibit CD40 agonist activity. The antibodies may comprise a modified IgG1 Fc domain, and exhibit minimal activation of immature dendritic cells. Compositions comprising antibodies, methods of use for treatment of diseases involving CD40 activity, and use in the preparation of a medicament for treatment of a disease involving CD40 activity are provided. 113-. (canceled)14. A nucleic acid encoding an isolated antibody or antigen binding portion thereof , that specifically binds to human CD40 , wherein said antibody comprises a heavy chain , and a light chain , wherein:said heavy chain comprises a CDR1 comprising GYTFTDLSMHW (SEQ ID NO: 1), a CDR2 comprising YITPSSGYTAYNQKFKG (SEQ ID NO: 2), a CDR3 comprising LILQRGAY (SEQ ID NO: 3) and a human heavy chain constant region; andsaid light chain comprises a CDR1 comprising RASKNVDSYGNSFMHW (SEQ ID NO: 4), a CDR2 comprising RASNLES (SEQ ID NO: 5), and a CDR3 comprising QQSNEDPLT (SEQ ID NO: 6) and a human light chain constant region, andsaid human heavy chain constant region is a human IgG1 Fc domain comprising either (1) a mutation at Kabat position 238 that reduces binding to Fc-gamma-receptors (FcgRs), wherein proline 238 (P238) is mutated to one of the residues selected from the group consisting of lysine, serine, alanine, arginine and tryptophan, and wherein the antibody or antigen binding portion has reduced FcgR binding; or (2) or an alanine substituted at Kabat position 297.15. An expression vector comprising the nucleic acid molecule of .16. A cell transformed with the expression vector of .17. A method of preparing an anti-human CD40 antibody claim 15 , or antigen binding portion thereof claim 15 , comprising:{'claim-ref': {'@idref': 'CLM-00016', 'claim 16'}, 'a) expressing the antibody, or antigen binding portion thereof, in the cell of ; ...

MICROPARTICULATE SYSTEM FOR COLONIC DRUG DELIVERY

A delivery system that allows for targeted released of therapeutics in selected regions of the GI tract is provided. The delivery system is adapted to deliver a certain type of therapeutic, such as a protein-based therapeutic, to a certain area of the GI tract, such the colon of a subject. The delivery vehicle comprises a microbead coated with layers that include: a subcoat layer and a therapeutic agent layer. The delivery vehicles may also include an enteric coating layer and/or a sustained release layer. 1. A delivery vehicle comprising a microbead coated with a subcoat layer , a therapeutic agent layer , and an enteric coating layer ,wherein the microbead comprises one or more physiologically inert substances;wherein the subcoat layer substantially coats the microbead;wherein the therapeutic agent layer substantially coats the subcoat layer, and wherein the therapeutic agent layer comprises a therapeutic agent and an excipient; andwherein the enteric coating layer substantially coats the therapeutic agent layer, and wherein the enteric coating layer comprises a pH-resistant composition.2. The delivery vehicle of claim 1 , wherein the microbead comprises one or more of a sugar claim 1 , a starch claim 1 , microcrystalline cellulose (MCC) claim 1 , a biodegradable polymer claim 1 , sodium phosphate claim 1 , and calcium phosphate.3. The delivery vehicle of claim 2 , wherein the sugar is selected from the group consisting of lactose claim 2 , sucrose claim 2 , mannitol claim 2 , trehalose claim 2 , maltodextrin claim 2 , dextrose claim 2 , fructose and a polysaccharide.4. The delivery vehicle of claim 2 , wherein the biodegradable polymer is poly(lactic-co-glycolic acid) (PLGA) or a copolymer of L-lactic acid and glycolic acid.5. The delivery vehicle of claim 1 , wherein the microbead further comprises a medicament.6. The delivery vehicle of claim 1 , wherein the microbead has an average particle diameter of between 1 and 1000 μm.7. The delivery vehicle of claim 1 , ...

Erbb2-targeting antibody

The present invention relates to an antibody, particularly a monoclonal antibody, which binds a novel epitope of the ERBB2 tyrosine kinase receptor, wherein the unique features of said binding enable interference with receptor-mediated signalling and downstream biological effects in a novel and unanticipated fashion not obtainable with state-of-the-art therapeutic antibodies. The present invention relates to compositions comprising such an antibody and its humanized derivative, as well as methods using such an antibody and derivative, particularly in ERBB2-low/non-amplified breast cancers, particularly in combination with Trastuzumab and Pertuzumab.

MODIFIED ANTIBODIES AND RELATED COMPOUNDS, COMPOSITIONS AND METHODS OF USE

Provided herein are modified antibodies, compounds used to make them, and intermediates in their synthesis; corn positions; formulations and methods, including methods of treating diseases, disorders or conditions, for example, cancer, in humans. 5. The method of claim 1 , wherein the bond represents a single bond.6. The method of claim 1 , wherein each Y and Y′ is independently selected from the group consisting of a halo claim 1 , a substituted thiol claim 1 , and a substituted sulfonate.7. The method of claim 1 , wherein each Y and Y′ is independently selected from the group consisting of chloro claim 1 , bromo claim 1 , fluoro claim 1 , and iodo.8. The method of claim 1 , wherein each Y and Y′ is independently selected from an optionally substituted thiophenyl claim 1 , an optionally substituted thionaphthyl claim 1 , an optionally substitued thiopyridyl claim 1 , an optionally substituted isoquinolinyl claim 1 , and an optionally substituted phenylsulfonate.15. The modified antibody of claim 11 , wherein the bond represents a single bond.16. The modified antibody of claim 11 , wherein n is 4.17. The modified antibody of claim 11 , wherein A is an antibody that is specific to a cancer antigen.18. The modified antibody of claim 11 , wherein A is selected from the group consisting of alemtuzumab claim 11 , anitumumab claim 11 , bevacizumab claim 11 , brentuximab claim 11 , cetuximab claim 11 , gemtuzumab claim 11 , glembatumumab claim 11 , inotuzumab claim 11 , ipilimumab claim 11 , lovortumumab claim 11 , milatuzumab claim 11 , ofatumumab claim 11 , rituximab claim 11 , tositumomab claim 11 , and trastuzumab.19. A modified antibody or a formulation thereof obtainable by the method of .20. A process claim 1 , which comprises:(i) reducing one or more interchain cysteine-cysteine disulfide bonds in an antibody with a reducing agent; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(ii) reacting the free thiol groups from the one or more reduced interchain ...

Human Anti-SOD1 Antibodies

Provided are novel human copper-zinc superoxide dismutase, also known as superoxide dismutase 1 or SOD1, specific antibodies as well as fragments, derivatives and variants thereof as well as methods related thereto. Assays, kits, and solid supports related to antibodies specific for SOD1 are also disclosed. The antibody, immunoglobulin chain(s), as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for SOD1 targeted immunotherapy and diagnosis, respectively. 1. A human monoclonal anti-SOD1 antibody , preferably characterized in that the antibody is capable of binding to misfolded or aggregated SOD1; and wherein the antibody binds to physiological SOD1 dimers , preferentially recognizes the misfolded or aggregated SOD1 over physiological SOD1 dimers , or does not substantially recognize physiological SOD1 dimers; and/or preferably binds to human wildtype and murine SOD1.2. The antibody of claim 1 , which specifically binds an SOD1 epitope which comprises or consists of the amino acid sequence DGVADVS (SEQ ID NO: 2) claim 1 , GGPKDEERHVG (SEQ ID NO: 51) claim 1 , LKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHE FGDNT (SEQ ID NO: 52) claim 1 , IIGRTLV (SEQ ID NO: 53) claim 1 , LGNVTADKDGV (SEQ ID NO: 54) claim 1 , HEKADDLGKGGNEES (SEQ ID NO: 55) claim 1 , EDSVISL (SEQ ID NO: 56) claim 1 , KTGNAGS (SEQ ID NO: 57) claim 1 , LGNVTADKDGV (SEQ ID NO: 58) or GGPKDEE (SEQ ID NO: 59).3. The antibody of or or an SOD1 binding fragment thereof comprising in its variable region at least one complementarity determining region (CDR) as depicted in any one of -IL claim 1 , preferably comprising an amino acid sequence of the Vand/or Vregion as depicted in any one of -IL.4. An antibody or antigen-binding molecule which competes with an antibody of any one of to for specific binding to SOD1.5. The antibody of any one of to claim 1 , which is selected from the group consisting of a chimeric murine-human or a murinized antibody ...

Anti-Neuropilin Antigen-Binding Proteins and Methods of Use Thereof

Provided herein are antigen-binding proteins (ABPs) that selectively bind to NRP-1 and its isoforms and homologs, and compositions comprising the ABPs. Also provided are methods of using the ABPs, such as therapeutic and diagnostic methods.

MODIFIED ANTIBODIES AND RELATED COMPOUNDS, COMPOSITIONS, AND METHODS OF USE

Provided herein are modified antibodies, compounds used to make them, and intermediates in their synthesis; compositions; formulations and methods, including methods of treating diseases, disorders or conditions, for example, cancer, in humans. 5. The method of claim 1 , wherein the bond represents a single bond.6. The method of claim 1 , wherein each Y and Y′ is independently selected from the group consisting of a halo claim 1 , a substituted thiol claim 1 , and a substituted sulfonate.7. The method of claim 1 , wherein each Y and Y′ is independently selected from the group consisting of chloro claim 1 , bromo claim 1 , fluoro claim 1 , and iodo.8. The method of claim 1 , wherein each Y and Y′ is independently selected from an optionally substituted thiophenyl claim 1 , an optionally substituted thionaphthyl claim 1 , an optionally substituted thiopyridyl claim 1 , an optionally substituted isoquinolinyl claim 1 , and an optionally substituted phenylsulfonate.15. The modified antibody of claim 11 , wherein the bond represents a single bond.16. The modified antibody of claim 11 , wherein n is 4.17. The modified antibody of claim 11 , wherein A is an antibody that is specific to a cancer antigen.18. The modified antibody of claim 11 , wherein A is selected from the group consisting of alemtuzumab claim 11 , anitumumab claim 11 , bevacizumab claim 11 , brentuximab claim 11 , cetuximab claim 11 , gemtuzumab claim 11 , glembatumumab claim 11 , inotuzumab claim 11 , ipilimumab claim 11 , lovortumumab claim 11 , milatuzumab claim 11 , ofatumumab claim 11 , rituximab claim 11 , tositumomab claim 11 , and trastuzumab.19. A modified antibody or a formulation thereof obtainable by the method of .20. A process claim 1 , which comprises:(i) reducing one or more interchain cysteine-cysteine disulfide bonds in an antibody with a reducing agent; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(ii) reacting the free thiol groups from the one or more reduced interchain ...

Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions

The disclosure pertains to methods of treating or preventing a disease or condition associated with and/or induced by soluble A-beta oligomer such as Alzheimer's disease by administering to a subject in need thereof conformation specific and/or selective antibodies or binding fragments thereof and related products.

PROTEIN STANDARD COMPOSITIONS AND METHODS OF MAKING AND USING THE SAME

The invention generally relates to protein standard compositions and methods of making the same. Also contemplated are kits including the protein standard compositions or kits for making the protein standard compositions and methods of using the protein standard compositions to quantify the abundance of a phosphorylated protein in a sample. 1. A protein standard comprising a kinase domain of a tyrosine kinase protein comprising a phosphorylated amino acid residue and a cysteine residue with a blocked sulfhydryl group.2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. The protein standard of claim 1 , wherein the kinase domain is a kinase domain from an Anaplastic Lymphoma Kinase (ALK) protein.8. The protein standard of claim 7 , wherein the kinase domain comprises SEQ ID NO: 1 or a polypeptide having at least 95% sequence identity to SEQ ID NO: 1.9. The protein standard of claim 8 , wherein the kinase domain comprises SEQ ID NO: 2 or a polypeptide having at least 95% sequence identity to SEQ ID NO: 2.10. The protein standard of claim 8 , wherein the kinase domain comprises a phosphorylated tyrosine residue at position 31 of SEQ ID NO: 1 claim 8 , at position 218 of SEQ ID NO: 1 claim 8 , or both.11. The protein standard of claim 9 , wherein the kinase domain comprises a phosphorylated tyrosine residue at position 69 of SEQ ID NO: 2 claim 9 , at position 256 of SEQ ID NO: 2 claim 9 , or both.12. The protein standard of claim 8 , wherein the kinase domain comprises 2-11 cysteine residues with a blocked sulfhydryl group.13. The protein standard of claim 1 , wherein the blocked sulfhydryl group comprises an alkylated sulfhydryl group.14. The protein standard of claim 1 , further comprising a buffer.15. (canceled)16. (canceled)17. (canceled)18. (canceled)19. (canceled)20. (canceled)21. (canceled)22. (canceled)23. (canceled)24. (canceled)25. (canceled)26. A method for quantitating the abundance of a phosphorylated protein in a sample claim 1 , the method ...

Human antibodies to the glucagon receptor

The present invention provides antibodies that bind to the human glucagon receptor, designated GCGR and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human GCGR. The antibodies of the invention are useful for lowering blood glucose levels and blood ketone levels and are also useful for the treatment of diseases and disorders associated with one or more GCGR biological activities, including the treatment of diabetes, diabetic ketoacidosis and long-term complications associated with diabetes, or other metabolic disorders characterized in part by elevated blood glucose levels.

GLYCOENGINEERED BINDING PROTEIN COMPOSITIONS

Provided are glycoengineered populations of Fc domain-containing binding proteins with a reduced anti-drug immune response (ADA). Also provided are methods of treating disease using such compositions, and methods and host for making such compositions. 1. A glycoengineered binding protein composition comprising a population of Fc domain-containing binding proteins having an G/M ratio of at least 10:1 , wherein the total percent amount of G1 and G2 glycoforms in the population is more than 50% , wherein the total percent amount of M3-M9 glycoforms is less than 10% , wherein Fc domain containing binding proteins of the composition comprise the same polypeptide sequence , and wherein the glycoengineered binding protein composition exhibits a lower ADA response and/or a greater serum half-life than a non-hypergalactosylated population of Fc domain-containing binding proteins.2. The composition of claim 1 , wherein the total percent amount of G1 and G2 glycoforms in the population is more than 80% claim 1 , or more than 99%.3. The composition of claim 1 , wherein less than 5% claim 1 , or less than 1% claim 1 , or less than 0.1% of the Fc domain-containing binding proteins in the population comprise M3-M9 glycoforms.4. The composition of claim 1 , wherein the population of Fc domain-containing binding proteins is selected from the group consisting of:(1) a population of Fc domain-containing binding proteins having a G1/2:M ratio of at least 10:1, at least 50:1, at least 80:1, or at least 99:1,(2) a population of Fc domain-containing binding proteins having a GS:M ratio of at least 10:1, at least 50:1, at least 80:1, or at least 99:1 and(3) a population of Fc domain-containing binding proteins having a Gtotal:M ratio of at least 10:1, at least 50:1, at least 80:1, or at least 99:1.5. (canceled)6. (canceled)7. The composition of claim 1 , wherein the Fc domain-containing binding proteins in the population comprises an antigen-binding portion of an antibody or a non-antibody ...

Novel cell wall polymers of enterococcus faecalis and uses thereof

The present invention relates to enterococcal cell wall polymers and their uses in the prevention and therapy of bacterial infection.

COMPLEX-SPECIFIC ANTIBODIES AND ANTIBODY FRAGMENTS AND ITS USE

The present invention provides antibodies and fragments thereof that specifically detect the complex of a specific cognate antigen-binding moiety, in particular antibodies, and its antigen. The antibodies of the present disclosure do not bind either said cognate antigen binding moiety or said antigen alone and this can be used e.g. to directly detect antigen-bound antigen-binding moieties. Further disclosed are methods for production and use of said antibodies and antibody fragments. 1. A method to identify an isolated monoclonal antibody , or fragment thereof which specifically binds to the complex of a cognate antibody and its antigen and does not bind either said cognate antibody or said antigen alone , said method comprising(a) screening a library of antibodies or antibody fragments against a complex of a specific cognate antibody and its antigen in the presence of the unbound antigen and an antibody that has the same isotype as the specific cognate antibody,(b) isolating said complex of a specific cognate antibody and its antigen and the bound antibodies or antibody fragments, and(c) identifying and isolating said antibodies or antibody fragments.2. The method according to claim 1 , wherein the epitope of said isolated monoclonal antibody or fragment thereof includes one or more amino acids of a variable region of the specific cognate antibody.3. The method according to claim 1 , wherein said isolated monoclonal antibody or fragment thereof is a humanized or human monoclonal antibody or fragment.4. The method according to claim 1 , wherein said specific cognate antibody is a murine claim 1 , chimeric claim 1 , humanized or human monoclonal antibody or fragment thereof.5. The method according to claim 4 , wherein the specific cognate antibody or fragment thereof is selected from the group consisting of Adalimumab claim 4 , MOR103 claim 4 , Rituximab claim 4 , Trastuzumab claim 4 , Alemtuzumab claim 4 , Bevacizumab claim 4 , Cetuximab claim 4 , Gemtuzumab claim 4 ...

ANTI-C (EPSILON)MX ANTIBODIES CAPABLE OF BINDING TO HUMAN MIGE ON B LYMPHOCYTES

The invention pertains to the generation and utility of antibodies that can bind effectively to CεmX domain on membrane-bound IgE (mIgE) expressed on the surface of human B lymphocytes. The CεmX domain of 52 amino acid residues, located between the CH4 domain and the C-terminal membrane-anchor peptide on human membrane-bound epsilon chain, had been suggested as an antigenic site for immunological targeting of B cells expressing mIgE. Previous reported monoclonal antibodies, including a20, which bind to RADWPGPP (SEQ ID NO:1) peptide at the C-terminal of CεmX, have now been found to bind poorly to mIgE on human B cells. We have discovered that only monoclonal antibodies specific for certain segments, such as GLAGGSAQSQRAPDRVL (SEQ ID NO:2) and HSGQQQGLPRAAGGSVPHPR (SEQ ID NO:3), of CεmX can bind effectively to mIgE on human B cells and hence have the utility for targeting those B cells for the treatment of diseases mediated by IgE. 1. A CεmX-specific antibody capable of binding to membrane-bound IgE on human B lymphocytes and incapable of binding to RADWPGPP peptide.2. An antibody of claim 1 , wherein the antibody is a mouse monoclonal antibody.3. An antibody of claim 1 , wherein the antibody is a chimeric antibody comprising the variable regions of a mouse monoclonal antibody and constant regions of human antibodies.4. An antibody of claim 1 , wherein the antibody is a humanized monoclonal antibody comprising essentially the hypervariable regions of a mouse monoclonal antibody and the framework regions and constant regions of human antibodies.5. An antibody of claim 1 , wherein the antibody is a human antibody.6. A fragment of a CεmX -specific antibody of claim 1 , capable of binding to membrane-bound IgE on human B lymphocytes and incapable of binding to RADWPGPP peptide.7. A fragment of an antibody of claim 6 , wherein the fragment is Fab claim 6 , F(ab)′ claim 6 , or single-chain Fv.8. A therapeutic method of using an antibody of to treat IgE-mediated diseases.9. ...

ANTIBODY DRUG CONJUGATES

The present invention relates to anti-cKIT antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer. 1. An antibody drug conjugate of the formula{'br': None, 'sub': m', 'n, 'Ab-(L-(D))'}or a pharmaceutically acceptable salt thereof; whereinAb is an antibody or antigen binding fragment thereof that specifically binds to an epitope of human cKIT;L is a linker;D is a drug moiety;m is an integer from 1 to 8; andn is an integer from 1 to 10.2. The antibody drug conjugate of claim 1 , wherein said n is 3 or 4.3. The antibody drug conjugate of or claim 1 , wherein said antibody or antigen binding fragment thereof specifically binds the extracellular domain of cKIT (SEQ ID NO.160).4. The antibody drug conjugate of or claim 1 , wherein said antibody or antigen binding fragment specifically binds to an epitope of human cKIT at domains 1-3 (SEQ ID NO.155).5. The antibody drug conjugate of or claim 1 , wherein said antibody or antigen binding fragment thereof specifically binds human cKIT at SEQ ID NO. 161 and SEQ ID NO. 162.6. The antibody drug conjugate of any of - claim 1 , wherein said antibody or antigen binding fragment thereof comprises:(i) a heavy chain variable region that comprises (a) a HCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO: 76, (b) a HCDR2 of SEQ ID NO: 77, (c) a HCDR3 of SEQ ID NO: 78; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 85, (e) a LCDR2 of SEQ ID NO: 86, and (f) a LCDR3 of SEQ ID NO: 87;(ii) a heavy chain variable region that comprises (a) a HCDR1 of SEQ ID NO: 22, (b) a HCDR2 of SEQ ID NO: 23, (c) a HCDR3 of SEQ ID NO: 24; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 31, (e) a LCDR2 of SEQ ID NO: 32, and (f) a LCDR3 of SEQ ID NO: 33;(iii) a heavy chain variable region that comprises (a) a HCDR1 of SEQ ID NO: 130, (b) a HCDR2 of SEQ ID NO: 131, (c) a HCDR3 of SEQ ID NO: 132; and a light chain variable region that comprises: (d) a ...

USE OF CD28-SPECIFIC MONOCLONAL ANTIBODIES FOR PRODUCING A PHARMACEUTICAL COMPOSITION FOR TREATING VIRUS INFECTIONS

The invention relates to the use of monoclonal antibodies which are specific for CD28 and activate the T lymphocytes of several up to all subgroups without the occupation of an antigen receptor of the T lymphocytes and which therefor activate said lymphocytes in an antigen unspecific manner or the invention relates to the use of an analogue thereof for producing a pharmaceutical composition in the form of a preparation or a preparation packet for treating virus infections in humans or lower warm-blooded animals having infected T lymphocytes. The pharmaceutical composition additionally contains a virus inhibitor. The invention also relates to a corresponding pharmaceutical composition and a treatment plan including the pharmaceutical composition. 118.-. (canceled)19. A method for treating a retroviral infection , comprising administering to a subject in need thereof , a pharmaceutical composition comprising an effective amount of: a monoclonal antibody specific for CD28 and which is capable of activating T lymphocytes of several to all sub-groups without occupying an antigen receptor of the T lymphocytes , a virus inhibitor comprising a pyrimidine nucleoside analog; and optionally one or more of a reverse transcriptase inhibitor and a protease inhibitor.20. The method of claim 19 , wherein the retroviral infection is a human immunodeficiency virus (HIV) infection.21. The method of claim 19 , wherein the monoclonal antibody specific for CD28 is CMY-2 (DSM ACC2353) claim 19 , ANC28.1/5D10 claim 19 , or a humanized variant thereof.22. The method of claim 19 , wherein the pyrimidine nucleoside analog is 3′-azido-3′-desoxythymidine (AZT or zidovudine).23. The method of claim 19 , wherein reverse transcriptase inhibitor is pyrimidine nucleoside analog.24. The method of claim 23 , wherein the pyrimidine nucleoside analog is selected from 3TC claim 23 , d4T (stavudine) claim 23 , ddl (didanosine) and ddC (zalcitabine).25. The method of claim 19 , wherein reverse ...

Multi-specific binding molecules targeting aberrant cells

Described are proteinaceous molecules comprising at least two, preferably three to six, binding domains that bind specifically to at least two different binding sites on aberrant cells. These multi-domain and multi-specific binding molecules are preferably used in selectively modulating biological processes. The provided binding molecules are of particular use in pharmaceutical compositions for the treatment of diseases related to cellular aberrancies, such as cancers and autoimmune diseases.

NOVEL T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME

The present invention pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular the TAA Serine protease inhibitor Kazal-type 2 (SPINK2). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and SPINK2 binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of SPINK2 expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention. 1. A method of treating a patient who has cancer , comprising administering to the patient a population of transformed T cells expressing at least one vector encoding a T cell receptor (TCR) , SEQ ID NOs: 1, 3, 7, and 9, or', 'SEQ ID NOs: 13, 15, 19, and 21, or', 'SEQ ID NOs: 25, 27, 31, and 33, or', 'SEQ ID NOs: 37, 39, 43, and 45, or', 'SEQ ID NOs: 49, 51, 55, and 57, or', 'SEQ ID NOs: 61, 63, 67, and 69, or', 'SEQ ID NOs: 73, 75, 79, and 81, or', 'SEQ ID NOs: 85, 87, 91, and 93, or', 'SEQ ID NOs: 97, 99, 103, and 105, or', 'SEQ ID NOs: 109, 111, 115, and 117,, 'wherein the TCR comprises'}wherein each of SEQ ID NOs: 1, 3, 7, 9, 13, 15, 19, 21, 25, 27, 31, 33, 37, 39, 43, 45, 49, 51, 55, 57, 61, 63, 67, 69, 73, 75, 79, 81, 85, 87, 91, 93, 97, 99, 103, 105, 109, 111, 115, and 117 comprises at most one conservative amino acid substitution,wherein the TCR binds to a peptide consisting of the amino acid sequence of ALSVLRLAL (SEQ ID NO: 133) in a complex with an MHC class I molecule, andwherein the cancer is selected from acute lymphocytic cancer, acute myeloid leukemia, alveolar rhabdomyosarcoma, bone cancer, brain cancer, breast cancer, cancer of the anus, anal canal, or anorectum, cancer of the ...

Methods and Compositions for the Treatment of Immune Disorders

The present invention provides a method of treating an immune-related disorder in a subject, comprising administering to the subject an effective amount of an inhibitor of plexin-A4 activity, which results in reducing the plexin-A4 activity in the subject, and thereby treating the immune-related disorder. Inhibitors of plexin-A4 activity include, for example, plexin-A4 antibodies and plexin-A4 fusion proteins. The present invention further provides a method of treating an immune-related disorder in a subject, comprising administering to the subject an effective amount of an inhibitor of semaphorin-3A (Sema3A) activity, which results in reducing the Sema3A activity in the subject, thereby treating the immune-related disorder. Inhibitors of Sema3A activity include, for example, Sema3A antibodies and Sema3A fusion proteins. 1. A method of treating an immune-related and/or inflammatory disorder in a subject , comprising administering to the subject an effective amount of an inhibitor of plexin-A4 activity , whereby the plexin-A4 activity in said subject is reduced , thereby treating the immune-related disorder and/or inflammatory disorder.2. A method of reducing cytokine production in a subject , comprising administering to the subject an effective amount of an inhibitor of plexin-A4 activity , thereby reducing the cytokine production the subject.3. The method of claim 1 , wherein the inhibitor of plexin-A4 activity is selected from the group consisting of a plexin-A4 fusion protein claim 1 , a plexin-A4 antibody or an active fragment thereof claim 1 , or any combination thereof.4. The method of claim 3 , wherein the plexin-A4 antibody or active fragment thereof is a monoclonal antibody or is derived from a monoclonal antibody.5. The method of claim 3 , wherein the plexin-A4 fusion protein comprises the extracellular domain of plexin-A4 and the Fc region of IgG.6. The method of claim 5 , wherein the extracellular domain of plexin-A4 and the IgG1 Fc region is human.7. ...

Anti-TLR4 Antibodies and Methods of Use Thereof

This invention relates generally to anti-Toll-like Receptor 4 (TLR4 antagonists) including antibodies that specifically bind Toll-like Receptor 4 (TLR-4), to methods of using the anti-TLR4 antagonists as therapeutics and to methods of using the anti-TLR4 antagonists for inhibiting, delaying the progression of, or otherwise ameliorating a symptom of Graft-versus-Host disease (GvHD) and/or improving survival of GvHD subjects and/or transplanted biological materials in subjects.

ANTIBODIES AND ANTIGEN-BINDING FRAGMENTS THAT SPECIFICALLY BIND TO MICROTUBULE-ASSOCIATED PROTEIN TAU

The disclosure relates to antibodies and antigen-binding fragments that specifically bind to microtubule-associated protein tau. The disclosure also relates to diagnostic, prophylactic and therapeutic methods using anti-tau antibodies. 1. A monoclonal antibody , wherein the antibody binds tau deposits in human Alzheimer's disease (“AD”) brain tissue or a functional variant of the antibody.2. The antibody of claim 1 , wherein the antibody comprises:antigen-binding variable region from a human antibody that binds specifically to tau, anda recombinant constant region of a human IgG1, andwherein the chimeric antibody is different from the human antibody.3. The antibody of claim 1 , wherein the antibody comprises:antigen-binding variable region from a human antibody that binds specifically to tau, anda recombinant constant region of a human IgG1,wherein the constant region of the chimeric antibody differs from the constant region of the human antibody.4. The antibody of claim 1 , wherein the antibody comprises:a naturally occurring human antigen-binding variable region that binds specifically to tau, anda recombinant constant region of a human IgG1 antibody.5. The antibody of claim 1 , wherein the antibody comprises:naturally occurring human light and heavy chain variable regions from a human antibody, andrecombinant human IgG1 heavy and light chain constant regions.6. The antibody of claim 1 , wherein the antibody comprises:heavy and light chain variable regions from a naturally occurring human antibody, and recombinant human IgG1 heavy and light chain constant regions.7. The antibody of claim 1 , wherein the antibody comprises:heavy and light chain variable regions from a human antibody, andrecombinant human IgG1 heavy and light chain constant regions.8. The antibody of claim 1 , wherein the antibody binds tau deposits in human AD brain tissue claim 1 , but does not bind tau in normal human brain tissue and does not bind tau deposits in Progressive Supranuclear Palsy ...

DE-N-Acetyl Sialic Acid Antigens, Antibodies Thereto, and Methods of Use in Cancer Therapy

The present invention generally provides compositions methods and composition relating to the diagnosis and/or treatment of cancers having a cell surface de-N-acetylated sialic acid antigen, e.g., an at least partially de-N-acetylated ganglioside and/or a de-N-acetylated sialic acid-modified cell surface protein. 144.-. (canceled)45. An antibody that specifically binds a de-N-acetylated sialic acid (deNAc SA) epitope on an extracellularly accessible surface of a cancerous cell , the deNAc SA epitope minimally defined by a dimer containing at least one de-N-acetylated sialic acid residue having a free amine adjacent an N-acylated sialic acid residue or a sialic acid derivative residue , wherein:the antibody binds to the deNAc SA epitope on the surface of CHP-134 neuroblastoma cells, and [ a VH CDR1 comprising amino acid residues 26 to 35 of SEQ ID NO:7,', 'a VH CDR2 comprising amino acid residues 50 to 66 of SEQ ID NO:7,', 'and', 'a VH CDR3 comprising amino acid residues 101 to 108 of SEQ ID NO:7;'}], 'a heavy chain polypeptide comprising, a VL CDR1 comprising amino acid residues 24 to 39 of SEQ ID NO:3,', 'a VL CDR2 comprising amino acid residues 55 to 61 of SEQ ID NO:3, and', 'a VL CDR3 comprising amino acid residues 94 to 100 of SEQ ID NO:3., 'a light chain polypeptide comprising], 'the antibody competes for binding to the deNAc SA epitope with an antibody comprising46. The antibody of claim 45 , wherein the antibody is selected from the group consisting of: an IgG claim 45 , a F(ab′)2 claim 45 , a F(ab) claim 45 , an Fv claim 45 , or an scFv.47. The antibody of claim 45 , wherein the antibody is a humanized antibody or a fully human antibody.48. The antibody of claim 45 , wherein the antibody comprises: a VH CDR1 comprising amino acid residues 26 to 35 of SEQ ID NO:7,', 'a VH CDR2 comprising amino acid residues 50 to 66 of SEQ ID NO:7, and', 'a VH CDR3 comprising amino acid residues 101 to 108 of SEQ ID NO:7; and, 'a heavy chain polypeptide comprising a VL CDR1 ...

Antibodies against clostridium difficile toxins and methods of using the same

Monoclonal antibodies, or antigen-binding fragments thereof, that bind to Clostridium difficile ( C. difficile ) toxin A or toxin B and methods of using the same to detect or treat C. difficile infections and/or C. difficile -associated disease.

Method for inhibiting intracellular activated ras using intact immunoglobulin-type antibody having cytosol-penetrating ability and use thereof

The present invention relates to a method for inhibiting intracellular activated RAS using an intact immunoglobulin-type antibody having the ability to penetrate the cytosol. The present invention also relates to a heavy-chain variable region (VH) which induces an intact immunoglobulin-type antibody to actively penetrate the cytosol of living cells through endocytosis and endosomal escape and to bind to activated RAS in the cytosol, and to an antibody comprising the same. The present invention also relates to a method of inhibiting the growth of cancer or tumor cells and a method of treating cancer or tumor, by use of the antibody. The present invention also relates to a method for screening a heavy-chain variable region that binds specifically to RAS in the cytosol. The present invention also relates to a biologically active molecule fused to the antibody and selected from the group consisting of peptides, proteins, small-molecule drugs, nanoparticles and liposomes. The present invention also relates to a composition for prevention, treatment or diagnosis of cancer, comprising: the antibody; or a biological active molecule fused to the antibody and selected from the group consisting of peptides, proteins, small-molecule drugs, nanoparticles and liposomes. The present invention also relates to a polynucleotide that encodes the light-chain variable region and the antibody. According to the present invention, the method for inhibiting intracellular activated RAS using an intact immunoglobulin-type antibody having the ability to penetrate the cytosol is achieved by allowing the antibody to penetrate living cells and to specifically recognize activated (GTP-bound) RAS in the cytosol. Thus, the antibody can target activated (GTP-bound) RAS in the cytosol of living cells and inhibit the activity of the RAS. Furthermore, the antibody light-chain variable region according to the present invention and an antibody comprising the same is able to penetrate living cells and ...

Human anti-tau antibodies

Provided are novel human tau-specific antibodies as well as fragments, derivatives and variants thereof as well as methods related thereto. Assays, kits, and solid supports related to antibodies specific for tau are also disclosed. The antibody, immunoglobulin chain(s), as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for tau targeted immunotherapy and diagnosis, respectively.

ANTI-CXCR5 ANTIBODIES AND COMPOSITIONS AND USES THEREOF

The invention provides antibodies, and antigen-binding fragments thereof, that specifically bind to CXCR5. The antibodies can be afucosylated and exhibit increased ADCC compared with the otherwise identical fucosylated antibodies. The invention includes uses, and associated methods of using the antibodies. 1. An isolated antibody , or antigen-binding fragment thereof , that specifically binds C—X—C-chemokine receptor 5 (CXCR5) ,wherein the antibody , or antigen-binding fragment thereof , is at least one antibody , or antigen-binding fragment thereof , selected from the group consisting of:a) an antibody, or antigen-binding fragment thereof, comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:2; a CDR-L2 comprising the amino acid sequence of SEQ ID NO:3; a CDR-L3 comprising the amino acid sequence of SEQ ID NO:4; a CDR-H1 comprising the amino acid sequence of SEQ ID NO:7; a CDR-H2 comprising the amino acid sequence of SEQ ID NO:8; and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:9;b) an antibody, or antigen-binding fragment thereof, comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:2; a CDR-L2 comprising the amino acid sequence of SEQ ID NO:3; a CDR-L3 comprising the amino acid sequence of SEQ ID NO:4; a CDR-H1 comprising the amino acid sequence of SEQ ID NO:7; a CDR-H2 comprising the amino acid sequence of SEQ ID NO:8; and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:11;c) an antibody, or antigen-binding fragment thereof, comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:14; a CDR-L2 comprising the amino acid sequence of SEQ ID NO:15; a CDR-L3 comprising the amino acid sequence of SEQ ID NO:16; a CDR-H1 comprising the amino acid sequence of SEQ ID NO:19; a CDR-H2 comprising the amino acid sequence of SEQ ID NO:20; and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:21;d) an antibody, or antigen-binding fragment thereof, comprising a VL comprising an amino acid sequence encoded by ...