RU2010107175A - Антитела человека к cd20 человека и способ их использования - Google Patents

Антитела человека к cd20 человека и способ их использования Download PDF

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RU2010107175A
RU2010107175A RU2010107175/10A RU2010107175A RU2010107175A RU 2010107175 A RU2010107175 A RU 2010107175A RU 2010107175/10 A RU2010107175/10 A RU 2010107175/10A RU 2010107175 A RU2010107175 A RU 2010107175A RU 2010107175 A RU2010107175 A RU 2010107175A
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antibody
antigen
human
binding fragment
fragment
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Джоэл Х. МАРТИН (US)
Джоэл Х. МАРТИН
Ли-Сыэнь ВАН (US)
Ли-Сыэнь ВАН
Шон СТИВЕНС (US)
Шон СТИВЕНС
Эрин М. ЭЛЛИСОН (US)
Эрин М. ЭЛЛИСОН
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Ридженерон Фармасьютикалз, Инк. (Us)
Ридженерон Фармасьютикалз, Инк.
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Abstract

1. Антитело человека или антиген-связывающий фрагмент антитела, который специфически связывается с CD20 человека и способен индуцировать комплемент-зависимую цитотоксичность (CDC) с концентрацией антитела приблизительно 5 нМ или менее, и увеличивать время бессимптомного выживания приблизительно от 2-х до приблизительно 9-ти раз или более, относительно контроля у животных на мышиной модели лимфомы человека, где антитело или фрагмент антитела содержит: ! - определяющую комплементарность область 1 тяжелой цепи (HCDR1) и CDR1 легкой цепи (LCDR1), где HCDR1 и LCDR1 выбраны из группы, состоящей из SEQ ID NO: 341 и 349; ! - определяющую комплементарность область 2 тяжелой цепи (HCDR2) и CDR2 легкой цепи (LCDR2), где HCDR2 и LCDR2 выбраны из группы, состоящей из SEQ ID NO: 343 и 351; и !- определяющую комплементарность область 3 тяжелой цепи (HCDR3) и CDR3 легкой цепи (LCDR3), где HCDR3 и LCDR3 выбраны из группы, состоящей из SEQ ID NO: 345 и 353. ! 2. Антитело человека или антиген-связывающий фрагмент антитела, который специфически связывается с CD20 человека и способен индуцировать комплемент-зависимую цитотоксичность (CDC) с концентрацией антитела приблизительно 5 нМ или менее, где антитело или его фрагмент содержат последовательность вариабельной области тяжелой цепи (HCVR) и последовательность вариабельной области легкой цепи (LCVR), где последовательности HCVR и LCVR выбраны из группы, состоящей из SEQ ID NO: 339 и 347. ! 3. Антитело человека или антиген-связывающий фрагмент по п.1, где концентрация антитела, которая требуется для индукции CDC, составляет 1 нМ или менее. ! 4. Антитело человека или антиген-связывающий фрагмент по п.3, дополнительно отличающиеся тем, что значение их EC50 составляет 0,2 нМ или менее, как и�

Claims (15)

1. Антитело человека или антиген-связывающий фрагмент антитела, который специфически связывается с CD20 человека и способен индуцировать комплемент-зависимую цитотоксичность (CDC) с концентрацией антитела приблизительно 5 нМ или менее, и увеличивать время бессимптомного выживания приблизительно от 2-х до приблизительно 9-ти раз или более, относительно контроля у животных на мышиной модели лимфомы человека, где антитело или фрагмент антитела содержит:
- определяющую комплементарность область 1 тяжелой цепи (HCDR1) и CDR1 легкой цепи (LCDR1), где HCDR1 и LCDR1 выбраны из группы, состоящей из SEQ ID NO: 341 и 349;
- определяющую комплементарность область 2 тяжелой цепи (HCDR2) и CDR2 легкой цепи (LCDR2), где HCDR2 и LCDR2 выбраны из группы, состоящей из SEQ ID NO: 343 и 351; и
- определяющую комплементарность область 3 тяжелой цепи (HCDR3) и CDR3 легкой цепи (LCDR3), где HCDR3 и LCDR3 выбраны из группы, состоящей из SEQ ID NO: 345 и 353.
2. Антитело человека или антиген-связывающий фрагмент антитела, который специфически связывается с CD20 человека и способен индуцировать комплемент-зависимую цитотоксичность (CDC) с концентрацией антитела приблизительно 5 нМ или менее, где антитело или его фрагмент содержат последовательность вариабельной области тяжелой цепи (HCVR) и последовательность вариабельной области легкой цепи (LCVR), где последовательности HCVR и LCVR выбраны из группы, состоящей из SEQ ID NO: 339 и 347.
3. Антитело человека или антиген-связывающий фрагмент по п.1, где концентрация антитела, которая требуется для индукции CDC, составляет 1 нМ или менее.
4. Антитело человека или антиген-связывающий фрагмент по п.3, дополнительно отличающиеся тем, что значение их EC50 составляет 0,2 нМ или менее, как измерено на клетках Daudi, или значение EC50 составляет 0,4 нМ или менее, как измерено с помощью клеток RL
5. Антитело человека или антиген-связывающий фрагмент по любому из пп.1-4, отличающиеся тем, что значение их KD или EC50 по меньшей мере составляет 10-11 M при измерении связывания с антигеном, представленным на поверхности клетки.
6. Молекула нуклеиновой кислоты, кодирующая антитело человека или фрагмент антитела по п.5.
7. Экспрессионный вектор, содержащий молекулу нуклеиновой кислоты по п.6.
8. Способ получения антитела против CD20 человека или антиген-связывающего фрагмента антитела, включающий стадии введения экспрессионного вектора по п.7 в выделенную клетку-хозяина, выращивание клетки в условиях, позволяющих осуществлять выработку антитела или фрагмента антитела, и обратное получение антитела или фрагмента антитела, созданного таким образом.
9. Способ по п.8, где клетка-хозяин представляет собой клетку E.coli, клетку CHO или клетку COS.
10. Фармацевтическая композиция, которая содержит антитело или его антиген-связывающий фрагмент по любому из пп.1-5.
11. Антитело или антиген-связывающий фрагмент антитела по любому из пп.1-5 для использования для уменьшения тяжести или подавления заболевания или состояния, опосредованного CD20, у человека.
12. Антитело или антиген-связывающий фрагмент антитела по п.11, где заболевание или состояние, на которое направлено лечение, выбрано из группы, состоящей из неходжкинской лимфомы, ревматоидного артрита, системной красной волчанки, болезни Крона, хронического лимфоцитарного лейкоза и воспалительных заболеваний.
13. Способ уменьшения тяжести или подавления заболевания или состояния, опосредованного CD20, у человека, который включает введение терапевтически эффективного количества антитела или антиген-связывающего фрагмента антитела по любому из пп.1-5.
14. Применение антитела или антиген-связывающего фрагмента антитела по любому из пп.1-5 для получения лекарственного средства для уменьшения тяжести или подавления заболевания или состояния, опосредованного CD20, у человека.
15. Применение по п.14, где заболевание или состояние, на которое направлено лечение, представляет собой неходжкинскую лимфому, ревматоидный артрит, системную красную волчанку, болезнь Крона, хронический лимфоцитарный лейкоз и воспалительные заболевания.
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Families Citing this family (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US20090137416A1 (en) 2001-01-16 2009-05-28 Regeneron Pharmaceuticals, Inc. Isolating Cells Expressing Secreted Proteins
CA2527694C (en) 2003-05-30 2015-07-14 Hendricus Renerus Jacobus Mattheus Hoogenboom Fab library for the preparation of anti vegf and anti rabies virus fabs
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
US8877199B2 (en) 2009-05-15 2014-11-04 The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services B cell surface reactive antibodies
DK2517556T4 (da) 2009-07-08 2023-05-15 Kymab Ltd Fremgangsmåde til punkt-specifik rekombination, gnavere og gnaverceller i stand til at udtrykke kimære antistoffer eller kæder
US9445581B2 (en) 2012-03-28 2016-09-20 Kymab Limited Animal models and therapeutic molecules
HUE038684T2 (hu) 2009-12-21 2018-11-28 Regeneron Pharma Humanizált FC gamma R génnel rendelkezõ egér
CA2846319A1 (en) 2011-09-19 2013-03-28 Kymab Limited Antibodies, variable domains & chains tailored for human use
WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
BR112014019331A2 (pt) * 2012-02-06 2022-07-12 Inhibrx Inc anticorpos para cd47 e métodos de uso desses
US10251377B2 (en) 2012-03-28 2019-04-09 Kymab Limited Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies
GB2502127A (en) 2012-05-17 2013-11-20 Kymab Ltd Multivalent antibodies and in vivo methods for their production
JOP20200236A1 (ar) * 2012-09-21 2017-06-16 Regeneron Pharma الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها
TWI675044B (zh) * 2012-11-14 2019-10-21 美商再生元醫藥公司 重組細胞表面捕捉蛋白質
US20140140991A1 (en) * 2012-11-20 2014-05-22 Celgene Avilomics Research, Inc. Methods of treating a disease or disorder associated with bruton's tyrosine kinase
US9145387B2 (en) 2013-02-08 2015-09-29 Celgene Avilomics Research, Inc. ERK inhibitors and uses thereof
AR095196A1 (es) 2013-03-15 2015-09-30 Regeneron Pharma Medio de cultivo celular libre de suero
US9788534B2 (en) 2013-03-18 2017-10-17 Kymab Limited Animal models and therapeutic molecules
NZ629456A (en) 2013-04-17 2017-06-30 Signal Pharm Llc Methods for treating cancer using tor kinase inhibitor combination therapy
MX2015014455A (es) 2013-04-17 2016-07-21 Signal Pharm Llc Terapia de combinacion que comprende un inhibidor de tor cinasa y n-(3-(5-fluoro-2-(4-(2-metoxietoxi)fenilamino)pirimidin-4-ilamino )fenil)acrilamida para tratar cancer.
US9474757B2 (en) 2013-04-17 2016-10-25 Signal Pharmaceuticals, Llc Methods for treating cancer using TOR kinase inhibitor combination therapy
US9783618B2 (en) 2013-05-01 2017-10-10 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
US9783593B2 (en) 2013-05-02 2017-10-10 Kymab Limited Antibodies, variable domains and chains tailored for human use
US11707056B2 (en) 2013-05-02 2023-07-25 Kymab Limited Animals, repertoires and methods
EP2991651A1 (en) 2013-05-03 2016-03-09 Celgene Corporation Methods for treating cancer using combination therapy
US9492471B2 (en) 2013-08-27 2016-11-15 Celgene Avilomics Research, Inc. Methods of treating a disease or disorder associated with Bruton'S Tyrosine Kinase
EP3794941B1 (en) 2013-10-01 2024-09-25 Kymab Limited Animal models and therapeutic molecules
JP6478989B2 (ja) * 2013-11-07 2019-03-06 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ 抗ｃｄ２０抗体とｂｔｋ阻害剤とを用いた併用療法
TWI701042B (zh) 2014-03-19 2020-08-11 美商再生元醫藥公司 用於腫瘤治療之方法及抗體組成物
ES2741785T3 (es) 2014-08-13 2020-02-12 Celgene Car Llc Formas y composiciones de un inhibidor de ERK
GB201419084D0 (en) 2014-10-27 2014-12-10 Agency Science Tech & Res Anti-PD-1 antibodies
ES2809455T3 (es) 2014-11-17 2021-03-04 Regeneron Pharma Métodos para tratamiento tumoral usando anticuerpo biespecífico CD3xCD20
RS60441B1 (sr) 2015-05-30 2020-07-31 Molecular Templates Inc De-imunizovane, strukture shiga toksin a podjedinice i ciljani ćelijski molekuli koji sadrže isti
CA2985718A1 (en) 2015-06-24 2016-12-29 F. Hoffmann-La Roche Ag Anti-transferrin receptor antibodies with tailored affinity
TW202340452A (zh) 2015-08-04 2023-10-16 美商再生元醫藥公司 補充牛磺酸之細胞培養基及用法
AR106189A1 (es) 2015-10-02 2017-12-20 Hoffmann La Roche ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO
EP3356406A1 (en) 2015-10-02 2018-08-08 H. Hoffnabb-La Roche Ag Bispecific anti-human cd20/human transferrin receptor antibodies and methods of use
RS64588B1 (sr) 2015-12-22 2023-10-31 Regeneron Pharma Kombinacija anti-pd-1 antitela i bispecifičnih anti-cd20/anti-cd3 antitela za lečenje kancera
KR102098919B1 (ko) * 2016-07-19 2020-04-23 (주) 아이벤트러스 이중 특이성 단백질 및 이의 제조 방법
EP3504328A1 (en) 2016-08-24 2019-07-03 Regeneron Pharmaceuticals, Inc. Host cell protein modification
WO2018106931A1 (en) 2016-12-07 2018-06-14 Progenity Inc. Gastrointestinal tract detection methods, devices and systems
US11524994B2 (en) 2016-12-19 2022-12-13 Vanderbilt University Antibodies to human respiratory syncytial virus protein F pre-fusion conformation and methods of use therefor
CN108395482B (zh) 2017-02-08 2021-02-05 西比曼生物科技（香港）有限公司 一种靶向cd20抗原嵌合抗原受体的构建及其工程化t细胞的活性鉴定
EP4108183A1 (en) 2017-03-30 2022-12-28 Biora Therapeutics, Inc. Treatment of a disease of the gastrointestinal tract with an immune modulatory agent released using an ingestible device
CN110914293B (zh) 2017-07-06 2024-08-13 里珍纳龙药品有限公司 用于制备糖蛋白的细胞培养工艺
WO2019036855A1 (en) 2017-08-21 2019-02-28 Adagene Inc. ANTI-CD137 MOLECULES AND THEIR USE
AU2018392334A1 (en) 2017-12-22 2020-05-28 Regeneron Pharmaceuticals, Inc. System and method for characterizing drug product impurities
WO2019152303A1 (en) 2018-01-31 2019-08-08 Regeneron Pharmaceuticals, Inc. Systems and methods for characterizing drug product impurities
WO2019148445A1 (en) 2018-02-02 2019-08-08 Adagene Inc. Precision/context-dependent activatable antibodies, and methods of making and using the same
TWI786265B (zh) 2018-02-02 2022-12-11 美商再生元醫藥公司 用於表徵蛋白質二聚合之系統及方法
AU2019227531A1 (en) 2018-02-28 2020-10-15 Regeneron Pharmaceuticals, Inc. Systems and methods for identifying viral contaminants
WO2019182901A1 (en) 2018-03-19 2019-09-26 Regeneron Pharmaceuticals, Inc. Microchip capillary electrophoresis assays and reagents
TW202016125A (zh) 2018-05-10 2020-05-01 美商再生元醫藥公司 用於定量及調節蛋白質黏度之系統與方法
WO2019246317A1 (en) 2018-06-20 2019-12-26 Progenity, Inc. Treatment of a disease or condition in a tissue originating from the endoderm
US20230041197A1 (en) 2018-06-20 2023-02-09 Progenity, Inc. Treatment of a disease of the gastrointestinal tract with an immunomodulator
CN112218877A (zh) 2018-08-27 2021-01-12 瑞泽恩制药公司 拉曼光谱在下游纯化中的应用
US11754569B2 (en) 2018-08-30 2023-09-12 Regeneron Pharmaceuticals, Inc. Methods for characterizing protein complexes
WO2020047389A1 (en) 2018-08-31 2020-03-05 Regeneron Pharmaceuticals, Inc. Dosing strategy that mitigates cytokine release syndrome for cd3/c20 bispecific antibodies
CN112955172A (zh) 2018-09-17 2021-06-11 美国卫生和人力服务部 靶向cd19和cd20的双顺反子嵌合抗原受体及其用途
EA202190926A1 (ru) 2018-10-01 2021-06-25 Эдисет Био, Инк. Композиции и способы в отношении сконструированных и несконструированных t-клеток для лечения гематологических опухолей
CN116726361A (zh) 2018-11-19 2023-09-12 比奥拉治疗股份有限公司 用生物治疗剂治疗疾病的方法和装置
SG11202104237YA (en) 2019-01-16 2021-05-28 Regeneron Pharma Methods for identifying free thiols in proteins
WO2020231992A1 (en) 2019-05-13 2020-11-19 Regeneron Pharmaceuticals, Inc. Improved competitive ligand binding assays
US20220323937A1 (en) 2019-09-24 2022-10-13 Regeneron Pharmaceuticals, Inc. Systems and methods for chromatography use and regeneration
CN114760986A (zh) 2019-11-25 2022-07-15 里珍纳龙药品有限公司 使用非水性乳液的持续释放调配物
EP3870261B1 (en) 2019-12-13 2024-01-31 Biora Therapeutics, Inc. Ingestible device for delivery of therapeutic agent to the gastrointestinal tract
BR122023021668A2 (pt) 2020-01-21 2024-01-09 Regeneron Pharmaceuticals, Inc. Método para determinar a estabilidade de uma proteína de interesse
MX2023002417A (es) 2020-08-31 2023-03-22 Regeneron Pharma Estrategias de suministro de asparagina para mejorar el rendimiento del cultivo celular y mitigar las variantes de secuencia de asparagina.
AU2021385363A1 (en) 2020-11-25 2023-06-08 Regeneron Pharmaceuticals, Inc. Sustained release formulations using non-aqueous membrane emulsification
KR20230121854A (ko) 2020-12-17 2023-08-21 리제너론 파아마슈티컬스, 인크. 단백질-캡슐화 마이크로겔의 제작
TW202233827A (zh) 2021-01-20 2022-09-01 美商再生元醫藥公司 改良細胞培養中蛋白質效價的方法
US20220404369A1 (en) 2021-03-03 2022-12-22 Regeneron Pharmaceuticals, Inc. Systems and methods for quantifying and modifying protein viscosity
WO2022204282A1 (en) 2021-03-24 2022-09-29 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Bicistronic chimeric antigen receptors designed to reduce retroviral recombination and uses thereof
WO2022204728A1 (en) 2021-03-26 2022-09-29 Regeneron Pharmaceuticals, Inc. Methods and systems for developing mixing protocols
MX2023014246A (es) 2021-06-01 2024-01-17 Regeneron Pharma Ensayos y reactivos de microchips de electroforesis capilar.
WO2023039457A1 (en) 2021-09-08 2023-03-16 Regeneron Pharmaceuticals, Inc. A high-throughput and mass-spectrometry-based method for quantitating antibodies and other fc-containing proteins
KR20240058201A (ko) 2021-09-20 2024-05-03 리제너론 파마슈티칼스 인코포레이티드 항체 이질성을 제어하는 방법
AU2022360838A1 (en) 2021-10-07 2024-03-28 Regeneron Pharmaceuticals, Inc. Systems and methods of ph modeling and control
EP4413359A1 (en) 2021-10-07 2024-08-14 Regeneron Pharmaceuticals, Inc. Ph meter calibration and correction
WO2023076340A1 (en) 2021-10-26 2023-05-04 Regeneron Pharmaceuticals, Inc. Systems and methods for generating laboratory water and distributing laboratory water at different temperatures
AR128824A1 (es) 2022-03-18 2024-06-19 Regeneron Pharma Métodos de análisis y cuantificación de variantes polipeptídicas de carga
WO2023196903A1 (en) 2022-04-06 2023-10-12 Regeneron Pharmaceuticals, Inc. Bispecific antigen-binding molecules that bind and cd3 and tumor associated antigens (taas) and uses thereof
WO2023215560A1 (en) 2022-05-05 2023-11-09 Atoosa Corporation Tumor cell/immune cell multivalent receptor engager – bio-nanoparticle (timre-bnp)
US20240198253A1 (en) 2022-12-16 2024-06-20 Regeneron Pharmaceuticals, Inc. Methods and systems for assessing chromatographic column integrity
US20240245779A1 (en) 2023-01-25 2024-07-25 Regeneron Pharmaceuticals, Inc. Methods of modeling liquid protein composition stability
WO2024158961A1 (en) 2023-01-25 2024-08-02 Regeneron Pharmaceuticals, Inc. Mass spectrometry-based characterization of antibodies co-expressed in vivo
US20240255519A1 (en) 2023-02-01 2024-08-01 Regeneron Pharmaceuticals, Inc. Asymmetrical flow field-flow fractionation with mass spectrometry for biomacromolecule analysis
WO2024178213A2 (en) 2023-02-22 2024-08-29 Regeneron Pharmaceuticals, Inc. System suitability parameters and column aging
US20240285762A1 (en) 2023-02-28 2024-08-29 Juno Therapeutics, Inc. Cell therapy for treating systemic autoimmune diseases

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6893625B1 (en) * 1986-10-27 2005-05-17 Royalty Pharma Finance Trust Chimeric antibody with specificity to human B cell surface antigen
IL85035A0 (en) * 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
MX9204374A (es) * 1991-07-25 1993-03-01 Idec Pharma Corp Anticuerpo recombinante y metodo para su produccion.
PT752248E (pt) * 1992-11-13 2001-01-31 Idec Pharma Corp Aplicacao terapeutica de anticorpos quimericos e marcados radioactivamente contra antigenios de diferenciacao restrita de linfocitos b humanos para o tratamento do linfoma de celulas b
US5736137A (en) * 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
US6528624B1 (en) * 1998-04-02 2003-03-04 Genentech, Inc. Polypeptide variants
NZ573838A (en) * 1998-08-11 2011-01-28 Biogen Idec Inc Combination therapies for b-cell lymphomas comprising administration of anti-cd20 antibody
US6224866B1 (en) * 1998-10-07 2001-05-01 Biocrystal Ltd. Immunotherapy of B cell involvement in progression of solid, nonlymphoid tumors
CA2704600C (en) * 1999-04-09 2016-10-25 Kyowa Hakko Kirin Co., Ltd. A method for producing antibodies with increased adcc activity
KR20080039550A (ko) 1999-05-07 2008-05-07 제넨테크, 인크. Ｂ 세포 표면 마커에 결합하는 길항물질을 이용한 자가면역질환의 치료
ITMI991299A1 (it) 1999-06-11 2000-12-11 Consiglio Nazionale Ricerche Uso di anticorpi contro antigeni di superficie per il trattamento della malattia trapianto contro ospite
US20040093621A1 (en) * 2001-12-25 2004-05-13 Kyowa Hakko Kogyo Co., Ltd Antibody composition which specifically binds to CD20
WO2003068821A2 (en) * 2002-02-14 2003-08-21 Immunomedics, Inc. Anti-cd20 antibodies and fusion proteins thereof and methods of use
US20030233797A1 (en) * 2002-06-25 2003-12-25 Anderson Dean A. Air handling system including shroud and grille, and method of use
NZ568769A (en) 2002-10-17 2010-04-30 Genmab As Human monoclonal antibodies against CD20
US6736137B1 (en) * 2003-02-28 2004-05-18 Tmr-A, Llc Protective hooded respirator with oral-nasal cup breathing interface
US8084582B2 (en) * 2003-03-03 2011-12-27 Xencor, Inc. Optimized anti-CD20 monoclonal antibodies having Fc variants
EP1626993B1 (en) 2003-05-09 2015-03-11 Duke University Cd20-specific antibodies and methods of employing same
AR044388A1 (es) * 2003-05-20 2005-09-07 Applied Molecular Evolution Moleculas de union a cd20
DE10334793A1 (de) * 2003-07-30 2005-02-24 BSH Bosch und Siemens Hausgeräte GmbH Geschirrspülmaschine
WO2005023302A2 (en) * 2003-08-29 2005-03-17 Genentech, Inc. Anti-cd20 therapy of ocular disorders
KR20060107555A (ko) * 2003-12-19 2006-10-13 제넨테크, 인크. 이식 거부에서 ｃｄ20의 검출
US7850962B2 (en) * 2004-04-20 2010-12-14 Genmab A/S Human monoclonal antibodies against CD20
MXPA06012674A (es) * 2004-05-05 2007-03-26 Genentech Inc Prevencion de enfermedades autoinmunes.
AU2005251764A1 (en) * 2004-06-04 2005-12-22 Genentech, Inc. Method for treating lupus
KR20070100228A (ko) * 2004-10-05 2007-10-10 제넨테크, 인크. 혈관염의 치료 방법
TW200714289A (en) * 2005-02-28 2007-04-16 Genentech Inc Treatment of bone disorders
CN1331888C (zh) * 2005-03-02 2007-08-15 中国人民解放军军事医学科学院生物工程研究所 一种抗人b细胞淋巴瘤的单链双特异性抗体
AR053579A1 (es) * 2005-04-15 2007-05-09 Genentech Inc Tratamiento de la enfermedad inflamatoria intestinal (eii)
US20060240007A1 (en) * 2005-04-22 2006-10-26 Genentech, Inc. Method for treating dementia or Alzheimer's disease
WO2006130458A2 (en) * 2005-06-02 2006-12-07 Astrazeneca Ab Antibodies directed to cd20 and uses thereof

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