JP2015525071A - 共通の軽鎖を用いて完全ヒト型二重特異性抗体を作製するための方法 - Google Patents

共通の軽鎖を用いて完全ヒト型二重特異性抗体を作製するための方法 Download PDF

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JP2015525071A
JP2015525071A JP2015516160A JP2015516160A JP2015525071A JP 2015525071 A JP2015525071 A JP 2015525071A JP 2015516160 A JP2015516160 A JP 2015516160A JP 2015516160 A JP2015516160 A JP 2015516160A JP 2015525071 A JP2015525071 A JP 2015525071A
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human
light chain
heavy chain
mouse
antigen
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JP2015525071A5 (cg-RX-API-DMAC7.html
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ロバート バブ,
ロバート バブ,
ジョン マクワーター,
ジョン マクワーター,
リン マクドナルド,
リン マクドナルド,
ショーン スティーブンズ,
ショーン スティーブンズ,
サミュエル デイビス,
サミュエル デイビス,
デイビッド アール. バックラー,
デイビッド アール. バックラー,
カロリーナ エー. ホシアワ,
カロリーナ エー. ホシアワ,
アンドリュー ジェイ. マーフィー,
アンドリュー ジェイ. マーフィー,
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Regeneron Pharmaceuticals Inc
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Regeneron Pharmaceuticals Inc
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Priority claimed from US13/488,628 external-priority patent/US20130045492A1/en
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Publication of JP2015525071A5 publication Critical patent/JP2015525071A5/ja
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    • C07ORGANIC CHEMISTRY
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    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • AHUMAN NECESSITIES
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    • A01K2217/00Genetically modified animals
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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • C07K2317/00Immunoglobulins specific features
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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    • C07ORGANIC CHEMISTRY
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    • C07K2317/00Immunoglobulins specific features
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    • C07K2317/31Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
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    • C07K2317/51Complete heavy chain or Fd fragment, i.e. VH + CH1
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    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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    • C07K2317/567Framework region [FR]
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    • C07ORGANIC CHEMISTRY
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    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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    • C07ORGANIC CHEMISTRY
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    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

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JP2015516160A 2012-06-05 2013-06-05 共通の軽鎖を用いて完全ヒト型二重特異性抗体を作製するための方法 Pending JP2015525071A (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US13/488,628 US20130045492A1 (en) 2010-02-08 2012-06-05 Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
US13/488,628 2012-06-05
PCT/US2013/044257 WO2013184761A1 (en) 2012-06-05 2013-06-05 Methods for making fully human bispecific antibodies using a common light chain

Publications (2)

Publication Number Publication Date
JP2015525071A true JP2015525071A (ja) 2015-09-03
JP2015525071A5 JP2015525071A5 (cg-RX-API-DMAC7.html) 2016-07-21

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EP (1) EP2854523A1 (cg-RX-API-DMAC7.html)
JP (1) JP2015525071A (cg-RX-API-DMAC7.html)
KR (1) KR20150023535A (cg-RX-API-DMAC7.html)
CN (1) CN104582476B (cg-RX-API-DMAC7.html)
AU (1) AU2013271737A1 (cg-RX-API-DMAC7.html)
CA (1) CA2874846A1 (cg-RX-API-DMAC7.html)
HK (1) HK1208994A1 (cg-RX-API-DMAC7.html)
IL (1) IL235781A0 (cg-RX-API-DMAC7.html)
MX (1) MX2014014891A (cg-RX-API-DMAC7.html)
RU (1) RU2014153674A (cg-RX-API-DMAC7.html)
SG (2) SG10201609535TA (cg-RX-API-DMAC7.html)
WO (1) WO2013184761A1 (cg-RX-API-DMAC7.html)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
US20130045492A1 (en) 2010-02-08 2013-02-21 Regeneron Pharmaceuticals, Inc. Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
US9796788B2 (en) 2010-02-08 2017-10-24 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire
WO2011097603A1 (en) 2010-02-08 2011-08-11 Regeneron Pharmaceuticals, Inc. Common light chain mouse
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
AU2013204581B2 (en) 2012-03-16 2015-06-25 Regeneron Pharmaceuticals, Inc. Non-human animals expressing pH-sensitive immunoglobulin sequences
HUE045537T2 (hu) 2012-03-16 2019-12-30 Regeneron Pharma PH-érzékeny immunglobulin-szekvenciákat expresszáló rágcsálók
RU2644684C2 (ru) 2012-03-16 2018-02-13 Регенерон Фармасьютикалз, Инк. Антитела со встроенным в легкие цепи гистидином и генетически модифицированные отличные от человека животные для их получения
US20140013456A1 (en) 2012-03-16 2014-01-09 Regeneron Pharmaceuticals, Inc. Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same
MX360110B (es) 2012-04-20 2018-10-23 Merus Nv Metodos y medios para la produccion de moleculas de tipo ig.
TWI682941B (zh) 2013-02-01 2020-01-21 美商再生元醫藥公司 含嵌合恆定區之抗體
CA2903696A1 (en) * 2013-03-13 2014-10-02 Regeneron Pharmaceuticals, Inc. Common light chain mouse
TWI754319B (zh) 2014-03-19 2022-02-01 美商再生元醫藥公司 用於腫瘤治療之方法及抗體組成物
ES2809455T3 (es) 2014-11-17 2021-03-04 Regeneron Pharma Métodos para tratamiento tumoral usando anticuerpo biespecífico CD3xCD20
PT3221357T (pt) * 2014-11-20 2020-07-28 Hoffmann La Roche Cadeias leves comuns e métodos de utilização
EP3023437A1 (en) 2014-11-20 2016-05-25 EngMab AG Bispecific antibodies against CD3epsilon and BCMA
CA2981312C (en) 2015-03-30 2023-09-26 Regeneron Pharmaceuticals, Inc. Heavy chain constant regions with reduced binding to fc gamma receptors
WO2016183222A1 (en) 2015-05-12 2016-11-17 Regeneron Pharmaceuticals, Inc. Multimeric protein purity determination
EA201890785A1 (ru) * 2015-09-23 2018-10-31 Ридженерон Фармасьютикалз, Инк. Оптимизированные биспецифические анти-cd3 антитела и их применение
TWI752920B (zh) 2015-10-12 2022-01-21 美商再生元醫藥公司 活化瘦素受體的抗原結合蛋白
KR102482103B1 (ko) 2016-01-13 2022-12-28 리제너론 파마슈티칼스 인코포레이티드 조작된 중쇄 다양성 영역을 갖는 설치류
HRP20250986T1 (hr) 2018-04-06 2025-10-24 Regeneron Pharmaceuticals, Inc. Antitijelo agonista leptinskog receptora za upotrebu u povećanju koštane mase kod osobe koja pati od metaboličke disfunkcije ili hipoleptinemije
IL318469A (en) 2018-06-14 2025-03-01 Regeneron Pharma Non-human animals capable of reorganizing transgenic DH-DH, and their uses
JP7605734B2 (ja) 2018-08-31 2024-12-24 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Cd3/c20二重特異性抗体のサイトカイン放出症候群を軽減する投与戦略
CN113302207B (zh) * 2018-11-16 2025-05-13 维尔托索宾科公司 Cd38和icam1抗体及其用途
AU2020226865A1 (en) 2019-02-22 2021-07-29 Regeneron Pharmaceuticals, Inc. Rodents having genetically modified sodium channels and methods of use thereof
KR20210095781A (ko) 2020-01-24 2021-08-03 주식회사 에이프릴바이오 항원결합 단편 및 생리활성 이펙터 모이어티로 구성된 융합 컨스트럭트를 포함하는 다중결합항체 및 이를 포함하는 약학조성물
IL301137A (en) 2020-09-11 2023-05-01 Regeneron Pharma Identification and production of antigen-specific antibodies
CN116848254A (zh) 2020-12-16 2023-10-03 瑞泽恩制药公司 表达人源化Fcα受体的小鼠
US12371487B2 (en) 2020-12-23 2025-07-29 Regeneron Pharmaceuticals, Inc. Methods for obtaining antibodies that bind transmembrane proteins and cells that produce the same
EP4559939A3 (en) 2020-12-23 2025-09-24 Regeneron Pharmaceuticals, Inc. Nucleic acids encoding anchor modified antibodies and uses therof
CN118496357A (zh) * 2023-02-15 2024-08-16 康源博创生物科技(北京)有限公司 一种多肽以及包含其作为轻链的抗体

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004524841A (ja) * 2001-02-16 2004-08-19 リジェネロン・ファーマシューティカルズ・インコーポレイテッド 真核生物細胞を改変する方法
JP2007054076A (ja) * 1993-04-26 2007-03-08 Genpharm Internatl Inc 異種抗体を産生することができるトランスジェニック非ヒト動物
WO2011097603A1 (en) * 2010-02-08 2011-08-11 Regeneron Pharmaceuticals, Inc. Common light chain mouse

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2146572T3 (es) * 1988-09-06 2000-08-16 Xoma Technology Ltd Elementos de expresion genica y la produccion de anticuerpos quimericos de raton-ser humano.
US5770429A (en) * 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
CN1671416B (zh) * 2001-07-12 2013-01-02 杰斐逊·富特 超人源化抗体
DE50115580D1 (de) * 2001-10-01 2010-09-16 Deutsches Krebsforsch Verfahren zur Herstellung von Protein-Bibliotheken und zur Selektion von Proteinen daraus
WO2003061363A2 (en) * 2002-01-17 2003-07-31 Albert Einstein College Of Medicine Of Yeshiva University Mutations caused by activation-induced cytidine deaminase
EP1519958B1 (en) * 2002-06-14 2014-10-15 Immunomedics, Inc. Humanized monoclonal antibody hpam4
CN101962408A (zh) * 2002-07-12 2011-02-02 杰斐逊·富特 超人源化抗体
DK2556747T3 (da) * 2008-06-27 2021-02-15 Merus Nv Antistofproducerende transgen mus
SI3865581T1 (sl) * 2011-08-05 2024-12-31 Regeneron Pharmaceuticals, Inc. Miši s humanizirano univerzalno lahko verigo

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007054076A (ja) * 1993-04-26 2007-03-08 Genpharm Internatl Inc 異種抗体を産生することができるトランスジェニック非ヒト動物
JP2004524841A (ja) * 2001-02-16 2004-08-19 リジェネロン・ファーマシューティカルズ・インコーポレイテッド 真核生物細胞を改変する方法
WO2011097603A1 (en) * 2010-02-08 2011-08-11 Regeneron Pharmaceuticals, Inc. Common light chain mouse

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EP2854523A1 (en) 2015-04-08
SG10201609535TA (en) 2017-01-27
CN104582476A (zh) 2015-04-29
SG11201407644UA (en) 2014-12-30
KR20150023535A (ko) 2015-03-05
WO2013184761A1 (en) 2013-12-12
MX2014014891A (es) 2015-06-17
IL235781A0 (en) 2015-01-29
CN104582476B (zh) 2017-03-08
RU2014153674A (ru) 2016-07-27
AU2013271737A1 (en) 2015-01-22
HK1208994A1 (en) 2016-03-24
CA2874846A1 (en) 2013-12-12

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