EA013122B1 - Способы лечения иммунных нарушений, связанных с пересадкой трансплантата, растворимым мутантным ctla4 - Google Patents
Способы лечения иммунных нарушений, связанных с пересадкой трансплантата, растворимым мутантным ctla4 Download PDFInfo
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- EA013122B1 EA013122B1 EA200702180A EA200702180A EA013122B1 EA 013122 B1 EA013122 B1 EA 013122B1 EA 200702180 A EA200702180 A EA 200702180A EA 200702180 A EA200702180 A EA 200702180A EA 013122 B1 EA013122 B1 EA 013122B1
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| PCT/US2006/012648 WO2006108035A1 (en) | 2005-04-06 | 2006-04-05 | Methods for treating immune disorders associated with graft transplantation with soluble ctla4 mutant molecules |
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| US7094874B2 (en) * | 2000-05-26 | 2006-08-22 | Bristol-Myers Squibb Co. | Soluble CTLA4 mutant molecules |
| PT1868635T (pt) * | 2005-04-06 | 2017-07-27 | Bristol Myers Squibb Co | Métodos para tratar distúrbios imunes associados a transplantação de enxerto com moléculas mutantes solúveis de ctla4 |
| US9309316B2 (en) | 2005-12-20 | 2016-04-12 | Bristol-Myers Squibb Company | Stable subcutaneous protein formulations and uses thereof |
| US7528111B2 (en) * | 2006-05-12 | 2009-05-05 | Bristol-Myers Squibb Company | Method of vaccinating subjects receiving immune modulating therapy |
| WO2008014035A2 (en) * | 2006-07-25 | 2008-01-31 | The Regents Of The University Of California | Modulation of nkg2d and method for treating or preventing solid organ allograft rejection |
| AU2008319053B2 (en) | 2007-11-01 | 2012-04-26 | Astellas Pharma Inc. | Immunosuppressive polypeptides and nucleic acids |
| CN102203125A (zh) * | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂及其使用方法 |
| ES2615861T3 (es) * | 2008-10-30 | 2017-06-08 | Yeda Research And Development Company Ltd. | Células T de memoria central anti-terceros, métodos de producción de las mismas y uso de las mismas en trasplante y tratamiento de enfermedades |
| US20100297123A1 (en) * | 2009-05-15 | 2010-11-25 | Garrison Fathman C | Combination therapy to inhibit t cell effector function |
| LT2536745T (lt) * | 2010-02-19 | 2016-09-26 | Xencor, Inc. | Nauji ctla4-ig imunoadhezinai |
| EP2545073B1 (en) | 2010-03-12 | 2015-09-30 | AbbVie Biotherapeutics Inc. | Ctla4 proteins and their uses |
| MX2013002667A (es) | 2010-09-08 | 2013-08-01 | Yeda Res & Dev | Una combinacion de farmacos inmunosupresores para un injerto estable y a largo plazo. |
| JP5977238B2 (ja) | 2010-09-08 | 2016-08-24 | イェダ リサーチ アンド デベロップメント カンパニー リミテッド | 抗白血病/リンパ腫処置のための抗第三者セントラルメモリーt細胞の使用 |
| WO2013035099A1 (en) | 2011-09-08 | 2013-03-14 | Yeda Research And Development Co. Ltd. | Anti third party central memory t cells, methods of producing same and use of same in transplantation and disease treatment |
| SMT202000091T1 (it) | 2011-10-13 | 2020-05-08 | Bristol Myers Squibb Co | Polipeptidi anticorpali che antagonizzano cd40l |
| US20160153990A1 (en) | 2013-03-28 | 2016-06-02 | Bristol-Myers Squibb Company | Methods for identifying patients at risk for costimulation blockade resistant rejection |
| CN104673822A (zh) * | 2013-11-27 | 2015-06-03 | 深圳先进技术研究院 | 一种重组载体及其制备方法和应用 |
| CN104740608A (zh) * | 2013-12-30 | 2015-07-01 | 上海中信国健药业股份有限公司 | 可溶性ctla4分子用于制备治疗类风湿性关节炎药物的用途 |
| AU2015231180B2 (en) | 2014-03-19 | 2017-06-15 | Bristol-Myers Squibb Company | Methods of treating transplant rejection using a domain antibody directed against CD40L |
| MA41459A (fr) * | 2015-02-03 | 2017-12-12 | Als Therapy Development Inst | Anticorps anti-cd40l et méthodes pour traiter des maladies ou des troubles liés aux cd40l |
| EP3875477A1 (en) | 2015-04-17 | 2021-09-08 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins with tunable affinities |
| CN108135938A (zh) | 2015-07-16 | 2018-06-08 | 耶达研究及发展有限公司 | 基因修饰的抗第三方中央型记忆t细胞及其在免疫疗法中的用途 |
| CN110392736A (zh) | 2017-01-18 | 2019-10-29 | 耶达研究及发展有限公司 | 遗传修饰的反抑细胞及其在免疫治疗中的用途 |
| US10751368B2 (en) | 2017-01-18 | 2020-08-25 | Yeda Research And Development Co. Ltd. | Methods of transplantation and disease treatment |
| US10286036B2 (en) | 2017-05-12 | 2019-05-14 | Aurinia Pharmaceuticals Inc. | Protocol for treatment of lupus nephritis |
| US20190224275A1 (en) | 2017-05-12 | 2019-07-25 | Aurinia Pharmaceuticals Inc. | Protocol for treatment of lupus nephritis |
| KR102813968B1 (ko) * | 2017-10-10 | 2025-05-29 | 알파인 이뮨 사이언시즈, 인코포레이티드 | Ctla-4 변이체 면역조절 단백질 및 이의 용도 |
| US12297253B2 (en) | 2018-01-03 | 2025-05-13 | Alpine Immune Sciences, Inc. | Multi-domain immunomodulatory proteins and methods of use thereof |
| WO2019246577A1 (en) | 2018-06-22 | 2019-12-26 | Mayo Foundation For Medical Education And Research | Methods and materials for improving arteriovenous fistula maturation and maintaining arteriovenous fistula functionality |
| WO2020010259A1 (en) * | 2018-07-06 | 2020-01-09 | Mayo Foundation For Medical Education And Research | Methods and materials for improving transplant outcomes |
| IL322315A (en) | 2019-05-14 | 2025-09-01 | Provention Bio Inc | Methods and preparations for preventing type 1 diabetes |
| MX2022015872A (es) | 2020-06-11 | 2023-05-16 | Provention Bio Inc | Metodos y composiciones para prevenir diabetes tipo 1. |
| CN115089718B (zh) * | 2021-11-30 | 2024-05-28 | 杭州瑞普晨创科技有限公司 | 用于异种移植的免疫抑制剂组合和免疫抑制方法 |
| KR20240122658A (ko) | 2023-02-03 | 2024-08-13 | 이뮤노바이옴 주식회사 | 이식 거부 반응의 예방 또는 치료용 조성물 |
| WO2024211211A1 (en) | 2023-04-03 | 2024-10-10 | Regeneron Pharmaceuticals, Inc. | Methods of improving transplant survival using il-2 receptor gamma chain antibodies |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002094202A2 (en) * | 2001-05-23 | 2002-11-28 | Bristol-Myers Squibb Company | Methods for protecting allogeneic islet transplant using soluble ctla4 mutant molecules |
| WO2003088991A1 (en) * | 2002-04-19 | 2003-10-30 | Bristol-Myers Squibb Company | Methods for treating an autoimmune disease using a soluble ctla4 molecule and a dmard or nsaid |
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|---|---|---|---|---|
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US5844095A (en) | 1991-06-27 | 1998-12-01 | Bristol-Myers Squibb Company | CTLA4 Ig fusion proteins |
| US5851795A (en) | 1991-06-27 | 1998-12-22 | Bristol-Myers Squibb Company | Soluble CTLA4 molecules and uses thereof |
| US6090914A (en) | 1991-06-27 | 2000-07-18 | Bristol-Myers Squibb Company | CTLA4/CD28Ig hybrid fusion proteins and uses thereof |
| DE69226871T3 (de) | 1991-06-27 | 2009-09-24 | Bristol-Myers Squibb Co. | CTL4A-Rezeptor, ihn enthaltenden Fusionsproteine und deren Verwendung |
| US5637481A (en) | 1993-02-01 | 1997-06-10 | Bristol-Myers Squibb Company | Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell |
| US5773253A (en) | 1993-01-22 | 1998-06-30 | Bristol-Myers Squibb Company | MYPPPY variants of CTL A4 and uses thereof |
| US6750334B1 (en) | 1996-02-02 | 2004-06-15 | Repligen Corporation | CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor |
| US6051228A (en) | 1998-02-19 | 2000-04-18 | Bristol-Myers Squibb Co. | Antibodies against human CD40 |
| US7094874B2 (en) | 2000-05-26 | 2006-08-22 | Bristol-Myers Squibb Co. | Soluble CTLA4 mutant molecules |
| PL375139A1 (en) * | 2001-01-26 | 2005-11-28 | Emory University | Methods of inducing organ transplant tolerance and correcting hemoglobinopathies |
| CA2511520A1 (en) | 2002-12-23 | 2004-07-15 | Bristol-Myers Squibb Company | Mammalian cell culture processes for protein production |
| TWI328614B (en) | 2002-12-23 | 2010-08-11 | Bristol Myers Squibb Co | Product quality enhancement in mammalian cell culture processes for protein production |
| US7563443B2 (en) | 2004-09-17 | 2009-07-21 | Domantis Limited | Monovalent anti-CD40L antibody polypeptides and compositions thereof |
| PT1868635T (pt) * | 2005-04-06 | 2017-07-27 | Bristol Myers Squibb Co | Métodos para tratar distúrbios imunes associados a transplantação de enxerto com moléculas mutantes solúveis de ctla4 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002094202A2 (en) * | 2001-05-23 | 2002-11-28 | Bristol-Myers Squibb Company | Methods for protecting allogeneic islet transplant using soluble ctla4 mutant molecules |
| WO2003088991A1 (en) * | 2002-04-19 | 2003-10-30 | Bristol-Myers Squibb Company | Methods for treating an autoimmune disease using a soluble ctla4 molecule and a dmard or nsaid |
Non-Patent Citations (4)
| Title |
|---|
| ADAMS A.B. ET AL.: "CALCINEURIN INHIBITOR-FREE CD28 BLOCKADE-BASED PROTOCOL PROTECTS ALLOGENEIC ISLETS IN NONHUMAN PRIMATES", DIABETES, NEW YORK, NY, US, vol. 51, no. 2, February 2002 (2002-02), pages 265-270, XP008054843, ISSN: 0012-1797, cited in the application, the whole document * |
| ADAMS ANDREW B. ET AL.: "Development of a chimeric anti-CD40 monoclonal antibody that synergizes with LEA29Y to prolong islet allograft survival", JOURNAL OF IMMUNOLOGY, vol. 174, no. 1, 1 January 2005 (2005-01-01), pages 542-550, XP002393472, ISSN: 0022-1767, the whole document * |
| LARSEN C.P. ET AL.: "Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties", AMERICAN JOURNAL OF TRANSPLANTATION 2005 DENMARK, vol. 5, no. 3, March 2005 (2005-03), pages 443-453, XP002393471, ISSN: 1600-6135, cited in the application, the whole document * |
| VINCENTI FLAVIO ET AL.: "Costimulation blockade with belatacept in renal transplantation". THE NEW ENGLAND JOURNAL OF MEDICINE. 25 AUG 2005, vol. 353, no. 8, 25 August 2005 (2005-08-25), pages 770-781, XP009070530, ISSN: 1533-4406, the whole document * |
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