CA2939198A1 - Multimeric fc proteins - Google Patents
Multimeric fc proteins Download PDFInfo
- Publication number
- CA2939198A1 CA2939198A1 CA2939198A CA2939198A CA2939198A1 CA 2939198 A1 CA2939198 A1 CA 2939198A1 CA 2939198 A CA2939198 A CA 2939198A CA 2939198 A CA2939198 A CA 2939198A CA 2939198 A1 CA2939198 A1 CA 2939198A1
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- Prior art keywords
- fusion protein
- residue
- multimeric fusion
- igg4
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- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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| AU2017279538A1 (en) | 2016-06-07 | 2019-01-03 | Gliknik Inc. | Cysteine-optimized stradomers |
| US20190389941A1 (en) | 2016-07-22 | 2019-12-26 | Gliknik Inc. | Fusion proteins of human protein fragments to create orderly multimerized immunoglobulin fc compositions with enhanced fc receptor binding |
| BR112019009495A2 (pt) | 2016-12-09 | 2019-08-06 | Gliknik Inc | métodos de tratamento de distúrbios inflamatórios com compostos de fc multivalentes |
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| CN110546162B (zh) * | 2017-03-28 | 2021-09-07 | 礼进生物医药科技（上海）有限公司 | 用于增强肿瘤微环境中免疫应答的治疗剂和方法 |
| JP2020513019A (ja) | 2017-04-05 | 2020-04-30 | ノヴォ ノルディスク アー／エス | オリゴマー伸長インスリン−Ｆｃコンジュゲート |
| KR101913743B1 (ko) | 2017-04-07 | 2018-11-01 | 국민대학교 산학협력단 | 혈중 반감기 연장을 위한 항체 Fc 변이체들 |
| MX2019014576A (es) * | 2017-06-05 | 2020-07-29 | Janssen Biotech Inc | Anticuerpos multiespecíficos manipulados genéticamente y otras proteínas multiméricas con mutaciones asimétricas en la región ch2-ch3. |
| WO2019115745A1 (en) | 2017-12-14 | 2019-06-20 | CSL Behring Lengnau AG | RECOMBINANT igG Fc MULTIMERS FOR THE TREATMENT OF NEUROMYELITIS OPTICA |
| WO2019175605A1 (en) * | 2018-03-16 | 2019-09-19 | Liverpool School Of Tropical Medicine | Chimeric fc receptor binding proteins and uses thereof |
| KR102232659B1 (ko) * | 2018-07-16 | 2021-03-26 | 전북대학교 산학협력단 | 항원전달용 폴리펩타이드, 이를 포함하는 Fc-융합 단백질 및 이의 용도 |
| US12492231B2 (en) | 2018-11-14 | 2025-12-09 | Jn Biosciences Llc | Multimeric hybrid Fc proteins for replacement of IVIG |
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Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
| US20020147326A1 (en) * | 1996-06-14 | 2002-10-10 | Smithkline Beecham Corporation | Hexameric fusion proteins and uses therefor |
| US5980898A (en) | 1996-11-14 | 1999-11-09 | The United States Of America As Represented By The U.S. Army Medical Research & Material Command | Adjuvant for transcutaneous immunization |
| GB9625640D0 (en) | 1996-12-10 | 1997-01-29 | Celltech Therapeutics Ltd | Biological products |
| US6114515A (en) | 1997-08-25 | 2000-09-05 | Smithkline Beecham Corporation | PIGRL-1, a member of immunoglobulin gene superfamily |
| GB9720054D0 (en) | 1997-09-19 | 1997-11-19 | Celltech Therapeutics Ltd | Biological products |
| DE69937291T2 (de) | 1998-04-02 | 2008-07-10 | Genentech, Inc., South San Francisco | Antikörpervarianten und fragmente davon |
| US6284536B1 (en) | 1998-04-20 | 2001-09-04 | The Regents Of The University Of California | Modified immunoglobin molecules and methods for use thereof |
| US6737056B1 (en) * | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
| MY129566A (en) | 1999-01-19 | 2007-04-30 | Nestle Sa | A hypoallergenic composition containing tolerogenic peptides inducing oral tolerance |
| US6475749B1 (en) | 1999-08-11 | 2002-11-05 | The Regents Of The University Of California | Rh hybrid antibody |
| DE10001372A1 (de) | 2000-01-14 | 2001-08-02 | Deutsches Krebsforsch | Anti-CD3-Einzelketten-Antikörper mit humanem Cmu3- und Cmu4- Domänen |
| US7148321B2 (en) | 2001-03-07 | 2006-12-12 | Emd Lexigen Research Center Corp. | Expression technology for proteins containing a hybrid isotype antibody moiety |
| KR100453877B1 (ko) | 2001-07-26 | 2004-10-20 | 메덱스젠 주식회사 | 연쇄체화에 의한 면역 글로블린 융합 단백질의 제조 방법 및 이 방법에 의해 제조된 ＴＮＦＲ/Ｆｃ 융합 단백질, 상기 단백질을 코딩하는 ＤＮＡ, 상기 ＤＮＡ를 포함하는벡터, 및 상기 벡터에 의한 형질전환체 |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
| EP3321282A1 (en) | 2002-09-27 | 2018-05-16 | Xencor, Inc. | Optimized fc variants and methods for their generation |
| US8388955B2 (en) * | 2003-03-03 | 2013-03-05 | Xencor, Inc. | Fc variants |
| GB0315450D0 (en) | 2003-07-01 | 2003-08-06 | Celltech R&D Ltd | Biological products |
| HRP20151252T4 (hr) | 2003-07-01 | 2018-11-30 | Ucb Biopharma Sprl | Modificirani fab ulomci protutijela |
| GB0315457D0 (en) | 2003-07-01 | 2003-08-06 | Celltech R&D Ltd | Biological products |
| US20060134105A1 (en) | 2004-10-21 | 2006-06-22 | Xencor, Inc. | IgG immunoglobulin variants with optimized effector function |
| WO2005063815A2 (en) | 2003-11-12 | 2005-07-14 | Biogen Idec Ma Inc. | Fcϝ receptor-binding polypeptide variants and methods related thereto |
| PL2471813T3 (pl) | 2004-07-15 | 2015-09-30 | Xencor Inc | Zoptymalizowane warianty Fc |
| US8409577B2 (en) | 2006-06-12 | 2013-04-02 | Emergent Product Development Seattle, Llc | Single chain multivalent binding proteins with effector function |
| JPWO2008032833A1 (ja) | 2006-09-14 | 2010-01-28 | 株式会社医学生物学研究所 | Ａｄｃｃ活性を増強させた抗体及びその製造方法 |
| NZ581395A (en) | 2007-05-14 | 2012-08-31 | Biogen Idec Inc | Single-chain fc (scfc) regions, binding polypeptides comprising same, and methods related thereto |
| JP5600588B2 (ja) * | 2007-06-01 | 2014-10-01 | ユニバーシティー オブ メリーランド，ボルティモア | 免疫グロブリン定常領域Ｆｃ受容体結合因子 |
| EP2260057B1 (en) | 2008-03-13 | 2016-11-23 | Biotest AG | Anti-CD4 antibody dosage regimen for treating autoimmune disease |
| WO2010085682A2 (en) * | 2009-01-23 | 2010-07-29 | Biogen Idec Ma Inc. | Stabilized fc polypeptides with reduced effector function and methods of use |
| CN102781963B (zh) | 2009-10-27 | 2018-02-16 | Ucb医药有限公司 | 功能修饰性NAv1.7抗体 |
| GB0922209D0 (en) * | 2009-12-18 | 2010-02-03 | Univ Nottingham | Proteins, nucleic acid molecules and compositions |
| DK2598533T3 (en) | 2010-07-28 | 2019-04-23 | Gliknik Inc | Fusion proteins of natural human protein fragments to create in an orderly fashion multimerized immunoglobulin FC compositions |
| UA117901C2 (uk) | 2011-07-06 | 2018-10-25 | Ґенмаб Б.В. | Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування |
| EP2760891B1 (en) * | 2011-09-26 | 2018-11-07 | JN Biosciences LLC | Hybrid constant regions |
| MX356402B (es) | 2011-12-21 | 2018-05-28 | Amgen Inc | Polipeptidos fc variantes con ligacion mejorada al receptor fc neonatal. |
| KR102041412B1 (ko) | 2011-12-30 | 2019-11-11 | 한미사이언스 주식회사 | 면역글로불린 Ｆｃ 단편 유도체 |
| US11180572B2 (en) | 2012-07-06 | 2021-11-23 | Genmab B.V. | Dimeric protein with triple mutations |
| WO2014022592A1 (en) * | 2012-08-02 | 2014-02-06 | Jn Biosciences Llc | Antibodies or fusion proteins multimerized via cysteine mutation and a mu tailpiece |
| ES2633894T3 (es) | 2012-08-02 | 2017-09-25 | F. Hoffmann-La Roche Ag | Procedimiento para producir moléculas monoméricas y multiméricas y usos de las mismas |
| RU2015109591A (ru) | 2012-08-20 | 2016-10-20 | Гликник Инк. | Молекулы с антигенсвязывающей активностью и способностью к поливалентному связыванию с fc-гамма-рецепторами |
| BR112015008663B1 (pt) | 2012-10-17 | 2021-01-12 | CSL Behring Lengnau AG | Uso de uma quantidade eficaz de uma proteína polimérica compreendendo seis unidades demonômero de polipeptídeo |
| CN106132994A (zh) | 2014-03-05 | 2016-11-16 | Ucb生物制药私人有限公司 | 多聚体Fc蛋白 |
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| JP2017518965A (ja) | 2014-05-02 | 2017-07-13 | モメンタ ファーマシューティカルズ インコーポレイテッ | エンジニアリングされたＦｃ構築物に関連する組成物および方法 |
| CA2978501A1 (en) | 2015-03-05 | 2016-09-09 | Ucb Biopharma Sprl | Polymeric fc proteins and methods of screening to alter their functional characteristics |
| GB201511787D0 (en) | 2015-07-06 | 2015-08-19 | Ucb Biopharma Sprl | Proteins |
-
2015
- 2015-03-05 TW TW104107000A patent/TW201619188A/zh unknown
- 2015-03-05 CA CA2939198A patent/CA2939198A1/en not_active Abandoned
- 2015-03-05 UY UY0001036021A patent/UY36021A/es not_active Application Discontinuation
- 2015-03-05 RU RU2016139006A patent/RU2016139006A/ru not_active Application Discontinuation
- 2015-03-05 US US15/123,038 patent/US11352414B2/en active Active
- 2015-03-05 AU AU2015226100A patent/AU2015226100B2/en not_active Ceased
- 2015-03-05 KR KR1020167027642A patent/KR20160130463A/ko not_active Withdrawn
- 2015-03-05 EP EP15708208.2A patent/EP3114143B1/en active Active
- 2015-03-05 SG SG11201606597QA patent/SG11201606597QA/en unknown
- 2015-03-05 JP JP2016555527A patent/JP6851200B2/ja not_active Expired - Fee Related
- 2015-03-05 WO PCT/EP2015/054687 patent/WO2015132364A1/en not_active Ceased
- 2015-03-05 CN CN201580011851.9A patent/CN106068274A/zh active Pending
- 2015-03-05 BR BR112016020368-2A patent/BR112016020368A2/pt not_active Application Discontinuation
- 2015-03-05 MX MX2016010951A patent/MX2016010951A/es unknown
-
2016
- 2016-08-03 IL IL247096A patent/IL247096A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR112016020368A2 (pt) | 2018-01-23 |
| EP3114143B1 (en) | 2020-07-08 |
| WO2015132364A1 (en) | 2015-09-11 |
| EP3114143A1 (en) | 2017-01-11 |
| US20170088603A1 (en) | 2017-03-30 |
| US11352414B2 (en) | 2022-06-07 |
| JP2017512063A (ja) | 2017-05-18 |
| MX2016010951A (es) | 2016-11-29 |
| JP6851200B2 (ja) | 2021-03-31 |
| UY36021A (es) | 2015-09-30 |
| TW201619188A (zh) | 2016-06-01 |
| AU2015226100A1 (en) | 2016-08-25 |
| IL247096A0 (en) | 2016-09-29 |
| RU2016139006A (ru) | 2018-04-05 |
| KR20160130463A (ko) | 2016-11-11 |
| AU2015226100B2 (en) | 2020-05-07 |
| CN106068274A (zh) | 2016-11-02 |
| SG11201606597QA (en) | 2016-09-29 |
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