JP2004504007A5 - - Google Patents
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- JP2004504007A5 JP2004504007A5 JP2001548557A JP2001548557A JP2004504007A5 JP 2004504007 A5 JP2004504007 A5 JP 2004504007A5 JP 2001548557 A JP2001548557 A JP 2001548557A JP 2001548557 A JP2001548557 A JP 2001548557A JP 2004504007 A5 JP2004504007 A5 JP 2004504007A5
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IBPCT/IB99/02054 | 1999-12-28 | ||
| IB9902054 | 1999-12-28 | ||
| IBPCT/IB00/00218 | 2000-03-01 | ||
| IBPCT/IB00/00218 | 2000-03-01 | ||
| PCT/IB2000/001892 WO2001048017A1 (en) | 1999-12-28 | 2000-12-18 | Intrabodies with defined framework that is stable in a reducing environment and applications thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010240199A Division JP5783703B2 (ja) | 1999-12-28 | 2010-10-26 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2004504007A JP2004504007A (ja) | 2004-02-12 |
| JP2004504007A5 true JP2004504007A5 (enExample) | 2010-12-24 |
| JP4698109B2 JP4698109B2 (ja) | 2011-06-08 |
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Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001548557A Expired - Fee Related JP4698109B2 (ja) | 1999-12-28 | 2000-12-18 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
| JP2010240199A Expired - Fee Related JP5783703B2 (ja) | 1999-12-28 | 2010-10-26 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
| JP2013096838A Withdrawn JP2013224294A (ja) | 1999-12-28 | 2013-05-02 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
| JP2015208555A Pending JP2016020388A (ja) | 1999-12-28 | 2015-10-23 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010240199A Expired - Fee Related JP5783703B2 (ja) | 1999-12-28 | 2010-10-26 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
| JP2013096838A Withdrawn JP2013224294A (ja) | 1999-12-28 | 2013-05-02 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
| JP2015208555A Pending JP2016020388A (ja) | 1999-12-28 | 2015-10-23 | 還元環境下において安定な、規定されたフレームワークを有するイントラボディーおよびそれらの用途 |
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|---|---|
| US (3) | US7258986B2 (enExample) |
| EP (3) | EP1479694B1 (enExample) |
| JP (4) | JP4698109B2 (enExample) |
| AT (1) | ATE273323T1 (enExample) |
| AU (1) | AU768827B2 (enExample) |
| CA (1) | CA2396534C (enExample) |
| DE (1) | DE60012980T2 (enExample) |
| DK (1) | DK1242457T3 (enExample) |
| ES (1) | ES2225269T3 (enExample) |
| WO (1) | WO2001048017A1 (enExample) |
Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999028502A1 (en) * | 1997-11-28 | 1999-06-10 | Invitrogen Corporation | Single chain monoclonal antibody fusion reagents that regulate transcription in vivo |
| IT1317922B1 (it) * | 2000-10-24 | 2003-07-15 | S I S S A Scuola Internaz Supe | Metodo per identificare in vivo epitopi intracellulari. |
| US6610472B1 (en) * | 2000-10-31 | 2003-08-26 | Genetastix Corporation | Assembly and screening of highly complex and fully human antibody repertoire in yeast |
| WO2003025124A2 (en) * | 2001-09-14 | 2003-03-27 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Immunoglobulin having particular framework scaffold and methods of making and using |
| AU2003219277A1 (en) * | 2002-03-14 | 2003-09-29 | Medical Research Council | Intracellular antibodies |
| AU2012211497C1 (en) * | 2002-05-22 | 2021-07-29 | Novartis Ag | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
| AU2015202410B2 (en) * | 2002-05-22 | 2017-09-14 | Novartis Ag | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
| AU2013203288B2 (en) * | 2002-05-22 | 2015-04-23 | Novartis Ag | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
| CN103739706B (zh) | 2002-05-22 | 2015-11-18 | 艾斯巴技术-诺华有限责任公司 | 在胞内环境中表现出增强的稳定性的免疫球蛋白构架及其鉴定方法 |
| EP1621616A4 (en) * | 2003-04-30 | 2007-07-04 | Japan Science & Tech Agency | HUMAN ANTI-HUMAN INTERLEUKIN-18 ANTIBODY, FRAGMENT AND METHOD FOR THEIR USE |
| WO2005052002A2 (en) * | 2003-11-20 | 2005-06-09 | Massachusetts Institute Of Technology | Single-domain antibodies and uses thereof |
| EP1761561B1 (en) * | 2004-01-20 | 2015-08-26 | KaloBios Pharmaceuticals, Inc. | Antibody specificity transfer using minimal essential binding determinants |
| KR100635370B1 (ko) | 2005-03-04 | 2006-10-17 | 주식회사 녹십자홀딩스 | ＳｃＦｖ 형태의 항체 라이브러리를 제작하기 위한 항체 ＳｃＦｖ 발현벡터 |
| ES2558338T3 (es) * | 2005-03-25 | 2016-02-03 | National Research Council Of Canada | Método para aislamiento de polipéptidos solubles |
| FR2883886B1 (fr) * | 2005-04-05 | 2010-12-03 | Biomethodes | Methode d'obtention de variants solubles ou mieux exprimes d'une proteine d'interet |
| ES2424042T3 (es) | 2005-06-07 | 2013-09-26 | Esbatech - A Novartis Company Llc | Anticuerpos estables y solubles que inhiben TNF± |
| JP4938263B2 (ja) * | 2005-08-19 | 2012-05-23 | 独立行政法人農業生物資源研究所 | 一本鎖抗体によるサイトゾルタンパク質の機能阻害法およびその利用 |
| WO2007024877A2 (en) * | 2005-08-22 | 2007-03-01 | Cornell Research Foundation, Inc. | Compositions and methods for analyzing protein interactions |
| RU2460540C2 (ru) * | 2006-04-28 | 2012-09-10 | Деленекс Терапьютикс Аг | Антитела, связывающиеся с внеклеточным доменом тирозинкиназного рецептора (alk) |
| EP3093026B1 (en) | 2006-07-10 | 2020-07-01 | ESBATech, an Alcon Biomedical Research Unit LLC | Scfv antibodies which pass epithelial and/or endothelial layers |
| WO2008089132A2 (en) * | 2007-01-12 | 2008-07-24 | Cornell Research Foundation, Inc. | Genetic selection for protein folding and solubility in the bacterial periplasm |
| RU2009137582A (ru) | 2007-03-12 | 2011-04-20 | Эсбатек Аг (Ch) | Инженерия и оптимизация одноцепочечных антител на основе последовательности |
| ES2384006T3 (es) | 2007-03-15 | 2012-06-28 | Inserm | Métodos para producir anticuerpos scFv activos y bibliotecas para los mismos |
| ES2721753T3 (es) * | 2007-05-21 | 2019-08-05 | Alderbio Holdings Llc | Anticuerpos contra IL-6 y usos de los mismos |
| EP2164961B1 (en) | 2007-06-25 | 2015-01-07 | ESBATech, an Alcon Biomedical Research Unit LLC | Sequence based engineering and optimization of single chain antibodies |
| BRPI0813645A2 (pt) * | 2007-06-25 | 2014-12-30 | Esbatech Alcon Biomed Res Unit | Métodos para modificar anticorpos, e anticorpos modificados com propriedades funcionais aperfeiçoadas |
| KR20100074181A (ko) | 2007-09-13 | 2010-07-01 | 델레넥스 쎄라퓨틱스 아게 | β-아밀로이드 펩티드에 대한 인간화 항체 |
| KR101834797B1 (ko) | 2008-06-25 | 2018-03-07 | 에스바테크 - 어 노바티스 컴파니 엘엘씨 | 보편적 항체 프레임워크를 사용한 래빗 항체의 인간화 |
| MX345039B (es) * | 2008-06-25 | 2017-01-16 | Esbatech Alcon Biomed Res Unit | Anticuerpos estables y solubles que inhiben el tnfa. |
| PT2307454T (pt) | 2008-06-25 | 2017-04-26 | Esbatech Alcon Biomed Res Unit | Anticorpos estáveis e solúveis que inibem o vegf |
| SI3628686T1 (sl) | 2008-06-25 | 2022-01-31 | Novartis Ag | Humaniziranje zajčjih protiteles z uporabo univerzalnega ogrodja protitelesa |
| CA2728829C (en) | 2008-06-25 | 2018-01-02 | Esbatech, An Alcon Biomedical Research Unit Llc | Solubility optimization of immunobinders |
| US8399624B1 (en) | 2009-06-25 | 2013-03-19 | Esbatech, An Alcon Biomedical Research Unit Llc | Acceptor framework for CDR grafting |
| AR083495A1 (es) | 2010-10-22 | 2013-02-27 | Esbatech Alcon Biomed Res Unit | Anticuerpos estables y solubles |
| CA2874521A1 (en) | 2012-05-24 | 2013-11-28 | Dana-Farber Cancer Institute, Inc. | Targeting the glutamine to pyruvate pathway for treatment of oncogenic kras-associated cancer |
| WO2014014518A1 (en) | 2012-07-18 | 2014-01-23 | Dana-Farber Cancer Institute, Inc. | Methods for treating, preventing and predicting risk of developing breast cancer |
| AU2013378628A1 (en) * | 2013-02-15 | 2015-06-11 | Esbatech - A Novartis Company Llc | Acceptor framework for CDR grafting |
| WO2014127811A1 (en) | 2013-02-20 | 2014-08-28 | Esbatech - A Novartis Company Llc | Acceptor framework for cdr grafting |
| CA2927543C (en) | 2013-10-15 | 2021-07-20 | The California Institute For Biomedical Research | Peptidic chimeric antigen receptor t cell switches and uses thereof |
| US10350264B2 (en) | 2014-03-27 | 2019-07-16 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for modulating NCOA4-mediated autophagic targeting of ferritin |
| EP4008725A1 (en) | 2014-05-02 | 2022-06-08 | The Trustees of the University of Pennsylvania | Compositions and methods of chimeric autoantibody receptor t cells |
| GB201409558D0 (en) | 2014-05-29 | 2014-07-16 | Ucb Biopharma Sprl | Method |
| US9212225B1 (en) | 2014-07-01 | 2015-12-15 | Amphivena Therapeutics, Inc. | Bispecific CD33 and CD3 binding proteins |
| EP3169702A4 (en) * | 2014-07-14 | 2018-04-18 | The Regents of The University of California | A protein tagging system for in vivo single molecule imaging and control of gene transcription |
| GB201412658D0 (en) | 2014-07-16 | 2014-08-27 | Ucb Biopharma Sprl | Molecules |
| GB201412659D0 (en) | 2014-07-16 | 2014-08-27 | Ucb Biopharma Sprl | Molecules |
| WO2016038550A1 (en) | 2014-09-11 | 2016-03-17 | Novartis Ag | Inhibition of prmt5 to treat mtap-deficiency-related diseases |
| WO2016089883A1 (en) | 2014-12-01 | 2016-06-09 | Novartis Ag | Compositions and methods for diagnosis and treatment of prostate cancer |
| WO2016154621A1 (en) | 2015-03-26 | 2016-09-29 | The California Institute For Biomedical Research | SWITCHABLE NON-scFv CHIMERIC RECEPTORS, SWITCHES, AND USES THEREOF |
| US11091546B2 (en) | 2015-04-15 | 2021-08-17 | The Scripps Research Institute | Optimized PNE-based chimeric receptor T cell switches and uses thereof |
| KR102537102B1 (ko) | 2015-05-29 | 2023-05-25 | 엠피베나 테라퓨틱스, 인크. | 이중특이적 cd33 및 cd3 결합 단백질을 사용하는 방법 |
| GB201601075D0 (en) | 2016-01-20 | 2016-03-02 | Ucb Biopharma Sprl | Antibodies molecules |
| GB201601077D0 (en) | 2016-01-20 | 2016-03-02 | Ucb Biopharma Sprl | Antibody molecule |
| GB201601073D0 (en) | 2016-01-20 | 2016-03-02 | Ucb Biopharma Sprl | Antibodies |
| GB201521383D0 (en) | 2015-12-03 | 2016-01-20 | Ucb Biopharma Sprl And Ucb Celltech | Method |
| GB201521393D0 (en) | 2015-12-03 | 2016-01-20 | Ucb Biopharma Sprl | Antibodies |
| GB201521389D0 (en) | 2015-12-03 | 2016-01-20 | Ucb Biopharma Sprl | Method |
| GB201521382D0 (en) | 2015-12-03 | 2016-01-20 | Ucb Biopharma Sprl | Antibodies |
| GB201521391D0 (en) | 2015-12-03 | 2016-01-20 | Ucb Biopharma Sprl | Antibodies |
| ES3030503T3 (en) | 2016-10-19 | 2025-06-30 | Scripps Research Inst | Chimeric antigen receptor effector cell switches with humanized targeting moieties and/or optimized chimeric antigen receptor interacting domains and uses thereof |
| US11530413B2 (en) | 2017-07-21 | 2022-12-20 | Novartis Ag | Compositions and methods to treat cancer |
| BR112020015999A2 (pt) | 2018-04-06 | 2020-12-15 | Dana-Farber Cancer Institute, Inc. | Kir3dl3 como um receptor de hhla2, anticorpos anti-hhla2 e usos dos mesmos |
| US20210123016A1 (en) | 2018-05-02 | 2021-04-29 | Novartis Ag | Regulators of human pluripotent stem cells and uses thereof |
| WO2020069349A1 (en) * | 2018-09-27 | 2020-04-02 | Colorado State University Research Foundation | Scfv's for live cell imaging and other uses |
| WO2023229535A1 (en) | 2022-05-27 | 2023-11-30 | Engine Biosciences Pte. Ltd. | Bet polypeptide therapeutic agents for generating synthetic lethality in tumors |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5618920A (en) | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
| FR2627508B1 (fr) | 1988-02-22 | 1990-10-05 | Eurolysine | Procede pour l'integration d'un gene choisi sur le chromosome d'une bacterie et bacterie obtenue par ledit procede |
| FR2648713B1 (fr) | 1989-06-26 | 1994-06-10 | Commissariat Energie Atomique | Proteines hybrides entre une enzyme extracytoplasmique et une autre proteine, leur procede de preparation, ainsi que leur application comme agent de diagnostic |
| WO1992022324A1 (en) | 1991-06-14 | 1992-12-23 | Xoma Corporation | Microbially-produced antibody fragments and their conjugates |
| JPH05105700A (ja) | 1991-07-15 | 1993-04-27 | Tosoh Corp | 酵母に対する血清又は抗体、それらの調製方法及びそれらの使用方法 |
| JPH0597704A (ja) | 1991-10-07 | 1993-04-20 | Hisashi Ishihara | 新抗体ワクチン製造技法 |
| JPH0630778A (ja) | 1992-07-17 | 1994-02-08 | Tosoh Corp | ピキア酵母により抗体を製造するためのベクタ−、該ベクタ−で形質転換されたピキア酵母及び形質転換ピキア酵母を培養することを特徴とする抗体の製造方法 |
| EP0698097B1 (en) | 1993-04-29 | 2001-08-16 | Unilever N.V. | Production of antibodies or (functionalized) fragments thereof derived from heavy chain immunoglobulins of camelidae |
| DE69427974T2 (de) | 1993-04-29 | 2001-12-06 | Unilever N.V., Rotterdam | Herstellung von antikörpern oder funktionstüchtig gemachten teilen davon, abgeleitet von schweren ketten von immunglobulinen von camelidae |
| JPH0920798A (ja) | 1995-07-11 | 1997-01-21 | Asahi Chem Ind Co Ltd | ヒト抗ＨＢｓ抗体 |
| EP1295952A3 (en) * | 1996-01-23 | 2003-07-09 | The Board of Trustees of The Leland Stanford Junior University | Methods for screening for transdominant effector peptides and RNA molecules |
| WO1997044447A2 (en) * | 1996-05-03 | 1997-11-27 | President And Fellows Of Harvard College | Transcriptional activation system, activators, and uses therefor |
| US6300065B1 (en) | 1996-05-31 | 2001-10-09 | Board Of Trustees Of The University Of Illinois | Yeast cell surface display of proteins and uses thereof |
| US20030017149A1 (en) * | 1996-10-10 | 2003-01-23 | Hoeffler James P. | Single chain monoclonal antibody fusion reagents that regulate transcription in vivo |
| JP4041913B2 (ja) | 1997-02-13 | 2008-02-06 | 独立行政法人農業・食品産業技術総合研究機構 | 抗腫瘍タンパク質およびその遺伝子 |
| JPH11174A (ja) | 1997-06-13 | 1999-01-06 | Asahi Breweries Ltd | 酵母を用いた抗体Ｆａｂ断片の製造法 |
| WO1999028502A1 (en) * | 1997-11-28 | 1999-06-10 | Invitrogen Corporation | Single chain monoclonal antibody fusion reagents that regulate transcription in vivo |
| GB2344886B (en) * | 1999-03-10 | 2000-11-01 | Medical Res Council | Selection of intracellular immunoglobulins |
-
2000
- 2000-12-18 ES ES00979875T patent/ES2225269T3/es not_active Expired - Lifetime
- 2000-12-18 EP EP04017280.1A patent/EP1479694B1/en not_active Expired - Lifetime
- 2000-12-18 DK DK00979875T patent/DK1242457T3/da active
- 2000-12-18 CA CA2396534A patent/CA2396534C/en not_active Expired - Fee Related
- 2000-12-18 DE DE60012980T patent/DE60012980T2/de not_active Expired - Lifetime
- 2000-12-18 EP EP00979875A patent/EP1242457B1/en not_active Expired - Lifetime
- 2000-12-18 EP EP10010030.4A patent/EP2392596A3/en not_active Withdrawn
- 2000-12-18 WO PCT/IB2000/001892 patent/WO2001048017A1/en not_active Ceased
- 2000-12-18 AU AU17252/01A patent/AU768827B2/en not_active Ceased
- 2000-12-18 AT AT00979875T patent/ATE273323T1/de active
- 2000-12-18 JP JP2001548557A patent/JP4698109B2/ja not_active Expired - Fee Related
- 2000-12-18 US US10/169,179 patent/US7258986B2/en not_active Expired - Lifetime
- 2000-12-28 US US09/750,424 patent/US7258985B2/en not_active Expired - Lifetime
-
2007
- 2007-08-20 US US11/894,097 patent/US20080233110A1/en not_active Abandoned
-
2010
- 2010-10-26 JP JP2010240199A patent/JP5783703B2/ja not_active Expired - Fee Related
-
2013
- 2013-05-02 JP JP2013096838A patent/JP2013224294A/ja not_active Withdrawn
-
2015
- 2015-10-23 JP JP2015208555A patent/JP2016020388A/ja active Pending
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