JP7442443B2 - 多重特異性抗体 - Google Patents
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- JP7442443B2 JP7442443B2 JP2020519761A JP2020519761A JP7442443B2 JP 7442443 B2 JP7442443 B2 JP 7442443B2 JP 2020519761 A JP2020519761 A JP 2020519761A JP 2020519761 A JP2020519761 A JP 2020519761A JP 7442443 B2 JP7442443 B2 JP 7442443B2
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- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/35—Valency
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
-
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- C07K2317/75—Agonist effect on antigen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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| CA3053803A1 (en) | 2017-02-24 | 2018-08-30 | Macrogenics, Inc. | Bispecific binding molecules that are capable of binding cd137 and tumor antigens, and uses thereof |
| JP7130678B2 (ja) * | 2017-06-05 | 2022-09-05 | ヌマブ セラピューティクス アクチェンゲゼルシャフト | 新規抗ｈｓａ抗体 |
| CA3075337A1 (en) * | 2017-10-10 | 2019-04-18 | Numab Therapeutics AG | Antibodies targeting cd137 and methods of use thereof |
| KR20200083574A (ko) * | 2017-11-13 | 2020-07-08 | 크레센도 바이오로직스 리미티드 | Cd137 및 psma에 결합하는 분자 |
| TWI839395B (zh) * | 2018-10-09 | 2024-04-21 | 瑞士商Ｎｕｍａｂ治療公司 | 靶向cd137的抗體及其使用方法 |
| WO2021013142A1 (zh) * | 2019-07-22 | 2021-01-28 | 江苏恒瑞医药股份有限公司 | 抗4-1bb抗体、其抗原结合片段及双特异性抗体 |
| JP7634001B2 (ja) | 2019-10-11 | 2025-02-20 | ナンチン リーズ バイオラブス カンパニー，リミティド | ４－１ｂｂに結合する抗体およびその用途 |
| EP3816185A1 (en) * | 2019-11-04 | 2021-05-05 | Numab Therapeutics AG | Multispecific antibody directed against pd-l1 and a tumor-associated antigen |
| JP7675083B2 (ja) * | 2020-01-09 | 2025-05-12 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | 新規４－１ｂｂｌ三量体含有抗原結合分子 |
| CN116249555A (zh) | 2020-05-19 | 2023-06-09 | 勃林格殷格翰国际有限公司 | 用于癌症治疗的结合分子 |
| CA3184899A1 (en) * | 2020-05-29 | 2021-12-02 | Numab Therapeutics AG | Multispecific antibody |
| CN114195900B (zh) * | 2020-09-17 | 2024-02-23 | 普米斯生物技术(珠海)有限公司 | 一种抗4-1bb/pd-l1双特异性抗体及其用途 |
| EP3988568A1 (en) | 2020-10-21 | 2022-04-27 | Numab Therapeutics AG | Combination treatment |
| WO2022136693A1 (en) | 2020-12-23 | 2022-06-30 | Numab Therapeutics AG | Antibody variable domains and antibodies having decreased immunogenicity |
| EP4373848A2 (en) | 2021-07-22 | 2024-05-29 | University of Dundee | Therapeutic muteins |
| IL316376A (en) | 2022-05-06 | 2024-12-01 | Numab Therapeutics AG | Antibody variable domains and antibodies having decreased immunogenicity |
| EP4273162A1 (en) | 2022-05-06 | 2023-11-08 | Numab Therapeutics AG | Antibody variable domains and antibodies having decreased immunogenicity |
| WO2024240690A2 (en) | 2023-05-19 | 2024-11-28 | Numab Therapeutics AG | Antibody variable domains and antibodies having decreased immunogenicity |
| WO2025133389A1 (en) | 2023-12-22 | 2025-06-26 | Numab Therapeutics AG | Antibody binding domains having specificity for lilrb2 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017123650A2 (en) | 2016-01-11 | 2017-07-20 | Inhibrx Lp | Multivalent and multispecific 41bb-binding fusion proteins |
| JP2020537520A (ja) | 2017-10-10 | 2020-12-24 | ヌマブ セラピューティクス アクチェンゲゼルシャフト | Ｃｄ１３７を標的とする抗体とその利用方法 |
| JP2021501569A (ja) | 2017-10-10 | 2021-01-21 | ヌマブ セラピューティックス アーゲー | Ｐｄｌ１を標的とする抗体及びそれを用いる方法 |
Family Cites Families (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| CA1247080A (en) | 1983-03-08 | 1988-12-20 | Commonwealth Serum Laboratories Commission | Antigenically active amino acid sequences |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US4881175A (en) | 1986-09-02 | 1989-11-14 | Genex Corporation | Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides |
| US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
| US5013653A (en) | 1987-03-20 | 1991-05-07 | Creative Biomolecules, Inc. | Product and process for introduction of a hinge region into a fusion protein to facilitate cleavage |
| EP0318554B2 (en) | 1987-05-21 | 2005-01-12 | Micromet AG | Targeted multifunctional proteins |
| US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
| US5132405A (en) | 1987-05-21 | 1992-07-21 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| SE509359C2 (sv) | 1989-08-01 | 1999-01-18 | Cemu Bioteknik Ab | Användning av stabiliserade protein- eller peptidkonjugat för framställning av ett läkemedel |
| US6267964B1 (en) | 1989-08-01 | 2001-07-31 | Affibody Technology Sweden Ab | Stabilized protein or peptide conjugates able to bond albumin having extended biological half-lives |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| GB9114948D0 (en) | 1991-07-11 | 1991-08-28 | Pfizer Ltd | Process for preparing sertraline intermediates |
| EP1291360A1 (en) | 1991-12-13 | 2003-03-12 | Xoma Corporation | Methods and materials for preparation of modified antibody variable domains and therapeutic uses thereof |
| DE19819846B4 (de) | 1998-05-05 | 2016-11-24 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Multivalente Antikörper-Konstrukte |
| CA2921260A1 (en) | 1999-12-24 | 2001-06-28 | Genentech, Inc. | Methods and compositions for prolonging elimination half-times of bioactive compounds |
| US7211395B2 (en) | 2001-03-09 | 2007-05-01 | Dyax Corp. | Serum albumin binding moieties |
| US20030157561A1 (en) * | 2001-11-19 | 2003-08-21 | Kolkman Joost A. | Combinatorial libraries of monomer domains |
| WO2003048731A2 (en) | 2001-12-03 | 2003-06-12 | Abgenix, Inc. | Antibody categorization based on binding characteristics |
| WO2004001064A2 (en) | 2002-06-21 | 2003-12-31 | Dyax Corporation | Serum protein-associated target-specific ligands and identification method therefor |
| DK1517921T3 (da) | 2002-06-28 | 2006-10-09 | Domantis Ltd | Immunglobulin-enkeltvariable antigen-bindende domæner og dobbeltspecifikke konstruktioner deraf |
| US9321832B2 (en) | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
| US6887673B2 (en) | 2002-07-30 | 2005-05-03 | Bristol-Myers Squibb Company | Humanized antibodies against human 4-1BB |
| US7217797B2 (en) | 2002-10-15 | 2007-05-15 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
| CA2502413A1 (en) | 2002-11-01 | 2004-05-21 | The Regents Of The University Of Colorado, A Body Corporate | Quantitative analysis of protein isoforms using matrix-assisted laser desorption/ionization time of flight mass spectrometry |
| JP2008500830A (ja) | 2004-06-01 | 2008-01-17 | ドマンティス リミテッド | 増加した血清半減期を有する二重特異性融合抗体 |
| WO2006059106A2 (en) | 2004-12-02 | 2006-06-08 | Domantis Limited | Bispecific domain antibodies targeting serum albumin and glp-1 or pyy |
| CN104356236B (zh) | 2005-07-01 | 2020-07-03 | E.R.施贵宝&圣斯有限责任公司 | 抗程序性死亡配体1(pd-l1)的人单克隆抗体 |
| US8921279B2 (en) | 2007-06-26 | 2014-12-30 | F-Star Biotechnologische Forschungs—und Entwicklungsges. m.b.H | Display of binding agents |
| EP2195341B1 (en) | 2007-09-26 | 2017-03-22 | UCB Biopharma SPRL | Dual specificity antibody fusions |
| CA2737241C (en) | 2008-09-26 | 2017-08-29 | Ucb Pharma S.A. | Multivalent antibody fusion proteins |
| TW202442680A (zh) | 2008-12-09 | 2024-11-01 | 美商建南德克公司 | 抗pd-l1抗體及其於增進t細胞功能之用途 |
| JP2012532620A (ja) | 2009-07-16 | 2012-12-20 | グラクソ グループ リミテッド | 改良型抗血清アルブミン結合単一可変ドメイン |
| MX343747B (es) | 2009-11-24 | 2016-11-22 | Medimmune Ltd | Agentes de union diana contra b7-h1. |
| GB201000467D0 (en) | 2010-01-12 | 2010-02-24 | Ucb Pharma Sa | Antibodies |
| DK2614082T3 (en) | 2010-09-09 | 2018-11-26 | Pfizer | 4-1BB BINDING MOLECULES |
| MX349096B (es) | 2011-11-28 | 2017-07-11 | Merck Patent Gmbh | Anticuerpos anti-pd-l1 y sus usos. |
| MA41044A (fr) * | 2014-10-08 | 2017-08-15 | Novartis Ag | Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer |
| RS62332B1 (sr) * | 2014-11-26 | 2021-10-29 | Xencor Inc | Heterodimerna antitela koja vezuju cd3 i cd20 |
| CN107921104A (zh) * | 2015-02-22 | 2018-04-17 | 索伦托治疗有限公司 | 结合cd137的抗体疗法 |
| IL292449B2 (en) * | 2015-03-13 | 2024-02-01 | Cytomx Therapeutics Inc | Nucleic acids encoding anti-pdl1 antibodie and methods of producing same |
| MX395604B (es) | 2015-06-15 | 2025-03-25 | Numab Therapeutics AG | Formato de anticuerpo multiespecífico heterodimérico. |
| WO2017102835A1 (en) * | 2015-12-14 | 2017-06-22 | Complix Nv | Binding molecule comprising an alphabody-polypeptide and an antibody |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017123650A2 (en) | 2016-01-11 | 2017-07-20 | Inhibrx Lp | Multivalent and multispecific 41bb-binding fusion proteins |
| JP2020537520A (ja) | 2017-10-10 | 2020-12-24 | ヌマブ セラピューティクス アクチェンゲゼルシャフト | Ｃｄ１３７を標的とする抗体とその利用方法 |
| JP2021501569A (ja) | 2017-10-10 | 2021-01-21 | ヌマブ セラピューティックス アーゲー | Ｐｄｌ１を標的とする抗体及びそれを用いる方法 |
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| MA50352A (fr) | 2020-08-19 |
| US12202911B2 (en) | 2025-01-21 |
| CL2021000028A1 (es) | 2021-05-28 |
| IL273576A (en) | 2020-05-31 |
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