CA2972800A1 - Bispecific antibodies against plasma kallikrein and factor xii - Google Patents
Bispecific antibodies against plasma kallikrein and factor xii Download PDFInfo
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- CA2972800A1 CA2972800A1 CA2972800A CA2972800A CA2972800A1 CA 2972800 A1 CA2972800 A1 CA 2972800A1 CA 2972800 A CA2972800 A CA 2972800A CA 2972800 A CA2972800 A CA 2972800A CA 2972800 A1 CA2972800 A1 CA 2972800A1
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- antibody
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- bispecific antibody
- heavy chain
- polypeptide
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
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| US62/261,609 | 2015-12-01 | ||
| PCT/US2015/068238 WO2016109774A1 (en) | 2015-01-02 | 2015-12-31 | Bispecific antibodies against plasma kallikrein and factor xii |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU2015373910B2 (en) | 2015-01-02 | 2021-11-18 | Takeda Pharmaceutical Company Limited | Bispecific antibodies against plasma kallikrein and factor XII |
| US10913802B2 (en) * | 2015-07-21 | 2021-02-09 | Dyax Corp. | Monoclonal antibody inhibitor of factor XIIA |
| WO2018053260A1 (en) * | 2016-09-16 | 2018-03-22 | Dyax Corp. | Rna biomarkers for hereditary angioedema |
| IL268554B2 (en) | 2017-02-08 | 2025-03-01 | Dragonfly Therapeutics Inc | Multi-specific binding proteins for activation of natural killer cells and therapeutic uses thereof to treat cancer |
| CA3235295C (en) | 2017-02-20 | 2024-11-19 | Dragonfly Therapeutics, Inc. | Proteins binding her2, nkg2d and cd16 |
| JP2020531438A (ja) * | 2017-08-16 | 2020-11-05 | ドラゴンフライ セラピューティクス， インコーポレイテッド | Ｎｋｇ２ｄ、ｃｄ１６、およびｅｇｆｒ、ｈｌａ−ｅ、ｃｃｒ４、またはｐｄ−ｌ１に結合するタンパク質 |
| WO2019079496A2 (en) * | 2017-10-18 | 2019-04-25 | Regenxbio, Inc. | FULLY HUMAN ANTIBODY-BASED THERAPEUTIC AGENTS HAVING POST-TRANSLATION MODIFICATION |
| US11067584B2 (en) * | 2018-01-12 | 2021-07-20 | Genzyme Corporation | Methods for the quantitation of polypeptides |
| US12384847B2 (en) | 2018-02-08 | 2025-08-12 | Dragonfly Therapeutics, Inc. | Cancer therapy involving an anti-PD1 antibody and a multi-specific binding protein that binds NKG2D, CD16, and a tumor-associated antigen |
| US11884733B2 (en) | 2018-02-08 | 2024-01-30 | Dragonfly Therapeutics, Inc. | Antibody variable domains targeting the NKG2D receptor |
| US12215157B2 (en) | 2018-02-20 | 2025-02-04 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins that bind CD33, NKG2D, and CD16, and methods of use |
| CA3103088A1 (en) * | 2018-06-08 | 2019-12-12 | Modalis Therapeutics Corporation | Modified cas9 protein and use thereof |
| CA3106108A1 (en) * | 2018-07-11 | 2020-01-16 | Momenta Pharmaceuticals, Inc. | Compositions and methods related to engineered fc-antigen binding domain constructs targeted to pd-l1 |
| EA202091888A1 (ru) | 2018-08-08 | 2020-10-23 | Драгонфлай Терапьютикс, Инк. | Вариабельные домены антител, нацеленные на рецептор nkg2d |
| AU2019319906A1 (en) * | 2018-08-08 | 2021-03-04 | Dragonfly Therapeutics, Inc. | Proteins binding NKG2D, CD16 and a tumor-associated antigen |
| MA53284A (fr) * | 2018-08-08 | 2022-01-26 | Dragonfly Therapeutics Inc | Protéines de liaison à nkg2d, à cd16 et à un antigène associé à une tumeur |
| EP3833392A4 (en) * | 2018-08-08 | 2022-05-18 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins that bind bcma, nkg2d and cd16, and methods of use |
| JP2022512688A (ja) * | 2018-10-24 | 2022-02-07 | シャイア－エヌピーエス ファーマシューティカルズ インコーポレイテッド | Ｇｌｐ－２融合ポリペプチドならびに消化管の状態の処置および予防のための使用 |
| CA3147735A1 (en) | 2019-07-26 | 2021-02-04 | Janssen Biotech, Inc. | Proteins comprising kallikrein related peptidase 2 antigen binding domains and their uses |
| TW202208428A (zh) | 2020-05-06 | 2022-03-01 | 美商蜻蜓醫療公司 | 結合ｎｋｇ２ｄ、ｃｄ１６及ｃｌｅｃ１２ａ之蛋白質 |
| US20230390418A1 (en) * | 2020-10-29 | 2023-12-07 | Regenxbio Inc. | Vectorized factor xii antibodies and administration thereof |
| CN114790246A (zh) * | 2021-01-25 | 2022-07-26 | 成都康弘生物科技有限公司 | 一种抗体及其用途 |
| CN114790245A (zh) * | 2021-01-25 | 2022-07-26 | 成都康弘生物科技有限公司 | 一种抗体及其用途 |
| EP4301774A4 (en) | 2021-03-03 | 2025-08-13 | Dragonfly Therapeutics Inc | METHODS OF TREATING CANCER USING MULTI-SPECIFIC BINDING PROTEINS THAT BIND TO NKG2D, CD16, AND A TUMOR-ASSOCIATED ANTIGEN |
| TW202241968A (zh) * | 2021-04-22 | 2022-11-01 | 大陸商廣東菲鵬制藥股份有限公司 | 雙特異性多功能融合多肽 |
| WO2024238407A2 (en) * | 2023-05-12 | 2024-11-21 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Methods of treating dilated cardiomyopathy and heart failure |
Family Cites Families (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US4485045A (en) | 1981-07-06 | 1984-11-27 | Research Corporation | Synthetic phosphatidyl cholines useful in forming liposomes |
| US4544545A (en) | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
| US4777127A (en) | 1985-09-30 | 1988-10-11 | Labsystems Oy | Human retrovirus-related products and methods of diagnosing and treating conditions associated with said retrovirus |
| GB8702816D0 (en) | 1987-02-07 | 1987-03-11 | Al Sumidaie A M K | Obtaining retrovirus-containing fraction |
| US5219740A (en) | 1987-02-13 | 1993-06-15 | Fred Hutchinson Cancer Research Center | Retroviral gene transfer into diploid fibroblasts for gene therapy |
| US5422120A (en) | 1988-05-30 | 1995-06-06 | Depotech Corporation | Heterovesicular liposomes |
| AP129A (en) | 1988-06-03 | 1991-04-17 | Smithkline Biologicals S A | Expression of retrovirus gag protein eukaryotic cells |
| US4963657A (en) | 1988-06-09 | 1990-10-16 | Temple University Of The Commonwealth System Of Higher Education | Monoclonal antibodies to the light chain region of human factor XII and methods of preparing and using the same |
| WO1990007936A1 (en) | 1989-01-23 | 1990-07-26 | Chiron Corporation | Recombinant therapies for infection and hyperproliferative disorders |
| GB8901859D0 (en) | 1989-01-27 | 1989-03-15 | Shield Diagnostics Limited | Diagnostic test |
| US5500349A (en) | 1989-01-27 | 1996-03-19 | Coagen Limited | Blood-coagulation factor XIIA β monoclonal antibody and immunoassay |
| DE69034078T2 (de) | 1989-03-21 | 2004-04-01 | Vical, Inc., San Diego | Expression von exogenen Polynukleotidsequenzen in Wirbeltieren |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| EP1645635A3 (en) | 1989-08-18 | 2010-07-07 | Oxford Biomedica (UK) Limited | Replication defective recombinant retroviruses expressing a palliative |
| US5585362A (en) | 1989-08-22 | 1996-12-17 | The Regents Of The University Of Michigan | Adenovirus vectors for gene therapy |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| ZA911974B (en) | 1990-03-21 | 1994-08-22 | Res Dev Foundation | Heterovesicular liposomes |
| EP0534988A1 (en) | 1990-05-10 | 1993-04-07 | Cetus Corporation | Inhibitors of factor xii activation and applications thereof |
| DK0648271T3 (da) | 1991-08-20 | 2003-07-21 | Us Gov Health & Human Serv | Adenovirusmedieret overførsel af gener til mave-/tarmkanal |
| WO1993010218A1 (en) | 1991-11-14 | 1993-05-27 | The United States Government As Represented By The Secretary Of The Department Of Health And Human Services | Vectors including foreign genes and negative selective markers |
| GB9125623D0 (en) | 1991-12-02 | 1992-01-29 | Dynal As | Cell modification |
| US6093399A (en) * | 1992-03-05 | 2000-07-25 | Board Of Regents, The University Of Texas System | Methods and compositions for the specific coagulation of vasculature |
| FR2688514A1 (fr) | 1992-03-16 | 1993-09-17 | Centre Nat Rech Scient | Adenovirus recombinants defectifs exprimant des cytokines et medicaments antitumoraux les contenant. |
| EP0650370A4 (en) | 1992-06-08 | 1995-11-22 | Univ California | METHODS AND COMPOSITIONS TARGETED ON SPECIFIC TISSUES. |
| WO1993025698A1 (en) | 1992-06-10 | 1993-12-23 | The United States Government As Represented By The | Vector particles resistant to inactivation by human serum |
| GB2269175A (en) | 1992-07-31 | 1994-02-02 | Imperial College | Retroviral vectors |
| EP1024198A3 (en) | 1992-12-03 | 2002-05-29 | Genzyme Corporation | Pseudo-adenoviral vectors for the gene therapy of haemophiliae |
| US5981568A (en) | 1993-01-28 | 1999-11-09 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
| ES2188612T3 (es) | 1993-04-22 | 2003-07-01 | Skyepharma Inc | Liposomas multivesiculares de ciclodextrina para encapsular compuestos farmacologicos y metodos para su uso. |
| JP3532566B2 (ja) | 1993-06-24 | 2004-05-31 | エル． グラハム，フランク | 遺伝子治療のためのアデノウイルスベクター |
| US6015686A (en) | 1993-09-15 | 2000-01-18 | Chiron Viagene, Inc. | Eukaryotic layered vector initiation systems |
| CA2158937C (en) | 1993-09-15 | 2006-01-03 | Thomas W. Dubensky, Jr. | Recombinant alphavirus vectors |
| DE69435223D1 (de) | 1993-10-25 | 2009-09-03 | Canji Inc | Rekombinanter Adenoviren-Vektor und Verfahren zur Verwendung |
| CN1099868C (zh) | 1993-11-16 | 2003-01-29 | 斯卡法玛公司 | 具有控制释放活性成分作用的囊 |
| EP0772689B1 (en) | 1994-05-09 | 2007-12-19 | Oxford Biomedica (UK) Limited | Retroviral vectors having a reduced recombination rate |
| AU4594996A (en) | 1994-11-30 | 1996-06-19 | Chiron Viagene, Inc. | Recombinant alphavirus vectors |
| GB9609262D0 (en) | 1996-05-02 | 1996-07-03 | Isis Innovation | Peptide library and method |
| WO1997042338A1 (en) | 1996-05-06 | 1997-11-13 | Chiron Corporation | Crossless retroviral vectors |
| EP1158997A2 (en) | 1999-03-09 | 2001-12-05 | University Of Southern California | Method of promoting myocyte proliferation and myocardial tissue repair |
| CN101255196A (zh) * | 2002-06-28 | 2008-09-03 | 多曼蒂斯有限公司 | 免疫球蛋白单个变体抗原结合区及其特异性构建体 |
| WO2006066878A1 (en) | 2004-12-23 | 2006-06-29 | Csl Behring Gmbh | Prevention of thrombus formation and/or stabilization |
| GB0500487D0 (en) | 2005-01-11 | 2005-02-16 | Axis Shield Diagnostics Ltd | Forms of factor XIIa |
| US7932021B2 (en) | 2005-07-28 | 2011-04-26 | American Diagnostica, Inc. | Lupus anticoagulant testing |
| GB0607515D0 (en) | 2006-04-13 | 2006-05-24 | Axis Shield Diagnostics Ltd | Anti-factor xlla therapy |
| TWI465247B (zh) | 2008-04-11 | 2014-12-21 | Catalyst Biosciences Inc | 經修飾的因子ｖｉｉ多肽和其用途 |
| TWI496582B (zh) | 2008-11-24 | 2015-08-21 | 必治妥美雅史谷比公司 | 雙重專一性之ｅｇｆｒ／ｉｇｆｉｒ結合分子 |
| ES2720594T3 (es) | 2008-12-18 | 2019-07-23 | Univ Oregon Health & Science | Anticuerpos anti-fXI y métodos de uso |
| HRP20181419T1 (hr) | 2010-01-06 | 2018-11-16 | Dyax Corp. | Plazma kalikrein vezni proteini |
| RU2620071C2 (ru) | 2010-11-17 | 2017-05-22 | Чугаи Сеияку Кабушики Каиша | Мультиспецифическая связывающая антиген молекула, которая обладает альтернативной функцией к функции фактора свертывания крови viii |
| IL269565B2 (en) | 2011-01-06 | 2024-06-01 | Dyax Corp | Plasma kallikrein binding proteins |
| AU2012289001B2 (en) | 2011-07-22 | 2016-03-03 | Csl Behring Gmbh | Inhibitory anti -factor XII/XIIa monoclonal antibodies and their uses |
| EP2548892A1 (en) | 2011-07-22 | 2013-01-23 | CSL Behring GmbH | Inhibitory anti-Factor XII/XIIa monoclonal Antibodies and their uses |
| JP5653860B2 (ja) | 2011-07-28 | 2015-01-14 | 富士フイルム株式会社 | 管壁の硬度測定方法および装置 |
| JP6271251B2 (ja) | 2011-10-05 | 2018-01-31 | 中外製薬株式会社 | 糖鎖受容体結合ドメインを含む抗原の血漿中からの消失を促進する抗原結合分子 |
| PL2794905T3 (pl) * | 2011-12-20 | 2020-11-02 | Medimmune, Llc | Zmodyfikowane polipeptydy dla rusztowań przeciwciał dwuswoistych |
| EP2623110A1 (en) * | 2012-01-31 | 2013-08-07 | CSL Behring GmbH | Factor XII inhibitors for the treatment of neurological inflammatory disorders |
| SG10201609322QA (en) | 2012-05-10 | 2017-01-27 | Bayer Pharma AG | Antibodies capable of binding to the coagulation factor xi and/or its activated form factor xia and uses thereof |
| US20140038204A1 (en) | 2012-07-31 | 2014-02-06 | Baxter Healthcare S.A. | Selective measurement of active human protease coagulation factors |
| US9574013B2 (en) | 2012-12-07 | 2017-02-21 | Vanderbilt University | Antibodies against factor XII and uses thereof |
| KR102209796B1 (ko) * | 2013-01-20 | 2021-01-29 | 다이액스 코포레이션 | pKal 매개 장애의 평가, 검정 및 치료 |
| CA3208188A1 (en) | 2013-03-15 | 2014-09-25 | Takeda Pharmaceutical Company Limited | Anti-plasma kallikrein antibodies |
| US20160166660A1 (en) * | 2013-06-28 | 2016-06-16 | Csl Behring Gmbh | Combination therapy using a factor xii inhibitor and a c-1 inhibitor |
| HRP20220553T1 (hr) | 2013-07-25 | 2022-06-10 | Cytomx Therapeutics Inc. | Polispecifična protutijela, polispecifična protutijela koja se mogu aktivirati i postupci uporabe navedenih protutijela |
| AU2015373910B2 (en) | 2015-01-02 | 2021-11-18 | Takeda Pharmaceutical Company Limited | Bispecific antibodies against plasma kallikrein and factor XII |
| US10913802B2 (en) | 2015-07-21 | 2021-02-09 | Dyax Corp. | Monoclonal antibody inhibitor of factor XIIA |
| EP3263803B1 (en) | 2016-06-30 | 2019-08-14 | ABB Schweiz AG | Substation |
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