IE76288B1 - Bispecific monoclonal antibodes their production and use - Google Patents
Bispecific monoclonal antibodes their production and useInfo
- Publication number
- IE76288B1 IE76288B1 IE107991A IE107991A IE76288B1 IE 76288 B1 IE76288 B1 IE 76288B1 IE 107991 A IE107991 A IE 107991A IE 107991 A IE107991 A IE 107991A IE 76288 B1 IE76288 B1 IE 76288B1
- Authority
- IE
- Ireland
- Prior art keywords
- antibody
- bispecific
- thrombolytic
- moab
- activity
- Prior art date
Links
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6871—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting an enzyme
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- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6875—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody being a hybrid immunoglobulin
- A61K47/6877—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody being a hybrid immunoglobulin the antibody being an immunoglobulin containing regions, domains or residues from different species
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- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
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- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
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Landscapes
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- Diabetes (AREA)
- Microbiology (AREA)
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- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
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| JP8898590 | 1990-04-02 | ||
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| IE911079A1 IE911079A1 (en) | 1991-10-09 |
| IE76288B1 true IE76288B1 (en) | 1997-10-08 |
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| IE107991A IE76288B1 (en) | 1990-04-02 | 1991-03-28 | Bispecific monoclonal antibodes their production and use |
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| HU (1) | HUT63203A (cg-RX-API-DMAC7.html) |
| IE (1) | IE76288B1 (cg-RX-API-DMAC7.html) |
| TW (1) | TW212184B (cg-RX-API-DMAC7.html) |
Families Citing this family (89)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6001355A (en) * | 1982-12-14 | 1999-12-14 | Dowdle; Eugene Bernard Davey | Pro-tPA for the treatment of thrombosis, embolism and related conditions |
| US5620675A (en) | 1992-06-23 | 1997-04-15 | Diatech, Inc. | Radioactive peptides |
| US6017512A (en) * | 1992-06-23 | 2000-01-25 | Diatide, Inc. | Radiolabeled peptides |
| AU702250B2 (en) * | 1994-07-11 | 1999-02-18 | Board Of Regents, The University Of Texas System | Methods and compositions for the specific coagulation of vasculature |
| US5869274A (en) * | 1995-08-09 | 1999-02-09 | Zymed Laboratories, Inc. | Immuno-histochemical method that reduces background staining |
| US6548663B1 (en) | 1998-03-31 | 2003-04-15 | Bristol-Myers Squibb Pharma Company | Benzodiazepine vitronectin receptor antagonist pharmaceuticals |
| US6537520B1 (en) | 1998-03-31 | 2003-03-25 | Bristol-Myers Squibb Pharma Company | Pharmaceuticals for the imaging of angiogenic disorders |
| US6524553B2 (en) | 1998-03-31 | 2003-02-25 | Bristol-Myers Squibb Pharma Company | Quinolone vitronectin receptor antagonist pharmaceuticals |
| US6312689B1 (en) | 1998-07-23 | 2001-11-06 | Millennium Pharmaceuticals, Inc. | Anti-CCR2 antibodies and methods of use therefor |
| CN1356913A (zh) | 1998-12-18 | 2002-07-03 | 杜邦药品公司 | 玻连蛋白受体拮抗剂药物 |
| US6569402B1 (en) | 1998-12-18 | 2003-05-27 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
| US6511649B1 (en) | 1998-12-18 | 2003-01-28 | Thomas D. Harris | Vitronectin receptor antagonist pharmaceuticals |
| US6794518B1 (en) | 1998-12-18 | 2004-09-21 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
| EP1140864A2 (en) | 1998-12-18 | 2001-10-10 | Du Pont Pharmaceuticals Company | Vitronectin receptor antagonist pharmaceuticals |
| US7660415B2 (en) * | 2000-08-03 | 2010-02-09 | Selinfreund Richard H | Method and apparatus for controlling access to storage media |
| US7288390B2 (en) | 2000-08-07 | 2007-10-30 | Centocor, Inc. | Anti-dual integrin antibodies, compositions, methods and uses |
| UA81743C2 (uk) | 2000-08-07 | 2008-02-11 | Центокор, Инк. | МОНОКЛОНАЛЬНЕ АНТИТІЛО ЛЮДИНИ, ЩО СПЕЦИФІЧНО ЗВ'ЯЗУЄТЬСЯ З ФАКТОРОМ НЕКРОЗУ ПУХЛИН АЛЬФА (ФНПα), ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ, ЩО ЙОГО МІСТИТЬ, ТА СПОСІБ ЛІКУВАННЯ РЕВМАТОЇДНОГО АРТРИТУ |
| US6902734B2 (en) | 2000-08-07 | 2005-06-07 | Centocor, Inc. | Anti-IL-12 antibodies and compositions thereof |
| RU2318829C2 (ru) | 2001-11-14 | 2008-03-10 | Сентокор, Инк. | Антитела против il-6, композиции, способы и применение |
| US9708410B2 (en) | 2003-05-30 | 2017-07-18 | Janssen Biotech, Inc. | Anti-tissue factor antibodies and compositions |
| WO2005035753A1 (ja) * | 2003-10-10 | 2005-04-21 | Chugai Seiyaku Kabushiki Kaisha | 機能蛋白質を代替する二重特異性抗体 |
| EP2311945A1 (en) * | 2003-10-14 | 2011-04-20 | Chugai Seiyaku Kabushiki Kaisha | Bispecific antibodies substituting for functional proteins |
| EP2135619A1 (en) | 2003-12-10 | 2009-12-23 | Millennium Pharmaceuticals, Inc. | Humanized anti-CCR2 antibodies and methods of use therefor |
| JP5620626B2 (ja) | 2005-03-31 | 2014-11-05 | 中外製薬株式会社 | 会合制御によるポリペプチド製造方法 |
| DK1876236T3 (da) * | 2005-04-08 | 2014-10-20 | Chugai Pharmaceutical Co Ltd | Antistof som funktionel erstatning for blodkoagulationsfaktor VIII |
| PA8672101A1 (es) | 2005-04-29 | 2006-12-07 | Centocor Inc | Anticuerpos anti-il-6, composiciones, métodos y usos |
| EP2364998A1 (en) | 2005-06-16 | 2011-09-14 | The Feinstein Institute for Medical Research | Antibodies against HMGB1 and fragments thereof |
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| DK2548577T3 (en) | 2005-12-29 | 2017-03-13 | Janssen Biotech Inc | HUMAN ANTI-IL-23 ANTIBODIES, COMPOSITIONS, PROCEDURES AND APPLICATIONS |
| EP4218801A3 (en) | 2006-03-31 | 2023-08-23 | Chugai Seiyaku Kabushiki Kaisha | Antibody modification method for purifying bispecific antibody |
| CA2647846C (en) | 2006-03-31 | 2016-06-21 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
| PL2202245T3 (pl) | 2007-09-26 | 2017-02-28 | Chugai Seiyaku Kabushiki Kaisha | Sposób modyfikowania punktu izoelektrycznego przeciwciała poprzez podstawienie aminokwasu w cdr |
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| RS56904B1 (sr) | 2010-03-30 | 2018-05-31 | Janssen Biotech Inc | Humanizovna il-25 antitela |
| AU2011268110B2 (en) | 2010-06-19 | 2016-05-19 | Memorial Sloan-Kettering Cancer Center | Anti-GD2 antibodies |
| CN103298937B (zh) | 2010-11-17 | 2016-05-25 | 中外制药株式会社 | 具有代替凝血因子viii的功能的功能的多特异性抗原结合分子 |
| WO2014144763A2 (en) | 2013-03-15 | 2014-09-18 | Memorial Sloan Kettering Cancer Center | High affinity anti-gd2 antibodies |
| JP2016527225A (ja) | 2013-07-15 | 2016-09-08 | ノヴォ ノルディスク アー／エス | ウロキナーゼ型プラスミノーゲン活性化因子に結合する抗体 |
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| MX2018012648A (es) | 2016-04-28 | 2019-01-30 | Chugai Pharmaceutical Co Ltd | Preparaciones que contienen anticuerpos. |
| CA3035081A1 (en) | 2016-09-02 | 2018-03-08 | Dana-Farber Cancer Institute, Inc. | Composition and methods of treating b cell disorders |
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| MX2019005661A (es) | 2016-11-16 | 2019-10-07 | Janssen Biotech Inc | Método para tratar la psoriasis con el anticuerpo específico anti-il23. |
| WO2018129029A1 (en) | 2017-01-04 | 2018-07-12 | Immunogen, Inc. | Met antibodies and immunoconjugates and uses thereof |
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| MA47442A (fr) | 2017-02-07 | 2019-12-18 | Janssen Biotech Inc | Anticorps anti-tnf, compositions et méthodes pour le traitement de la spondylarthrite ankylosante active |
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Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4714681A (en) * | 1981-07-01 | 1987-12-22 | The Board Of Reagents, The University Of Texas System Cancer Center | Quadroma cells and trioma cells and methods for the production of same |
| US4474893A (en) * | 1981-07-01 | 1984-10-02 | The University of Texas System Cancer Center | Recombinant monoclonal antibodies |
| JP3177776B2 (ja) * | 1988-09-27 | 2001-06-18 | 武田薬品工業株式会社 | ハイブリッドモノクローナル抗体，抗体産生ポリドーマおよび抗体含有薬剤 |
| CA1213229A (en) * | 1982-04-12 | 1986-10-28 | Gary S. David | Antibodies having dual specificities, their preparation and uses therefor |
| JPH0617909B2 (ja) * | 1984-04-23 | 1994-03-09 | ボストン バイオメディカル リサーチ インスティテュート，インコーポレイテッド | 双特異性抗体決定子 |
| DE3426903A1 (de) * | 1984-07-20 | 1986-01-23 | Biotest Pharma GmbH, 6000 Frankfurt | Eine immunglobulinpraeparation in kombination mit einer anderen pharmakologisch wirksamen praeparation zur verwendung bei der behandlung von krankheiten |
| JP2635343B2 (ja) * | 1986-04-14 | 1997-07-30 | ザ・ジェネラル・ホスピタル・コーポレーション | ヘテロ二官能性抗体および利用方法 |
| US4889922A (en) * | 1986-08-13 | 1989-12-26 | Monsanto Co. | Monoclonal antibody specific for human colon fibroblast-derived T-PA |
| DE3909708A1 (de) * | 1989-03-23 | 1990-09-27 | Boehringer Mannheim Gmbh | Verfahren zur herstellung bispezifischer antikoerper |
-
1991
- 1991-03-20 TW TW080102180A patent/TW212184B/zh active
- 1991-03-27 AT AT91104844T patent/ATE141285T1/de not_active IP Right Cessation
- 1991-03-27 DE DE69121272T patent/DE69121272T2/de not_active Expired - Fee Related
- 1991-03-27 EP EP91104844A patent/EP0450479B1/en not_active Expired - Lifetime
- 1991-03-27 CA CA002039259A patent/CA2039259A1/en not_active Abandoned
- 1991-03-28 IE IE107991A patent/IE76288B1/en not_active IP Right Cessation
- 1991-03-28 HU HU911027A patent/HUT63203A/hu unknown
- 1991-04-02 KR KR1019910005314A patent/KR910018039A/ko not_active Ceased
-
1994
- 1994-12-06 US US08/350,497 patent/US5496549A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE69121272T2 (de) | 1997-01-09 |
| KR910018039A (ko) | 1991-11-30 |
| IE911079A1 (en) | 1991-10-09 |
| CA2039259A1 (en) | 1991-10-03 |
| US5496549A (en) | 1996-03-05 |
| DE69121272D1 (de) | 1996-09-19 |
| EP0450479A1 (en) | 1991-10-09 |
| TW212184B (cg-RX-API-DMAC7.html) | 1993-09-01 |
| ATE141285T1 (de) | 1996-08-15 |
| HUT63203A (en) | 1993-07-28 |
| EP0450479B1 (en) | 1996-08-14 |
| HU911027D0 (en) | 1991-10-28 |
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| MM4A | Patent lapsed |