MA30634B1 - Anticorps antagoniste pour le traitement du cancer - Google Patents
Anticorps antagoniste pour le traitement du cancerInfo
- Publication number
- MA30634B1 MA30634B1 MA31625A MA31625A MA30634B1 MA 30634 B1 MA30634 B1 MA 30634B1 MA 31625 A MA31625 A MA 31625A MA 31625 A MA31625 A MA 31625A MA 30634 B1 MA30634 B1 MA 30634B1
- Authority
- MA
- Morocco
- Prior art keywords
- class
- antibodies
- cytotoxic
- eph receptors
- cancer
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- 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
- A61K47/6849—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 a receptor, a cell surface antigen or a cell surface determinant
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against enzymes
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/575—Immunoassay; Biospecific binding assay; Materials therefor for cancer
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/575—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/5758—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites
- G01N33/5759—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites involving compounds localised on the membrane of tumour or cancer cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- 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
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- G01N2333/91205—Phosphotransferases in general
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Cell Biology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Mycology (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
ANTICORPS ANTAGONISTE POUR LE TRAITEMENT DU CANCER La présente invention concerne des anticorps, des anticorps humanisés, des anticorps resurfacés, des fragments d'anticorps, des dérivés d'anticorps, et des conjugués de ceux-ci avec des agents cytotoxiques, qui se lient spécifiquement à et inhibent la classe A des récepteurs Eph, ont une action antagoniste sur les effets des facteurs de croissance sur la croissance et la survie de cellules tumorales, et qui ont une activité agoniste minimale ou sont de préférence dépourvus d'activité agoniste. Lesdits anticorps et fragments de ceux-ci peuvent être utilisés dans le traitement de tumeurs qui expriment des taux élevés de la classe A des récepteurs Eph, telles que le cancer du sein, le cancer du côlon, le cancer du poumon, le carcinome ovarien, le sarcome synovial et le cancer pancréatique, et lesdits dérivés d'anticorps peuvent être utilisés dans le diagnostic et l'imagerie de tumeurs qui expriment des taux élevés de la classe A des récepteurs Eph. La présente invention concerne également des conjugués cytotoxiques comprenant un agent de liaison cellulaire et un agent cytotoxique, des compositions thérapeutiques contenant le conjugué, des procédés pour utiliser les conjugués dans l'inhibition de la croissance cellulaire et le traitement de maladies, et un kit comprenant le conjugué cytotoxique, tous étant des modes de réalisation de l'invention. En particulier, l'agent de liaison cellulaire est un anticorps monoclonal, et des fragments se liant à un épitope de celui-ci, qui reconnaît et se lie à la classe A des récepteurs Eph.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06291160 | 2006-07-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MA30634B1 true MA30634B1 (fr) | 2009-08-03 |
Family
ID=37635710
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MA31625A MA30634B1 (fr) | 2006-07-18 | 2009-02-10 | Anticorps antagoniste pour le traitement du cancer |
Country Status (31)
| Country | Link |
|---|---|
| US (4) | USRE47123E1 (fr) |
| EP (1) | EP2044122B1 (fr) |
| JP (2) | JP5622390B2 (fr) |
| KR (1) | KR101528939B1 (fr) |
| CN (1) | CN101622276B (fr) |
| AR (1) | AR061911A1 (fr) |
| AU (1) | AU2007274738B2 (fr) |
| BR (1) | BRPI0714871A2 (fr) |
| CA (1) | CA2658276A1 (fr) |
| CL (2) | CL2007002085A1 (fr) |
| CO (1) | CO6160239A2 (fr) |
| CR (1) | CR10558A (fr) |
| EA (1) | EA020324B1 (fr) |
| EC (1) | ECSP099074A (fr) |
| ES (1) | ES2673822T3 (fr) |
| GT (1) | GT200900002A (fr) |
| IL (2) | IL196470A (fr) |
| MA (1) | MA30634B1 (fr) |
| ME (1) | ME00581B (fr) |
| MX (1) | MX2009000709A (fr) |
| MY (1) | MY157757A (fr) |
| NI (1) | NI200900005A (fr) |
| NO (1) | NO20090758L (fr) |
| NZ (1) | NZ574215A (fr) |
| PE (2) | PE20080430A1 (fr) |
| SV (1) | SV2009003151A (fr) |
| TN (1) | TN2009000007A1 (fr) |
| TW (1) | TW200821329A (fr) |
| UY (1) | UY30492A1 (fr) |
| WO (1) | WO2008010101A2 (fr) |
| ZA (1) | ZA200900545B (fr) |
Families Citing this family (163)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110166319A1 (en) * | 2005-02-11 | 2011-07-07 | Immunogen, Inc. | Process for preparing purified drug conjugates |
| US7999541B2 (en) * | 2005-05-16 | 2011-08-16 | Rapiscan Security Products, Inc. | System and method for improving the analysis of polymorphic chemical substance forms and concentrations using NQR |
| CA3000520C (fr) | 2005-08-24 | 2023-04-04 | Immunogen, Inc. | Procede de preparation de conjugues maytansinoides-anticorps |
| MX2009000709A (es) | 2006-07-18 | 2009-02-04 | Sanofi Aventis | Anticuerpo antagonista contra epha2 para el tratamiento de cancer. |
| EP2173379B2 (fr) | 2007-07-02 | 2023-07-05 | Oncomed Pharmaceuticals, Inc. | Compositions et procédés de traitement et de diagnostic d'un cancer |
| SI2019104T1 (sl) * | 2007-07-19 | 2013-12-31 | Sanofi | Citotoksična sredstva, ki obsegajo nove tomaimicinske derivate, in njihova terapevtska uporaba |
| BRPI0816094A2 (pt) | 2007-08-30 | 2015-03-03 | Daiichi Sankyo Co Ltd | Anticorpo, polipeptídeo, hibridoma, composição farmacêutica, método para inibir o desenvolvimento de tumor em um mamífero, polinucleotídeo, célula hospedeira, e, método para produzir um anticorpo. |
| EP2177630A1 (fr) * | 2008-10-02 | 2010-04-21 | Institut Gustave Roussy | Procédés de prédiction ou de suivi du fait qu'un patient atteint d'un cancer répond à une traitement par une molécule de la famille des taxoïdes |
| CN102282167B (zh) | 2008-12-15 | 2014-08-13 | 西兰制药公司 | 胰高血糖素类似物 |
| JP5635531B2 (ja) | 2008-12-15 | 2014-12-03 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン類似体 |
| ES2477880T3 (es) | 2008-12-15 | 2014-07-18 | Zealand Pharma A/S | Análogos del glucagón |
| EP2370462B1 (fr) | 2008-12-15 | 2014-07-16 | Zealand Pharma A/S | Analogues du glucagon |
| SG10201810743WA (en) | 2009-06-03 | 2018-12-28 | Immunogen Inc | Conjugation methods |
| FR2947269B1 (fr) | 2009-06-29 | 2013-01-18 | Sanofi Aventis | Nouveaux composes anticancereux |
| AU2010272944B2 (en) | 2009-07-13 | 2015-11-19 | Zealand Pharma A/S | Acylated glucagon analogues |
| FR2949469A1 (fr) | 2009-08-25 | 2011-03-04 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application en therapeutique |
| UY32914A (es) * | 2009-10-02 | 2011-04-29 | Sanofi Aventis | Anticuerpos que se usan específicamente al receptor epha2 |
| TW201117814A (en) * | 2009-10-02 | 2011-06-01 | Sanofi Aventis | New maytansinoids and the use of said maytansinoids to prepare conjugates with an antibody |
| DK2498796T3 (en) | 2009-11-09 | 2018-03-05 | Aal Scient Inc | HEART DISEASE TREATMENT |
| WO2011057251A2 (fr) * | 2009-11-09 | 2011-05-12 | The Brigham And Women's Hospital, Inc. | Traitement d'une cardiopathie |
| JP6190113B2 (ja) | 2010-03-03 | 2017-08-30 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | オリゴマー特異アミロイドベータエピトープおよび抗体 |
| JP5875083B2 (ja) | 2010-04-15 | 2016-03-02 | メディミューン リミテッド | 増殖性疾患治療用ピロロベンゾジアゼピン |
| CA2795349C (fr) | 2010-04-15 | 2016-11-29 | Seattle Genetics, Inc. | Conjugues de pyrrolobenzodiazapine cibles |
| UY33462A (es) | 2010-06-23 | 2012-01-31 | Zealand Pharma As | Analogos de glucagon |
| US9169310B2 (en) | 2010-06-24 | 2015-10-27 | Zealand Pharma A/S | Glucagon analogues |
| FR2963007B1 (fr) | 2010-07-26 | 2013-04-05 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application therapeutique |
| NZ611428A (en) * | 2010-12-08 | 2015-07-31 | Stemcentrx Inc | Novel modulators and methods of use |
| ME03353B (fr) | 2011-03-29 | 2019-10-20 | Immunogen Inc | Préparation de conjugués de maytansinoïde anticorps par procédé en une étape |
| JP6185463B2 (ja) | 2011-07-15 | 2017-08-23 | オンコメッド ファーマシューティカルズ インコーポレイテッド | Rspo結合剤およびその使用法 |
| SG11201400770SA (en) | 2011-09-20 | 2014-04-28 | Spirogen Sarl | Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates |
| EP2751111B1 (fr) | 2011-10-14 | 2017-04-26 | MedImmune Limited | Dérivés asymmetriques de bis-(5H-pyrrolo[2,1-c][1,4]benzodiazépin-5-one) pour le traitement de maladies prolifératives ou auto-immunes |
| AU2012322932B2 (en) | 2011-10-14 | 2016-11-10 | Medimmune Limited | Pyrrolobenzodiazepines |
| CN103997893B (zh) | 2011-10-14 | 2019-04-12 | 西雅图基因公司 | 吡咯并苯并二氮杂卓和靶向结合物 |
| CA2850373C (fr) | 2011-10-14 | 2019-07-16 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines et conjugues cibles |
| IN2014CN04401A (fr) | 2011-12-23 | 2015-09-04 | Zealand Pharma As | |
| AR090549A1 (es) | 2012-03-30 | 2014-11-19 | Genentech Inc | Anticuerpos anti-lgr5 e inmunoconjugados |
| US9056910B2 (en) | 2012-05-01 | 2015-06-16 | Genentech, Inc. | Anti-PMEL17 antibodies and immunoconjugates |
| IN2014MN02304A (fr) | 2012-05-03 | 2015-08-07 | Zealand Pharma As | |
| AR091703A1 (es) | 2012-07-09 | 2015-02-25 | Genentech Inc | Anticuerpos e inmunoconjugados que comprenden anticuerpos anti-cd22 |
| IN2014DN10652A (fr) | 2012-07-09 | 2015-09-11 | Genentech Inc | |
| US9181333B2 (en) * | 2012-07-13 | 2015-11-10 | Oncomed Pharmaceuticals, Inc. | RSPO3 binding agents and uses thereof |
| IN2015DN00544A (fr) | 2012-07-23 | 2015-06-26 | Zealand Pharma As | |
| JP2015528818A (ja) | 2012-08-02 | 2015-10-01 | ジェネンテック, インコーポレイテッド | 抗etbr抗体およびイムノコンジュゲート |
| TWI608013B (zh) | 2012-09-17 | 2017-12-11 | 西蘭製藥公司 | 升糖素類似物 |
| RU2661083C2 (ru) | 2012-10-04 | 2018-07-11 | Иммуноджен, Инк. | Использование пвдф-мембраны для очистки конъюгатов клеточно-связывающий агент - цитотоксический агент |
| JP6392765B2 (ja) | 2012-10-12 | 2018-09-19 | エイディーシー・セラピューティクス・エス・アーAdc Therapeutics Sa | ピロロベンゾジアゼピン−抗体結合体 |
| RS57694B1 (sr) | 2012-10-12 | 2018-11-30 | Adc Therapeutics Sa | Pirolobenzodiazepin - anti-psma konjugati antitela |
| ES2680153T3 (es) | 2012-10-12 | 2018-09-04 | Adc Therapeutics Sa | Conjugados de anticuerpos anti-PSMA-pirrolobenzodiazepinas |
| MX338711B (es) | 2012-10-12 | 2016-04-28 | Medimmune Ltd | Pirrolobenzodiazepinas y conjugados de las mismas. |
| HRP20182129T1 (hr) | 2012-10-12 | 2019-02-08 | Adc Therapeutics Sa | Konjugati protutijelo - pirolobenzodiazepin |
| HRP20190366T1 (hr) | 2012-10-12 | 2019-04-19 | Medimmune Limited | Pirolobenzodiazepini i njihovi konjugati |
| EP2906296B1 (fr) | 2012-10-12 | 2018-03-21 | ADC Therapeutics SA | Conjugués anticorps - pyrrolobenzodiazépine |
| EP2906297B1 (fr) | 2012-10-12 | 2017-12-06 | ADC Therapeutics SA | Conjugués anticorps - pyrrolobenzodiazépine |
| EP2906249B1 (fr) | 2012-10-12 | 2018-06-27 | MedImmune Limited | Synthèse et intermédiaires de dérivés de pyrrolobenzodiazépine pour conjugaison |
| DK3199552T3 (da) | 2012-11-20 | 2020-03-30 | Sanofi Sa | Anti-ceacam5-antistoffer og anvendelser heraf |
| HK1210713A1 (en) | 2012-12-27 | 2016-05-06 | Sanofi | Anti-lamp1 antibodies and antibody drug conjugates, and uses thereof |
| AU2014229529B2 (en) | 2013-03-13 | 2018-02-15 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| TWI680766B (zh) | 2013-03-13 | 2020-01-01 | 英商梅迪繆思有限公司 | 吡咯并苯并二氮呯及其共軛物 |
| JP6436965B2 (ja) | 2013-03-14 | 2018-12-12 | ジェネンテック, インコーポレイテッド | 抗b7−h4抗体及びイムノコンジュゲート |
| US9562099B2 (en) | 2013-03-14 | 2017-02-07 | Genentech, Inc. | Anti-B7-H4 antibodies and immunoconjugates |
| BR112016002829A2 (pt) | 2013-08-12 | 2017-09-19 | Genentech Inc | Composto e processo para preparar o composto de conjugado anticorpo-¿droga, composição farmacêutica, método de tratamento do câncer, kit para o tratamento do câncer, intermediário ligante¿-droga, porção e composto de porção droga de dímero cbi |
| JP2016537399A (ja) | 2013-09-17 | 2016-12-01 | ジェネンテック, インコーポレイテッド | 抗lgr5抗体を使用する方法 |
| GB201317981D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| WO2015052534A1 (fr) | 2013-10-11 | 2015-04-16 | Spirogen Sàrl | Conjugués anticorps-pyrrolobenzodiazépine |
| EP3054983B1 (fr) | 2013-10-11 | 2019-03-20 | Medimmune Limited | Conjugués anticorps-pyrrolobenzodiazépines |
| WO2015052535A1 (fr) | 2013-10-11 | 2015-04-16 | Spirogen Sàrl | Conjugués anticorps-pyrrolobenzodiazépine |
| US9988429B2 (en) | 2013-10-17 | 2018-06-05 | Zealand Pharma A/S | Glucagon analogues |
| PL3057984T3 (pl) | 2013-10-17 | 2018-12-31 | Zealand Pharma A/S | Acylowane analogi glukagonu |
| WO2015067715A2 (fr) | 2013-11-06 | 2015-05-14 | Zealand Pharma A/S | Composés agonistes doubles de gip et glp-1 et procédés associés |
| CN105829339B (zh) | 2013-11-06 | 2021-03-12 | 西兰制药公司 | 胰高血糖素-glp-1-gip三重激动剂化合物 |
| SG11201604784XA (en) | 2013-12-13 | 2016-07-28 | Genentech Inc | Anti-cd33 antibodies and immunoconjugates |
| EP3082876B1 (fr) | 2013-12-16 | 2018-01-17 | Genentech, Inc. | Composés conjugués anticorps-médicament dimérique à base de 1-(chlorométhyl)-2,3-dihydro-1 h-benzo [e]indole, et méthodes d'utilisation et de traitement |
| WO2015179658A2 (fr) | 2014-05-22 | 2015-11-26 | Genentech, Inc. | Immunoconjugués et anticorps anti-gpc3 |
| TWI734975B (zh) * | 2014-06-27 | 2021-08-01 | 美商C2N醫療診斷有限責任公司 | 人類化抗-tau抗體 |
| DK4074735T3 (da) | 2014-08-28 | 2025-07-14 | Bioatla Inc | Betinget aktive kimæriske antigenreceptorer til modificerede t-celler |
| SG11201701128YA (en) | 2014-09-12 | 2017-03-30 | Genentech Inc | Cysteine engineered antibodies and conjugates |
| LT3191135T (lt) | 2014-09-12 | 2020-11-25 | Genentech, Inc. | Anti-her2 antikūnai ir imunokonjugatai |
| MA40579A (fr) | 2014-09-12 | 2016-03-17 | Genentech Inc | Anticorps anti-cll-1 et immunoconjugués |
| WO2016040724A1 (fr) | 2014-09-12 | 2016-03-17 | Genentech, Inc. | Anticorps anti-b7-h4 et immunoconjugués |
| GB201416112D0 (en) | 2014-09-12 | 2014-10-29 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
| CA2961374A1 (fr) | 2014-09-16 | 2016-03-24 | Oncomed Pharmaceuticals, Inc. | Traitement de maladies fibrotiques |
| MX2017003472A (es) | 2014-09-17 | 2017-10-31 | Genentech Inc | Inmunoconjugados que comprenden anticuerpos anti-her2. |
| KR102620911B1 (ko) | 2014-10-29 | 2024-01-05 | 질랜드 파마 에이/에스 | Gip 효능제 화합물 및 방법 |
| CN107148285B (zh) | 2014-11-25 | 2022-01-04 | Adc治疗股份有限公司 | 吡咯并苯并二氮杂䓬-抗体缀合物 |
| WO2016168388A2 (fr) | 2015-04-14 | 2016-10-20 | Palatin Technologies, Inc. | Thérapies pour l'obésité, le diabète et indications associées |
| GB201506402D0 (en) | 2015-04-15 | 2015-05-27 | Berkel Patricius H C Van And Howard Philip W | Site-specific antibody-drug conjugates |
| GB201506411D0 (en) | 2015-04-15 | 2015-05-27 | Bergenbio As | Humanized anti-axl antibodies |
| DK3283507T3 (da) | 2015-04-16 | 2020-01-02 | Zealand Pharma As | Acyleret glucagonanalog |
| KR101636882B1 (ko) * | 2015-06-25 | 2016-07-06 | 전남대학교 산학협력단 | 인간 피브로넥틴 도메인 Ⅲ 기본 골격의 신규 인간 EphA2 특이적 결합 단백질 및 그의 용도 |
| CA3289997A1 (en) | 2015-09-20 | 2026-03-02 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Monoclonal Antibodies Specific for Fibroblast Growth Factor Receptor 4 (FGFR4) and Methods of Their Use |
| MA43354A (fr) | 2015-10-16 | 2018-08-22 | Genentech Inc | Conjugués médicamenteux à pont disulfure encombré |
| TWI714661B (zh) | 2015-11-05 | 2021-01-01 | 法商賽諾菲公司 | 新穎念珠藻素化合物及接合物、其製備與其治療用途 |
| GB201601431D0 (en) | 2016-01-26 | 2016-03-09 | Medimmune Ltd | Pyrrolobenzodiazepines |
| GB201602356D0 (en) | 2016-02-10 | 2016-03-23 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| GB201602359D0 (en) | 2016-02-10 | 2016-03-23 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| US11534466B2 (en) | 2016-03-09 | 2022-12-27 | Aal Scientifics, Inc. | Pancreatic stem cells and uses thereof |
| SMT202600033T1 (it) | 2016-04-15 | 2026-03-09 | Bioatla Inc | Anticorpi anti-axl, frammenti di anticorpo e loro immunoconiugati e loro utilizzi |
| GB201607478D0 (en) | 2016-04-29 | 2016-06-15 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| WO2017196847A1 (fr) | 2016-05-10 | 2017-11-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anticorps anti-nouveau récepteur variable d'antigène (vnar) et conjugués d'anticorps ciblant des antigènes tumoraux et viraux |
| PL3455261T3 (pl) | 2016-05-13 | 2022-12-12 | Bioatla, Inc. | Przeciwciała anty-ror2, fragmenty przeciwciał, ich immunokoniugaty oraz ich zastosowania |
| EP3465221B1 (fr) | 2016-05-27 | 2020-07-22 | H. Hoffnabb-La Roche Ag | Procédé bioanalytique pour la caractérisation de conjugués anticorps-médicament spécifiques d'un site |
| WO2017214182A1 (fr) | 2016-06-07 | 2017-12-14 | The United States Of America. As Represented By The Secretary, Department Of Health & Human Services | Anticorps entièrement humain ciblant pdi pour l'immunothérapie anticancéreuse |
| EP3494135A1 (fr) | 2016-08-02 | 2019-06-12 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Anticorps monoclonaux ciblant le glypican-2 (gpc2) et leur utilisation |
| CN109689111B (zh) | 2016-08-11 | 2024-04-05 | 基因泰克公司 | 吡咯并苯并二氮杂䓬前药及其抗体缀合物 |
| GB201617466D0 (en) | 2016-10-14 | 2016-11-30 | Medimmune Ltd | Pyrrolobenzodiazepine conjugates |
| KR20220150408A (ko) * | 2016-11-14 | 2022-11-10 | 항저우 디에이씨 바이오테크 씨오, 엘티디 | 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용 |
| EP4015532A1 (fr) | 2016-11-21 | 2022-06-22 | cureab GmbH | Anticorps et immunoconjugués anti-gp73 |
| AU2017382883B2 (en) | 2016-12-21 | 2024-07-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Human monoclonal antibodies specific for FLT3 and uses thereof |
| RS61795B1 (sr) | 2017-02-08 | 2021-06-30 | Adc Therapeutics Sa | Konjugati pirolobenzodiazepin antitela |
| GB201702031D0 (en) | 2017-02-08 | 2017-03-22 | Medlmmune Ltd | Pyrrolobenzodiazepine-antibody conjugates |
| US10093731B2 (en) | 2017-02-24 | 2018-10-09 | Kindred Biosciences, Inc. | Anti-IL31 antibodies for veterinary use |
| CN110582505B (zh) | 2017-04-18 | 2021-04-02 | 免疫医疗有限公司 | 吡咯并苯并二氮杂*缀合物 |
| WO2018193102A1 (fr) | 2017-04-20 | 2018-10-25 | Adc Therapeutics Sa | Polythérapie avec un conjugué anticorps anti-axl-médicament |
| TN2019000303A1 (en) | 2017-05-10 | 2021-05-07 | Sanofi Sa | Peptidic linkers and cryptophycin conjugates, useful in therapy, and their preparation |
| WO2018213064A1 (fr) | 2017-05-19 | 2018-11-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anticorps monoclonal humain ciblant tnfer2 en immunothérapie anticancéreuse |
| CA3064804A1 (fr) | 2017-06-14 | 2018-12-20 | Adc Therapeutics Sa | Regimes posologiques pour l'administration d'un cam anti-cd19 |
| WO2019005208A1 (fr) | 2017-06-30 | 2019-01-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anticorps de la mésothéline humaine et utilisations dans une thérapie anticancéreuse |
| WO2019006280A1 (fr) | 2017-06-30 | 2019-01-03 | Lentigen Technology, Inc. | Anticorps monoclonaux humains spécifiques de cd33 et leurs procédés d'utilisation |
| KR102270107B1 (ko) | 2017-08-18 | 2021-06-30 | 메디뮨 리미티드 | 피롤로벤조디아제핀 컨쥬게이트 |
| NZ762505A (en) | 2017-09-29 | 2026-03-27 | Daiichi Sankyo Co Ltd | Antibody-pyrrolobenzodiazepine derivative conjugate |
| TWI825046B (zh) * | 2017-12-19 | 2023-12-11 | 英商拜西可泰克斯有限公司 | Epha2特用之雙環胜肽配位基 |
| GB201803342D0 (en) | 2018-03-01 | 2018-04-18 | Medimmune Ltd | Methods |
| CN108490180B (zh) * | 2018-03-12 | 2020-03-10 | 南通大学附属医院 | EphA8基因在制备胃癌药物及其诊断试剂盒中的应用 |
| GB201806022D0 (en) | 2018-04-12 | 2018-05-30 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
| US11939377B2 (en) | 2018-07-12 | 2024-03-26 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Affinity matured CD22-specific monoclonal antibody and uses thereof |
| EP3833684A1 (fr) | 2018-08-08 | 2021-06-16 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Anticorps monoclonaux à haute affinité ciblant le glypicane-2 et leurs utilisations |
| CA3125484A1 (fr) | 2019-01-08 | 2020-07-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anticorps a domaine unique heterospecifiques ciblant la mesotheline pour le traitement de tumeurs solides |
| US12122843B2 (en) | 2019-01-22 | 2024-10-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | High affinity monoclonal antibodies targeting glypican-1 and methods of use |
| WO2020161214A1 (fr) | 2019-02-07 | 2020-08-13 | Sanofi | Utilisation d'immunoconjugués anti-ceacam5 pour le traitement du cancer du poumon |
| EP3693023A1 (fr) | 2019-02-11 | 2020-08-12 | Sanofi | Utilisation d'immuno-conjugués anti-ceacam5 pour le traitement du cancer du poumon |
| CN113631560B (zh) | 2019-03-15 | 2025-02-18 | 麦迪穆有限责任公司 | 氮杂环丁烷并苯并二氮杂䓬二聚体和用于治疗癌症的包含它们的缀合物 |
| WO2020227640A1 (fr) * | 2019-05-08 | 2020-11-12 | Agilvax, Inc. | Compositions et méthodes relatives à des anticorps xct |
| CA3156761A1 (fr) | 2019-10-22 | 2021-04-29 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Nanocorps a haute affinite ciblant b7h3 (cd276) pour traiter des tumeurs solides multiples |
| WO2021118968A1 (fr) | 2019-12-12 | 2021-06-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Conjugués anticorps-médicament spécifiques à cd276 et leurs utilisations |
| AU2021335257A1 (en) | 2020-09-04 | 2023-03-09 | Merck Patent Gmbh | Anti-CEACAM5 antibodies and conjugates and uses thereof |
| US20230391852A1 (en) | 2020-10-26 | 2023-12-07 | The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Single domain antibodies targeting sars coronavirus spike protein and uses thereof |
| AU2021379882A1 (en) | 2020-11-10 | 2023-06-29 | Sanofi | Ceacam5 antibody-drug conjugate formulation |
| AR124414A1 (es) | 2020-12-18 | 2023-03-22 | Century Therapeutics Inc | Sistema de receptor de antígeno quimérico con especificidad de receptor adaptable |
| US12162945B2 (en) | 2021-03-05 | 2024-12-10 | Immunome, Inc. | EPHA2 antibodies |
| WO2022232612A1 (fr) | 2021-04-29 | 2022-11-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Nanocorps spécifiques du virus de lassa et leurs méthodes d'utilisation |
| CN113151473A (zh) * | 2021-04-30 | 2021-07-23 | 宁夏医科大学 | 一种用于检测浸润性乳腺癌中EphA2 DNA甲基化的方法及用途 |
| US20240245722A1 (en) | 2021-05-25 | 2024-07-25 | Vaxcell-Bio | Monobody-based chimeric antigen receptor and immune cell including same |
| US20240270851A1 (en) | 2021-06-09 | 2024-08-15 | The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Cross species single domain antibodies targeting pd-l1 for treating solid tumors |
| JP2024536382A (ja) | 2021-10-07 | 2024-10-04 | サノフイ | イミダゾ[4,5-c]キノリン-4-アミン化合物及びそのコンジュゲート、それらの調製並びにそれらの治療用途 |
| CN118103388A (zh) * | 2021-10-14 | 2024-05-28 | 西藏海思科制药有限公司 | EphA2的双环肽配体及其缀合物 |
| AU2022382383A1 (en) | 2021-11-05 | 2024-06-20 | Eli Lilly And Company | Antitumor combinations containing anti-ceacam5 antibody-drug conjugates and anti-vegfr-2 antibodies |
| AU2022402334A1 (en) | 2021-12-02 | 2024-07-18 | Sanofi | Ceacam5 adc–anti-pd1/pd-l1 combination therapy |
| EP4440603A1 (fr) | 2021-12-02 | 2024-10-09 | Sanofi | Dosage du cea pour la sélection d'un patient dans une thérapie anticancéreuse |
| WO2023172968A1 (fr) | 2022-03-09 | 2023-09-14 | Merck Patent Gmbh | Anticorps anti-gd2, immunoconjugués et leurs utilisations thérapeutiques |
| US20250179210A1 (en) | 2022-03-09 | 2025-06-05 | Merck Patent Gmbh | Anti-ceacam5 antibodies and conjugates and uses thereof |
| AU2023264069A1 (en) | 2022-05-03 | 2024-10-24 | Genentech, Inc. | Anti-ly6e antibodies, immunoconjugates, and uses thereof |
| JP2026508856A (ja) | 2023-03-01 | 2026-03-13 | サノフイ | Ceacam5を発現する神経内分泌がんを処置するための抗ceacam5免疫複合体の使用 |
| EP4427763A1 (fr) | 2023-03-06 | 2024-09-11 | Sanofi | Combinaisons antitumorales contenant des conjugués anticorps anti-ceacam5-médicament, anticorps anti-vegfr-2 et anticorps anti-pd1/pd-l1 |
| KR20250169564A (ko) | 2023-03-23 | 2025-12-03 | 사노피 | 암 치료법에서 환자 선택을 위한 CEACAM5 mRNA 검정 |
| EP4719483A1 (fr) | 2023-06-05 | 2026-04-08 | Sanofi | Combinaisons antitumorales contenant des conjugués anticorps anti-ceacam5-médicament, des anticorps anti-pd1/pd-l1 et des anticorps anti-ctla4 |
| AU2024295016A1 (en) | 2023-07-20 | 2026-02-05 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Fully human monoclonal antibodies and chimeric antigen receptors against cd276 for the treatment of solid tumors |
| EP4509142A1 (fr) | 2023-08-16 | 2025-02-19 | Ona Therapeutics S.L. | Fgfr4 comme cible dans le traitement du cancer |
| WO2025171238A1 (fr) | 2024-02-07 | 2025-08-14 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anticorps monoclonaux qui se lient à la région juxtamembranaire de la mésothéline et leurs utilisations |
| TW202600175A (zh) | 2024-02-15 | 2026-01-01 | 德商馬克專利公司 | 用於治療gd2陽性癌症之抗gd2抗體及免疫結合物 |
| WO2025210264A1 (fr) | 2024-04-04 | 2025-10-09 | Merck Patent Gmbh | Conjugués anticorps-médicament se liant à napi2b |
| WO2025242845A1 (fr) | 2024-05-22 | 2025-11-27 | Merck Patent Gmbh | Traitement du cancer colorectal |
| WO2026082894A1 (fr) | 2024-10-17 | 2026-04-23 | Sanofi | Conjugué anticorps-médicament ceacam5 destiné à être utilisé dans le traitement du cancer |
Family Cites Families (126)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1516743A (fr) | 1966-04-01 | 1968-02-05 | Rhone Poulenc Sa | Nouvel antibiotique et son procédé de préparation par culture de streptomyces croceus |
| US4307016A (en) | 1978-03-24 | 1981-12-22 | Takeda Chemical Industries, Ltd. | Demethyl maytansinoids |
| US4256746A (en) | 1978-11-14 | 1981-03-17 | Takeda Chemical Industries | Dechloromaytansinoids, their pharmaceutical compositions and method of use |
| JPS55102583A (en) | 1979-01-31 | 1980-08-05 | Takeda Chem Ind Ltd | 20-acyloxy-20-demethylmaytansinoid compound |
| JPS55162791A (en) | 1979-06-05 | 1980-12-18 | Takeda Chem Ind Ltd | Antibiotic c-15003pnd and its preparation |
| JPS5645483A (en) | 1979-09-19 | 1981-04-25 | Takeda Chem Ind Ltd | C-15003phm and its preparation |
| JPS5645485A (en) | 1979-09-21 | 1981-04-25 | Takeda Chem Ind Ltd | Production of c-15003pnd |
| EP0028683A1 (fr) | 1979-09-21 | 1981-05-20 | Takeda Chemical Industries, Ltd. | Antibiotique C-15003 PHO et sa préparation |
| US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
| WO1982001188A1 (fr) | 1980-10-08 | 1982-04-15 | Takeda Chemical Industries Ltd | Composes 4,5-deoxymaytansinoide et leur procede de preparation |
| US4450254A (en) | 1980-11-03 | 1984-05-22 | Standard Oil Company | Impact improvement of high nitrile resins |
| US4315929A (en) | 1981-01-27 | 1982-02-16 | The United States Of America As Represented By The Secretary Of Agriculture | Method of controlling the European corn borer with trewiasine |
| US4313946A (en) | 1981-01-27 | 1982-02-02 | The United States Of America As Represented By The Secretary Of Agriculture | Chemotherapeutically active maytansinoids from Trewia nudiflora |
| JPS57192389A (en) | 1981-05-20 | 1982-11-26 | Takeda Chem Ind Ltd | Novel maytansinoid |
| US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| JP3101690B2 (ja) | 1987-03-18 | 2000-10-23 | エス・ビィ・2・インコーポレイテッド | 変性抗体の、または変性抗体に関する改良 |
| US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
| IL89489A0 (en) | 1988-03-09 | 1989-09-10 | Hybritech Inc | Chimeric antibodies directed against human carcinoembryonic antigen |
| WO1989009622A1 (fr) | 1988-04-15 | 1989-10-19 | Protein Design Labs, Inc. | Anticorps chimeriques specifiques au recepteur il-2 |
| ES2070172T3 (es) | 1988-04-16 | 1995-06-01 | Celltech Ltd | Procedimiento para producir proteinas mediante adn recombinante. |
| EP0436597B1 (fr) | 1988-09-02 | 1997-04-02 | Protein Engineering Corporation | Production et selection de proteines de liaison diversifiees de recombinaison |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| US5780225A (en) | 1990-01-12 | 1998-07-14 | Stratagene | Method for generating libaries of antibody genes comprising amplification of diverse antibody DNAs and methods for using these libraries for the production of diverse antigen combining molecules |
| AU7247191A (en) | 1990-01-11 | 1991-08-05 | Molecular Affinities Corporation | Production of antibodies using gene libraries |
| DE69120146T2 (de) | 1990-01-12 | 1996-12-12 | Cell Genesys Inc | Erzeugung xenogener antikörper |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| WO1996033735A1 (fr) | 1995-04-27 | 1996-10-31 | Abgenix, Inc. | Anticorps humains derives d'une xenosouris immunisee |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5698426A (en) | 1990-09-28 | 1997-12-16 | Ixsys, Incorporated | Surface expression libraries of heteromeric receptors |
| CA2095633C (fr) | 1990-12-03 | 2003-02-04 | Lisa J. Garrard | Methode d'enrichissement de proteines variantes aux proprietes liantes alterees |
| ATE414768T1 (de) | 1991-04-10 | 2008-12-15 | Scripps Research Inst | Bibliotheken heterodimerer rezeptoren mittels phagemiden |
| US6797492B2 (en) * | 1991-05-17 | 2004-09-28 | Merck & Co., Inc. | Method for reducing the immunogenicity of antibody variable domains |
| EP0519596B1 (fr) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | Procédé pour réduire l'immunogénicité des domaines variables d'anticorps |
| EP1400536A1 (fr) | 1991-06-14 | 2004-03-24 | Genentech Inc. | Procédé pour fabriquer des anticorps humanisés |
| WO1992022324A1 (fr) | 1991-06-14 | 1992-12-23 | Xoma Corporation | Fragments d'anticorps produits par des microbes et leurs conjugues |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| US5546806A (en) * | 1991-10-17 | 1996-08-20 | Kain; Aron Z. | Microwave vector displacement and acceleration transducer |
| PT1024191E (pt) | 1991-12-02 | 2008-12-22 | Medical Res Council | Produção de auto-anticorpos a partir de reportórios de segmentos de anticorpo e exibidos em fagos |
| GB9203459D0 (en) | 1992-02-19 | 1992-04-08 | Scotgen Ltd | Antibodies with germ-line variable regions |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| EP0563475B1 (fr) | 1992-03-25 | 2000-05-31 | Immunogen Inc | Conjugués d'agents ciblés et de dérivés du CC-1065 |
| AU4025193A (en) | 1992-04-08 | 1993-11-18 | Cetus Oncology Corporation | Humanized C-erbB-2 specific antibodies |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| US5656727A (en) * | 1992-09-15 | 1997-08-12 | The Administrators Of The Tulane Educational Fund | Antagonists of LHRH |
| WO1995015982A2 (fr) | 1993-12-08 | 1995-06-15 | Genzyme Corporation | Procede de generation d'anticorps specifiques |
| DE69534347T2 (de) | 1994-01-31 | 2006-05-24 | Trustees Of Boston University, Boston | Bibliotheken aus Polyklonalen Antikörpern |
| US5516637A (en) | 1994-06-10 | 1996-05-14 | Dade International Inc. | Method involving display of protein binding pairs on the surface of bacterial pili and bacteriophage |
| NZ298145A (en) * | 1994-12-29 | 1998-08-26 | Yamanouchi Pharma Co Ltd | Monoclonal antibodies having inhibitory effect on type ii phospholipase a2, proteins forming part thereof, cells producing them, dna encoding them, recombinant vector comprising the dna and medicament |
| US6130364A (en) | 1995-03-29 | 2000-10-10 | Abgenix, Inc. | Production of antibodies using Cre-mediated site-specific recombination |
| US5739277A (en) | 1995-04-14 | 1998-04-14 | Genentech Inc. | Altered polypeptides with increased half-life |
| WO1996034096A1 (fr) | 1995-04-28 | 1996-10-31 | Abgenix, Inc. | Anticorps humains derives de xeno-souris immunisees |
| JP2978435B2 (ja) | 1996-01-24 | 1999-11-15 | チッソ株式会社 | アクリロキシプロピルシランの製造方法 |
| AU724579B2 (en) * | 1996-04-01 | 2000-09-28 | Sankyo Company Limited | Anti-Fas recombinant antibodies and DNA therefor |
| US6107090A (en) * | 1996-05-06 | 2000-08-22 | Cornell Research Foundation, Inc. | Treatment and diagnosis of prostate cancer with antibodies to extracellur PSMA domains |
| US6420140B1 (en) | 1996-10-11 | 2002-07-16 | Abgenix, Inc. | Production of multimeric protein by cell fusion method |
| US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
| US6986890B1 (en) * | 1996-11-21 | 2006-01-17 | Kyowa Hakko Kogyo Co., Ltd. | Anti-human VEGF receptor Flt-1 monoclonal antibody |
| CA2722378C (fr) | 1996-12-03 | 2015-02-03 | Amgen Fremont Inc. | Anticorps humains qui se lient au tnf.alpha. |
| BRPI9809391B8 (pt) | 1997-04-14 | 2021-05-25 | Amgen Res Munich Gmbh | processo para a produção de um receptor de antígeno anti-humano, anticorpo humano e composição farmacêutica |
| US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| DK1071700T3 (da) | 1998-04-20 | 2010-06-07 | Glycart Biotechnology Ag | Glykosylerings-modifikation af antistoffer til forbedring af antistofafhængig cellulær cytotoksicitet |
| DE69925133T2 (de) | 1998-08-27 | 2006-01-19 | Spirogen Ltd., Ryde | Pyrrolobenzodiazepine |
| GB9818731D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Compounds |
| DE69932695T2 (de) * | 1998-12-11 | 2007-09-13 | Sony Corp. | Technik zur Datenkopiersteuerung |
| ES2261230T3 (es) * | 1999-08-17 | 2006-11-16 | Purdue Research Foundation | Tratamiento de la enfermedad metastasica. |
| CA2388063C (fr) | 1999-11-24 | 2010-06-08 | Immunogen, Inc. | Agents cytotoxiques comprenant des taxanes et leur utilisation therapeutique |
| AU767394C (en) | 1999-12-29 | 2005-04-21 | Immunogen, Inc. | Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use |
| FR2807767B1 (fr) | 2000-04-12 | 2005-01-14 | Lab Francais Du Fractionnement | Anticorps monoclonaux anti-d |
| US6333410B1 (en) | 2000-08-18 | 2001-12-25 | Immunogen, Inc. | Process for the preparation and purification of thiol-containing maytansinoids |
| US7101976B1 (en) | 2000-09-12 | 2006-09-05 | Purdue Research Foundation | EphA2 monoclonal antibodies and methods of making and using same |
| CA2953239A1 (fr) | 2000-10-06 | 2002-04-18 | Kyowa Hakko Kirin Co., Ltd. | Cellules produisant des compositions d'anticorps |
| US7408041B2 (en) * | 2000-12-08 | 2008-08-05 | Alexion Pharmaceuticals, Inc. | Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof |
| US6441163B1 (en) | 2001-05-31 | 2002-08-27 | Immunogen, Inc. | Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents |
| US6716821B2 (en) | 2001-12-21 | 2004-04-06 | Immunogen Inc. | Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| AU2003217912A1 (en) | 2002-03-01 | 2003-09-16 | Xencor | Antibody optimization |
| US6756397B2 (en) | 2002-04-05 | 2004-06-29 | Immunogen, Inc. | Prodrugs of CC-1065 analogs |
| US6534660B1 (en) | 2002-04-05 | 2003-03-18 | Immunogen, Inc. | CC-1065 analog synthesis |
| CA2481658A1 (fr) | 2002-04-09 | 2003-10-16 | Kyowa Hakko Kogyo Co., Ltd. | Procede d'amelioration de l'activite d'une composition d'anticorps de liaison avec le recepteur fcy iiia |
| EP1498490A4 (fr) | 2002-04-09 | 2006-11-29 | Kyowa Hakko Kogyo Kk | Procede de production de composition anticorps |
| JP4585968B2 (ja) | 2002-05-10 | 2010-11-24 | パーデュー・リサーチ・ファウンデーション | EphA2アゴニストモノクローナル抗体およびその使用法 |
| ATE525398T1 (de) * | 2002-05-10 | 2011-10-15 | Medimmune Inc | Epha2 monoklonale antikörper und deren anwendungsverfahren |
| US6596757B1 (en) | 2002-05-14 | 2003-07-22 | Immunogen Inc. | Cytotoxic agents comprising polyethylene glycol-containing taxanes and their therapeutic use |
| US7538195B2 (en) * | 2002-06-14 | 2009-05-26 | Immunogen Inc. | Anti-IGF-I receptor antibody |
| BR0313197A (pt) | 2002-08-02 | 2005-08-09 | Immunogen Inc | Agentes citotóxicos contendo potentes taxanos e seu uso terapêutico |
| US7390898B2 (en) | 2002-08-02 | 2008-06-24 | Immunogen Inc. | Cytotoxic agents containing novel potent taxanes and their therapeutic use |
| EP1553975B8 (fr) | 2002-09-27 | 2023-04-12 | Xencor, Inc. | Variants fc optimises et methodes destinees a leur generation |
| ZA200503075B (en) | 2002-11-07 | 2006-09-27 | Immunogen Inc | Anti-CD33 antibodies and method for treatment of acute myeloid leukemia using the same |
| US20040223970A1 (en) * | 2003-02-28 | 2004-11-11 | Daniel Afar | Antibodies against SLC15A2 and uses thereof |
| US20050281828A1 (en) * | 2003-03-04 | 2005-12-22 | Bowdish Katherine S | Method of treating autoimmune disease by inducing antigen presentation by tolerance inducing antigen presenting cells |
| EP1618184A4 (fr) | 2003-04-11 | 2006-06-21 | Medimmune Inc | Epha2, troubles cellulaires hypoproliferatifs, et reconstitution epitheliale et endotheliale |
| CA2525929A1 (fr) * | 2003-05-13 | 2004-11-25 | Chiron Corporation | Methodes de modulation de metastase et d'evenements lies au squelette resultant de metastases |
| CN1816356A (zh) * | 2003-05-14 | 2006-08-09 | 免疫原公司 | 药物缀合物组合物 |
| US7276497B2 (en) | 2003-05-20 | 2007-10-02 | Immunogen Inc. | Cytotoxic agents comprising new maytansinoids |
| WO2005010049A2 (fr) * | 2003-07-09 | 2005-02-03 | Eli Lilly And Company | Compositions de liaison et reactifs associes |
| AU2004280066A1 (en) | 2003-10-09 | 2005-04-21 | Kyowa Hakko Kirin Co., Ltd. | Genomically modified cell |
| WO2005040170A2 (fr) | 2003-10-22 | 2005-05-06 | Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Derives de pyrrolobenzodiazepine, compositions comprenant ces derives et methodes s'y rapportant |
| WO2005085260A1 (fr) | 2004-03-09 | 2005-09-15 | Spirogen Limited | Pyrrolobenzodiazepines |
| NZ579482A (en) * | 2004-06-01 | 2011-02-25 | Genentech Inc | Antibody drug conjugates and methods |
| US7541330B2 (en) * | 2004-06-15 | 2009-06-02 | Kosan Biosciences Incorporated | Conjugates with reduced adverse systemic effects |
| EP2471813B1 (fr) | 2004-07-15 | 2014-12-31 | Xencor, Inc. | Variantes optimisées de Fc |
| US20060223147A1 (en) | 2004-08-05 | 2006-10-05 | Kyowa Hakko Kogyo Co., Ltd., | Process for producing glycoprotein composition |
| EP1778726A4 (fr) | 2004-08-16 | 2009-03-18 | Medimmune Inc | Antagonistes de l'intégrine possédant une action cytotoxique à médiation cellulaire dépendante de l'anticorps améliorée |
| WO2006047350A2 (fr) | 2004-10-21 | 2006-05-04 | Xencor, Inc. | Variants d'immunoglobuline igg a fonction effectrice optimisee |
| AU2005299353A1 (en) * | 2004-10-27 | 2006-05-04 | Medimmune, Llc | Use of modulators of EphA2 and EphrinA1 for the treatment and prevention of infections |
| CN101155830B (zh) * | 2005-02-04 | 2014-06-18 | 雷文生物技术公司 | 结合epha2的抗体及其使用方法 |
| WO2006105338A2 (fr) | 2005-03-31 | 2006-10-05 | Xencor, Inc. | Variants fc presentant des proprietes optimisees |
| EP1928912A4 (fr) * | 2005-09-07 | 2010-02-24 | Medimmune Inc | Anticorps anti-recepteur eph conjugues a des toxines |
| WO2007041635A2 (fr) | 2005-10-03 | 2007-04-12 | Xencor, Inc. | Variants de fc dotés de propriétés de liaison aux récepteurs fc optimisées |
| RS52060B (sr) | 2006-01-25 | 2012-04-30 | Sanofi | Citotoksični agensi koji sadrže nove derivate tomaimicina |
| EP1832577A1 (fr) | 2006-03-07 | 2007-09-12 | Sanofi-Aventis | Promédicament amélioré d'analogues de CC-1065 |
| MX2009000709A (es) | 2006-07-18 | 2009-02-04 | Sanofi Aventis | Anticuerpo antagonista contra epha2 para el tratamiento de cancer. |
| US7840452B2 (en) * | 2006-08-30 | 2010-11-23 | International Business Machines Corporation | Application, method and process for managing part exchangeability across functional boundaries |
| MX338397B (es) | 2007-08-29 | 2016-04-15 | Sanofi Aventis | Anticuerpos anti - cxcr5 humanizados, derivados de los mismos y su uso. |
| UY32914A (es) | 2009-10-02 | 2011-04-29 | Sanofi Aventis | Anticuerpos que se usan específicamente al receptor epha2 |
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