NI200900005A - Anticuerpo antagonista para el tratamiento del cáncer - Google Patents
Anticuerpo antagonista para el tratamiento del cáncerInfo
- Publication number
- NI200900005A NI200900005A NI200900005A NI200900005A NI200900005A NI 200900005 A NI200900005 A NI 200900005A NI 200900005 A NI200900005 A NI 200900005A NI 200900005 A NI200900005 A NI 200900005A NI 200900005 A NI200900005 A NI 200900005A
- Authority
- NI
- Nicaragua
- Prior art keywords
- antibodies
- cytotoxic
- cancer
- conjugates
- class
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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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- 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 [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
- C07K16/2866—Immunoglobulins [IGs], 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 [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
- C07K16/30—Immunoglobulins [IGs], 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 [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], 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
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57492—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds localized on the membrane of tumor 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)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Urology & Nephrology (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Food Science & Technology (AREA)
- Mycology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Pathology (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)
Abstract
Anticuerpos, anticuerpos humanizados, anticuerpos modificados en superficie, fragmentos de anticuerpos, anticuerpos derivatizados, y conjugados de éstos con agentes citotóxicos, que se unen especificamente a, e inhiben la clase A de los receptores Eph, antagonizan los efectos de factores de crecimiento en el crecimiento y supervivencia de células tumorales, y que tienen una actividad agonista mínima o que preferiblemente carecen de actividad agonista. Dichos anticuerpos y fragmentos de éstos pueden utilizarse en el tratamiento de tumores que expresan niveles elevados de la clase A de receptores Eph, tales como cáncer de mama, cáncer de colon, cáncer de pulmón, carcinoma de ovario, sarcoma sinovial y cáncer pancreático, y dichos anticuerpos derivatizados pueden utilizarse en el diagnóstico y en la obtención de imágenes de tumores que expresan niveles elevados de la clase A de receptores Eph. También se proporcionan conjugados citotóxicos que comprenden un agente de unión a células y un agente citotóxico, se describen composiciones terapéuticas que comprenden el conjugado, método para utilizar los conjugados en la inhibición del crecimiento celular y en el tratamiento de la enfermedad, y un kit que comprende el conjugado citotóxico, siendo todas las realizaciones de la invención. En particular, el agente de unión a células es un anticuerpo monoclonal, y fragmentos de éste que se unen al epítopo, que reconoce y se une a la clase A de receptores Eph.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06291160 | 2006-07-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
NI200900005A true NI200900005A (es) | 2010-01-26 |
Family
ID=37635710
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NI200900005A NI200900005A (es) | 2006-07-18 | 2009-01-16 | Anticuerpo antagonista para el tratamiento del cáncer |
Country Status (31)
Country | Link |
---|---|
US (4) | US8460667B2 (es) |
EP (1) | EP2044122B1 (es) |
JP (2) | JP5622390B2 (es) |
KR (1) | KR101528939B1 (es) |
CN (1) | CN101622276B (es) |
AR (1) | AR061911A1 (es) |
AU (1) | AU2007274738B2 (es) |
BR (1) | BRPI0714871A2 (es) |
CA (1) | CA2658276A1 (es) |
CL (2) | CL2007002085A1 (es) |
CO (1) | CO6160239A2 (es) |
CR (1) | CR10558A (es) |
EA (1) | EA020324B1 (es) |
EC (1) | ECSP099074A (es) |
ES (1) | ES2673822T3 (es) |
GT (1) | GT200900002A (es) |
IL (2) | IL196470A (es) |
MA (1) | MA30634B1 (es) |
ME (1) | ME00581A (es) |
MX (1) | MX2009000709A (es) |
MY (1) | MY157757A (es) |
NI (1) | NI200900005A (es) |
NO (1) | NO20090758L (es) |
NZ (1) | NZ574215A (es) |
PE (2) | PE20080430A1 (es) |
SV (1) | SV2009003151A (es) |
TN (1) | TN2009000007A1 (es) |
TW (1) | TW200821329A (es) |
UY (1) | UY30492A1 (es) |
WO (1) | WO2008010101A2 (es) |
ZA (1) | ZA200900545B (es) |
Families Citing this family (147)
Publication number | Priority date | Publication date | Assignee | Title |
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US20110166319A1 (en) * | 2005-02-11 | 2011-07-07 | Immunogen, Inc. | Process for preparing purified drug conjugates |
WO2006122355A1 (en) * | 2005-05-16 | 2006-11-23 | Qrsciences Pty Ltd | A system and method for improving the analysis of chemical substances using nqr |
AU2006283726C1 (en) | 2005-08-24 | 2015-05-07 | Immunogen, Inc. | Process for preparing maytansinoid antibody conjugates |
ES2673822T3 (es) | 2006-07-18 | 2018-06-25 | Sanofi | Anticuerpo antagonista contra EphA2 para el tratamiento de cáncer |
SI2173379T1 (sl) | 2007-07-02 | 2015-12-31 | Oncomed Pharmaceuticals, Inc. | Sestavki in postopki za zdravljenje in diagnosticiranje raka |
ES2435779T3 (es) * | 2007-07-19 | 2013-12-23 | Sanofi | Agentes citotóxicos que comprenden nuevos derivados de tomaimicina y su uso terapéutico |
TWI443109B (zh) | 2007-08-30 | 2014-07-01 | Daiichi Sankyo Co Ltd | 抗epha2抗體 |
EP2177630A1 (en) * | 2008-10-02 | 2010-04-21 | Institut Gustave Roussy | Methods for predicting or monitoring whether a patient affected by a cancer is responsive to a treatment with a molecule of the taxoid family |
MA32970B1 (fr) | 2008-12-15 | 2012-01-02 | Zealand Pharma As | Analogues du glucagon |
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 |
CN102292347A (zh) | 2008-12-15 | 2011-12-21 | 西兰制药公司 | 胰高血糖素类似物 |
WO2010070255A1 (en) | 2008-12-15 | 2010-06-24 | Zealand Pharma A/S | Glucagon analogues |
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 |
ME02220B (me) | 2009-07-13 | 2016-02-20 | Zealand Pharma As | Analozi acilovanog glukagona |
FR2949469A1 (fr) | 2009-08-25 | 2011-03-04 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application en therapeutique |
TW201116297A (en) | 2009-10-02 | 2011-05-16 | Sanofi Aventis | Antibodies that specifically bind to the EphA2 receptor |
AR078471A1 (es) | 2009-10-02 | 2011-11-09 | Sanofi Aventis | COMPUESTOS MAITANSINOIDES Y EL USO DE ESTOS PARA PREPARAR CONJUGADOS CON UN ANTICUERPO LOS CUALES SE UTILIZAN COMO AGENTES ANTICANCERIGENOS Y EL PROCEDIMIENTO DE PREPARACIoN DE ESTOS CONJUGADOS |
WO2011057251A2 (en) * | 2009-11-09 | 2011-05-12 | The Brigham And Women's Hospital, Inc. | Treatment of heart disease |
US20120321595A1 (en) | 2009-11-09 | 2012-12-20 | The Brigham And Women's Hospital, Inc. | Treatment of heart disease |
CN102858796B (zh) * | 2010-03-03 | 2016-05-11 | 不列颠哥伦比亚大学 | 寡聚体特异性淀粉样蛋白β表位和抗体 |
AU2011239522B2 (en) | 2010-04-15 | 2014-10-23 | Medimmune Limited | Targeted pyrrolobenzodiazapine conjugates |
AU2011239525B2 (en) | 2010-04-15 | 2015-04-09 | Medimmune Limited | Pyrrolobenzodiazepines used to treat proliferative diseases |
UY33462A (es) | 2010-06-23 | 2012-01-31 | Zealand Pharma As | Analogos de glucagon |
BR112012033225A2 (pt) | 2010-06-24 | 2017-06-20 | Zealand Pharma As | análogos do glucagon |
FR2963007B1 (fr) | 2010-07-26 | 2013-04-05 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application therapeutique |
RU2592672C9 (ru) * | 2010-12-08 | 2016-11-27 | СтемСентРкс, Инк. | Новые модуляторы и способы их применения |
SI2691155T1 (sl) | 2011-03-29 | 2019-03-29 | Immunogen, Inc. | Priprava majtanzinoidnih konjugatov protiteles v postopku z enim korakom |
US8802097B2 (en) | 2011-07-15 | 2014-08-12 | Oncomed Pharmaceuticals, Inc. | Anti-RSPO1 antibodies |
CA2849039C (en) | 2011-09-20 | 2018-09-18 | Spirogen Sarl | Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates |
EA036202B1 (ru) | 2011-10-14 | 2020-10-14 | Сиэтл Дженетикс, Инк. | Пирролбензодиазепины и конъюгаты направленного действия |
EP3388435B1 (en) | 2011-10-14 | 2023-05-03 | Seagen Inc. | Pyrrolobenzodiazepines and targeted conjugates |
BR112014008888A2 (pt) | 2011-10-14 | 2017-04-18 | Seattle Genetics Inc | pirrolobenzodiazepinas |
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BR112014015681A2 (pt) | 2011-12-23 | 2019-09-24 | Boehringer Ingelheim Int | análogos de glucagon |
AR090549A1 (es) | 2012-03-30 | 2014-11-19 | Genentech Inc | Anticuerpos anti-lgr5 e inmunoconjugados |
CA2867824A1 (en) | 2012-05-01 | 2013-11-07 | Genentech, Inc. | Anti-pmel17 antibodies and immunoconjugates |
US10100097B2 (en) | 2012-05-03 | 2018-10-16 | Zealand Pharma A/S | GIP-GLP-1 dual agonist compounds and methods |
MA37840B1 (fr) | 2012-07-09 | 2020-05-29 | Genentech Inc | Immunoconjugués comprenant des anticorps anti-cd79b |
CA2873889A1 (en) | 2012-07-09 | 2014-01-16 | Genentech, Inc. | Anti-cd22 antibodies and immunoconjugates |
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CN104662038B (zh) | 2012-07-23 | 2018-11-06 | 西兰制药公司 | 胰高血糖素类似物 |
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TWI608013B (zh) | 2012-09-17 | 2017-12-11 | 西蘭製藥公司 | 升糖素類似物 |
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WO2014057114A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sàrl | Pyrrolobenzodiazepine-anti-psma antibody conjugates |
NZ707534A (en) | 2012-10-12 | 2018-08-31 | Adc Therapeutics Sa | Pyrrolobenzodiazepine-antibody conjugates |
SI3199552T1 (sl) | 2012-11-20 | 2020-06-30 | Sanofi | Protitelesa proti-CEACAM5 in njihove uporabe |
EA201690004A1 (ru) * | 2012-12-27 | 2016-07-29 | Санофи | Антитела против lamp1 и конъюгаты антитела и лекарственного средства, а также их применение |
CN105142674B (zh) | 2013-03-13 | 2018-11-13 | 麦迪穆有限责任公司 | 吡咯并苯并二氮杂卓和其结合物 |
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MX2015010777A (es) | 2013-03-14 | 2016-04-25 | Genentech Inc | Anticuerpos e inmunoconjugados anti-b7-h4. |
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EA201690195A1 (ru) | 2013-08-12 | 2016-05-31 | Дженентек, Инк. | Конъюгатные соединения антитело-лекарство на основе димера 1-(хлорметил)-2,3-дигидро-1h-бензо[e]индола и способы применения и лечения |
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WO2015052534A1 (en) | 2013-10-11 | 2015-04-16 | Spirogen Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
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