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)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Urology & Nephrology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Mycology (AREA)
- General Physics & Mathematics (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (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) | USRE47123E1 (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 (151)
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 |
EP2662096A1 (en) | 2005-08-24 | 2013-11-13 | ImmunoGen, Inc. | Process for preparing maytansinoid antibody conjugates |
MX2009000709A (es) | 2006-07-18 | 2009-02-04 | Sanofi Aventis | Anticuerpo antagonista contra epha2 para el tratamiento de cancer. |
AU2008270972B2 (en) | 2007-07-02 | 2013-10-24 | Oncomed Pharmaceuticals, Inc. | Compositions and methods for treating and diagnosing cancer |
ES2435779T3 (es) * | 2007-07-19 | 2013-12-23 | Sanofi | Agentes citotóxicos que comprenden nuevos derivados de tomaimicina y su uso terapéutico |
SI2199390T1 (sl) | 2007-08-30 | 2017-02-28 | Daiichi Sankyo Company, Limited | Proti-epha2 protitelo |
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 |
EP2799447B1 (en) | 2008-12-15 | 2016-11-23 | Zealand Pharma A/S | Glucagon analogues |
AU2008365557A1 (en) | 2008-12-15 | 2011-07-21 | Zealand Pharma A/S | Glucagon analogues |
US8680049B2 (en) | 2008-12-15 | 2014-03-25 | Zealand Pharma A/S | Glucagon analogues |
US8642540B2 (en) | 2008-12-15 | 2014-02-04 | Zealand Pharma A/S | Glucagon analogues |
EP2437790B1 (en) | 2009-06-03 | 2019-02-20 | Immunogen, Inc. | Conjugation methods |
FR2947269B1 (fr) | 2009-06-29 | 2013-01-18 | Sanofi Aventis | Nouveaux composes anticancereux |
NZ597981A (en) | 2009-07-13 | 2014-02-28 | Zealand Pharma As | Acylated glucagon analogues |
FR2949469A1 (fr) * | 2009-08-25 | 2011-03-04 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application en therapeutique |
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 |
AR078470A1 (es) * | 2009-10-02 | 2011-11-09 | Sanofi Aventis | Anticuerpos que se unen especificamente al receptor epha2 |
EP2498796B1 (en) | 2009-11-09 | 2017-12-27 | AAL Scientifics, Inc. | Treatment of heart disease |
US20120288481A1 (en) * | 2009-11-09 | 2012-11-15 | The Brigham And Women's Hospital, Inc. | Treatment of heart disease |
MX341536B (es) | 2010-03-03 | 2016-08-24 | The Univ Of British Columbia * | Epitopo y anticuerpos beta amiloide de oligomero especifico. |
BR112012026801B8 (pt) | 2010-04-15 | 2021-05-25 | Medimmune Ltd | conjugados de pirrolobenzodiazepina direcionados, composição farmacêutica, uso dos mesmos para tratamento de uma doença proliferativa ou autoimune e ligante de medicamento |
US8697688B2 (en) | 2010-04-15 | 2014-04-15 | Seattle Genetics Inc. | Pyrrolobenzodiazepines used to treat proliferative diseases |
AR081975A1 (es) | 2010-06-23 | 2012-10-31 | Zealand Pharma As | Analogos de glucagon |
AP2013006671A0 (en) | 2010-06-24 | 2013-01-31 | Zealand Pharma As | Glucagon analogues |
FR2963007B1 (fr) | 2010-07-26 | 2013-04-05 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application therapeutique |
TWI585106B (zh) * | 2010-12-08 | 2017-06-01 | 艾伯維史坦森特瑞斯有限責任公司 | 新穎調節劑及其使用方法 |
CN107537040A (zh) | 2011-03-29 | 2018-01-05 | 伊缪诺金公司 | 通过一步法制备类美登素抗体缀合物 |
BR112014000765A2 (pt) | 2011-07-15 | 2017-06-13 | Oncomed Pharm Inc | agentes de ligação a rspo e seus usos |
KR101860174B1 (ko) | 2011-09-20 | 2018-05-21 | 메디뮨 리미티드 | 표적 접합체 내의 내포를 위한 비대칭 이량체 pbd 화합물로서 피롤로벤조디아제핀 |
JP6170497B2 (ja) | 2011-10-14 | 2017-07-26 | メドイミューン・リミテッドMedImmune Limited | ピロロベンゾジアゼピン |
EP2755642B1 (en) | 2011-10-14 | 2018-07-18 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines and targeted conjugates |
MX358757B (es) | 2011-10-14 | 2018-09-03 | Seattle Genetics Inc | Pirrolobenzodiazepinas y conjugados dirigidos. |
CA2850264C (en) | 2011-10-14 | 2019-11-05 | Spirogen Sarl | Pyrrolobenzodiazepines |
IN2014CN04401A (es) | 2011-12-23 | 2015-09-04 | Zealand Pharma As | |
AR090549A1 (es) | 2012-03-30 | 2014-11-19 | Genentech Inc | Anticuerpos anti-lgr5 e inmunoconjugados |
SG11201407106XA (en) | 2012-05-01 | 2014-11-27 | Genentech Inc | Anti-pmel17 antibodies and immunoconjugates |
MX356641B (es) | 2012-05-03 | 2018-06-07 | Zealand Pharma As | Compuestos agonistas dobles de gip-glp-1 y procedimientos. |
BR112015000437A2 (pt) | 2012-07-09 | 2017-06-27 | Genentech Inc | imunoconjugados, formulação farmacêutica, métodos de tratamento e de inbir a proliferação de uma célula |
JP2015527318A (ja) | 2012-07-09 | 2015-09-17 | ジェネンテック, インコーポレイテッド | 抗cd22を含む免疫複合体 |
EA032038B1 (ru) | 2012-07-13 | 2019-03-29 | Онкомед Фармасьютикалс, Инк. | Rspo3-связывающие агенты и их применение |
ES2620111T3 (es) | 2012-07-23 | 2017-06-27 | Zealand Pharma A/S | Análogos de glucagón |
RU2015106673A (ru) | 2012-08-02 | 2016-09-20 | Дженентек, Инк. | Антитела к рецептору эндотелина типа в (etbr) и иммуноконъюгаты |
TWI608013B (zh) | 2012-09-17 | 2017-12-11 | 西蘭製藥公司 | 升糖素類似物 |
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KR20200003278A (ko) | 2012-10-12 | 2020-01-08 | 메디뮨 리미티드 | 피롤로벤조디아제핀 및 그의 컨주게이트 |
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KR102408660B1 (ko) | 2012-11-20 | 2022-06-15 | 사노피 | 항-ceacam5 항체 및 이의 용도 |
JP6441232B2 (ja) | 2012-12-27 | 2018-12-19 | サノフイSanofi | 抗lamp1抗体および抗体薬物コンジュゲート、ならびにその使用 |
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CN105636612B (zh) | 2013-08-12 | 2020-01-14 | 基因泰克公司 | 抗体-药物缀合物及使用和治疗方法 |
KR20160055252A (ko) | 2013-09-17 | 2016-05-17 | 제넨테크, 인크. | 항-lgr5 항체의 사용 방법 |
GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
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