CL2018000457A1 - Anticuerpos anti-mesotelina completamente humanos y células con efecto inmune dirigido a la mesotelina - Google Patents
Anticuerpos anti-mesotelina completamente humanos y células con efecto inmune dirigido a la mesotelinaInfo
- Publication number
- CL2018000457A1 CL2018000457A1 CL2018000457A CL2018000457A CL2018000457A1 CL 2018000457 A1 CL2018000457 A1 CL 2018000457A1 CL 2018000457 A CL2018000457 A CL 2018000457A CL 2018000457 A CL2018000457 A CL 2018000457A CL 2018000457 A1 CL2018000457 A1 CL 2018000457A1
- Authority
- CL
- Chile
- Prior art keywords
- mesothelin
- cells
- fully human
- immune effect
- human anti
- Prior art date
Links
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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
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
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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
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- 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
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- 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
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70517—CD8
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, CD152
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0646—Natural killers cells [NK], NKT cells
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70535—Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
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- 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
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- 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
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
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- 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
Abstract
ANTICUERPOS ANTI-MESOTELINA COMPLETAMENTE HUMANOS Y CÉLULAS CON EFECTO INMUNE DIRIGIDO A LA MESOTELINA.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510519214 | 2015-08-21 |
Publications (1)
Publication Number | Publication Date |
---|---|
CL2018000457A1 true CL2018000457A1 (es) | 2018-08-24 |
Family
ID=58099641
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CL2018000457A CL2018000457A1 (es) | 2015-08-21 | 2018-02-20 | Anticuerpos anti-mesotelina completamente humanos y células con efecto inmune dirigido a la mesotelina |
Country Status (15)
Country | Link |
---|---|
US (1) | US10793641B2 (es) |
EP (1) | EP3339326A4 (es) |
JP (1) | JP6994456B2 (es) |
KR (1) | KR20180055824A (es) |
CN (1) | CN106467573B (es) |
AU (1) | AU2016312015A1 (es) |
BR (1) | BR112018003339A8 (es) |
CA (1) | CA2996060A1 (es) |
CL (1) | CL2018000457A1 (es) |
HK (1) | HK1251948A1 (es) |
IL (1) | IL257563A (es) |
NZ (1) | NZ740855A (es) |
RU (1) | RU2748281C2 (es) |
SG (1) | SG11201801351RA (es) |
WO (1) | WO2017032293A1 (es) |
Families Citing this family (51)
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CN110981964B (zh) | 2013-01-14 | 2023-09-15 | Xencor股份有限公司 | 新型异二聚体蛋白 |
US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
CA2967426A1 (en) | 2014-11-26 | 2016-06-02 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and tumor antigens |
WO2019042282A1 (zh) | 2017-08-28 | 2019-03-07 | 上海易乐生物技术有限公司 | 多肽及结合多肽的抗体 |
CN107557336B (zh) * | 2017-09-15 | 2020-02-14 | 山东兴瑞生物科技有限公司 | 一种抗muc16安全型嵌合抗原受体修饰的免疫细胞及其应用 |
CN107488636A (zh) * | 2017-09-30 | 2017-12-19 | 山东兴瑞生物科技有限公司 | 一种携带分子开关的抗her2嵌合抗原受体修饰的免疫细胞及其应用 |
KR101966362B1 (ko) | 2017-10-20 | 2019-04-05 | 주식회사 녹십자 | 항-msln 항체 및 이를 포함하는 암 치료용 약학적 조성물 |
JP6339283B1 (ja) | 2017-10-31 | 2018-06-06 | 国立大学法人 岡山大学 | Dna、ポリペプチド、抗メソセリン抗体、腫瘍イメージング剤及び複合体 |
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CN109971714B (zh) * | 2017-12-28 | 2023-06-20 | 上海细胞治疗研究院 | 自表达pd-1抗体并靶向间皮素的嵌合抗原受体修饰t细胞及其用途 |
CN109608549B (zh) * | 2017-12-29 | 2022-02-18 | 郑州大学第一附属医院 | 基于人源间皮素抗体的嵌合抗原受体、慢病毒表达载体及其应用 |
JP2021512875A (ja) | 2018-02-02 | 2021-05-20 | カースゲン セラピューティクス カンパニー リミテッドCarsgen Therapeutics Co., Ltd. | 細胞免疫療法の組み合わせ |
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KR20210018838A (ko) | 2018-05-15 | 2021-02-18 | 카르스젠 테라퓨틱스 컴퍼니, 리미티드 | 유전자 조작된 세포 및 응용 |
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KR20210055034A (ko) | 2018-07-24 | 2021-05-14 | 카파 테라퓨틱스 리미티드 | 면역 이펙터 세포를 사용하여 종양을 치료하는 방법 |
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CN113788896A (zh) * | 2021-08-25 | 2021-12-14 | 南京蓝盾生物科技有限公司 | 抗msln单克隆内化抗体及其制备方法和应用 |
WO2023081806A2 (en) * | 2021-11-04 | 2023-05-11 | The General Hospital Corporation | Anti-mesothelin antibody reagents |
TW202332771A (zh) * | 2021-12-21 | 2023-08-16 | 大陸商深圳市菲鵬生物治療股份有限公司 | 轉基因免疫細胞及其構建方法和應用 |
CN116063529B (zh) * | 2021-12-29 | 2023-09-26 | 华道(上海)生物医药有限公司 | 一种抗间皮素的高亲和力纳米抗体及其应用 |
WO2023138666A1 (en) * | 2022-01-19 | 2023-07-27 | Utc Therapeutics (Shanghai) Co., Ltd. | Circular rna and use thereof |
WO2024012395A1 (en) * | 2022-07-11 | 2024-01-18 | Nona Biosciences (Suzhou) Co., Ltd. | Anti-mesothelin antibodies |
CN116003638B (zh) * | 2023-01-20 | 2023-09-05 | 北京基因启明生物科技有限公司 | 一种有效杀伤胆管型肝癌的CAR-iNKT细胞技术 |
CN117327184B (zh) * | 2023-12-01 | 2024-03-05 | 赛奥斯博生物科技(北京)有限公司 | 一种靶向msln的嵌合抗原受体及其应用 |
CN117843793A (zh) * | 2024-03-07 | 2024-04-09 | 深圳真实生物医药科技有限公司 | 抗间皮素抗体、抗原结合片段及其用途 |
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US7270960B2 (en) * | 2001-08-29 | 2007-09-18 | Pacific Northwest Research Institute | Diagnosis of ovarian carcinomas |
US7592426B2 (en) * | 2005-03-10 | 2009-09-22 | Morphotek, Inc. | Anti-mesothelin antibodies |
CA2700860C (en) * | 2007-10-01 | 2016-07-19 | Jonathan A. Terrett | Human antibodies that bind mesothelin, and uses thereof |
PL2215121T3 (pl) * | 2007-11-26 | 2016-07-29 | Bayer Ip Gmbh | Przeciwciała przeciwko mezotelinie i ich zastosowania |
EP2257572A1 (en) * | 2008-03-27 | 2010-12-08 | The Government of the United States of America as represented by The Secretary of the Department of Health and Human Services | Human anti-mesothelin monoclonal antibodies |
CA2756393C (en) | 2009-03-24 | 2017-06-20 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Anti-mesothelin antibodies |
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CN107098972A (zh) * | 2010-12-20 | 2017-08-29 | 霍夫曼-拉罗奇有限公司 | 抗间皮素抗体和免疫偶联物 |
WO2014004549A2 (en) * | 2012-06-27 | 2014-01-03 | Amgen Inc. | Anti-mesothelin binding proteins |
CA2882753C (en) | 2012-08-21 | 2021-08-24 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Mesothelin domain-specific monoclonal antibodies and use thereof |
AU2013324049B2 (en) | 2012-09-27 | 2017-09-21 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Mesothelin antibodies and methods for eliciting potent antitumor activity |
WO2015090230A1 (en) * | 2013-12-19 | 2015-06-25 | Novartis Ag | Human mesothelin chimeric antigen receptors and uses thereof |
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- 2016-08-22 RU RU2018107802A patent/RU2748281C2/ru active
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- 2016-08-22 JP JP2018509805A patent/JP6994456B2/ja active Active
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- 2016-08-22 CA CA2996060A patent/CA2996060A1/en not_active Abandoned
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WO2017032293A1 (zh) | 2017-03-02 |
CA2996060A1 (en) | 2017-03-02 |
SG11201801351RA (en) | 2018-03-28 |
HK1251948A1 (zh) | 2019-05-03 |
IL257563A (en) | 2018-04-30 |
AU2016312015A1 (en) | 2018-04-12 |
US10793641B2 (en) | 2020-10-06 |
JP2018529327A (ja) | 2018-10-11 |
RU2748281C2 (ru) | 2021-05-21 |
US20180244796A1 (en) | 2018-08-30 |
EP3339326A4 (en) | 2019-01-09 |
JP6994456B2 (ja) | 2022-02-04 |
NZ740855A (en) | 2022-04-29 |
EP3339326A1 (en) | 2018-06-27 |
KR20180055824A (ko) | 2018-05-25 |
CN106467573A (zh) | 2017-03-01 |
BR112018003339A2 (pt) | 2018-11-21 |
RU2018107802A (ru) | 2019-09-23 |
BR112018003339A8 (pt) | 2022-10-18 |
CN106467573B (zh) | 2021-05-25 |
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