JP6753851B2 - Gタンパク質共役受容体を標的化する抗体および使用の方法 - Google Patents
Gタンパク質共役受容体を標的化する抗体および使用の方法 Download PDFInfo
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- JP6753851B2 JP6753851B2 JP2017529742A JP2017529742A JP6753851B2 JP 6753851 B2 JP6753851 B2 JP 6753851B2 JP 2017529742 A JP2017529742 A JP 2017529742A JP 2017529742 A JP2017529742 A JP 2017529742A JP 6753851 B2 JP6753851 B2 JP 6753851B2
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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
-
- 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
- C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
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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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07K16/2863—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 growth factors, growth regulators
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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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
-
- 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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- 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
-
- 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
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
-
- 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
- G01N2333/435—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
- G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
- G01N2333/7051—T-cell receptor (TcR)-CD3 complex
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462088228P | 2014-12-05 | 2014-12-05 | |
| US62/088,228 | 2014-12-05 | ||
| PCT/US2015/064122 WO2016090329A2 (en) | 2014-12-05 | 2015-12-04 | Antibodies targeting g-protein coupled receptor and methods of use |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020081773A Division JP7027482B2 (ja) | 2014-12-05 | 2020-05-07 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018504890A JP2018504890A (ja) | 2018-02-22 |
| JP2018504890A5 JP2018504890A5 (enExample) | 2019-01-17 |
| JP6753851B2 true JP6753851B2 (ja) | 2020-09-09 |
Family
ID=56092679
Family Applications (6)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017529742A Active JP6753851B2 (ja) | 2014-12-05 | 2015-12-04 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
| JP2020081773A Active JP7027482B2 (ja) | 2014-12-05 | 2020-05-07 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
| JP2020140643A Withdrawn JP2020191900A (ja) | 2014-12-05 | 2020-08-24 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
| JP2022002183A Withdrawn JP2022044638A (ja) | 2014-12-05 | 2022-01-11 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
| JP2022082303A Withdrawn JP2022103382A (ja) | 2014-12-05 | 2022-05-19 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
| JP2024033776A Pending JP2024053016A (ja) | 2014-12-05 | 2024-03-06 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
Family Applications After (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020081773A Active JP7027482B2 (ja) | 2014-12-05 | 2020-05-07 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
| JP2020140643A Withdrawn JP2020191900A (ja) | 2014-12-05 | 2020-08-24 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
| JP2022002183A Withdrawn JP2022044638A (ja) | 2014-12-05 | 2022-01-11 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
| JP2022082303A Withdrawn JP2022103382A (ja) | 2014-12-05 | 2022-05-19 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
| JP2024033776A Pending JP2024053016A (ja) | 2014-12-05 | 2024-03-06 | Gタンパク質共役受容体を標的化する抗体および使用の方法 |
Country Status (16)
| Country | Link |
|---|---|
| US (4) | US10590196B2 (enExample) |
| EP (1) | EP3227324A4 (enExample) |
| JP (6) | JP6753851B2 (enExample) |
| KR (2) | KR102602417B1 (enExample) |
| CN (3) | CN113429484A (enExample) |
| AU (3) | AU2015357535B2 (enExample) |
| BR (1) | BR112017011932A8 (enExample) |
| CA (2) | CA2969886A1 (enExample) |
| IL (3) | IL307767A (enExample) |
| MX (3) | MX2017007247A (enExample) |
| MY (1) | MY195115A (enExample) |
| PH (1) | PH12017501039A1 (enExample) |
| RU (2) | RU2725819C2 (enExample) |
| SA (1) | SA517381664B1 (enExample) |
| SG (2) | SG10201913937QA (enExample) |
| WO (1) | WO2016090329A2 (enExample) |
Families Citing this family (90)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2015357535B2 (en) | 2014-12-05 | 2020-05-14 | Eureka Therapeutics, Inc. | Antibodies targeting G-protein coupled receptor and methods of use |
| DK3227339T3 (da) | 2014-12-05 | 2022-01-10 | Memorial Sloan Kettering Cancer Center | Kimæriske antigenreceptorer rettet mod g-protein-koblet receptor og anvendelser deraf |
| MX2018004721A (es) | 2015-10-23 | 2018-07-06 | Eureka Therapeutics Inc | Construcciones quimericas anticuerpo/receptor de celulas t y usos de las mismas. |
| TWI781108B (zh) * | 2016-07-20 | 2022-10-21 | 比利時商健生藥品公司 | 抗gprc5d抗體、結合gprc5d與cd3之雙特異性抗原結合分子及其用途 |
| CN110352068A (zh) | 2016-12-02 | 2019-10-18 | 南加利福尼亚大学 | 合成的免疫受体及其使用方法 |
| TW201837174A (zh) | 2017-02-07 | 2018-10-16 | 日商第一三共股份有限公司 | 抗gprc5d抗體及包含該抗體之分子 |
| WO2018200582A1 (en) | 2017-04-26 | 2018-11-01 | Eureka Therapeutics, Inc. | Chimeric antibody/t-cell receptor constructs and uses thereof |
| KR102755437B1 (ko) | 2017-08-09 | 2025-01-20 | 주노 쎄러퓨티크스 인코퍼레이티드 | 유전자 조작된 세포 조성물 및 관련 조성물의 제조 방법 |
| EP4516896A3 (en) | 2017-08-09 | 2025-05-14 | Juno Therapeutics, Inc. | Methods and compositions for preparing genetically engineered cells |
| MA50079A (fr) | 2017-09-07 | 2020-07-15 | Juno Therapeutics Inc | Procédés d'identification de caractéristiques cellulaires relatives à des réponses associées à une thérapie cellulaire |
| BR112020006860A2 (pt) | 2017-10-05 | 2020-10-20 | Daiichi Sankyo Company, Limited | composição para depleção de células t citotóxicas |
| JP7357626B2 (ja) | 2017-11-01 | 2023-10-06 | ジュノー セラピューティクス インコーポレイテッド | 操作された細胞の治療用組成物を生成するためのプロセス |
| US11066475B2 (en) | 2017-11-01 | 2021-07-20 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for B-cell maturation antigen and encoding polynucleotides |
| WO2019089858A2 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
| CA3080509A1 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Process for producing a t cell composition |
| WO2019089848A1 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Methods associated with tumor burden for assessing response to a cell therapy |
| MA51210A (fr) | 2017-12-01 | 2020-10-07 | Juno Therapeutics Inc | Procédés de dosage et de modulation de cellules génétiquement modifiées |
| BR112020011223A2 (pt) | 2017-12-08 | 2020-11-17 | Juno Therapeutics Inc | marcadores fenotípicos para terapia celular e mé-todos relacionados |
| AU2018379091A1 (en) | 2017-12-08 | 2020-06-25 | Juno Therapeutics, Inc. | Serum-free media formulation for culturing cells and methods of use thereof |
| CN119193493A (zh) | 2017-12-08 | 2024-12-27 | 朱诺治疗学股份有限公司 | 生产工程化t细胞组合物的过程 |
| TWI829667B (zh) | 2018-02-09 | 2024-01-21 | 瑞士商赫孚孟拉羅股份公司 | 結合gprc5d之抗體 |
| CN112888709B (zh) * | 2018-03-30 | 2024-10-29 | 优瑞科生物技术公司 | 标靶cd22的构建体和其用途 |
| WO2019210207A2 (en) * | 2018-04-27 | 2019-10-31 | The Trustees Of The University Of Pennsylvania | Chimeric antigen receptor t regulatory cells for the treatment of atherosclerosis |
| WO2019220368A1 (en) * | 2018-05-16 | 2019-11-21 | Janssen Biotech, Inc. | Bcma/cd3 and gprdc5d/cd3 bispecific antibodies for use in cancer therapy |
| BR112021002390A2 (pt) | 2018-08-09 | 2021-05-11 | Juno Therapeutics Inc | processos para gerar células modificadas e suas composições |
| CN112805378A (zh) | 2018-08-09 | 2021-05-14 | 朱诺治疗学股份有限公司 | 用于评估整合核酸的方法 |
| WO2020089343A1 (en) | 2018-10-31 | 2020-05-07 | Juno Therapeutics Gmbh | Methods for selection and stimulation of cells and apparatus for same |
| CN119569895A (zh) | 2018-11-01 | 2025-03-07 | 朱诺治疗学股份有限公司 | G蛋白偶合受体c类5族成员d(gprc5d)特异性嵌合抗原受体 |
| US12473345B2 (en) | 2018-11-01 | 2025-11-18 | Juno Therapeutics, Inc. | Methods for treatment using chimeric antigen receptors specific for B-cell maturation antigen |
| EP4427810A3 (en) | 2018-11-30 | 2024-12-04 | Juno Therapeutics, Inc. | Methods for treatment using adoptive cell therapy |
| SG11202111372VA (en) | 2019-05-01 | 2021-11-29 | Juno Therapeutics Inc | Cells expressing a chimeric receptor from a modified cd247 locus, related polynucleotides and methods |
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| WO2021018925A1 (en) | 2019-07-31 | 2021-02-04 | F. Hoffmann-La Roche Ag | Antibodies binding to gprc5d |
| KR20220066892A (ko) | 2019-08-22 | 2022-05-24 | 주노 쎄러퓨티크스 인코퍼레이티드 | T 세포 요법 및 제스트 동족체 2의 인핸서 (ezh2) 억제제의 병용 요법 및 관련 방법 |
| MX2022005145A (es) | 2019-10-30 | 2022-06-29 | Juno Therapeutics Gmbh | Dispositivos de estimulación y/o selección celular y método de uso. |
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