MX384191B - Molecula de union al antigeno especifico para el tejido objetivo. - Google Patents
Molecula de union al antigeno especifico para el tejido objetivo.Info
- Publication number
- MX384191B MX384191B MX2014014678A MX2014014678A MX384191B MX 384191 B MX384191 B MX 384191B MX 2014014678 A MX2014014678 A MX 2014014678A MX 2014014678 A MX2014014678 A MX 2014014678A MX 384191 B MX384191 B MX 384191B
- Authority
- MX
- Mexico
- Prior art keywords
- antigen
- binding molecule
- target tissue
- molecule specific
- target
- Prior art date
Links
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
- C07K16/005—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies constructed by phage libraries
-
- 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
-
- 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
- C07K16/24—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
- C07K16/248—IL-6
-
- 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
- C07K16/44—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
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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
- G01N33/563—Immunoassay; Biospecific binding assay; Materials therefor involving antibody fragments
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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
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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
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6845—Methods of identifying protein-protein interactions in protein mixtures
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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
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
- G01N33/6869—Interleukin
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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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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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
- C07K2317/21—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
- C07K2317/30—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
- C07K2317/50—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
- C07K2317/70—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
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- 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
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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
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
- G01N2333/5412—IL-6
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/20—Screening for compounds of potential therapeutic value cell-free systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Bioinformatics & Computational Biology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Los inventores de la presente invención han creado una molécula de unión al antígeno, que contiene un dominio de unión al antígeno cuya actividad de unión al antígeno varía dependiendo de la concentración de un compuesto específico para el tejido. Al usar la presente molécula de unión al antígeno permite que varias enfermedades que se originan en un tejido objetivo sean tratadas de una manera específica para el tejido objetivo.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2012123781 | 2012-05-30 | ||
| JP2012177311 | 2012-08-09 | ||
| PCT/JP2013/064975 WO2013180200A1 (ja) | 2012-05-30 | 2013-05-30 | 標的組織特異的抗原結合分子 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| MX2014014678A MX2014014678A (es) | 2015-02-10 |
| MX384191B true MX384191B (es) | 2025-03-14 |
Family
ID=49673387
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2014014678A MX384191B (es) | 2012-05-30 | 2013-05-30 | Molecula de union al antigeno especifico para el tejido objetivo. |
| MX2021007663A MX2021007663A (es) | 2012-05-30 | 2014-11-28 | Molecula de union al antigeno especifico para el tejido objetivo. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2021007663A MX2021007663A (es) | 2012-05-30 | 2014-11-28 | Molecula de union al antigeno especifico para el tejido objetivo. |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US20150166654A1 (es) |
| EP (2) | EP3795215A1 (es) |
| JP (7) | JPWO2013180200A1 (es) |
| KR (4) | KR102677704B1 (es) |
| CN (3) | CN107759686A (es) |
| AU (4) | AU2013268418B2 (es) |
| CA (1) | CA2874721A1 (es) |
| DK (1) | DK2857420T3 (es) |
| HK (1) | HK1245300A1 (es) |
| MX (2) | MX384191B (es) |
| RU (1) | RU2743463C2 (es) |
| SG (2) | SG10202006507XA (es) |
| TW (3) | TWI766939B (es) |
| WO (1) | WO2013180200A1 (es) |
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| ES2892925T3 (es) | 2006-03-31 | 2022-02-07 | Chugai Pharmaceutical Co Ltd | Métodos para controlar la farmacocinética en sangre de anticuerpos |
| AU2008304748C1 (en) | 2007-09-26 | 2014-06-12 | Chugai Seiyaku Kabushiki Kaisha | Modified antibody constant region |
| CN101874042B9 (zh) | 2007-09-26 | 2019-01-01 | 中外制药株式会社 | 利用cdr的氨基酸取代来改变抗体等电点的方法 |
| KR102057826B1 (ko) | 2008-04-11 | 2019-12-20 | 추가이 세이야쿠 가부시키가이샤 | 복수 분자의 항원에 반복 결합하는 항원 결합 분자 |
| TWI812066B (zh) | 2010-11-30 | 2023-08-11 | 日商中外製藥股份有限公司 | 具有鈣依存性的抗原結合能力之抗體 |
| CN112812184A (zh) | 2011-02-25 | 2021-05-18 | 中外制药株式会社 | FcγRIIb特异性Fc抗体 |
| CN109517059B (zh) | 2011-06-30 | 2023-03-28 | 中外制药株式会社 | 异源二聚化多肽 |
| BR112014004168A2 (pt) | 2011-08-23 | 2017-12-12 | Roche Glycart Ag | anticorpo biespecífico, composição farmacêutica, uso do anticorpo biespecífico, célula hospedeira procariótica ou eucariótica, método de produção de anticorpo e invenção |
| JP6322411B2 (ja) | 2011-09-30 | 2018-05-09 | 中外製薬株式会社 | 複数の生理活性を有する抗原の消失を促進する抗原結合分子 |
| TW201817744A (zh) | 2011-09-30 | 2018-05-16 | 日商中外製藥股份有限公司 | 具有促進抗原清除之FcRn結合域的治療性抗原結合分子 |
| TW201945034A (zh) | 2011-09-30 | 2019-12-01 | 日商中外製藥股份有限公司 | 包含依離子濃度之條件對抗原之結合活性會改變之抗原結合分域、及於pH中性之條件下對FcRn有結合活性之FcRn結合分域、且誘導對標的抗原的免疫反應之抗原結合分子 |
| JP6124800B2 (ja) | 2011-11-30 | 2017-05-10 | 中外製薬株式会社 | 免疫複合体を形成する細胞内への運搬体(キャリア)を含む医薬 |
| JP6226752B2 (ja) | 2012-02-09 | 2017-11-08 | 中外製薬株式会社 | 抗体のFc領域改変体 |
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| EP4310191A3 (en) | 2012-06-14 | 2024-05-15 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule containing modified fc region |
| TW202237660A (zh) | 2012-08-24 | 2022-10-01 | 日商中外製藥股份有限公司 | FcγRIIb特異性Fc區域變異體 |
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| EP2904016B1 (en) * | 2012-10-08 | 2018-11-14 | Roche Glycart AG | Fc-free antibodies comprising two fab-fragments and methods of use |
| US10766960B2 (en) | 2012-12-27 | 2020-09-08 | Chugai Seiyaku Kabushiki Kaisha | Heterodimerized polypeptide |
| AU2014250434B2 (en) * | 2013-04-02 | 2019-08-08 | Chugai Seiyaku Kabushiki Kaisha | Fc region variant |
| JP6534615B2 (ja) | 2013-09-27 | 2019-06-26 | 中外製薬株式会社 | ポリペプチド異種多量体の製造方法 |
| TWI712421B (zh) | 2013-11-11 | 2020-12-11 | 日商中外製藥股份有限公司 | 含改變的抗體可變區之抗原結合分子 |
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| TWI880146B (zh) | 2014-11-11 | 2025-04-11 | 日商中外製藥股份有限公司 | 包含經改變之抗體可變區之抗原結合分子的資料庫 |
| KR101860280B1 (ko) | 2014-12-19 | 2018-05-21 | 추가이 세이야쿠 가부시키가이샤 | 항-마이오스타틴 항체, 변이체 Fc 영역을 함유하는 폴리펩타이드, 및 사용 방법 |
| CN114773470A (zh) | 2015-02-05 | 2022-07-22 | 中外制药株式会社 | 包含离子浓度依赖性的抗原结合结构域的抗体,fc区变体,il-8-结合抗体及其应用 |
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| TW201945034A (zh) | 2011-09-30 | 2019-12-01 | 日商中外製藥股份有限公司 | 包含依離子濃度之條件對抗原之結合活性會改變之抗原結合分域、及於pH中性之條件下對FcRn有結合活性之FcRn結合分域、且誘導對標的抗原的免疫反應之抗原結合分子 |
| TW201817744A (zh) | 2011-09-30 | 2018-05-16 | 日商中外製藥股份有限公司 | 具有促進抗原清除之FcRn結合域的治療性抗原結合分子 |
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| JP6124800B2 (ja) | 2011-11-30 | 2017-05-10 | 中外製薬株式会社 | 免疫複合体を形成する細胞内への運搬体(キャリア)を含む医薬 |
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| EP2857419B1 (en) | 2012-05-30 | 2021-01-13 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule for eliminating aggregated antigens |
| EP3795215A1 (en) | 2012-05-30 | 2021-03-24 | Chugai Seiyaku Kabushiki Kaisha | Target tissue-specific antigen-binding molecule |
| TW202237660A (zh) | 2012-08-24 | 2022-10-01 | 日商中外製藥股份有限公司 | FcγRIIb特異性Fc區域變異體 |
| EP3597747B1 (en) | 2012-08-24 | 2023-03-15 | Chugai Seiyaku Kabushiki Kaisha | Mouse fcgammarii-specific fc antibody |
| AU2014250434B2 (en) | 2013-04-02 | 2019-08-08 | Chugai Seiyaku Kabushiki Kaisha | Fc region variant |
| TWI853985B (zh) | 2013-12-04 | 2024-09-01 | 日商中外製藥股份有限公司 | 因應化合物濃度使抗原結合能力變化的抗原結合分子及其資料庫 |
| JP6715491B2 (ja) | 2014-06-11 | 2020-07-01 | Idacセラノスティクス株式会社 | 免疫チェックポイント制御剤の副作用低減方法 |
| KR101860280B1 (ko) | 2014-12-19 | 2018-05-21 | 추가이 세이야쿠 가부시키가이샤 | 항-마이오스타틴 항체, 변이체 Fc 영역을 함유하는 폴리펩타이드, 및 사용 방법 |
| CN107207607B (zh) | 2014-12-19 | 2021-05-04 | 中外制药株式会社 | 抗-c5抗体及使用方法 |
| CN114773470A (zh) | 2015-02-05 | 2022-07-22 | 中外制药株式会社 | 包含离子浓度依赖性的抗原结合结构域的抗体,fc区变体,il-8-结合抗体及其应用 |
| RU2749113C2 (ru) | 2015-04-22 | 2021-06-04 | Куревак Аг | Содержащая рнк композиция для лечения опухолевых заболеваний |
| US20180171017A1 (en) | 2015-06-05 | 2018-06-21 | Chugai Seiyaku Kabushiki Kaisha | Combined use of immune activators |
| KR20230079500A (ko) | 2015-09-18 | 2023-06-07 | 추가이 세이야쿠 가부시키가이샤 | Il-8에 결합하는 항체 및 그의 사용 |
| CN108601752A (zh) | 2015-12-03 | 2018-09-28 | 安吉奥斯医药品有限公司 | 用于治疗mtap缺失型癌症的mat2a抑制剂 |
| TWI605057B (zh) | 2015-12-18 | 2017-11-11 | 中外製藥股份有限公司 | 抗肌抑素抗體、含變異fc區之多肽及使用方法 |
| EP3835321A4 (en) * | 2018-08-10 | 2022-11-02 | Chugai Seiyaku Kabushiki Kaisha | ANTI-CD137 ANTIGEN-BINDING MOLECULE AND USE THEREOF |
| CN113613676A (zh) | 2019-03-19 | 2021-11-05 | 中外制药株式会社 | 包含对抗原的结合活性因mta而变化的抗原结合结构域的抗原结合分子及用于获得该抗原结合结构域的文库 |
| TWI895351B (zh) | 2020-02-12 | 2025-09-01 | 日商中外製藥股份有限公司 | 用於癌症之治療的抗cd137抗原結合分子 |
| US12448451B2 (en) | 2021-06-25 | 2025-10-21 | Chugai Seiyaku Kabushiki Kaisha | Anti-CTLA-4 antibody and use thereof |
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