TWI596112B - 抗－ｃｘｃｒ３抗體 - Google Patents
抗－ｃｘｃｒ３抗體 Download PDFInfo
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- TWI596112B TWI596112B TW102102282A TW102102282A TWI596112B TW I596112 B TWI596112 B TW I596112B TW 102102282 A TW102102282 A TW 102102282A TW 102102282 A TW102102282 A TW 102102282A TW I596112 B TWI596112 B TW I596112B
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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
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- C07K2317/21—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
- C07K2317/34—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
- C07K2317/50—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
- C07K2317/70—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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- General Chemical & Material Sciences (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)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261588936P | 2012-01-20 | 2012-01-20 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201335188A TW201335188A (zh) | 2013-09-01 |
| TWI596112B true TWI596112B (zh) | 2017-08-21 |
Family
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Family Applications (1)
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| TW102102282A TWI596112B (zh) | 2012-01-20 | 2013-01-21 | 抗－ｃｘｃｒ３抗體 |
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| EP (1) | EP2804878B1 (enExample) |
| JP (3) | JP6352812B6 (enExample) |
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| AU (1) | AU2013209492B2 (enExample) |
| BR (1) | BR112014017814A8 (enExample) |
| CA (1) | CA2862222A1 (enExample) |
| CY (1) | CY1121335T1 (enExample) |
| DK (1) | DK2804878T3 (enExample) |
| ES (1) | ES2698606T3 (enExample) |
| HR (1) | HRP20181874T1 (enExample) |
| HU (1) | HUE041900T2 (enExample) |
| IL (2) | IL233694A0 (enExample) |
| LT (1) | LT2804878T (enExample) |
| MX (1) | MX359854B (enExample) |
| PL (1) | PL2804878T3 (enExample) |
| PT (1) | PT2804878T (enExample) |
| RS (1) | RS58141B1 (enExample) |
| RU (1) | RU2663141C2 (enExample) |
| SG (2) | SG10201700735PA (enExample) |
| SI (1) | SI2804878T1 (enExample) |
| TW (1) | TWI596112B (enExample) |
| UY (1) | UY34582A (enExample) |
| WO (1) | WO2013109974A2 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9592289B2 (en) | 2012-03-26 | 2017-03-14 | Sanofi | Stable IgG4 based binding agent formulations |
| SG11201701382PA (en) | 2014-08-22 | 2017-03-30 | Sorrento Therapeutics Inc | Antigen binding proteins that bind cxcr3 |
| EP3368575B1 (en) | 2015-10-29 | 2025-05-07 | Alector LLC | Anti-siglec-9 antibodies and methods of use thereof |
| US11104724B2 (en) | 2016-05-23 | 2021-08-31 | New York University | Compositions and methods for antibodies targeting staphylococcal leukotoxins |
| TW201840585A (zh) | 2016-12-22 | 2018-11-16 | 法商賽諾菲公司 | 用於白斑病的治療的抗人cxcr3抗體 |
| EP3559033A1 (en) | 2016-12-22 | 2019-10-30 | Sanofi | Humanized cxcr3 antibodies with depleting activity and methods of use thereof |
| CN110300763A (zh) * | 2016-12-22 | 2019-10-01 | 赛诺菲 | 用于治疗白癜风的抗人cxcr3抗体 |
| US20210061917A1 (en) * | 2018-02-16 | 2021-03-04 | Inserm (Institut National De La Santé Et De La Recherche Medicale) | Methods and compositions for treating vitiligo |
| KR102074798B1 (ko) * | 2018-06-15 | 2020-02-07 | 코아스템(주) | 자가면역질환 치료에 대한 유효성 예측용 바이오마커, 진단키트 및 치료용 용도 |
| EP3880239A4 (en) | 2018-11-14 | 2022-11-23 | Arch Oncology, Inc. | THERAPEUTIC SIRPalpha ANTIBODIES |
| MA56074B1 (fr) | 2020-02-26 | 2023-11-30 | Vir Biotechnology Inc | Anticorps contre le sars-cov-2 |
| AU2021264006A1 (en) * | 2020-04-30 | 2022-12-01 | Arch Oncology, Inc. | Therapeutic sirpalpha antibodies |
| US20240101673A1 (en) | 2021-02-03 | 2024-03-28 | Mozart Therapeutics, Inc. | Binding agents and methods of using the same |
| US20250277026A1 (en) * | 2021-03-02 | 2025-09-04 | Novarock Biotherapeutics, Ltd. | Antibodies against claudin-6 and uses thereof |
| CA3228654A1 (en) * | 2021-08-09 | 2023-02-16 | Brian Rabinovich | Proteins that decouple t cell-mediated tumor cytotoxicity from release of pro-inflammatory cytokines |
| WO2023076876A1 (en) | 2021-10-26 | 2023-05-04 | Mozart Therapeutics, Inc. | Modulation of immune responses to viral vectors |
| WO2024052445A1 (en) | 2022-09-09 | 2024-03-14 | Idorsia Pharmaceuticals Ltd | Pharmaceutical combination comprising an anti-cd3 antibody and a cxcr3 antagonist |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005030793A2 (en) * | 2003-09-24 | 2005-04-07 | Millennium Pharmaceuticals, Inc. | Antibodies which bind human cxcr3 |
| US20070178095A1 (en) * | 2004-03-23 | 2007-08-02 | Eli Lilly And Company | Anti-myostatin antibodies |
| WO2011104696A1 (en) * | 2010-02-26 | 2011-09-01 | Bioarctic Neuroscience Ab | Protofibril-binding antibodies and their use in therapeutic and diagnostic methods for parkinson's disease, dementia with lewy bodies and other alpha-synucleinopathies |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US565332A (en) | 1896-08-04 | Toy for making soap-bubbles | ||
| US4376110A (en) | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| DE229046T1 (de) | 1985-03-30 | 1987-12-17 | Marc Genf/Geneve Ballivet | Verfahren zum erhalten von dns, rns, peptiden, polypeptiden oder proteinen durch dns-rekombinant-verfahren. |
| US5618920A (en) | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US5763192A (en) | 1986-11-20 | 1998-06-09 | Ixsys, Incorporated | Process for obtaining DNA, RNA, peptides, polypeptides, or protein, by recombinant DNA technique |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| DE69233482T2 (de) | 1991-05-17 | 2006-01-12 | Merck & Co., Inc. | Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen |
| US6800738B1 (en) | 1991-06-14 | 2004-10-05 | Genentech, Inc. | Method for making humanized antibodies |
| ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
| EP0571613B1 (en) | 1991-12-13 | 2003-09-17 | Xoma Corporation | Methods and materials for preparation of modified antibody variable domains and therapeutic uses thereof |
| ES2338321T3 (es) | 1992-08-21 | 2010-05-06 | Vrije Universiteit Brussel | Inmunoglobulinas desprovistas de cadenas ligeras. |
| US6005079A (en) | 1992-08-21 | 1999-12-21 | Vrije Universiteit Brussels | Immunoglobulins devoid of light chains |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| DE69427974T2 (de) | 1993-04-29 | 2001-12-06 | Unilever N.V., Rotterdam | Herstellung von antikörpern oder funktionstüchtig gemachten teilen davon, abgeleitet von schweren ketten von immunglobulinen von camelidae |
| JP2826272B2 (ja) | 1993-10-26 | 1998-11-18 | タイガースポリマー株式会社 | 中空樹脂成形品の製造装置及び製造方法 |
| US5565352A (en) | 1993-11-24 | 1996-10-15 | Arch Development Corporation | Deubiquitinating enzyme: compositions and methods |
| US5714352A (en) | 1996-03-20 | 1998-02-03 | Xenotech Incorporated | Directed switch-mediated DNA recombination |
| US6140064A (en) * | 1996-09-10 | 2000-10-31 | Theodor-Kocher Institute | Method of detecting or identifying ligands, inhibitors or promoters of CXC chemokine receptor 3 |
| DE69737656T2 (de) * | 1996-09-10 | 2008-01-03 | Theodor Kocher Institut | Cxcr3 chemokine rezeptor, antikoerper, nukleinsaeure und deren verfahren zur anwendung |
| US7115396B2 (en) | 1998-12-10 | 2006-10-03 | Compound Therapeutics, Inc. | Protein scaffolds for antibody mimics and other binding proteins |
| AU2001249546A1 (en) * | 2000-03-27 | 2001-10-08 | Corixa Corporation | Methods for treating disease with antibodies to cxcr3 |
| AU2001298053A1 (en) | 2001-09-27 | 2003-04-14 | Pieris Proteolab Ag | Muteins of apolipoprotein D |
| KR20060106631A (ko) * | 2003-06-30 | 2006-10-12 | 바이오-테크널러지 제너럴 (이스라엘) 리미티드 | 항체 및 이의 용도 |
| US20080181892A1 (en) | 2004-08-11 | 2008-07-31 | Trubion Pharmaceuticals | Binding Domain Fusion Protein |
| EP2007808A4 (en) | 2006-04-14 | 2010-07-21 | Trubion Pharmaceuticals Inc | BINDING PROTEINS HAVING AN IMMUNOGLOBULIN HINGE AND FC REGIONS WITH ALTERED EFFECTOR FUNCTIONS |
| CN101796073B (zh) * | 2007-02-01 | 2014-08-13 | 特瓦生物制药美国有限公司 | 针对cxcr3的人源化抗体 |
| HUE037489T2 (hu) | 2007-08-29 | 2018-08-28 | Sanofi Sa | Humanizált anti-CXCR5 antitestek, azok származékai és alkalmazásuk |
| WO2010056907A2 (en) | 2008-11-12 | 2010-05-20 | The Scripps Research Institute | Compounds that induce pancreatic beta-cell expansion |
| WO2010103517A1 (en) * | 2009-03-12 | 2010-09-16 | Rappaport Family Institute For Research In The Medical Sciences | Soluble compositions for the treatment of cxcr3-ligand associated diseases |
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2013
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- 2013-01-18 RU RU2014134043A patent/RU2663141C2/ru active
- 2013-01-18 WO PCT/US2013/022280 patent/WO2013109974A2/en not_active Ceased
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- 2013-01-18 US US13/745,377 patent/US8865870B2/en not_active Expired - Fee Related
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- 2013-01-18 KR KR1020207002561A patent/KR20200014441A/ko not_active Ceased
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2014
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2018
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005030793A2 (en) * | 2003-09-24 | 2005-04-07 | Millennium Pharmaceuticals, Inc. | Antibodies which bind human cxcr3 |
| US20070178095A1 (en) * | 2004-03-23 | 2007-08-02 | Eli Lilly And Company | Anti-myostatin antibodies |
| WO2011104696A1 (en) * | 2010-02-26 | 2011-09-01 | Bioarctic Neuroscience Ab | Protofibril-binding antibodies and their use in therapeutic and diagnostic methods for parkinson's disease, dementia with lewy bodies and other alpha-synucleinopathies |
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