UA125136C2 - Антитіла, які зв'язуються з сортиліном і пригнічують зв'язування програнуліну - Google Patents
Антитіла, які зв'язуються з сортиліном і пригнічують зв'язування програнуліну Download PDFInfo
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- UA125136C2 UA125136C2 UAA201800574A UAA201800574A UA125136C2 UA 125136 C2 UA125136 C2 UA 125136C2 UA A201800574 A UAA201800574 A UA A201800574A UA A201800574 A UAA201800574 A UA A201800574A UA 125136 C2 UA125136 C2 UA 125136C2
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Classifications
-
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- C07K16/286—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against neuromediator receptors, e.g. serotonin receptor, dopamine receptor
-
- 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
-
- 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
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- 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
- C07K2317/70—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)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Mycology (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 That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1512215.3A GB201512215D0 (en) | 2015-07-13 | 2015-07-13 | Agents,uses and methods |
| PCT/EP2016/066516 WO2017009327A1 (en) | 2015-07-13 | 2016-07-12 | Antibodies that bind to sortilin and inhibit the binding of progranulin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA125136C2 true UA125136C2 (uk) | 2022-01-19 |
Family
ID=54013862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UAA201800574A UA125136C2 (uk) | 2015-07-13 | 2016-07-12 | Антитіла, які зв'язуються з сортиліном і пригнічують зв'язування програнуліну |
Country Status (35)
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10849992B1 (en) | 2015-04-07 | 2020-12-01 | Alector Llc | Methods of screening for sortilin binding antagonists |
| LT3280441T (lt) | 2015-04-07 | 2021-11-25 | Alector Llc | Anti-sortilino antikūnai ir jų naudojimo būdai |
| GB201512215D0 (en) | 2015-07-13 | 2015-08-19 | Lundbeck & Co As H | Agents,uses and methods |
| US10894833B2 (en) * | 2017-07-20 | 2021-01-19 | H. Lundbeck A/S | Agents, uses and methods for treatment |
| PE20210186A1 (es) | 2018-07-13 | 2021-02-02 | Alector Llc | Anticuerpos anti-sortilina y metodos para su uso |
| EP3666281A1 (en) * | 2018-12-14 | 2020-06-17 | Insusense ApS | Compositions comprising sortilin-1 |
| IL293994A (en) * | 2019-12-23 | 2022-08-01 | Denali Therapeutics Inc | Progranulin variants, compositions comprising same and uses thereof |
| CA3183994A1 (en) * | 2020-06-24 | 2021-12-30 | Philip James Dolan Iii | Antibodies recognizing sortilin |
| CN119403786A (zh) | 2022-06-23 | 2025-02-07 | 德罗普尼尔生物有限公司 | 选择性诱导细胞外靶标在溶酶体中降解的双功能分子 |
| CN118496354A (zh) * | 2023-02-15 | 2024-08-16 | 三优生物医药(上海)有限公司 | 包含共同轻链的抗体库、其制备方法及其用途 |
| WO2025031098A1 (zh) * | 2023-08-09 | 2025-02-13 | 瑞诺元(苏州)生物科技有限公司 | 一种分拣蛋白1特异性的纳米抗体、含有其的重组aav及应用 |
| WO2025132764A1 (en) * | 2023-12-21 | 2025-06-26 | Amylonix Ab | A sortilin-binding polypeptide |
Family Cites Families (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS5896026A (ja) | 1981-10-30 | 1983-06-07 | Nippon Chemiphar Co Ltd | 新規ウロキナ−ゼ誘導体およびその製造法ならびにそれを含有する血栓溶解剤 |
| US4609546A (en) | 1982-06-24 | 1986-09-02 | Japan Chemical Research Co., Ltd. | Long-acting composition |
| US4681581A (en) | 1983-12-05 | 1987-07-21 | Coates Fredrica V | Adjustable size diaper and folding method therefor |
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US4735210A (en) | 1985-07-05 | 1988-04-05 | Immunomedics, Inc. | Lymphographic and organ imaging method and kit |
| US5101827A (en) | 1985-07-05 | 1992-04-07 | Immunomedics, Inc. | Lymphographic and organ imaging method and kit |
| US5776093A (en) | 1985-07-05 | 1998-07-07 | Immunomedics, Inc. | Method for imaging and treating organs and tissues |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5750172A (en) | 1987-06-23 | 1998-05-12 | Pharming B.V. | Transgenic non human mammal milk |
| US5648471A (en) | 1987-12-03 | 1997-07-15 | Centocor, Inc. | One vial method for labeling antibodies with Technetium-99m |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| WO1991001754A1 (en) | 1989-08-09 | 1991-02-21 | Rhodes Buck A | Direct radiolabeling of antibodies and other proteins with technetium or rhenium |
| US5633076A (en) | 1989-12-01 | 1997-05-27 | Pharming Bv | Method of producing a transgenic bovine or transgenic bovine embryo |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| US5101990A (en) | 1990-03-23 | 1992-04-07 | Continental Pet Technologies, Inc. | Stretch blow molded oblong or oval container |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| WO1992022645A1 (en) | 1991-06-14 | 1992-12-23 | Genpharm International, Inc. | Transgenic immunodeficient non-human animals |
| EP0590058B1 (en) | 1991-06-14 | 2003-11-26 | Genentech, Inc. | HUMANIZED Heregulin ANTIBODy |
| JPH06508880A (ja) | 1991-07-08 | 1994-10-06 | ユニバーシティ オブ マサチューセッツ アット アムハースト | サーモトロピック液晶セグメント化ブロックコポリマー |
| ATE193301T1 (de) | 1993-03-09 | 2000-06-15 | Genzyme Corp | Verfahren zur isolierung von proteinen aus milch |
| AU6819494A (en) | 1993-04-26 | 1994-11-21 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
| US6077835A (en) | 1994-03-23 | 2000-06-20 | Case Western Reserve University | Delivery of compacted nucleic acid to cells |
| KR970029803A (ko) | 1995-11-03 | 1997-06-26 | 김광호 | 반도체 메모리장치의 프리차지 회로 |
| MXPA01007895A (es) | 1999-02-03 | 2003-07-21 | Biosante Pharmaceuticals Inc | Particulas terapeuticas de fosfato de calcio, metodos de manufactura y usos. |
| US6281005B1 (en) | 1999-05-14 | 2001-08-28 | Copernicus Therapeutics, Inc. | Automated nucleic acid compaction device |
| HK1049014A1 (zh) | 1999-07-29 | 2003-04-25 | Medarex, Inc. | 抗her2/neu的人类单克隆抗体 |
| EP1212422B1 (en) | 1999-08-24 | 2007-02-21 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
| DK1354034T3 (da) | 2000-11-30 | 2008-03-25 | Medarex Inc | Transgene transchromosomale gnavere til fremstilling af humane antistoffer |
| WO2004006955A1 (en) | 2001-07-12 | 2004-01-22 | Jefferson Foote | Super humanized antibodies |
| ATE545429T1 (de) | 2002-12-20 | 2012-03-15 | Lundbeck & Co As H | Modulation der neurotrophinaktivität;screeningsverfahren |
| US10155816B2 (en) | 2005-11-28 | 2018-12-18 | Genmab A/S | Recombinant monovalent antibodies and methods for production thereof |
| WO2008076262A2 (en) | 2006-12-15 | 2008-06-26 | Merck & Co., Inc. | Receptor for amyloid beta and uses thereof |
| EP3225251B1 (en) * | 2006-12-21 | 2020-02-12 | H. Lundbeck A/S | Modulation of activity of proneurotrophins |
| US9693539B2 (en) | 2007-08-10 | 2017-07-04 | E. R. Squibb & Sons, L.L.C. | HCO32 and HCO27 and related examples |
| CN102131826B (zh) | 2008-04-27 | 2014-07-02 | H.隆德贝克有限公司 | 人类分拣蛋白的晶体结构及其用于鉴定分拣蛋白的配体的用途 |
| EP2293667A4 (en) | 2008-05-27 | 2012-07-18 | Kyowa Hakko Kirin Co Ltd | INTERLEUKIN 10-RECEPTOR (IL-10R) ANTIBODY AND USE PROCESS |
| US20120039865A1 (en) | 2008-08-19 | 2012-02-16 | Yale University | Identification of sortilin as a neuronal receptor for the frontotemporal dementia protein, progranulin |
| US8703125B2 (en) | 2008-12-19 | 2014-04-22 | H. Lundbeck A/S | Modulation of the Vps10p-domain receptor family for the treatment of mental and behavioural disorders |
| RU2536232C2 (ru) * | 2011-07-01 | 2014-12-20 | Олег Ильич Эпштейн | Лекарственное средство для лечения болезни альцгеймера и способ лечения болезни альцгеймера |
| JP6239635B2 (ja) | 2012-11-02 | 2017-11-29 | ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッドＴｈｅ Ｂｒｉｇｈａｍ ａｎｄ Ｗｏｍｅｎ’ｓ Ｈｏｓｐｉｔａｌ， Ｉｎｃ． | 血管石灰化の誘導因子であるソルチリン１ |
| LT3280441T (lt) | 2015-04-07 | 2021-11-25 | Alector Llc | Anti-sortilino antikūnai ir jų naudojimo būdai |
| GB201512215D0 (en) | 2015-07-13 | 2015-08-19 | Lundbeck & Co As H | Agents,uses and methods |
| US10894833B2 (en) | 2017-07-20 | 2021-01-19 | H. Lundbeck A/S | Agents, uses and methods for treatment |
| PE20210186A1 (es) | 2018-07-13 | 2021-02-02 | Alector Llc | Anticuerpos anti-sortilina y metodos para su uso |
-
2015
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-
2016
- 2016-07-11 JO JOP/2016/0141A patent/JO3710B1/ar active
- 2016-07-12 TW TW105121903A patent/TWI760305B/zh not_active IP Right Cessation
- 2016-07-12 RU RU2018100824A patent/RU2735639C2/ru active
- 2016-07-12 AR ARP160102109A patent/AR105335A1/es not_active Application Discontinuation
- 2016-07-12 CR CR20180002A patent/CR20180002A/es unknown
- 2016-07-12 CN CN202210124752.3A patent/CN114478775A/zh active Pending
- 2016-07-12 EP EP16739087.1A patent/EP3322726B1/en active Active
- 2016-07-12 ES ES16739087T patent/ES3024469T3/es active Active
- 2016-07-12 UA UAA201800574A patent/UA125136C2/uk unknown
- 2016-07-12 PL PL16739087.1T patent/PL3322726T3/pl unknown
- 2016-07-12 HU HUE16739087A patent/HUE071424T2/hu unknown
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