CA2923160A1 - Immune system modulators - Google Patents
Immune system modulators Download PDFInfo
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- CA2923160A1 CA2923160A1 CA2923160A CA2923160A CA2923160A1 CA 2923160 A1 CA2923160 A1 CA 2923160A1 CA 2923160 A CA2923160 A CA 2923160A CA 2923160 A CA2923160 A CA 2923160A CA 2923160 A1 CA2923160 A1 CA 2923160A1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
- 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
- C07K14/70546—Integrin superfamily
-
- 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
- C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
- C07K14/7155—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
-
- 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
- C07K14/76—Albumins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361875598P | 2013-09-09 | 2013-09-09 | |
| US61/875,598 | 2013-09-09 | ||
| PCT/US2014/054612 WO2015035332A1 (en) | 2013-09-09 | 2014-09-08 | Immune system modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2923160A1 true CA2923160A1 (en) | 2015-03-12 |
Family
ID=51585229
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2923160A Abandoned CA2923160A1 (en) | 2013-09-09 | 2014-09-08 | Immune system modulators |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US9657059B2 (enExample) |
| EP (2) | EP3043810B1 (enExample) |
| JP (2) | JP6886816B2 (enExample) |
| KR (1) | KR102162323B1 (enExample) |
| CN (2) | CN111732652A (enExample) |
| AU (1) | AU2014317884B2 (enExample) |
| CA (1) | CA2923160A1 (enExample) |
| DK (1) | DK3043810T3 (enExample) |
| ES (1) | ES2777939T3 (enExample) |
| WO (1) | WO2015035332A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
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| DK2487186T3 (da) | 2007-05-08 | 2017-01-16 | Canimguide Therapeutics Ab | Immunregulatoriske strukturer fra normalt forekommende proteiner |
| EP3043810B1 (en) | 2013-09-09 | 2019-10-23 | CanImGuide Therapeutics AB | Immune system modulators |
| DK3265117T3 (da) * | 2015-03-06 | 2021-02-08 | Canimguide Therapeutics Ab | Immunsystemmodulatorer og præparater |
| US9793852B2 (en) | 2015-07-15 | 2017-10-17 | Solarcity Corporation | Clamp and bowl mounting system for photovoltaic modules |
| KR101896777B1 (ko) | 2016-10-06 | 2018-09-07 | 현대자동차주식회사 | 내습성이 향상된 배리어 필름의 제조방법 및 이에 의해 제조된 배리어 필름 |
| WO2020069408A1 (en) | 2018-09-28 | 2020-04-02 | Canimguide Therapeutics Ab | Pharmaceutical formulations of peptide inhibitors |
| EP3917509A4 (en) | 2019-01-28 | 2022-11-09 | Mitochondria Emotion, Inc. | TRANS-4-HYDROXYCYCLOHEXYLPHENYLAMIDE MITOFUSIN ACTIVATORS AND METHODS OF USE THEREOF |
| AU2019427489B2 (en) | 2019-01-28 | 2025-03-13 | Mitochondria Emotion, Inc. | Mitofusin activators and methods of use thereof |
| CN111649776A (zh) * | 2020-04-14 | 2020-09-11 | 东莞市创宏医疗科技有限公司 | 一种无屏检测系统 |
| GB202211043D0 (en) * | 2022-07-28 | 2022-09-14 | Univ Birmingham | Peptide agonist |
| KR20250040766A (ko) * | 2023-09-15 | 2025-03-25 | (주)케어젠 | 발모 촉진 및 탈모 억제 활성을 갖는 펩타이드 및 이의 용도 |
Family Cites Families (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US715368A (en) | 1902-05-29 | 1902-12-09 | Isaac N Graham | Cutter-bar for harvesters or mowers. |
| US4215051A (en) | 1979-08-29 | 1980-07-29 | Standard Oil Company (Indiana) | Formation, purification and recovery of phthalic anhydride |
| US5567610A (en) | 1986-09-04 | 1996-10-22 | Bioinvent International Ab | Method of producing human monoclonal antibodies and kit therefor |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
| US5229275A (en) | 1990-04-26 | 1993-07-20 | Akzo N.V. | In-vitro method for producing antigen-specific human monoclonal antibodies |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| EP0626012B1 (en) | 1992-02-11 | 2003-07-09 | Cell Genesys, Inc. | Homogenotization of gene-targeting events |
| US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
| IT1263831B (it) | 1993-01-29 | 1996-09-04 | Paolo Chiesi | Complessi di inclusione multicomponente ad elevata solubilita' costituiti da un farmaco di tipo basico, un acido ed una ciclodestrina |
| SE502408C2 (sv) | 1993-09-30 | 1995-10-16 | Dataliner Ab | Skalmönster vid lägesbestämning med hjälp av en snäv mätstråle |
| US5888767A (en) | 1996-11-27 | 1999-03-30 | The Johns Hopkins University School Of Medicine | Method of using a conditionally replicating viral vector to express a gene |
| SI1062201T1 (en) | 1998-03-11 | 2005-10-31 | G.D. Searle Llc | Halogenated amidino amino acid derivatives useful as nitric oxide synthase inhibitors |
| AUPP616498A0 (en) | 1998-09-25 | 1998-10-15 | University Of Queensland, The | Synthesis of cyclic peptides |
| US7024312B1 (en) | 1999-01-19 | 2006-04-04 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
| US6703491B1 (en) * | 1999-03-17 | 2004-03-09 | Exelixis, Inc. | Drosophila sequences |
| US20040031072A1 (en) * | 1999-05-06 | 2004-02-12 | La Rosa Thomas J. | Soy nucleic acid molecules and other molecules associated with transcription plants and uses thereof for plant improvement |
| WO2001052843A1 (en) | 2000-01-18 | 2001-07-26 | Mcgill University | β-TURN PEPTIDOMIMETIC CYCLIC COMPOUNDS |
| US6495674B1 (en) | 2000-02-25 | 2002-12-17 | The Salk Institute For Biological Studies | Evectins and their use |
| US7252952B2 (en) | 2000-03-06 | 2007-08-07 | Rigel Pharmaceuticals, Inc. | In vivo production of cyclic peptides for inhibiting protein—protein interaction |
| US6417237B1 (en) | 2000-06-08 | 2002-07-09 | The Board Of Trustees Of The University Of Illinois | Macromolecular drug complexes and compositions containing the same |
| AU2002257162A1 (en) * | 2001-04-30 | 2002-11-11 | Eli Lilly And Company | Humanized antibodies |
| KR100566911B1 (ko) | 2001-06-25 | 2006-04-03 | 주식회사 삼양사 | 약물 전달체용 음이온기-함유 양친성 블록 공중합체 및 그의 양이온성 약물과의 복합체 |
| US20040142325A1 (en) * | 2001-09-14 | 2004-07-22 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
| US7084257B2 (en) | 2001-10-05 | 2006-08-01 | Amgen Inc. | Fully human antibody Fab fragments with human interferon-gamma neutralizing activity |
| EP1806364B1 (fr) * | 2002-01-18 | 2013-07-31 | Pierre Fabre Medicament | Nouveaux anticorps anti-igf-ir et leurs applications |
| US7153685B2 (en) | 2002-03-11 | 2006-12-26 | The Board Of Trustees Of The University Of Illinois | Tamoxifen and 4-hydroxytamoxifen-activated system for regulated production of proteins in eukaryotic cells |
| US20050276812A1 (en) | 2004-06-01 | 2005-12-15 | Genentech, Inc. | Antibody-drug conjugates and methods |
| CA2526950C (en) | 2002-05-27 | 2012-06-26 | Leif Hakansson | Method for determining immune system affecting compounds |
| CA2488441C (en) | 2002-06-03 | 2015-01-27 | Genentech, Inc. | Synthetic antibody phage libraries |
| US7538195B2 (en) | 2002-06-14 | 2009-05-26 | Immunogen Inc. | Anti-IGF-I receptor antibody |
| JP4596916B2 (ja) | 2002-09-05 | 2010-12-15 | メディミューン，エルエルシー | Ｃｄ２拮抗薬を投与することによりｔ細胞悪性腫瘍を予防または治療する方法 |
| US20090183270A1 (en) * | 2002-10-02 | 2009-07-16 | Adams Thomas R | Transgenic plants with enhanced agronomic traits |
| WO2004064731A2 (en) | 2003-01-14 | 2004-08-05 | University Of Washington | Lipid-drug formulations and methods for targeted delivery of lipid-drug complexes to lymlplhoid tissues |
| EP1613774A2 (en) | 2003-03-10 | 2006-01-11 | Applera Corporation | Genetic polymorphisms associated with stenosis, methods of detection and uses thereof |
| WO2004087947A1 (en) | 2003-03-31 | 2004-10-14 | Mcmaster University | Aptamer selection method |
| AU2003902875A0 (en) * | 2003-06-10 | 2003-06-26 | The University Of Melbourne | Immunomodulating compositions, uses therefor and processes for their production |
| EP3679951A1 (en) | 2003-06-27 | 2020-07-15 | Amgen Fremont Inc. | Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof |
| DK1682583T3 (da) | 2003-11-13 | 2012-05-07 | Hanmi Holdings Co Ltd | Proteinkompleksdannelse under anvendelse af immunoglobulinfragment samt fremgangsmåde til fremstilling deraf |
| US8012468B2 (en) | 2004-06-11 | 2011-09-06 | Catholic Universtiy Industry Academic Cooperation Foundation | Dendrite cells transduced with recombinant adenovirus AdVCEA which generate CEA-specific cytotoxic T lymphocytes, vaccine and pharmaceutical composition comprising the same |
| FR2873699B1 (fr) * | 2004-07-29 | 2009-08-21 | Pierre Fabre Medicament Sa | Nouveaux anticorps anti igf ir rt leurs utilisations |
| SE0402536D0 (sv) | 2004-10-20 | 2004-10-20 | Therim Diagnostica Ab | Immunoregulation in cancer, chronic inflammatory and autoimmune diseases |
| EP1875246B1 (en) | 2005-04-15 | 2016-10-05 | CanImGuide Therapeutics AB | Diagnostic method for detecting cancer by measuring amount of a cytokine like il-6 |
| HRP20110404T1 (hr) | 2005-11-08 | 2011-08-31 | Ambrx | Ubrzivači za modifikaciju ne-prirodnih aminokiselina i polipeptida ne-prirodnih aminokiselina |
| JP2009519942A (ja) | 2005-12-14 | 2009-05-21 | アンブルックス，インコーポレイテッド | 非天然アミノ酸およびポリペプチドを含んでいる組成物、それらに関する方法、ならびに、それらの使用 |
| EP1973949A2 (en) | 2005-12-16 | 2008-10-01 | Genentech, Inc. | Anti-ox40l antibodies and methods using same |
| WO2008112941A1 (en) | 2007-03-13 | 2008-09-18 | Board Of Regents The University Of Texas System | Composition and method for the treatment of diseases affected by a peptide receptor |
| DK2487186T3 (da) | 2007-05-08 | 2017-01-16 | Canimguide Therapeutics Ab | Immunregulatoriske strukturer fra normalt forekommende proteiner |
| WO2009047360A1 (en) * | 2007-10-11 | 2009-04-16 | Novo Nordisk A/S | Il-21 antibodies |
| RU2360924C1 (ru) * | 2007-12-21 | 2009-07-10 | Институт биохимии им. А.А. Баха РАН | Маркер рака предстательной железы |
| WO2011119484A1 (en) * | 2010-03-23 | 2011-09-29 | Iogenetics, Llc | Bioinformatic processes for determination of peptide binding |
| AU2012261953A1 (en) * | 2011-06-03 | 2013-12-12 | University Of South Alabama | Methods and compositions for detecting endometrial or ovarian cancer |
| EP3043810B1 (en) | 2013-09-09 | 2019-10-23 | CanImGuide Therapeutics AB | Immune system modulators |
| DK3265117T3 (da) | 2015-03-06 | 2021-02-08 | Canimguide Therapeutics Ab | Immunsystemmodulatorer og præparater |
-
2014
- 2014-09-08 EP EP14771713.6A patent/EP3043810B1/en active Active
- 2014-09-08 CN CN202010645072.7A patent/CN111732652A/zh active Pending
- 2014-09-08 AU AU2014317884A patent/AU2014317884B2/en not_active Ceased
- 2014-09-08 WO PCT/US2014/054612 patent/WO2015035332A1/en not_active Ceased
- 2014-09-08 US US14/916,512 patent/US9657059B2/en not_active Expired - Fee Related
- 2014-09-08 JP JP2016540471A patent/JP6886816B2/ja not_active Expired - Fee Related
- 2014-09-08 DK DK14771713.6T patent/DK3043810T3/da active
- 2014-09-08 CN CN201480061392.0A patent/CN105744944B/zh not_active Expired - Fee Related
- 2014-09-08 ES ES14771713T patent/ES2777939T3/es active Active
- 2014-09-08 EP EP19204654.8A patent/EP3656391A1/en not_active Withdrawn
- 2014-09-08 CA CA2923160A patent/CA2923160A1/en not_active Abandoned
- 2014-09-08 KR KR1020167008914A patent/KR102162323B1/ko not_active Expired - Fee Related
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2017
- 2017-04-14 US US15/488,283 patent/US10301356B2/en not_active Expired - Fee Related
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2019
- 2019-04-09 US US16/379,654 patent/US20190375789A1/en not_active Abandoned
- 2019-10-04 JP JP2019183568A patent/JP2020019803A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20170298096A1 (en) | 2017-10-19 |
| US20160311854A1 (en) | 2016-10-27 |
| EP3043810B1 (en) | 2019-10-23 |
| AU2014317884B2 (en) | 2017-09-07 |
| WO2015035332A1 (en) | 2015-03-12 |
| CN111732652A (zh) | 2020-10-02 |
| US20190375789A1 (en) | 2019-12-12 |
| ES2777939T3 (es) | 2020-08-06 |
| DK3043810T3 (da) | 2020-01-27 |
| EP3656391A1 (en) | 2020-05-27 |
| CN105744944A (zh) | 2016-07-06 |
| US10301356B2 (en) | 2019-05-28 |
| CN105744944B (zh) | 2020-07-07 |
| JP2020019803A (ja) | 2020-02-06 |
| KR20160054531A (ko) | 2016-05-16 |
| JP6886816B2 (ja) | 2021-06-16 |
| EP3043810A1 (en) | 2016-07-20 |
| US9657059B2 (en) | 2017-05-23 |
| JP2016531583A (ja) | 2016-10-13 |
| KR102162323B1 (ko) | 2020-10-06 |
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