CA3069047A1 - A universal vaccine based on shared tumor neoantigens for prevention and treatment of micro satellite instable (msi) cancers - Google Patents
A universal vaccine based on shared tumor neoantigens for prevention and treatment of micro satellite instable (msi) cancers Download PDFInfo
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- CA3069047A1 CA3069047A1 CA3069047A CA3069047A CA3069047A1 CA 3069047 A1 CA3069047 A1 CA 3069047A1 CA 3069047 A CA3069047 A CA 3069047A CA 3069047 A CA3069047 A CA 3069047A CA 3069047 A1 CA3069047 A1 CA 3069047A1
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Classifications
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/10—Peptides having 12 to 20 amino acids
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- A—HUMAN NECESSITIES
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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- G—PHYSICS
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- G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
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- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
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- G16B30/00—ICT specially adapted for sequence analysis involving nucleotides or amino acids
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- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5152—Tumor cells
Landscapes
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Bioinformatics & Computational Biology (AREA)
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- Microbiology (AREA)
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- Oncology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP17181026 | 2017-07-12 | ||
| EP17181026.0 | 2017-07-12 | ||
| PCT/EP2018/069032 WO2019012082A1 (en) | 2017-07-12 | 2018-07-12 | UNIVERSAL VACCINE BASED ON SHARED TUMOR NEO-ANTIGENS FOR THE PREVENTION AND TREATMENT OF MICRO-SATELLITE INSTABILITY CANCER (MSI) |
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|---|---|
| CA3069047A1 true CA3069047A1 (en) | 2019-01-17 |
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| CA3069047A Pending CA3069047A1 (en) | 2017-07-12 | 2018-07-12 | A universal vaccine based on shared tumor neoantigens for prevention and treatment of micro satellite instable (msi) cancers |
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| PL (1) | PL3652606T3 (enExample) |
| PT (1) | PT3652606T (enExample) |
| SG (1) | SG11202000250PA (enExample) |
| WO (1) | WO2019012082A1 (enExample) |
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| EP3827265A1 (en) | 2018-07-26 | 2021-06-02 | Frame Pharmaceuticals B.V. | Cancer vaccines for kidney cancer |
| IL321691A (en) | 2018-07-26 | 2025-08-01 | Curevac Netherlands B V | arid1a, cdkn2a, kmt2b, kmt2d, tp53 and pten vaccines against cancer |
| IL280113B2 (en) | 2018-07-26 | 2025-11-01 | Curevac Netherlands B V | Cancer vaccines for uterine cancer |
| IL280112B2 (en) | 2018-07-26 | 2025-11-01 | Curevac Netherlands B V | Cancer vaccines for breast cancer |
| CA3106562A1 (en) | 2018-07-26 | 2020-01-30 | Frame Pharmaceuticals B.V. | Off-the-shelf cancer vaccines |
| CA3106573A1 (en) | 2018-07-26 | 2020-01-30 | Frame Pharmaceuticals B.V. | Cancer vaccines for colorectal cancer |
| TWI852977B (zh) * | 2019-01-10 | 2024-08-21 | 美商健生生物科技公司 | 前列腺新抗原及其用途 |
| WO2020163802A1 (en) * | 2019-02-07 | 2020-08-13 | Arizona Board Of Regents On Behalf Of Arizona State University | Cancer specific frameshift vaccines |
| CN114980920A (zh) | 2019-11-18 | 2022-08-30 | 詹森生物科技公司 | 基于突变体calr和jak2的疫苗及其用途 |
| WO2021228999A1 (en) * | 2020-05-12 | 2021-11-18 | Institut Curie | Neoantigenic epitopes associated with sf3b1 mutations |
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| CN1824325A (zh) * | 2005-12-16 | 2006-08-30 | 武汉大学 | 人乳头病毒dna嵌合疫苗及制备方法和应用 |
| BRPI0717651A2 (pt) * | 2006-10-17 | 2013-12-24 | Oncotherapy Science Inc | Vacinas de peptídeo para cânceres que expressam polipeptídeos mphosph1 ou depdc1 |
| TW201102081A (en) * | 2009-05-11 | 2011-01-16 | Oncotherapy Science Inc | TTK peptides and vaccines including the same |
| US8685896B2 (en) | 2009-05-29 | 2014-04-01 | Morphosys Ag | Collection and methods for its use |
| SG183945A1 (en) * | 2010-04-09 | 2012-10-30 | Oncotherapy Science Inc | Cdca5 peptides and vaccines including the same |
| ES2575980T3 (es) * | 2011-03-24 | 2016-07-04 | Institut National De La Santé Et De La Recherche Médicale (Inserm) | Mutante de HSP110 dominante negativo y su uso en el pronóstico y el tratamiento de cánceres |
| DK2742133T3 (en) * | 2011-08-12 | 2017-12-04 | Oncotherapy Science Inc | MPHOSPH1 PEPTIDES AND VACCINES CONTAINING THESE |
| JP5890769B2 (ja) * | 2012-12-13 | 2016-03-22 | ループレヒト−カルルス・ウニヴェルジテート・ハイデルベルクＲｕｐｒｅｃｈｔ−Ｋａｒｌｓ−Ｕｎｉｖｅｒｓｉｔａｅｔ Ｈｅｉｄｅｌｂｅｒｇ | がんの予防及び治療のためのｍｓｉ特異的なフレームシフトペプチド（ｆｓｐ） |
| US9205140B2 (en) * | 2012-12-13 | 2015-12-08 | Ruprecht-Karls-Universität | MSI-specific frameshift peptides (FSP) for prevention and treatment of cancer |
| KR101810840B1 (ko) * | 2012-12-13 | 2017-12-20 | 루프레히트-칼스-유니페어지테트 하이델베르크 | 암의 예방 및 치료용 msi-특이적 프레임쉬프트 펩티드(fsp) |
| US20140235456A1 (en) * | 2012-12-17 | 2014-08-21 | Virginia Tech Intellectual Properties, Inc. | Methods and Compositions for Identifying Global Microsatellite Instability and for Characterizing Informative Microsatellite Loci |
| US11098367B2 (en) * | 2014-01-27 | 2021-08-24 | Yale University | Methods of identifying patients responsive to immunotherapeutic strategies |
| PE20180670A1 (es) * | 2015-05-20 | 2018-04-19 | Broad Inst Inc | Neoantigenos compartidos |
| CN106350578A (zh) * | 2015-07-13 | 2017-01-25 | 中国人民解放军第二军医大学 | Ny-eso-1在微卫星不稳定性肠癌的诊断和治疗中的应用 |
| US12150980B2 (en) | 2015-07-30 | 2024-11-26 | Modernatx, Inc. | Concatemeric peptide epitope RNAs |
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| WO2019012082A9 (en) | 2019-05-02 |
| PT3652606T (pt) | 2023-03-16 |
| AU2018298849A1 (en) | 2020-01-02 |
| JP7274223B2 (ja) | 2023-05-16 |
| PL3652606T3 (pl) | 2023-04-24 |
| AU2018298849B2 (en) | 2022-07-14 |
| SG11202000250PA (en) | 2020-02-27 |
| DK3652606T3 (da) | 2023-03-13 |
| NZ759940A (en) | 2023-07-28 |
| CN111328420A (zh) | 2020-06-23 |
| IL271966A (en) | 2020-02-27 |
| RU2019144505A (ru) | 2021-08-12 |
| IL271966B2 (en) | 2025-01-01 |
| KR102709778B1 (ko) | 2024-09-26 |
| BR112020000590A2 (pt) | 2020-07-14 |
| US11578109B2 (en) | 2023-02-14 |
| US20200222519A1 (en) | 2020-07-16 |
| FI3652606T3 (fi) | 2023-03-16 |
| IL271966B1 (en) | 2024-09-01 |
| MX2020000413A (es) | 2020-09-28 |
| DK3652606T5 (da) | 2024-08-26 |
| EP3652606A1 (en) | 2020-05-20 |
| KR20200029443A (ko) | 2020-03-18 |
| CN111328420B (zh) | 2023-07-25 |
| HUE061840T2 (hu) | 2023-08-28 |
| JP2020532288A (ja) | 2020-11-12 |
| WO2019012082A1 (en) | 2019-01-17 |
| ES2940087T3 (es) | 2023-05-03 |
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