CZ294909B6 - Buňka imunitního systému s tyrosin-proteinkinázovými chimérickými receptory a léčivo - Google Patents
Buňka imunitního systému s tyrosin-proteinkinázovými chimérickými receptory a léčivo Download PDFInfo
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- CZ294909B6 CZ294909B6 CZ19972601A CZ260197A CZ294909B6 CZ 294909 B6 CZ294909 B6 CZ 294909B6 CZ 19972601 A CZ19972601 A CZ 19972601A CZ 260197 A CZ260197 A CZ 260197A CZ 294909 B6 CZ294909 B6 CZ 294909B6
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Classifications
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- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/13—Tumour cells, irrespective of tissue of origin
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
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- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/46—Viral antigens
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
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- 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
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
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- 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
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70514—CD4
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- 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
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70535—Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
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- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- General Engineering & Computer Science (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/394,177 US5912170A (en) | 1991-03-07 | 1995-02-24 | Redirection of cellular immunity by protein-tyrosine kinase chimeras |
Publications (2)
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|---|---|
| CZ260197A3 CZ260197A3 (cs) | 1998-05-13 |
| CZ294909B6 true CZ294909B6 (cs) | 2005-04-13 |
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| Application Number | Title | Priority Date | Filing Date |
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| CZ19972601A CZ294909B6 (cs) | 1995-02-24 | 1996-01-24 | Buňka imunitního systému s tyrosin-proteinkinázovými chimérickými receptory a léčivo |
Country Status (19)
| Country | Link |
|---|---|
| US (3) | US5912170A (2) |
| EP (1) | EP0812352B1 (2) |
| JP (1) | JP4170389B2 (2) |
| KR (1) | KR100454396B1 (2) |
| AT (1) | ATE323755T1 (2) |
| AU (1) | AU703125C (2) |
| CA (1) | CA2209301C (2) |
| CZ (1) | CZ294909B6 (2) |
| DE (1) | DE69636053T2 (2) |
| DK (1) | DK0812352T3 (2) |
| ES (1) | ES2258772T3 (2) |
| FI (1) | FI121012B (2) |
| HU (1) | HU225689B1 (2) |
| NO (1) | NO321459B1 (2) |
| NZ (2) | NZ501340A (2) |
| PT (1) | PT812352E (2) |
| RU (1) | RU2225870C2 (2) |
| WO (1) | WO1996026265A1 (2) |
| ZA (1) | ZA961476B (2) |
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| US5851828A (en) | 1991-03-07 | 1998-12-22 | The General Hospital Corporation | Targeted cytolysis of HIV-infected cells by chimeric CD4 receptor-bearing cells |
| US5912170A (en) | 1991-03-07 | 1999-06-15 | The General Hospital Corporation | Redirection of cellular immunity by protein-tyrosine kinase chimeras |
| US7049136B2 (en) | 1991-03-07 | 2006-05-23 | The General Hospital Corporation | Redirection of cellular immunity by receptor chimeras |
| US6753162B1 (en) | 1991-03-07 | 2004-06-22 | The General Hospital Corporation | Targeted cytolysis of HIV-infected cells by chimeric CD4 receptor-bearing cells |
| US6004811A (en) | 1991-03-07 | 1999-12-21 | The Massachussetts General Hospital | Redirection of cellular immunity by protein tyrosine kinase chimeras |
| AU708339B2 (en) * | 1995-02-24 | 1999-08-05 | General Hospital Corporation, The | Redirection of cellular immunity by receptor chimeras |
| GB9526131D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Recombinant chimeric receptors |
| DK1905457T3 (da) * | 1999-12-22 | 2012-05-29 | Scripps Research Inst | Farmaceutiske sammensætninger omfattende Src og/eller Yes samt anvendelse deraf |
| IL137419A0 (en) * | 2000-07-20 | 2001-07-24 | Yissum Res Dev Co | Nk cells activating receptors and their therapeutic and diagnostic uses |
| US9045739B2 (en) * | 2004-01-16 | 2015-06-02 | Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. | Immunokinases |
| US8883507B2 (en) | 2005-10-18 | 2014-11-11 | The Regents Of The University Of Colorado | Conditionally immortalized long-term hematopoietic stem cells and methods of making and using such cells |
| EP1800695A1 (en) * | 2005-12-21 | 2007-06-27 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Immuno-RNA-constructs |
| WO2008017517A1 (en) | 2006-08-11 | 2008-02-14 | Life Sciences Research Partners Vzw | Immunogenic peptides and their use in immune disorders |
| CN101828113B (zh) * | 2007-07-25 | 2014-04-16 | 德国弗劳恩霍夫协会债权安格万特学术研究所 | 自结合重组抗体融合蛋白 |
| US8450053B2 (en) * | 2007-09-11 | 2013-05-28 | University Of Maryland, Baltimore | ZAP-70 as predictor and modulator of effector function of T cells |
| SG10201803982TA (en) | 2008-05-16 | 2018-07-30 | Taiga Biotechnologies Inc | Antibodies and processes for preparing the same |
| US8784825B2 (en) | 2008-08-28 | 2014-07-22 | Taiga Biotechnologies, Inc. | Modulators of MYC, methods of using the same, and methods of identifying agents that modulate MYC |
| WO2011119920A2 (en) | 2010-03-25 | 2011-09-29 | Oregon Health & Science University | Cmv glycoproteins and recombinant vectors |
| ES2667425T3 (es) | 2011-06-10 | 2018-05-10 | Oregon Health & Science University | Glucoproteínas y vectores recombinantes de CMV |
| AU2012216792A1 (en) | 2011-09-12 | 2013-03-28 | International Aids Vaccine Initiative | Immunoselection of recombinant vesicular stomatitis virus expressing HIV-1 proteins by broadly neutralizing antibodies |
| EP2586461A1 (en) | 2011-10-27 | 2013-05-01 | Christopher L. Parks | Viral particles derived from an enveloped virus |
| GB201201511D0 (en) | 2012-01-30 | 2012-03-14 | Univ Leuven Kath | Modified epitopes for boosting CD4+ T-cell responses |
| EP2679596B1 (en) | 2012-06-27 | 2017-04-12 | International Aids Vaccine Initiative | HIV-1 env glycoprotein variant |
| JP6285930B2 (ja) | 2012-07-20 | 2018-02-28 | タイガ バイオテクノロジーズ,インク. | 造血コンパートメントの再構築及び自家再構築の増進 |
| EP2934532B1 (en) | 2012-12-20 | 2019-10-23 | Purdue Research Foundation | Chimeric antigen receptor-expressing t cells as anti-cancer therapeutics |
| US10272115B2 (en) | 2013-03-11 | 2019-04-30 | Taiga Biotechnologies, Inc. | Production and use of red blood cells |
| US20150065381A1 (en) | 2013-09-05 | 2015-03-05 | International Aids Vaccine Initiative | Methods of identifying novel hiv-1 immunogens |
| EP2873423B1 (en) | 2013-10-07 | 2017-05-31 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
| WO2015077717A1 (en) | 2013-11-25 | 2015-05-28 | The Broad Institute Inc. | Compositions and methods for diagnosing, evaluating and treating cancer by means of the dna methylation status |
| WO2015085147A1 (en) | 2013-12-05 | 2015-06-11 | The Broad Institute Inc. | Polymorphic gene typing and somatic change detection using sequencing data |
| JP7060324B2 (ja) | 2013-12-20 | 2022-04-26 | ザ・ブロード・インスティテュート・インコーポレイテッド | ネオ抗原ワクチンによる併用療法 |
| ES2688035T3 (es) | 2014-08-29 | 2018-10-30 | Gemoab Monoclonals Gmbh | Receptor de antígeno universal que expresa células inmunes para direccionamiento de antígenos múltiples diversos, procedimiento para fabricación del mismo y utilización del mismo para tratamiento de cáncer, infecciones y enfermedades autoinmunes |
| US10975442B2 (en) | 2014-12-19 | 2021-04-13 | Massachusetts Institute Of Technology | Molecular biomarkers for cancer immunotherapy |
| EP3234130B1 (en) | 2014-12-19 | 2020-11-25 | The Broad Institute, Inc. | Methods for profiling the t-cell- receptor repertoire |
| US10174292B2 (en) | 2015-03-20 | 2019-01-08 | International Aids Vaccine Initiative | Soluble HIV-1 envelope glycoprotein trimers |
| EP3072901A1 (en) | 2015-03-23 | 2016-09-28 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
| JP6913032B2 (ja) | 2015-05-20 | 2021-08-04 | ザ・ブロード・インスティテュート・インコーポレイテッド | 共通ネオ抗原 |
| AU2016279062A1 (en) | 2015-06-18 | 2019-03-28 | Omar O. Abudayyeh | Novel CRISPR enzymes and systems |
| US12241053B2 (en) | 2015-10-09 | 2025-03-04 | The Brigham And Women's Hospital, Inc. | Modulation of novel immune checkpoint targets |
| WO2017075465A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by detecting and targeting gata3 |
| WO2017075451A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by detecting and targeting pou2af1 |
| WO2017075478A2 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by use of immune cell gene signatures |
| CA3005878A1 (en) | 2015-11-19 | 2017-05-26 | The Brigham And Women's Hospital, Inc. | Lymphocyte antigen cd5-like (cd5l)-interleukin 12b (p40) heterodimers in immunity |
| CA3019835A1 (en) | 2016-04-08 | 2017-10-12 | Purdue Research Foundation | Methods and compositions for car t cell therapy |
| AU2017254477A1 (en) | 2016-04-18 | 2018-11-01 | Jennifer G. ABELIN | Improved HLA epitope prediction |
| US11630103B2 (en) | 2016-08-17 | 2023-04-18 | The Broad Institute, Inc. | Product and methods useful for modulating and evaluating immune responses |
| US20190262399A1 (en) | 2016-09-07 | 2019-08-29 | The Broad Institute, Inc. | Compositions and methods for evaluating and modulating immune responses |
| US12499971B2 (en) | 2016-09-28 | 2025-12-16 | The Broad Institute, Inc. | Systematic screening and mapping of regulatory elements in non-coding genomic regions, methods, compositions, and applications thereof |
| US12447213B2 (en) | 2016-10-07 | 2025-10-21 | The Broad Institute, Inc. | Modulation of novel immune checkpoint targets |
| WO2018089386A1 (en) | 2016-11-11 | 2018-05-17 | The Broad Institute, Inc. | Modulation of intestinal epithelial cell differentiation, maintenance and/or function through t cell action |
| US10583156B2 (en) | 2016-12-02 | 2020-03-10 | Taiga Biotechnologies, Inc. | Nanoparticle formulations |
| EP3574116A1 (en) | 2017-01-24 | 2019-12-04 | The Broad Institute, Inc. | Compositions and methods for detecting a mutant variant of a polynucleotide |
| AU2018219226B2 (en) | 2017-02-07 | 2024-12-19 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Phospholipid ether (PLE) CAR T cell tumor targeting (CTCT) agents |
| CN110809716B (zh) | 2017-02-12 | 2023-07-07 | 百欧恩泰美国公司 | 基于hla的方法和组合物及其用途 |
| CN110582288B (zh) | 2017-02-28 | 2024-09-20 | 恩多塞特公司 | 用于car t细胞疗法的组合物和方法 |
| US11963966B2 (en) | 2017-03-31 | 2024-04-23 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating ovarian tumors |
| EP3606518A4 (en) | 2017-04-01 | 2021-04-07 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR DETECTION AND MODULATION OF IMMUNOTHERAPY RESISTANCE GENE SIGNATURE IN CANCER |
| US12590288B2 (en) | 2017-04-12 | 2026-03-31 | The Broad Institute, Inc. | Method of treating an inflammatory disease by administering an agent which binds a surface receptor on a tuft cell that induces an ILC class 2 inflammatory response |
| US20200071773A1 (en) | 2017-04-12 | 2020-03-05 | Massachusetts Eye And Ear Infirmary | Tumor signature for metastasis, compositions of matter methods of use thereof |
| US20210293783A1 (en) | 2017-04-18 | 2021-09-23 | The General Hospital Corporation | Compositions for detecting secretion and methods of use |
| JP2020517259A (ja) | 2017-04-19 | 2020-06-18 | ボード・オブ・リージエンツ,ザ・ユニバーシテイ・オブ・テキサス・システム | 操作された抗原受容体を発現する免疫細胞 |
| US12226479B2 (en) | 2017-05-11 | 2025-02-18 | The General Hospital Corporation | Methods and compositions of use of CD8+ tumor infiltrating lymphocyte subtypes and gene signatures thereof |
| EP3625342B1 (en) | 2017-05-18 | 2022-08-24 | The Broad Institute, Inc. | Systems, methods, and compositions for targeted nucleic acid editing |
| EP3638218A4 (en) | 2017-06-14 | 2021-06-09 | The Broad Institute, Inc. | COMPOSITIONS AND METHOD OF TARGETING COMPLEMENTING COMPONENT 3 FOR INHIBITION OF TUMOR GROWTH |
| WO2019014581A1 (en) | 2017-07-14 | 2019-01-17 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR MODULATING THE ACTIVITY OF A CYTOTOXIC LYMPHOCYTE |
| EP4026554A1 (en) | 2017-08-03 | 2022-07-13 | Taiga Biotechnologies, Inc. | Methods and compositions for the treatment of melanoma |
| US10149898B2 (en) | 2017-08-03 | 2018-12-11 | Taiga Biotechnologies, Inc. | Methods and compositions for the treatment of melanoma |
| KR102338449B1 (ko) | 2017-09-21 | 2021-12-10 | 더 브로드 인스티튜트, 인코퍼레이티드 | 표적화된 핵산 편집을 위한 시스템, 방법, 및 조성물 |
| WO2019070755A1 (en) | 2017-10-02 | 2019-04-11 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR DETECTING AND MODULATING A GENETIC SIGNATURE OF IMMUNOTHERAPY RESISTANCE IN CANCER |
| US11732257B2 (en) | 2017-10-23 | 2023-08-22 | Massachusetts Institute Of Technology | Single cell sequencing libraries of genomic transcript regions of interest in proximity to barcodes, and genotyping of said libraries |
| WO2019094983A1 (en) | 2017-11-13 | 2019-05-16 | The Broad Institute, Inc. | Methods and compositions for treating cancer by targeting the clec2d-klrb1 pathway |
| US12171783B2 (en) | 2017-11-13 | 2024-12-24 | The Broad Institute, Inc. | Methods and compositions for targeting developmental and oncogenic programs in H3K27M gliomas |
| US11994512B2 (en) | 2018-01-04 | 2024-05-28 | Massachusetts Institute Of Technology | Single-cell genomic methods to generate ex vivo cell systems that recapitulate in vivo biology with improved fidelity |
| WO2019144095A1 (en) | 2018-01-22 | 2019-07-25 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Methods of use for car t cells |
| AU2019218729B2 (en) | 2018-02-06 | 2025-12-04 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Fluorescein-specific CARs exhibiting optimal T cell function against FL-PLE labelled tumors |
| WO2019165121A1 (en) | 2018-02-21 | 2019-08-29 | Board Of Regents, The University Of Texas System | Methods for activation and expansion of natural killer cells and uses therof |
| JP7568224B2 (ja) | 2018-02-23 | 2024-10-16 | エンドサイト・インコーポレイテッド | Car t細胞療法のための配列決定法 |
| KR20200130709A (ko) | 2018-03-06 | 2020-11-19 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 전립선-특이 막 항원 car 및 이의 사용 방법 |
| US11957695B2 (en) | 2018-04-26 | 2024-04-16 | The Broad Institute, Inc. | Methods and compositions targeting glucocorticoid signaling for modulating immune responses |
| WO2019232542A2 (en) | 2018-06-01 | 2019-12-05 | Massachusetts Institute Of Technology | Methods and compositions for detecting and modulating microenvironment gene signatures from the csf of metastasis patients |
| WO2019241273A1 (en) | 2018-06-11 | 2019-12-19 | The Broad Institute, Inc. | Lineage tracing using mitochondrial genome mutations and single cell genomics |
| US12036240B2 (en) | 2018-06-14 | 2024-07-16 | The Broad Institute, Inc. | Compositions and methods targeting complement component 3 for inhibiting tumor growth |
| US12391685B2 (en) | 2018-08-20 | 2025-08-19 | The Broad Institute, Inc. | Inhibitors of RNA-guided nuclease target binding and uses thereof |
| WO2020041384A1 (en) | 2018-08-20 | 2020-02-27 | The Broad Institute, Inc. | 3-phenyl-2-cyano-azetidine derivatives, inhibitors of rna-guided nuclease activity |
| WO2020041387A1 (en) | 2018-08-20 | 2020-02-27 | The Brigham And Women's Hospital, Inc. | Degradation domain modifications for spatio-temporal control of rna-guided nucleases |
| US20210382068A1 (en) | 2018-10-02 | 2021-12-09 | Dana-Farber Cancer Institute, Inc. | Hla single allele lines |
| WO2020081730A2 (en) | 2018-10-16 | 2020-04-23 | Massachusetts Institute Of Technology | Methods and compositions for modulating microenvironment |
| WO2020092455A2 (en) | 2018-10-29 | 2020-05-07 | The Broad Institute, Inc. | Car t cell transcriptional atlas |
| WO2020092057A1 (en) | 2018-10-30 | 2020-05-07 | Yale University | Compositions and methods for rapid and modular generation of chimeric antigen receptor t cells |
| WO2020131586A2 (en) | 2018-12-17 | 2020-06-25 | The Broad Institute, Inc. | Methods for identifying neoantigens |
| CA3124457A1 (en) | 2018-12-21 | 2020-06-25 | Biontech Us Inc. | Method and systems for prediction of hla class ii-specific epitopes and characterization of cd4+ t cells |
| US11739156B2 (en) | 2019-01-06 | 2023-08-29 | The Broad Institute, Inc. Massachusetts Institute of Technology | Methods and compositions for overcoming immunosuppression |
| WO2020186101A1 (en) | 2019-03-12 | 2020-09-17 | The Broad Institute, Inc. | Detection means, compositions and methods for modulating synovial sarcoma cells |
| EP3942023A1 (en) | 2019-03-18 | 2022-01-26 | The Broad Institute, Inc. | Compositions and methods for modulating metabolic regulators of t cell pathogenicity |
| EP3952909A4 (en) | 2019-04-08 | 2023-06-07 | Taiga Biotechnologies, Inc. | COMPOSITIONS AND METHODS FOR CRYOPRESERVING IMMUNE CELLS |
| SG11202112529WA (en) | 2019-05-14 | 2021-12-30 | Taiga Biotechnologies Inc | Compositions and methods for treating t cell exhaustion |
| US20220235340A1 (en) | 2019-05-20 | 2022-07-28 | The Broad Institute, Inc. | Novel crispr-cas systems and uses thereof |
| WO2020243371A1 (en) | 2019-05-28 | 2020-12-03 | Massachusetts Institute Of Technology | Methods and compositions for modulating immune responses |
| US20220282333A1 (en) | 2019-08-13 | 2022-09-08 | The General Hospital Corporation | Methods for predicting outcomes of checkpoint inhibition and treatment thereof |
| US12421557B2 (en) | 2019-08-16 | 2025-09-23 | The Broad Institute, Inc. | Methods for predicting outcomes and treating colorectal cancer using a cell atlas |
| US20220298501A1 (en) | 2019-08-30 | 2022-09-22 | The Broad Institute, Inc. | Crispr-associated mu transposase systems |
| US20220401537A1 (en) * | 2019-09-16 | 2022-12-22 | Fred Hutchinson Cancer Research Center | Chimeric receptor proteins and uses thereof |
| US12297426B2 (en) | 2019-10-01 | 2025-05-13 | The Broad Institute, Inc. | DNA damage response signature guided rational design of CRISPR-based systems and therapies |
| US12394502B2 (en) | 2019-10-02 | 2025-08-19 | The General Hospital Corporation | Method for predicting HLA-binding peptides using protein structural features |
| US12195725B2 (en) | 2019-10-03 | 2025-01-14 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for modulating and detecting tissue specific TH17 cell pathogenicity |
| US11981922B2 (en) | 2019-10-03 | 2024-05-14 | Dana-Farber Cancer Institute, Inc. | Methods and compositions for the modulation of cell interactions and signaling in the tumor microenvironment |
| US11793787B2 (en) | 2019-10-07 | 2023-10-24 | The Broad Institute, Inc. | Methods and compositions for enhancing anti-tumor immunity by targeting steroidogenesis |
| US11844800B2 (en) | 2019-10-30 | 2023-12-19 | Massachusetts Institute Of Technology | Methods and compositions for predicting and preventing relapse of acute lymphoblastic leukemia |
| US12195723B2 (en) | 2019-11-08 | 2025-01-14 | The Broad Institute, Inc. | Engineered antigen presenting cells and uses thereof |
| US12165747B2 (en) | 2020-01-23 | 2024-12-10 | The Broad Institute, Inc. | Molecular spatial mapping of metastatic tumor microenvironment |
| IL295063A (en) | 2020-02-04 | 2022-09-01 | Seattle Childrens Hospital Dba Seattle Childrens Res Inst | Chimeric antigen receptors (car) against dinitrophenol |
| CA3188988A1 (en) | 2020-08-13 | 2022-02-17 | Sidi CHEN | Compositions and methods for engineering and selection of car t cells with desired phenotypes |
| WO2023173137A1 (en) | 2022-03-11 | 2023-09-14 | Yale University | Compositions and methods for efficient and stable genetic modification of eukaryotic cells |
| US20250161360A1 (en) | 2022-05-10 | 2025-05-22 | Yale University | Compositions and methods of synthetic ctla-4 tails for reprogramming of car-t cells and enhancement of anti-tumor efficacy |
| EP4598949A1 (en) | 2022-10-07 | 2025-08-13 | The General Hospital Corporation | Methods and compositions for high-throughput discovery of peptide-mhc targeting binding proteins |
| WO2024124044A1 (en) | 2022-12-07 | 2024-06-13 | The Brigham And Women’S Hospital, Inc. | Compositions and methods targeting sat1 for enhancing anti¬ tumor immunity during tumor progression |
| WO2024155821A1 (en) | 2023-01-18 | 2024-07-25 | Yale University | Chimeric antigen receptors (car) with intrinsically disordered regions and methods of use thereof |
| WO2024192141A1 (en) | 2023-03-13 | 2024-09-19 | Dana-Farber Cancer Institute, Inc. | Treatment of cancers having a drug-resistant mesenchymal cell state |
| WO2024226838A2 (en) | 2023-04-25 | 2024-10-31 | The Brigham And Women's Hospital, Inc. | Treatment of autoimmune diseases having a pathogenic t cell state |
| WO2024226829A2 (en) | 2023-04-26 | 2024-10-31 | Yale University | Enpp3-binding molecules, compositions formed therefrom, and methods of use thereof for the treatment of cancer |
| WO2024238656A1 (en) | 2023-05-15 | 2024-11-21 | Yale Univeristy | Chimeric antigen receptor compositions, car-mast cells formed therefrom, and methods of use thereof |
| US12531162B1 (en) * | 2023-05-31 | 2026-01-20 | Northeastern University | Multi-dimensional phenotypic space for genotype to phenotype mapping and intelligent design of cancer drug therapies using a deep learning net |
| WO2025059533A1 (en) | 2023-09-13 | 2025-03-20 | The Broad Institute, Inc. | Crispr enzymes and systems |
| WO2025097055A2 (en) | 2023-11-02 | 2025-05-08 | The Broad Institute, Inc. | Compositions and methods of use of t cells in immunotherapy |
| US12562256B2 (en) * | 2023-11-07 | 2026-02-24 | New York University | Systems, methods and computer-accessible medium for identifying target pairs for CAR-T therapy |
| WO2025117544A1 (en) | 2023-11-29 | 2025-06-05 | The Broad Institute, Inc. | Engineered omega guide molecule and iscb compositions, systems, and methods of use thereof |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4873190A (en) * | 1984-06-13 | 1989-10-10 | Massachusetts Institute Of Technology | Heterodimeric T lymphocyte receptor |
| GB8422238D0 (en) * | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
| US4690915A (en) * | 1985-08-08 | 1987-09-01 | The United States Of America As Represented By The Department Of Health And Human Services | Adoptive immunotherapy as a treatment modality in humans |
| EP0281604B1 (en) * | 1986-09-02 | 1993-03-31 | Enzon Labs Inc. | Single polypeptide chain binding molecules |
| US4946778A (en) * | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US4808151A (en) * | 1987-04-27 | 1989-02-28 | E. I. Du Pont De Nemours And Company | Simplified method for the preparation of human lymphokine activated killer cells |
| US5091513A (en) * | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| JPS6463394A (en) * | 1987-09-04 | 1989-03-09 | Kyowa Hakko Kogyo Kk | Novel chimera polypeptide |
| NZ226414A (en) * | 1987-10-02 | 1992-07-28 | Genentech Inc | Cd4 peptide adhesion variants and their preparation and use |
| US5336603A (en) * | 1987-10-02 | 1994-08-09 | Genentech, Inc. | CD4 adheson variants |
| IL86278A (en) * | 1988-05-04 | 2003-06-24 | Yeda Res & Dev | Endowing cells with antibody specificity using chimeric t cell receptor |
| CA2000878C (en) * | 1988-10-18 | 1999-06-29 | Jean-Pierre Kinet | Cdnas coding for the subunit of the high-affinity receptor for immunoglobulin e |
| US5225538A (en) * | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
| FR2644463A1 (2) * | 1989-03-17 | 1990-09-21 | Pasteur Institut | |
| EP0394827A1 (en) * | 1989-04-26 | 1990-10-31 | F. Hoffmann-La Roche Ag | Chimaeric CD4-immunoglobulin polypeptides |
| WO1991010736A2 (en) * | 1990-01-19 | 1991-07-25 | Dana Farber Cancer Institute | CLONING AND CHARACTERIZATION OF THE CD3θ SUBUNIT |
| ATE145428T1 (de) * | 1990-12-14 | 1996-12-15 | Cell Genesys Inc | Chimärische ketten zur transduktion von rezeptorverbundenen signalwegen |
| US6004811A (en) * | 1991-03-07 | 1999-12-21 | The Massachussetts General Hospital | Redirection of cellular immunity by protein tyrosine kinase chimeras |
| US5851828A (en) | 1991-03-07 | 1998-12-22 | The General Hospital Corporation | Targeted cytolysis of HIV-infected cells by chimeric CD4 receptor-bearing cells |
| IE920716A1 (en) * | 1991-03-07 | 1992-09-09 | Gen Hospital Corp | Redirection of cellular immunity by receptor chimeras |
| US5912170A (en) | 1991-03-07 | 1999-06-15 | The General Hospital Corporation | Redirection of cellular immunity by protein-tyrosine kinase chimeras |
| WO1993019163A1 (en) * | 1992-03-18 | 1993-09-30 | Yeda Research And Development Co, Ltd. | Chimeric receptor genes and cells transformed therewith |
| JP3588115B2 (ja) * | 1993-07-16 | 2004-11-10 | ザ ジェネラル ホスピタル コーポレーション | レセプターキメラによる細胞性免疫の回復 |
| US5439819A (en) * | 1993-08-27 | 1995-08-08 | The Regents Of The University Of California | Chimeric protein tyrosine kinases |
| US5712149A (en) * | 1995-02-03 | 1998-01-27 | Cell Genesys, Inc. | Chimeric receptor molecules for delivery of co-stimulatory signals |
| JP3782521B2 (ja) | 1996-08-23 | 2006-06-07 | 富士通コンポーネント株式会社 | 押釦構造およびキーボード |
-
1995
- 1995-02-24 US US08/394,177 patent/US5912170A/en not_active Expired - Lifetime
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1996
- 1996-01-24 DE DE69636053T patent/DE69636053T2/de not_active Expired - Lifetime
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- 1997-08-22 FI FI973466A patent/FI121012B/fi not_active IP Right Cessation
- 1997-08-22 NO NO19973863A patent/NO321459B1/no not_active IP Right Cessation
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- 1999-06-15 US US09/333,636 patent/US6410014B1/en not_active Expired - Lifetime
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- 2002-02-25 US US10/179,778 patent/US20020176851A1/en not_active Abandoned
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