RU2553343C2 - Композиции прокариотической фенилаланин-аммиак-лиазы и способы лечения рака с использованием таких композиций - Google Patents
Композиции прокариотической фенилаланин-аммиак-лиазы и способы лечения рака с использованием таких композиций Download PDFInfo
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- RU2553343C2 RU2553343C2 RU2012134838/15A RU2012134838A RU2553343C2 RU 2553343 C2 RU2553343 C2 RU 2553343C2 RU 2012134838/15 A RU2012134838/15 A RU 2012134838/15A RU 2012134838 A RU2012134838 A RU 2012134838A RU 2553343 C2 RU2553343 C2 RU 2553343C2
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- avpal
- stabilizer
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- phenylalanine
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Cited By (2)
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| RU2815197C2 (ru) * | 2019-02-14 | 2024-03-12 | Сом Инновейшн Биотек, С.А. | Триамтерен или нолатрексед для применения в лечении фенилкетонурии |
| US12257253B2 (en) | 2019-02-14 | 2025-03-25 | Som Innovation Biotech, S.A. | Triamterene or nolatrexed for use in the treatment of phenylketonuria |
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| US7534595B2 (en) * | 2006-06-12 | 2009-05-19 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof |
| US7537923B2 (en) * | 2007-08-17 | 2009-05-26 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of treating cancer using compositions thereof |
| WO2009064838A1 (en) * | 2007-11-15 | 2009-05-22 | Amgen, Inc. | Aqueous formulation of erythropoiesis stimulating protein stablised by antioxidants for parenteral administration |
| US20110201022A1 (en) * | 2008-07-30 | 2011-08-18 | Biomarin Pharmaceutical Inc. | Assays for detection of phenylalanine ammonia-lyase and antibodies to phenylalanine ammonia-lyase |
| WO2011078667A2 (en) | 2009-12-22 | 2011-06-30 | Dsm Ip Assets B.V. | Method of finding a biocatalyst having ammonia lyase activity |
| DK3025728T3 (en) | 2010-02-04 | 2018-10-29 | Biomarin Pharm Inc | PROCEDURE FOR PURIFICATION OF PROKARYOTIC PHENYLALANINE AMMONIAK LYASE VARIATIONS |
| US20120148559A1 (en) | 2010-12-01 | 2012-06-14 | Board Of Regents The University Of Texas System | Compositions and method for deimmunization of proteins |
| US20150246083A1 (en) * | 2012-07-27 | 2015-09-03 | University Of North Texas | Genetically modified probiotic for the treatment of phenylketonuria (pku) disease |
| KR102218930B1 (ko) | 2013-04-18 | 2021-02-23 | 코덱시스, 인코포레이티드 | 조작된 페닐알라닌 암모니아 리아제 폴리펩티드 |
| AU2014348683B2 (en) | 2013-11-18 | 2020-11-05 | Rubius Therapeutics, Inc. | Synthetic membrane-receiver complexes |
| MX2020000621A (es) | 2014-04-01 | 2020-11-12 | Rubius Therapeutics Inc | Composiciones para usarse en inmunomodulacion. |
| CA2943432A1 (en) | 2014-04-16 | 2015-10-22 | Codexis, Inc. | Engineered tyrosine ammonia lyase |
| GB2535937B (en) | 2014-04-29 | 2017-05-31 | Bio-Cancer Treat Int Ltd | Arginase I for treating rheumatoid arthritis |
| EP3169791A1 (en) | 2014-07-14 | 2017-05-24 | Danmarks Tekniske Universitet | Processes for the production of hydroxycinnamic acids using polypeptides having tyrosine ammonia lyase activity |
| KR102702200B1 (ko) | 2014-12-22 | 2024-09-02 | 코덱시스, 인코포레이티드 | 인간 알파-갈락토시다제 변이체 |
| KR20230161535A (ko) | 2016-07-26 | 2023-11-27 | 바이오마린 파머수티컬 인크. | 신규 아데노-관련 바이러스 캡시드 단백질 |
| IT201600086488A1 (it) * | 2016-08-22 | 2018-02-22 | St Microelectronics Srl | Dispositivo a semiconduttore e corrispondente procedimento |
| WO2018148633A1 (en) * | 2017-02-13 | 2018-08-16 | Codexis, Inc. | Engineered phenylalanine ammonia lyase polypeptides |
| MX2020011937A (es) | 2018-05-09 | 2021-01-29 | Biomarin Pharm Inc | Metodos de tratamiento de fenilcetonuria. |
| TW202005978A (zh) | 2018-05-14 | 2020-02-01 | 美商拜奧馬林製藥公司 | 新穎肝靶向腺相關病毒載體 |
| US10900055B2 (en) | 2018-06-12 | 2021-01-26 | Codexis, Inc. | Engineered tyrosine ammonia lyase |
| WO2020123286A1 (en) | 2018-12-14 | 2020-06-18 | Codexis, Inc. | Engineered tyrosine ammonia lyase |
| CN113544268A (zh) | 2018-12-20 | 2021-10-22 | 科德克希思公司 | 人类α半乳糖苷酶变体 |
| JP2022543611A (ja) * | 2019-08-07 | 2022-10-13 | ラクテン・メディカル，インコーポレイテッド | セツキシマブ－ｉｒ７００コンジュゲート組成物 |
| KR20220106738A (ko) | 2019-08-30 | 2022-07-29 | 코덱시스, 인코포레이티드 | 조작된 리파제 변이체 |
| JP2023507575A (ja) | 2019-12-20 | 2023-02-24 | コデクシス， インコーポレイテッド | 操作された酸性アルファ－グルコシダーゼバリアント |
| KR20220137057A (ko) | 2020-02-04 | 2022-10-11 | 코덱시스, 인코포레이티드 | 조작된 류신 데카르복실라제 |
| TW202144575A (zh) | 2020-04-03 | 2021-12-01 | 美商拜奧馬林製藥公司 | 使用ａａｖ及治療調配物之苯酮尿症治療 |
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| EP4341394A4 (en) | 2021-05-19 | 2025-04-09 | BioMarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia lyase and methods for treating adolescent patients |
| EP4341395A4 (en) | 2021-05-21 | 2025-07-23 | Syntis Bio Inc | MODIFIED METHIONINE GAMMA LYASE VARIANTS |
| AU2022377148A1 (en) | 2021-11-01 | 2024-06-13 | Syntis Bio, Inc. | Engineered leucine decarboxylases |
| CN115873837A (zh) * | 2022-11-18 | 2023-03-31 | 安徽盈科生物科技有限公司 | 高表达的新型的苯丙氨酸解氨酶 |
| CN118931888A (zh) * | 2023-05-09 | 2024-11-12 | 重庆派金生物科技有限公司 | 苯丙氨酸裂解酶突变体及其偶联物或其药学上可接受的盐 |
| GB202307239D0 (en) | 2023-05-15 | 2023-06-28 | Evox Therapeutics Ltd | Gene therapies for Phenylketonuria |
| US20250161466A1 (en) | 2023-11-17 | 2025-05-22 | Biomarin Pharmaceutical Inc. | Conjugates of phenylalanine ammonia-lyase and poegma and methods for their use |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5753487A (en) * | 1993-06-25 | 1998-05-19 | Novo Nordisk A/S | Stabilised phenylalanine ammonia lyase |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4252822A (en) * | 1979-12-26 | 1981-02-24 | Children's Hospital Medical Center | Method for treating phenylketonuria |
| US4562151A (en) * | 1983-09-06 | 1985-12-31 | Monsanto Company | Stabilization of L-phenylalanine ammonia-lyase enzyme |
| US5206344A (en) * | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| US5766897A (en) * | 1990-06-21 | 1998-06-16 | Incyte Pharmaceuticals, Inc. | Cysteine-pegylated proteins |
| US5212939A (en) * | 1991-12-04 | 1993-05-25 | Pratt Jr John M | Marine mooring swivel fitting |
| DE69334292D1 (de) * | 1992-11-19 | 2009-10-08 | Anticancer Inc | Verwendung von Methioninase als Antitumormittel in der Antimethionin-chemotherapie |
| CA2149922C (en) | 1992-12-04 | 2007-05-15 | Thomas W. Macallister | Genetically engineered glutaminase and its use in antiviral and anticancer therapy |
| KR0164757B1 (ko) * | 1995-06-13 | 1999-01-15 | 김광호 | 공조장치의 살균집진장치와 그 방법 |
| EP0851925B1 (en) * | 1995-09-21 | 2005-08-03 | Genentech, Inc. | Human growth hormone variants |
| CU22585A1 (es) * | 1995-11-17 | 1999-11-03 | Centro Inmunologia Molecular | Anticuerpos monoclonales antiidiótipos (ab2) de tipo igg con alta conectividad idiotípica y composiciones farmacéuticas que los contienen. su uso como inmunoreguladores de la respuesta inmune. |
| US6548644B1 (en) * | 1997-03-10 | 2003-04-15 | Immunex Corporation | Site protected protein modification |
| US6183738B1 (en) * | 1997-05-12 | 2001-02-06 | Phoenix Pharamacologics, Inc. | Modified arginine deiminase |
| US5981239A (en) * | 1997-09-24 | 1999-11-09 | Great Lakes Chemical Corp. | Synthesis of optically active phenylalanine analogs using Rhodotorula graminis |
| US6451986B1 (en) * | 1998-06-22 | 2002-09-17 | Immunex Corporation | Site specific protein modification |
| US6461849B1 (en) | 1998-10-13 | 2002-10-08 | Novozymes, A/S | Modified polypeptide |
| US6686164B1 (en) | 1998-10-30 | 2004-02-03 | Novozymes A/S | Low allergenic protein variants |
| IL138990A0 (en) | 1999-02-12 | 2001-11-25 | Biostream Inc | Matrices for drug delivery and methods for making and using the same |
| US6586398B1 (en) * | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
| AU2001257032A1 (en) * | 2000-04-14 | 2001-10-30 | University Of South Carolina Research Foundation | Cloning, overexpression and therapeutic uses of bioactive histidine ammonia lyase |
| US6967097B2 (en) * | 2000-07-24 | 2005-11-22 | Pcbu Services, Inc. | Phenylalainine ammonia lyase polypeptide and polynucleotide sequences and methods of obtaining and using same |
| US6939941B2 (en) * | 2001-09-12 | 2005-09-06 | Toray Fine Chemicals Co., Ltd. | Preparation of polysulfide compositions |
| DE60323607D1 (de) | 2002-02-26 | 2008-10-30 | Du Pont | Verfahren zur rekombination genetischer elemente |
| CA2506026A1 (en) | 2002-11-14 | 2004-05-27 | The Scripps Research Institute | Crystalline form of fatty acid amine hydrolase (faah) |
| CA2580679A1 (en) | 2004-09-17 | 2006-03-30 | Biomarin Pharmaceutical Inc. | Variants and chemically-modified variants of phenylalanine ammonia-lyase |
| CA2614769A1 (en) * | 2005-03-10 | 2006-09-21 | Verenium Corporation | Lyase enzymes, nucleic acids encoding them and methods for making and using them |
| US7531341B1 (en) | 2006-06-12 | 2009-05-12 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof |
| US7534595B2 (en) | 2006-06-12 | 2009-05-19 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof |
| DE102006032167B4 (de) | 2006-07-12 | 2014-11-27 | Evonik Degussa Gmbh | Verfahren zur Herstellung von Triallylisocyanurat (TAIC) |
| WO2008069958A2 (en) | 2006-12-01 | 2008-06-12 | The Salk Institute For Biological Studies | Substrate switched ammonia lyases and mutases |
| US7537923B2 (en) | 2007-08-17 | 2009-05-26 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of treating cancer using compositions thereof |
| US20110201022A1 (en) | 2008-07-30 | 2011-08-18 | Biomarin Pharmaceutical Inc. | Assays for detection of phenylalanine ammonia-lyase and antibodies to phenylalanine ammonia-lyase |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5753487A (en) * | 1993-06-25 | 1998-05-19 | Novo Nordisk A/S | Stabilised phenylalanine ammonia lyase |
Non-Patent Citations (1)
| Title |
|---|
| MOFFITT M.c. et al, Discovery of two cyanobacterial phenylalanine ammonia lyases: kinetic and structural characterization, Biochemistry, 2007,Jan.30, 46(4), 1004-12. US20040127417 a1, 01.07.2004. * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2815197C2 (ru) * | 2019-02-14 | 2024-03-12 | Сом Инновейшн Биотек, С.А. | Триамтерен или нолатрексед для применения в лечении фенилкетонурии |
| US12257253B2 (en) | 2019-02-14 | 2025-03-25 | Som Innovation Biotech, S.A. | Triamterene or nolatrexed for use in the treatment of phenylketonuria |
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