DE69832993T2 - Arginin deiminase aus mycoplasma arthirtidis und sie enthaltende polymerkonjugate - Google Patents
Arginin deiminase aus mycoplasma arthirtidis und sie enthaltende polymerkonjugate Download PDFInfo
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- DE69832993T2 DE69832993T2 DE69832993T DE69832993T DE69832993T2 DE 69832993 T2 DE69832993 T2 DE 69832993T2 DE 69832993 T DE69832993 T DE 69832993T DE 69832993 T DE69832993 T DE 69832993T DE 69832993 T2 DE69832993 T2 DE 69832993T2
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- Prior art keywords
- arginine deiminase
- antigenic polymer
- adi
- seq
- polymer
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/50—Hydrolases (3) acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
-
- 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
- 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
- C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
- C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
- C12N11/10—Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a carbohydrate
-
- 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
- C12N9/14—Hydrolases (3)
- C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US792283 | 1991-11-14 | ||
| US08/792,283 US5804183A (en) | 1997-01-31 | 1997-01-31 | Arginine deminase derived from mycoplasma arthritidis and polymer conjugates containing the same |
| PCT/US1998/001635 WO1998033519A1 (en) | 1997-01-31 | 1998-01-27 | Arginine deiminase derived from mycoplasma arthritidis and polymer conjugates containing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69832993D1 DE69832993D1 (de) | 2006-02-02 |
| DE69832993T2 true DE69832993T2 (de) | 2006-09-07 |
Family
ID=25156365
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69832993T Expired - Lifetime DE69832993T2 (de) | 1997-01-31 | 1998-01-27 | Arginin deiminase aus mycoplasma arthirtidis und sie enthaltende polymerkonjugate |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US5804183A (https=) |
| EP (1) | EP1011717B1 (https=) |
| JP (1) | JP4126097B2 (https=) |
| AT (1) | ATE314086T1 (https=) |
| AU (1) | AU6047598A (https=) |
| DE (1) | DE69832993T2 (https=) |
| DK (1) | DK1011717T3 (https=) |
| ES (1) | ES2255147T3 (https=) |
| WO (1) | WO1998033519A1 (https=) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6635462B1 (en) * | 1997-05-12 | 2003-10-21 | Phoenix Pharmacologies, Inc. | Mutated form of arginine deiminase |
| US6183738B1 (en) * | 1997-05-12 | 2001-02-06 | Phoenix Pharamacologics, Inc. | Modified arginine deiminase |
| KR20040004449A (ko) * | 2000-11-28 | 2004-01-13 | 휘닉스 파머컬러직스, 인크. | 변형된 아르기닌 데이미나제 |
| US6645739B2 (en) * | 2001-07-26 | 2003-11-11 | Phoenix Pharmacologies, Inc. | Yeast expression systems, methods of producing polypeptides in yeast, and compositions relating to same |
| US8129330B2 (en) | 2002-09-30 | 2012-03-06 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
| US20040062748A1 (en) | 2002-09-30 | 2004-04-01 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
| WO2004046309A2 (en) * | 2002-11-18 | 2004-06-03 | Phoenix Pharmacologics, Inc. | Methods for inhibiting viral replication in vivo |
| FR2884717B1 (fr) * | 2005-04-25 | 2009-07-03 | Erytech Pharma Soc Par Actions | Erythrocytes renfermant de l'arginine deiminase |
| US20080096819A1 (en) * | 2006-05-02 | 2008-04-24 | Allozyne, Inc. | Amino acid substituted molecules |
| JP5313129B2 (ja) | 2006-05-02 | 2013-10-09 | アロザイン， インコーポレイテッド | 非天然アミノ酸置換ポリペプチド |
| FR2919804B1 (fr) | 2007-08-08 | 2010-08-27 | Erytech Pharma | Composition et vaccin therapeutique anti-tumoral |
| JP2009044997A (ja) * | 2007-08-20 | 2009-03-05 | Sony Corp | ビリルビンオキシダーゼ（ｂｏｄ）の被覆方法 |
| CA2707840A1 (en) | 2007-08-20 | 2009-02-26 | Allozyne, Inc. | Amino acid substituted molecules |
| EP2295560A1 (en) | 2009-09-14 | 2011-03-16 | RWTH Aachen University | Directed evolution of arginine deiminase for increased activity at physiological pH |
| US9255262B2 (en) * | 2013-03-06 | 2016-02-09 | Vision Global Holdings Ltd. | Albumin-binding arginine deminase and the use thereof |
| USRE48805E1 (en) | 2013-03-06 | 2021-11-02 | Vision Global Holdings Ltd. | Method for cancer targeting treatment and detection of arginine using albumin-binding arginine deiminase fusion protein |
| WO2014151982A2 (en) | 2013-03-15 | 2014-09-25 | Polaris Group | Arginine deiminase with reduced cross-reactivity toward adi – peg 20 antibodies for cancer treatment |
| WO2015143006A1 (en) * | 2014-03-18 | 2015-09-24 | Tdw Group | Engineered chimeric pegylated adi and methods of use |
| EP4104853B1 (en) | 2014-09-16 | 2026-05-06 | Polaris Group | Arginine deiminase with reduced cross-reactivity toward adi - peg 20 antibodies for cancer treatment |
| EP3344575B1 (en) | 2015-09-04 | 2020-04-15 | SQZ Biotechnologies Company | Intracellular delivery of biomolecules to cells comprising a cell wall |
| CA3023092A1 (en) | 2016-05-03 | 2017-11-09 | Sqz Biotechnologies Company | Intracellular delivery of biomolecules to induce tolerance |
| CN119950689A (zh) | 2016-07-05 | 2025-05-09 | 北极星药业集团股份有限公司 | 使用精氨酸耗竭剂的组合癌症免疫疗法 |
| TWI784982B (zh) | 2016-11-02 | 2022-12-01 | 開曼群島商北極星藥業集團股份有限公司 | 聚乙二醇化精胺酸脫亞胺酶之調配物 |
| KR20220150408A (ko) | 2016-11-14 | 2022-11-10 | 항저우 디에이씨 바이오테크 씨오, 엘티디 | 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용 |
| WO2018183671A1 (en) | 2017-03-29 | 2018-10-04 | Tdw Group | Protein conjugates |
| WO2019042628A1 (en) | 2017-08-31 | 2019-03-07 | Erytech Pharma | ARGININE DEIMINASE ENCAPSULATED WITHIN ERYTHROCYTES AND THEIR USE IN THE TREATMENT OF CANCER AND ARGINASE-1 DEFICIENCY |
| EP3449935A1 (en) | 2017-08-31 | 2019-03-06 | Erytech Pharma | Arginine deiminase encapsulated inside erythrocytes and their use in treating cancer and arginase-1 deficiency |
| KR20220053575A (ko) * | 2019-08-01 | 2022-04-29 | 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 | 항체 결합 및 중화 항체 억제를 위한 조성물 및 방법 |
| CA3128035A1 (en) | 2020-08-13 | 2022-02-13 | Bioasis Technologies, Inc. | Combination therapies for delivery across the blood brain barrier |
| EP4288445A1 (en) * | 2021-02-03 | 2023-12-13 | The University of North Carolina at Chapel Hill | Protein m analogs and fusion proteins and their use for inhibiting antibody function |
| EP4426727A2 (en) | 2021-11-03 | 2024-09-11 | Hangzhou Dac Biotech Co., Ltd. | Specific conjugation of an antibody |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPH0253490A (ja) * | 1988-08-16 | 1990-02-22 | Agency Of Ind Science & Technol | アルギニン・デイミナーゼ遺伝子 |
| US5122614A (en) * | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| JP2900279B2 (ja) * | 1989-08-02 | 1999-06-02 | 株式会社ジャパンエナジー | 新規なアルギニンデイミナーゼ、その製造法及び該酵素を有効成分とする制癌剤 |
| JP3209338B2 (ja) * | 1990-09-10 | 2001-09-17 | 株式会社ジャパンエナジー | ポリエチレングリコール修飾アルギニンデイミナーゼおよびその製造法 |
| US5372942A (en) * | 1992-02-10 | 1994-12-13 | Coriell Institute For Medical Research | Protease K resistant arginine deiminase, its method of preparation and its use as an anti-neoplastic agent |
| US5349001A (en) * | 1993-01-19 | 1994-09-20 | Enzon, Inc. | Cyclic imide thione activated polyalkylene oxides |
| US5359030A (en) * | 1993-05-10 | 1994-10-25 | Protein Delivery, Inc. | Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same |
-
1997
- 1997-01-31 US US08/792,283 patent/US5804183A/en not_active Expired - Lifetime
-
1998
- 1998-01-27 ES ES98903799T patent/ES2255147T3/es not_active Expired - Lifetime
- 1998-01-27 EP EP98903799A patent/EP1011717B1/en not_active Expired - Lifetime
- 1998-01-27 AT AT98903799T patent/ATE314086T1/de not_active IP Right Cessation
- 1998-01-27 WO PCT/US1998/001635 patent/WO1998033519A1/en not_active Ceased
- 1998-01-27 AU AU60475/98A patent/AU6047598A/en not_active Abandoned
- 1998-01-27 JP JP53303298A patent/JP4126097B2/ja not_active Expired - Fee Related
- 1998-01-27 DK DK98903799T patent/DK1011717T3/da active
- 1998-01-27 DE DE69832993T patent/DE69832993T2/de not_active Expired - Lifetime
- 1998-06-26 US US09/105,908 patent/US5916793A/en not_active Expired - Lifetime
-
1999
- 1999-03-18 US US09/271,713 patent/US6132713A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US5916793A (en) | 1999-06-29 |
| ATE314086T1 (de) | 2006-01-15 |
| DE69832993D1 (de) | 2006-02-02 |
| EP1011717B1 (en) | 2005-12-28 |
| EP1011717A1 (en) | 2000-06-28 |
| US6132713A (en) | 2000-10-17 |
| EP1011717A4 (en) | 2003-02-19 |
| JP4126097B2 (ja) | 2008-07-30 |
| ES2255147T3 (es) | 2006-06-16 |
| DK1011717T3 (da) | 2006-05-15 |
| JP2001512965A (ja) | 2001-08-28 |
| WO1998033519A1 (en) | 1998-08-06 |
| AU6047598A (en) | 1998-08-25 |
| US5804183A (en) | 1998-09-08 |
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