DK2638152T3 - Variante, rekombinante beta-glucocerebrosidase-proteiner med forøget stabilitet og forøget bevaret katalytisk aktivitet - Google Patents
Variante, rekombinante beta-glucocerebrosidase-proteiner med forøget stabilitet og forøget bevaret katalytisk aktivitet Download PDFInfo
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- DK2638152T3 DK2638152T3 DK11839428.7T DK11839428T DK2638152T3 DK 2638152 T3 DK2638152 T3 DK 2638152T3 DK 11839428 T DK11839428 T DK 11839428T DK 2638152 T3 DK2638152 T3 DK 2638152T3
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- 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
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
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- A61K38/46—Hydrolases (3)
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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Claims (15)
1. Variant, rekombinant humant β-glucocerebrosidase-protein, der har en mutation, der er udvalgt blandt: F316A og L317F; H145L; H145F; H145L, F316A og L317F; K321A; og K321V; i forhold til aminosyresekvensen ifølge SEQ ID NO: 1.
2. Variant, rekombinant humant β-glucocerebrosidase-protein ifølge krav 1, der omfatter mutationen F316A og L317F; eller H145L; og yderligere omfatter en mutation udvalgt blandt K321N, K321A og K321V, hvor mutationerne er i forhold til aminosyresekvensen ifølge SEQ ID NO: 1.
3. Variant, rekombinant humant β-glucocerebrosidase-protein ifølge krav 1 eller krav 2, der har aminosyresekvensen ifølge SEQ ID NO: 2 eller en hvilken som helst af SEQ ID NO: 4 til 16.
4. Variant, rekombinant humant β-glucocerebrosidase-protein ifølge et hvilket som helst af kravene 1 til 3, der er kendetegnet ved at have forøget stabilitet i forhold til vildtype, rekombinant β-glucocerebrosidase.
5. Variant, rekombinant humant β-glucocerebrosidase-protein ifølge krav 4, hvor den forøgede stabilitet er ved fysiologiske betingelser.
6. Variant, rekombinant humant β-glucocerebrosidase-protein ifølge krav 4, hvor den forøgede stabilitet er ved betingelser med neutralt pH og 37 °C.
7. Variant, rekombinant humant β-glucocerebrosidase-protein ifølge et hvilket som helst af kravene 1 til 3, der er kendetegnet ved at have en forlænget tilsyneladende halveringstid, der er mindst 2 gange længere end for vildtype, rekombinant β-glucocerebrosidase.
8. Variant, rekombinant humant β-glucocerebrosidase-protein ifølge krav 7, hvor den forlængede tilsyneladende halveringstid er målt efter inkubation ved betingelser med neutralt pH og 37 °C i et tidsrum på tre timer.
9. Variant, rekombinant humant β-glucocerebrosidase-protein ifølge et hvilket som helst af kravene 1 til 3, der er kendetegnet ved at bevare forøget katalytisk aktivitet i forhold til vildtype, rekombinant β-glucocerebrosidase.
10. Variant, rekombinant humant β-glucocerebrosidase-protein ifølge krav 9, hvor den forøgede katalytiske aktivitet er målt efter inkubation ved betingelser med neutralt pH og 37 °C i et tidsrum på tre timer.
11. Variant, rekombinant humant β-glucocerebrosidase-protein ifølge krav 9, hvor den forøgede katalytiske aktivitet bevares ved fysiologiske betingelser.
12. Sammensætning, der omfatter det variante, rekombinante humane β-glucocerebrosidase-protein ifølge et hvilket som helst af ovennævnte krav og et farmaceutisk acceptabelt bæremateriale.
13. Sammensætning, der omfatter det variante, rekombinante humane β-glucocerebrosidase-protein ifølge et hvilket som helst af kravene 1 til 11 og en farmaceutisk acceptabel buffer.
14. Variant, rekombinant β-glucocerebrosidase-protein ifølge et hvilket som helst af kravene 1 til 11 til anvendelse til behandling af en lysosomal aflejringssygdom.
15. Variant, rekombinant humant β-glucocerebrosidase-protein til anvendelse ifølge krav 14, hvor den lysosomale aflejringssygdom er Gauchers sygdom.
Applications Claiming Priority (3)
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| US41133110P | 2010-11-08 | 2010-11-08 | |
| US41218010P | 2010-11-10 | 2010-11-10 | |
| PCT/US2011/059731 WO2012064709A2 (en) | 2010-11-08 | 2011-11-08 | Variant, recombinant beta-glucocerebrosidase proteins with increased stability and increased retained catalytic activity |
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| DK2638152T3 true DK2638152T3 (da) | 2016-12-12 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20220125892A1 (en) * | 2019-02-01 | 2022-04-28 | OXYRANE UK Ltd. | Glucocerebrosidase polypeptides |
| KR20210148101A (ko) | 2019-02-04 | 2021-12-07 | 프리라인 테라퓨틱스 리미티드 | 폴리뉴클레오티드 |
| EP4028048A1 (en) * | 2019-09-09 | 2022-07-20 | F. Hoffmann-La Roche AG | Glucocerebrosidase mutants |
| CN115348884B (zh) * | 2020-03-29 | 2024-07-30 | 耶达研究及发展有限公司 | 用于治疗戈谢病的β-葡糖脑苷脂酶变体 |
| KR20230042513A (ko) * | 2020-07-29 | 2023-03-28 | 프리라인 테라퓨틱스 리미티드 | 폴리펩티드 |
| WO2023145812A1 (ja) * | 2022-01-31 | 2023-08-03 | 株式会社日本触媒 | グルコセレブロシダーゼ活性を有する糖鎖付加タンパク質 |
| JPWO2023145814A1 (da) * | 2022-01-31 | 2023-08-03 | ||
| WO2023145813A1 (ja) * | 2022-01-31 | 2023-08-03 | 株式会社日本触媒 | グルコセレブロシダーゼ活性を有するタンパク質およびその製造方法 |
| EP4508206A1 (en) | 2022-04-12 | 2025-02-19 | F. Hoffmann-La Roche AG | Fusion proteins targeted to the central nervous system |
| CN118715316B (zh) * | 2022-10-08 | 2025-09-19 | 凌意(杭州)生物科技有限公司 | 用于治疗GCase缺乏相关疾病的多核苷酸 |
| TW202532096A (zh) * | 2023-12-08 | 2025-08-16 | 美商戴納立製藥公司 | 經修飾之葡萄糖腦苷脂酶多肽及其使用方法 |
| WO2026006173A1 (en) * | 2024-06-24 | 2026-01-02 | Denali Therapeutics Inc. | Fusion proteins comprising modified glucocerebrosidase polypeptides and methods thereof |
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| JPH03503721A (ja) * | 1988-12-23 | 1991-08-22 | ジェンザイム コーポレイション | 酵素的に活性な組換えグルコセレブロシダーゼ |
| DE68926569T2 (de) | 1988-12-23 | 1996-09-26 | Genzyme Corp | Cho-zellen befähigt enzymatisch aktive rekombinante-glukocerebrosidase zu produzieren |
| EP0979311A1 (en) | 1997-04-30 | 2000-02-16 | Of The University Of Minnesota Regents | $i(IN VIVO) USE OF RECOMBINAGENIC OLIGONUCLEOBASES TO CORRECT GENETIC LESIONS IN HEPATOCYTES |
| US6524613B1 (en) | 1997-04-30 | 2003-02-25 | Regents Of The University Of Minnesota | Hepatocellular chimeraplasty |
| IL135578A0 (en) | 1997-10-29 | 2001-05-20 | Genzyme Corp | Compositions and methods for treating lysosomal storage disease |
| WO2000012740A2 (en) | 1998-08-28 | 2000-03-09 | Duke University | ADENOVIRUSES DELETED IN THE IVa2, 100K AND/OR PRETERMINAL PROTEIN SEQUENCES |
| US20020127219A1 (en) | 1999-12-30 | 2002-09-12 | Okkels Jens Sigurd | Lysosomal enzymes and lysosomal enzyme activators |
| AU2352201A (en) | 1999-12-30 | 2001-07-16 | Maxygen Aps | Improved lysosomal enzymes and lysosomal enzyme activators |
| WO2001077307A2 (en) | 2000-04-06 | 2001-10-18 | Exegenics, Inc. | Expression system for efficiently producing clinically effective lysosomal enzymes (glucocerebrosidase) |
| CA2412882A1 (en) * | 2000-06-30 | 2002-01-10 | Maxygen Aps | Peptide extended glycosylated polypeptides |
| US7855063B2 (en) * | 2003-04-16 | 2010-12-21 | Yeda Research And Development Co. Ltd. | Partially deglycosylated glucocerebrosidase polypeptide and crystals thereof |
| WO2005089047A2 (en) | 2004-03-18 | 2005-09-29 | Glycofi, Inc. | Glycosylated glucocerebrosidase expression in fungal hosts |
| MX2009011473A (es) * | 2007-04-26 | 2010-01-18 | Amicus Therapeutics Inc | Regimenes de dosificacion para el tratamiento de enfermedades por almacenamiento lisosomal que utilizan chaperonas farmacologicas. |
| CA2688850C (en) * | 2007-05-22 | 2015-08-11 | Amicus Therapeutics, Inc. | New method for preparing isofagomine and its derivatives |
| JP5513398B2 (ja) | 2007-11-02 | 2014-06-04 | ザ スクリプス リサーチ インスティチュート | 非天然アミノ酸を含有する蛋白質を使用する指向的進化 |
| WO2009059056A2 (en) | 2007-11-02 | 2009-05-07 | The Scripps Research Institute | A genetically encoded boronate amino acid |
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