DK2576776T3 - Modificerede beta-lactamaser og fremgangsmåder og anvendelser relateret dertil - Google Patents
Modificerede beta-lactamaser og fremgangsmåder og anvendelser relateret dertil Download PDFInfo
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- DK2576776T3 DK2576776T3 DK11786185.6T DK11786185T DK2576776T3 DK 2576776 T3 DK2576776 T3 DK 2576776T3 DK 11786185 T DK11786185 T DK 11786185T DK 2576776 T3 DK2576776 T3 DK 2576776T3
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- beta
- lactamase
- amino acid
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- 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)
- C12N9/86—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in cyclic amides, e.g. penicillinase (3.5.2)
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
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- 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)
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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
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4891—Coated capsules; Multilayered drug free capsule shells
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
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- C12N1/00—Microorganisms; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
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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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- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
- C12N15/75—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for Bacillus
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- C12Y305/02—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in cyclic amides (3.5.2)
- C12Y305/02006—Beta-lactamase (3.5.2.6)
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Claims (18)
1. Beta-lactamase, der omfatter en aminosyresekvens, der er mindst 80 % sekvensidentisk med SEQ ID NO: 1, kendetegnet ved, at beta-lactamasen har en hydrofil aminosyrerest, der ikke er en asparaginsyre (D), i en position svarende til position 276 ifølge Ambler-klassifikationen og den hydrofile aminosyre er udvalgt fra arginin (R), histidin (H), lysin (K), asparagin (N), glutamin (Q), serin (S) og threonin (T), og hydrolyserer penicilliner og/eller cephalosporiner.
2. Fremgangsmåde til modificering af en beta-lactamase, der omfatter en aminosyresekvens, der er mindst 80 % sekvensidentisk med SEQ ID NO: 1, kendetegnet ved, at en aminosyre af beta-lactamasen ved en position af SEQ ID NO: 1 svarende til position 276 ifølge Ambler-klassifikationen er erstattet med en hydrofil aminosyre, der ikke er en asparaginsyre (D), og den hydrofile aminosyre er udvalgt fra arginin (R), histidin (H), lysin (K), asparagin (N), glutamin (Q), serin (S), og threonin (T) for at opnå en beta-lactamase, der hydrolyserer penicilliner og/eller cephalosporiner.
3. Beta-lactamase ifølge krav 1, hvor beta-lactamasen omfatter en aminosyresekvens, der er mindst 90 % sekvensidentisk med SEQ ID NO: 1.
4. Beta-lactamase ifølge krav 1 eller fremgangsmåde ifølge krav 2 kendetegnet ved, at aminosyren i positionen SEQ ID NO: 1 svarende til position 276 er asparagin (N).
5. Beta-lactamase ifølge krav 1 eller fremgangsmåde ifølge krav 2 kendetegnet ved, at aminosyren i positionen af SEQ ID NO: 1 svarende til position 276 er arginin (R).
6. Beta-lactamase eller fremgangsmåde ifølge et hvilket som helst af de foregående krav kendetegnet ved, at den hydrofile aminosyre ved position af SEQ ID NO: 1 svarende til position 276 befinder sig i en alpha-helix.
7. Beta-lactamase eller fremgangsmåde ifølge et hvilket som helst af de foregående krav kendetegnet ved, at beta-lactamasen endvidere omfatter mindst én aminosyre, der er udvalgt fra gruppen bestående af Leu220 og Arg244 ifølge Ambler-klassifikationen.
8. Beta-lactamase eller fremgangsmåde ifølge et hvilket som helst af de foregående krav kendetegnet ved, at beta-lactamasen har forbedret katalytisk effektivitet på cephalosporiner sammenlignet med beta-lactamasen af SEQ ID NO: 1, der har asparaginsyre (D) ved positionen svarende til position 276 ifølge Amber-klassifikationen.
9. Beta-lactamase ifølge krav 1 eller fremgangsmåde ifølge krav 2 kendetegnet ved, at cephalosporinerne er udvalgt fra gruppen bestående af cefoperazon, ceftriaxon og cefazolin.
10. Fremgangsmåde til fremstilling af beta-lactamasen ifølge et hvilket som helst af kravene 1 eller 3-9 kendetegnet ved, at fremgangsmåden omfatter følgende trin: i) tilvejebringelse af et gen, der koder for beta-lactamasen ifølge et hvilket som helst af kravene 1 eller 3-9; ii) transformering af en værtscelle med genet; iii) opnåelse af en værtscelle, der fremstiller beta-lactamasen; iv) indvinding af beta-lactamasen.
11. Polynukleotid kendetegnet ved, at det omfatter en sekvens ifølge et hvilket som helst af SEQ ID NO: 2 eller 4 eller en degenereret variant deraf, eller det koder for beta-lactamasen ifølge et hvilket som helst af kravene 1 eller 3-9.
12. Værtscelle, der omfatter polynukleotidet ifølge krav 11.
13. Farmaceutisk sammensætning, der omfatter beta-lactamasen ifølge et hvilket som helst af kravene 1 eller 3-9.
14. Beta-lactamase ifølge et hvilket som helst af kravene 1 eller 3-9 til anvendelse som et medikament.
15. Anvendelse af beta-lactamasen ifølge et hvilket som helst af kravene 1 eller 3-9 til fremstilling af et medikament til behandling eller forebyggelse af beta-lactam-antibiotikainducerede bivirkninger i fordøjelseskanalen.
16. Anvendelse ifølge krav 15 kendetegnet ved, at beta-lactamase(r) administreres oralt.
17. Anvendelse ifølge krav 15 kendetegnet ved, at beta-lactamase(r) administreres direkte til en patients fordøjelseskanal.
18. Anvendelse ifølge et hvilket som helst af kravene 15-17 kendetegnet ved, at beta-lactamase(r) og beta-lactam-antibiotika administreres sammen i form af en syreresistent pille til et individ.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI20105572A FI20105572A0 (fi) | 2010-05-24 | 2010-05-24 | Muokattu beeta-laktamaasi ja siihen liittyvät menetelmät ja käytöt |
| PCT/FI2011/050450 WO2011148041A1 (en) | 2010-05-24 | 2011-05-17 | Modified beta-lactamases and methods and uses related thereto |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2576776T3 true DK2576776T3 (da) | 2016-10-03 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK11786185.6T DK2576776T3 (da) | 2010-05-24 | 2011-05-17 | Modificerede beta-lactamaser og fremgangsmåder og anvendelser relateret dertil |
Country Status (16)
| Country | Link |
|---|---|
| US (11) | US9034602B2 (da) |
| EP (1) | EP2576776B1 (da) |
| JP (1) | JP5827681B2 (da) |
| KR (1) | KR101708703B1 (da) |
| CN (1) | CN103038341B (da) |
| AU (1) | AU2011257092C1 (da) |
| BR (1) | BR112012030029B1 (da) |
| CA (1) | CA2800671C (da) |
| DK (1) | DK2576776T3 (da) |
| ES (1) | ES2588279T3 (da) |
| FI (1) | FI20105572A0 (da) |
| HU (1) | HUE030689T2 (da) |
| PL (1) | PL2576776T3 (da) |
| RU (1) | RU2570551C2 (da) |
| WO (1) | WO2011148041A1 (da) |
| ZA (1) | ZA201208948B (da) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8992422B2 (en) | 2006-03-23 | 2015-03-31 | Ethicon Endo-Surgery, Inc. | Robotically-controlled endoscopic accessory channel |
| FI20105572A0 (fi) | 2010-05-24 | 2010-05-24 | Prevab R Lcc | Muokattu beeta-laktamaasi ja siihen liittyvät menetelmät ja käytöt |
| BR112016023360B1 (pt) * | 2014-04-17 | 2023-03-07 | Synthetic Biologics, Inc | Beta-lactamase e seu uso |
| JP6803328B2 (ja) | 2014-08-28 | 2021-01-06 | シンセティック バイオロジクス,インコーポレイテッド | 大腸菌ベースでのベータラクタマーゼ生産 |
| WO2016057744A1 (en) | 2014-10-08 | 2016-04-14 | Synthetic Biologics, Inc. | Beta-lactamase formulations and uses thereof |
| FR3027307B1 (fr) * | 2014-10-16 | 2016-11-04 | Azurrx Sas | Molecule proteique hybride apte a inhiber au moins un antibiotique et composition pharmaceutique la comportant |
| EP3236993B1 (en) | 2014-12-23 | 2023-09-13 | Theriva Biologics, Inc. | Methods and compositions for inhibiting or preventing adverse effects of oral antibiotics |
| EP3261662B1 (en) | 2015-02-23 | 2021-07-21 | Synthetic Biologics Inc. | Carbapenemases for use with antibiotics for the protection of the intestinal microbiome |
| EP3265119B1 (en) | 2015-03-06 | 2023-10-11 | Theriva Biologics, Inc. | Safe and effective beta-lactamase dosing for microbiome protection |
| JP6845258B6 (ja) * | 2016-02-23 | 2021-04-28 | ダ・ボルテラ | ベータ−ラクタマーゼ変異体 |
| US11185555B2 (en) | 2016-04-11 | 2021-11-30 | Noah James Harrison | Method to kill pathogenic microbes in a patient |
| CN109562147B (zh) * | 2016-06-28 | 2023-09-01 | 特里瓦生物制剂有限公司 | 保护微生物组免受口服抗生素 |
| US20190275120A1 (en) * | 2016-11-01 | 2019-09-12 | Synthetic Biologics, Inc. | Methods and compositions for attenuating antibiotic resistance |
| CN110157699B (zh) * | 2018-02-12 | 2021-07-23 | 中国科学院微生物研究所 | β-内酰胺酶及其编码基因以及它们的应用 |
| US20210290741A1 (en) | 2018-08-05 | 2021-09-23 | Da Volterra | Compositions for the treatment of graft versus host disease |
| AU2019317986A1 (en) | 2018-08-05 | 2021-02-11 | Da Volterra | Method for improving anticancer agent efficacy |
| CN110777178A (zh) * | 2019-12-02 | 2020-02-11 | 河北慧林生物科技有限公司 | 固定化羧基酯水解酶在氯唑西林、双氯西林、氟氯西林及苯唑西林侧链合成中的应用 |
| CN114075560A (zh) * | 2020-08-18 | 2022-02-22 | 杭州俊丰生物工程有限公司 | 一种β-内酰胺酶的稳定组合物 |
| EP4148136A1 (en) | 2021-09-08 | 2023-03-15 | Da Volterra | An engineered yeast cell for the delivery of antibiotic-inactivating enzymes |
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| US7323303B2 (en) * | 2003-03-31 | 2008-01-29 | Hong Kong Polytechnic University | Modified β-lactamases and uses thereof |
| EP1564286A1 (en) | 2004-02-11 | 2005-08-17 | Université de Liège | Hybrid proteins of beta-lactamase class A |
| IL163821A0 (en) * | 2004-08-31 | 2005-12-18 | Ravgalai Ltd Rapax Consortium | Software for management of legal motions Methods and kits for the detection of biotoxic andantibiotic residues |
| ES2429095T3 (es) | 2005-05-18 | 2013-11-13 | Da Volterra | Aporte colónico de adsorbentes |
| FI119190B (fi) | 2006-06-21 | 2008-08-29 | Ipsat Therapies Oy | Modifioitu beta-laktamaasi ja menetelmä sen valmistamiseksi |
| FI119678B (fi) | 2006-11-28 | 2009-02-13 | Ipsat Therapies Oy | Beta-laktamaasin käyttö |
| FI20105572A0 (fi) | 2010-05-24 | 2010-05-24 | Prevab R Lcc | Muokattu beeta-laktamaasi ja siihen liittyvät menetelmät ja käytöt |
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2010
- 2010-05-24 FI FI20105572A patent/FI20105572A0/fi not_active Application Discontinuation
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2011
- 2011-05-17 CN CN201180035810.5A patent/CN103038341B/zh active Active
- 2011-05-17 KR KR1020127033615A patent/KR101708703B1/ko active Active
- 2011-05-17 AU AU2011257092A patent/AU2011257092C1/en active Active
- 2011-05-17 DK DK11786185.6T patent/DK2576776T3/da active
- 2011-05-17 CA CA2800671A patent/CA2800671C/en active Active
- 2011-05-17 US US13/699,434 patent/US9034602B2/en active Active
- 2011-05-17 BR BR112012030029-6A patent/BR112012030029B1/pt active IP Right Grant
- 2011-05-17 HU HUE11786185A patent/HUE030689T2/en unknown
- 2011-05-17 EP EP11786185.6A patent/EP2576776B1/en active Active
- 2011-05-17 PL PL11786185T patent/PL2576776T3/pl unknown
- 2011-05-17 ES ES11786185.6T patent/ES2588279T3/es active Active
- 2011-05-17 JP JP2013511709A patent/JP5827681B2/ja active Active
- 2011-05-17 RU RU2012155420/10A patent/RU2570551C2/ru not_active IP Right Cessation
- 2011-05-17 WO PCT/FI2011/050450 patent/WO2011148041A1/en not_active Ceased
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2012
- 2012-11-27 ZA ZA2012/08948A patent/ZA201208948B/en unknown
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2013
- 2013-10-07 US US14/047,882 patent/US8894994B2/en active Active
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2014
- 2014-10-17 US US14/517,539 patent/US9301995B2/en active Active
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2015
- 2015-04-01 US US14/676,559 patent/US9301996B2/en active Active
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2016
- 2016-02-26 US US15/054,292 patent/US9587234B2/en active Active
- 2016-04-26 US US15/138,767 patent/US9765320B2/en active Active
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2017
- 2017-01-27 US US15/417,501 patent/US10041056B2/en active Active
- 2017-07-27 US US15/661,416 patent/US10253306B2/en active Active
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2019
- 2019-02-19 US US16/279,547 patent/US11214787B2/en active Active
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2021
- 2021-11-23 US US17/533,739 patent/US20220090044A1/en not_active Abandoned
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2023
- 2023-05-10 US US18/315,122 patent/US20230332128A1/en not_active Abandoned
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