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1. KR1020190029684 - 고체-상 고정화된 미생물 트랜스글루타미나제 MTG 및 용액 중 MTG를 사용한 항체 리신 잔기에의 부위-특이적 접합

Office Republic of Korea
Application Number 1020197004547
Application Date 11.07.2017
Publication Number 1020190029684
Publication Date 20.03.2019
Grant Number 102138195
Grant Date 28.07.2020
Publication Kind B1
IPC
C12N 11/08
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
11Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
02Enzymes or microbial cells immobilised on or in an organic carrier
08the carrier being a synthetic polymer
C12N 9/10
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12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
9Enzymes, e.g. ligases (6.); Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating, or purifying enzymes
10Transferases (2.)
CPC
C12N 11/08
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
11Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
02Enzymes or microbial cells immobilised on or in an organic carrier
08the carrier being a synthetic polymer
A61K 47/64
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
50the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
51the non-active ingredient being a modifying agent
62the modifying agent being a protein, peptide or polyamino acid
64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/6803
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
50the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
51the non-active ingredient being a modifying agent
68the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
C12N 9/1044
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12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
9Enzymes; Proenzymes; Compositions thereof
10Transferases (2.)
1025Acyltransferases (2.3)
104Aminoacyltransferases (2.3.2)
1044Protein-glutamine gamma-glutamyltransferase (2.3.2.13), i.e. transglutaminase or factor XIII
C12Y 203/02013
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12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
YENZYMES
203Acyltransferases (2.3)
02Aminoacyltransferases (2.3.2)
02013Protein-glutamine gamma-glutamyltransferase (2.3.2.13), i.e. transglutaminase or factor XIII
Applicants 폴 슈레 앙스띠뛰
Inventors 스파이체르, 필립 레네
베헤, 마틴
쉬블리, 로저
후르비츠, 데이비드
크라이스, 올리비에
Agents 양영준
김영
Priority Data 16180382 20.07.2016 EP
Title
(KO) 고체-상 고정화된 미생물 트랜스글루타미나제 MTG 및 용액 중 MTG를 사용한 항체 리신 잔기에의 부위-특이적 접합
Abstract
(KO)
미생물 트랜스글루타미나제 (MTG)를 사용한 단백질의 부위-특이적 변형은 생리학적 조건 하에서 제어된 방식으로 단백질을 변형시킬 수 있는 강력한 다용도 전략법이다. 본 발명자들은 scFV, Fab-단편 및 항체를 포함한, 치료 관련 단백질에 추가의 하류 적용에 중요한 상이한 관능성 분자를 부위-특이적으로 및 효율적으로 부착시키는데 고체-상 마이크로비드 고정화가 사용될 수 있다는 증거를 제공한다. 본 발명자들은 MTG는 검출가능한 칼럼 블리딩 없이, 단단히 고정화된 상태 그대로 유지되었고, 효소 활성은 연속 조작 동안 그대로 지속되었고, 이를 통해, 효소는 편리하게 재사용될 수 있었는 바, 이에, 용액-상 MTG 접합을 넘어서서 그보다 우수하다는 것을 증명한다. 추가적으로, 고정화된 MTG는, 접합이 용액 중에서 수행되었다면, 모두가 표적화되는 수개의 반응성 잔기의 존재 하에 특정 잔기에 대하여 증진된 선택성을 보인다는 것을 제시한다. 고정화된 MTG 및 용액 중 MTG를 사용한, 강력한 글루타민 함유 펩티드를 사용하는 항체의 부위-특이적 리신 접합을 또한 보고한다. 추가적으로, 고정화된 MTG 및 용액 중 MTG를 사용한, 이중 부위-특이적으로 접합된 IgG1의 생성, 즉, IgG1 항체의 글루타민 및 리신 잔기에의 부위-특이적 접합을 보고한다. 리신 잔기 및 관능성 모이어티를 함유하는 소형 펩티드와의 부위-특이적 글루타민 접합을 또한 기술한다.