JP2018502068A - 可溶性ユニバーサルadcc増強合成融合遺伝子およびペプチド技術ならびにその使用 - Google Patents
可溶性ユニバーサルadcc増強合成融合遺伝子およびペプチド技術ならびにその使用 Download PDFInfo
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Abstract
Description
本出願は、2014年12月8日に出願された米国仮特許出願第62/089,097号、および2015年8月3日に出願された同第62/200,557号に対する優先権および利益を主張し、その両方は、その全体が本明細書に参考として援用される。
本発明は、免疫エフェクター細胞、特にT細胞、が抗体依存性細胞傷害性(ADCC)を媒介することを可能とするように使用され得る合成生物学的生成物およびプロセス、ならびにがん、感染性疾患、炎症性および自己免疫疾患ならびに他の疾患の処置および防止においてそれらを使用するための方法に関する。
哺乳動物、特に高等脊椎動物(ヒトを含む)は、複数の機構およびエフェクターを使用して、外来病原体ならびに罹病したかもしくはストレスを受けた自己由来細胞を検出、破壊もしくは少なくとも封じ込める、非常に複雑な免疫系を発達させた。これらの罹病細胞は、ウイルスもしくは細菌によって感染した可能性があるか、またはがんになった可能性がある。
本発明により新たなアプローチがもたらされ、がん、感染および他の疾患に対する免疫系の防御が改善される。本発明は、T細胞の細胞傷害性および増殖ポテンシャルを抗体に基づく治療法に結び付ける、新規の自由に会合する(free−associating)アダプター様ADCCエンハンサーを考案する。
(I.定義)
別段示されなければ、技術用語は、従来の使用法に従って使用される。分子生物学における一般用語の定義は、例えば、Benjamin Lewin, Genes VII,Oxford University Pressにより出版,2000 (ISBN
019879276X); Kendrew et al.(編); The Encyclopedia of Molecular Biology,Blackwell
Publishersにより出版,1994 (ISBN 0632021829);およびRobert A. Meyers(編), Molecular Biology and Biotechnology: a Comprehensive Desk Reference,Wiley, John & Sons, Inc.により出版, 1995(ISBN 0471186341);ならびに他の類似の技術的参考文献に見出され得る。
II.組成物
T細胞のためのアダプター
(a)Fc結合ドメイン
(b)CD3結合ドメイン
III.治療薬およびワクチン
(1)T細胞アダプター構築
本発明の様々な実施形態によって、アダプター様ADCCエンハンサー、すなわち、高親和性CD3結合ドメインに連結された高親和性Fc結合ドメインを有する融合タンパク質を開発し、検査した。
(2)発現および精製
(4)細胞傷害性増強
Claims (12)
- 高親和性Fc結合ドメインと、高親和性CD3結合ドメインとを含む融合タンパク質。
- 前記高親和性Fc結合ドメインが、CD64のエクトドメイン、高親和性CD16改変体およびヒトFcに対し高親和性を有する抗体フラグメントからなる群より選択される、請求項1に記載の融合タンパク質。
- 高親和性CD3結合ドメインが、OKT3モノクローナル抗体のscFvである、請求項1に記載の融合タンパク質。
- 前記OKT3モノクローナル抗体が、dhOKT3である、請求項3に記載の融合タンパク質。
- 請求項1〜4に記載の融合タンパク質と、薬学的に受容可能な賦形剤とを含む薬学的組成物。
- 処置の必要性のある被験体を、ある状態について治療的に処置する方法であって、前記被験体に治療上有効な量の請求項5に記載の薬学的組成物を投与する工程を含む方法。
- 前記状態を示す少なくとも1種の細胞表面抗原に対する治療用抗体を投与する工程をさらに含む、請求項6に記載の方法。
- 前記抗体が、ヒトIgG4と実質的に同様のFc領域を含む、請求項7に記載の方法。
- 前記状態が、がん、炎症性疾患、自己免疫性疾患、移植片拒絶および感染からなる群より選択される、請求項6に記載の方法。
- 処置の必要性のある被験体を、ある状態について予防的に処置する方法であって、前記被験体に予防上有効な量の請求項5に記載の薬学的組成物を投与する工程を含む方法。
- 前記状態に対するワクチンを投与する工程をさらに含む、請求項10に記載の方法。
- 前記状態が、がんである、請求項10に記載の方法。
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WO2022004805A1 (ja) * | 2020-06-30 | 2022-01-06 | 株式会社ガイアバイオメディシン | Nk細胞と抗体との結合を安定化する方法、及びその利用 |
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EA035037B1 (ru) | 2013-12-12 | 2020-04-21 | Шанхай Хэнжуй Фармасьютикал Ко., Лтд. | Антитело к pd-1, его антигенсвязывающий фрагмент и их медицинское применение |
US11434291B2 (en) | 2019-05-14 | 2022-09-06 | Provention Bio, Inc. | Methods and compositions for preventing type 1 diabetes |
KR20230092863A (ko) | 2020-06-11 | 2023-06-26 | 프로벤션 바이오, 인코포레이티드 | 제1형 당뇨병을 예방하기 위한 방법 및 조성물 |
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KR20170089003A (ko) | 2017-08-02 |
RU2017124141A (ru) | 2019-01-10 |
AU2015360642B2 (en) | 2019-04-04 |
US20170362299A1 (en) | 2017-12-21 |
RU2017124141A3 (ja) | 2019-06-19 |
NZ732073A (en) | 2019-04-26 |
RU2725807C2 (ru) | 2020-07-06 |
JP2021035994A (ja) | 2021-03-04 |
JP7095992B2 (ja) | 2022-07-05 |
WO2016094456A1 (en) | 2016-06-16 |
EP3230311A4 (en) | 2018-05-30 |
EP3230311A1 (en) | 2017-10-18 |
CA2968987C (en) | 2022-05-10 |
CN107108718A (zh) | 2017-08-29 |
US20220235115A1 (en) | 2022-07-28 |
AU2015360642A1 (en) | 2017-06-08 |
KR102654033B1 (ko) | 2024-04-02 |
SG11201704124YA (en) | 2017-06-29 |
CA2968987A1 (en) | 2016-06-16 |
CN107108718B (zh) | 2022-07-22 |
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