A fusion protein comprising an antigen binding domain and a cytokine trimer domain

The present invention relates to a new type of fusion protein (RACE (receptor-antibody conjugated (cell) engager)) combining antibodies and cytokine trimeric domains, wherein the fusion protein includes a cytokine trimeric domain in which a dimer of a first monomer and a second monomer connected by...

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Bibliographische Detailangaben
Hauptverfasser: SON KKA BI, BAK JEONG HYEON, LEE DAE HEE, JANG SE IL
Format: Patent
Sprache:eng ; kor
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Zusammenfassung:The present invention relates to a new type of fusion protein (RACE (receptor-antibody conjugated (cell) engager)) combining antibodies and cytokine trimeric domains, wherein the fusion protein includes a cytokine trimeric domain in which a dimer of a first monomer and a second monomer connected by a linker and a third monomer are coupled by a knob-into-hole, and the fusion protein is prepared by replacing a constant region (Fc) of an antibody with the cytokine trimeric domain. It has been confirmed that RACE according to the present invention not only exhibits superior binding ability to a target receptor than a parent antibody, but also exhibits excellent simultaneous binding ability to an antigen and the target receptor, and thus can be usefully used as a bispecific pharmaceutical composition. The fusion protein includes an antigen-binding domain and a cytokine trimeric domain. 본 발명은 링커로 연결된 제 1 단량체 및 제 2 단량체(dimer)와 제 3 단량체(monomer)가 노브-인투-홀에 의해 결합된 사이토카인 삼량체 도메인 및 항체의 불변 영역(Fc)를 상기 사이토카인 삼량체 도메인으로 대체하여 제조한, 항체 및 사이토카인 삼량체 도메인이 결합된 새로운 형태의 융합 단백질(RACE(Receptor-Antibody Conjugated (cell) Engager))에 대한 것으로, 본 발명에 따른 RACE는 타겟 수용체에 대해 모항체보다 우수한 결합능을 보일 뿐만 아니라 항원 및 타겟 수용체에 대해 우수한 동시 결합능을 보임을 확인한 바, 이를 이중특이성 약학적 조성물로 유용하게 활용할 수 있다.