Ajou University Industry-academic Cooperation Foundation

Ji Hee Ha

Yong Sung Kim

Hye Ji Choi

Ye Jin Kim

Keunok Jung

Dong Ki Choi

The present invention relates to a heterodimeric Fc-fused protein comprising a first Fc region and a second Fc region of an immunoglobulin Fc pair and a physiologically active protein composed of two or more different subunits, wherein one or more subunits of the physiologically active protein are linked separately to one or more ends of the N-terminus or C-terminus of the first Fc region and/or the second Fc region, and CH3 domains of the first Fc region and the second Fc region are mutated so as to promote the heterodimeric Fc formation. Moreover, the present invention relates to a pharmaceutical composition comprising the heterodimeric Fc-fused protein.

Heterodimeric Fc-fused cytokine and pharmaceutical composition comprising the same

The present invention relates to a heterodimeric Fc-fused protein comprising a first Fc region and a second Fc region of an immunoglobulin Fc pair and a physiologically active protein composed of two or more different subunits, wherein one or more subunits of the physiologically active protein are linked separately to one or more ends of the N-terminus or C-terminus of the first Fc region and/or the second Fc region, and CH3 domains of the first Fc region and the second Fc region are mutated so as to promote the heterodimeric Fc formation. Moreover, the present invention relates to a pharmaceutical composition comprising the heterodimeric Fc-fused protein. The heterodimeric Fc-fused protein according to the present invention has an advantage in that it can retain the activity of a naturally occurring physiologically active protein whose two or more different subunits exhibit physiological activity by forming a protein complex, because the physiologically active protein can be linked to an immunoglobulin heterodimeric Fc such that the naturally occurring form and structure of the fused protein thereof can be maintained. When the heterodimeric Fc-fused protein according to the present invention is used, there is an advantage in that the in vivo half-life of the physiologically active protein contained in the heterodimeric Fc-fused protein can be significantly increased due to the Fc-mediated long half-life such that various physiological activities thereof in vivo can be long-lasting.

A method for evaluating and screening a mutant inducing the high-efficiency formation of heterodimers from a human antibody heavy chain constant region mutant pair combination library in order to increase the yield of formation of human antibody heterodimeric heavy chain constant regions. A heterodimeric heavy chain constant region (heterodimeric F) library is obtained by the method. A CH3 domain mutant pair, in which the formation of the heterodimeric heavy chain constant regions is preferred in the library, forms heterodimeric heavy chain constant regions at a high yield of at least 80-90%, and also has excellent thermal stability and retains binding ability to the heavy chain constant region receptor (FcRn).

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Suwon-si, South Korea

Ji Hee Ha