US 12,358,964 B2
Heterodimeric Fc-fused cytokine and pharmaceutical composition comprising the same
Yong Sung Kim, Suwon (KR); Keunok Jung, Suwon (KR); Ji Hee Ha, Daegu (KR); Dong Ki Choi, Daejeon (KR); Hye Ji Choi, Suwon (KR); and Ye Jin Kim, Busan (KR)
Assigned to Ajou University Industry-Academic Cooperation Foundation, Suwon-si (KR)
Filed by Ajou University Industry-Academic Cooperation Foundation, Suwon (KR)
Filed on May 24, 2023, as Appl. No. 18/323,124.
Application 18/323,124 is a division of application No. 16/886,184, filed on May 28, 2020, granted, now 11,692,019.
Application 16/886,184 is a division of application No. 16/323,839, granted, now 10,696,722, issued on Jun. 30, 2020, previously published as PCT/KR2017/008676, filed on Aug. 10, 2017.
Claims priority of application No. 10-2016-0101823 (KR), filed on Aug. 10, 2016; and application No. 10-2017-0101594 (KR), filed on Aug. 10, 2017.
Prior Publication US 2023/0416325 A1, Dec. 28, 2023
Int. Cl. A61K 38/20 (2006.01); A61K 38/00 (2006.01); C07K 14/54 (2006.01); C07K 14/59 (2006.01)
CPC C07K 14/5434 (2013.01) [A61K 38/208 (2013.01); C07K 14/54 (2013.01); C07K 14/59 (2013.01); A61K 38/00 (2013.01); C07K 2319/30 (2013.01)] 12 Claims
 
1. A method of reducing growth of a solid tumor, the method comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a heterodimeric Fc-fused protein comprising a first Fc region and a second Fc region of an immunoglobulin fragment crystallizable (Fc) pair and p40 and p35 subunits of IL-12, wherein
(a) the p40 and p35 subunits are linked separately to the first Fc region and the second Fc region, or to the second Fc region and the first Fc region, respectively;
(b) the p40 and p35 subunits are each linked to the N-terminus or C-terminus of the Fc regions; and
(c) CH3 domains of the first Fc region and the second Fc region each comprise one or more mutations promoting heterodimerization selected from the group consisting of:
(i) glutamic acid (E) substitution of the amino acid residue at position 360 in the CH3 domain of the first Fc region,
(ii) tryptophan (W) substitution of the amino acid residue at position 409 in the CH3 domain of the first Fc region, and
(iii) threonine (T) substitution of the amino acid residue at position 405 in the CH3 domain of the second Fc region and valine (V) substitution of the amino acid residue at position 399 in the CH3 domain of the second Fc region;
wherein the mutation positions are numbered according to the EU index.