Il-21 (heterodimeric fc-fused il-21) fused to immunoglobulin heavy chain constant region heterodimer (heterodimeric fc), and pharmaceutical composition comprising same

Patent metadata

Field	Value
Publication number	US-2020399336-A1
Application number	US-202017015875-A
Country	US
Kind code	A1
Filing date	Sep 9, 2020
Priority date	Sep 2, 2016
Publication date	Dec 24, 2020
Grant date	—

Abstract

A heterodimeric Fc-fused protein and a pharmaceutical composition comprising the heterodimeric Fc-fused protein are disclosed. The heterodimeric Fc-fused protein includes first and second Fc regions of an immunoglobulin heavy chain constant region (Fc) pair and in which IL-21 is bound to at least one of the N-terminus or the C-terminus of the first Fc region and/or the second Fc region, wherein CH3 domains of the first Fc region and the second Fc region are mutated such that the formation of a heterodimer is promoted. When the heterodimeric Fc-fused protein is used, an in vivo half-life of IL-21 included in the heterodimeric Fc-fused protein may be significantly increased.

First claim

1 . A method of treating a disease in a subject in need thereof comprising administering a heterodimeric Fc-fused protein to the subject,
wherein the heterodimeric Fc-fused protein comprising first and second Fc regions of an immunoglobulin heavy chain constant region (Fc) pair and in which IL-21 is bound to at least one of the N-terminus or the C-terminus of the first Fc region and/or the second Fc region, wherein CH3 domains of the first Fc region and the second Fc region are mutated such that the formation of heterodimeric Fc is promoted.

2 . The method according to claim 1 , wherein the disease is cancer.

3 . The method according to claim 2 , wherein the cancer is selected from the group consisting of colon cancer, melanoma, breast cancer, pancreatic cancer, kidney cancer, prostate cancer, ovarian cancer, small intestine cancer, esophageal cancer, cervical cancer, lung cancer, lymphoma, and blood cancer.

4 . The method according to claim 2 , wherein the method is intended for co-treatment with other anticancer agents.

5 . The method according to claim 1 , wherein IL-21 is bound to only any one of the N-terminus and the C-terminus of the first Fc region or the second Fc region.

6 . The method according to claim 1 , wherein each of the first Fc region and the second Fc region is derived from an Fc region selected from the group consisting of human IgG1, IgG2, IgG3, IgG4, IgM, IgA, IgD, and IgE.

7 . The method according to claim 1 , wherein the first Fc region and the second Fc region are included in a whole antibody form consisting of human IgG1, IgG2, IgG3, IgG4, IgM, IgA, IgD, and IgE.

8 . The method according to claim 1 , wherein mutation of the CH3 domain of the first Fc region or the second Fc region comprises one or more mutations selected from the following groups:
(1) K360E amino acid residue substitution at position K360 of the CH3 domain of the first Fc region; (2) Q347R amino acid residue substitution at position Q347 of the CH3 domain of the second Fc region; (3) K409W amino acid residue substitution at position K409 of the CH3 domain of the first Fc region; and (4) F405T amino acid residue substitution at position F405 of the CH3 domain of the second Fc region and D399V amino acid residue substitution at position D399 of the CH3 domain of the second Fc region, wherein amino acid residue numbers are in accordance with EU index.

9 . A method for anti-cancer immunotherapy comprising administering NK cells and a heterodimeric Fc-fused protein to a subject in need thereof,
wherein the heterodimeric Fc-fused protein comprising first and second Fc regions of an immunoglobulin heavy chain constant region (Fc) pair and in which IL-21 is bound to at least one of the N-terminus or the C-terminus of the first Fc region and/or the second Fc region, wherein CH3 domains of the first Fc region and the second Fc region are mutated such that the formation of heterodimeric Fc is promoted.

10 . The method according to claim 9 , further comprising administering IL-2.

11 . The method according to claim 9 , wherein the cancer is selected from the group consisting of colon cancer, melanoma, breast cancer, pancreatic cancer, kidney cancer, prostate cancer, ovarian cancer, small intestine cancer, esophageal cancer, cervical cancer, lung cancer, lymphoma, and blood cancer.

Assignees

• Univ Korea Res & Bus Found
• Univ Ajou Ind Academic Coop Found

Inventors

• Lee Kyung-Mi
• Lim Seon Ah
• Kim Yong Sung
• Kim Ye Jin

Classifications

• A61K40/42

  Cancer antigens · CPC title

• A61K40/15

  Natural-killer [NK] cells; Natural-killer T [NKT] cells · CPC title

• A61K2239/31

  characterized by the route of administration · CPC title

• A61K2239/38

  characterised by the dose, timing or administration schedule · CPC title

• C07K14/54 Primary

  Interleukins [IL] · CPC title