# US 2020/0399336 A1 · Il-21 (heterodimeric fc-fused il-21) fused to immunoglobulin heavy chain constant region heterodimer (heterodimeric fc), and pharmaceutical composition comprising same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2020/0399336 A1 - Document ID: US20200399336A1 - Status: Published application - Kind: A1 - Application number: 17/015,875 - Filed: 2020-09-09 - Published: 2020-12-24 - Earliest claimed: 2016-09-02 - Assignees: Korea University Research and Business Foundation; Ajou University Industry-Academic Cooperation Foundation - Applicants: Korea University Research and Business Foundation; Ajou University Industry-Academic Cooperation Foundation - Inventors: Kyung-Mi LEE; Seon Ah LIM; Yong Sung KIM; Ye Jin KIM - Web page: https://patentgrep.com/patent/US20200399336A1 ## CPC - C07K 14/54: Interleukins [IL] - A61K 38/20: Interleukins [IL] - A61K 38/2013: {IL-2} - A61K 40/15: Natural-killer [NK] cells; Natural-killer T [NKT] cells - A61K 40/42: Cancer antigens - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/68: the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment - A61P 35/00: Antineoplastic agents - A61K 2239/31: characterized by the route of administration - A61K 2239/38: characterised by the dose, timing or administration schedule - C07K 2317/526: CH3 domain - C07K 2317/53: Hinge - C07K 2317/71: Decreased effector function due to an Fc-modification - C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## 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. ## Claims ### 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. ### Claim 2 (depends on 1) The method according to claim 1, wherein the disease is cancer. ### Claim 3 (depends on 2) 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. ### Claim 4 (depends on 2) The method according to claim 2, wherein the method is intended for co-treatment with other anticancer agents. ### Claim 5 (depends on 1) 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. ### Claim 6 (depends on 1) 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. ### Claim 7 (depends on 1) 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. ### Claim 8 (depends on 1) 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. ### Claim 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. ### Claim 10 (depends on 9) The method according to claim 9, further comprising administering IL-2. ### Claim 11 (depends on 9) 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.