# US 11,897,930 B2 · Interleukin-2 polypeptides and fusion proteins thereof, and their pharmaceutical compositions and therapeutic applications > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,897,930 B2 - Document ID: US11897930B2 - Status: Granted - Kind: B2 - Application number: 17/241,074 - Filed: 2021-04-27 - Published: 2021-11-04 - Granted: 2024-02-13 - Earliest claimed: 2020-04-28 - Assignees: Anwita Biosciences, Inc. - Applicants: Anwita Biosciences, Inc. - Inventors: Fan Ye; Eric Liao; Ella Li; Matthew Siegel; Jianing Huang; Ziyang Zhong - Web page: https://patentgrep.com/patent/US11897930B2 ## CPC - C07K 14/55: IL-2 - C07K 14/5443: {IL-15} - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C07K 2319/00: Fusion polypeptide - C07K 2319/31: fusions, other than Fc, for prolonged plasma life, e.g. albumin - C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies - 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) ## Abstract Provided herein are an interleukin-2 polypeptide and a fusion protein thereof. Also provided herein are their pharmaceutical compositions and methods of use for treating, preventing, or ameliorating one or more symptoms of a proliferative disease. ## Claims ### Claim 1 An interleukin-2 polypeptide comprising an amino acid sequence of SEQ ID NO: 1, 2, 3, 4, or 5, wherein the interleukin-2 polypeptide comprises a replacement of the amino acid residues from positions 29 to 50 as set forth in SEQ ID NO: 1, 2, 3, 4, or 5 with a peptide comprising the amino acid sequence of an IL-15 hinge or a fragment thereof. ### Claim 2 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide further comprises an amino acid substitution at position 8, 9, 13, 15, 16, 19, 23, 76, 79, 81, 84, 87, 88, 91, 92, 95, 127, or 130 as set forth in SEQ ID NO: 1, 2, 3, 4, or 5. ### Claim 3 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide further comprises an amino acid substitution at position 15 as set forth in SEQ ID NO: 1, 2, 3, 4, or 5. ### Claim 4 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide further comprises an amino acid substitution of E15K. ### Claim 5 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide further comprises an amino acid substitution at position 16 as set forth in SEQ ID NO: 1, 2, 3, 4, or 5. ### Claim 6 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide further comprises an amino acid substitution of H16D, H16E, H16N, or H16Q. ### Claim 7 (depends on 1) A fusion protein comprising (i) an interleukin-2 polypeptide domain having an amino acid sequence of the interleukin-2 polypeptide of claim 1 and (ii) a half-life-extension domain. ### Claim 8 (depends on 1) A pharmaceutical composition comprising the interleukin-2 polypeptide of claim 1 and a pharmaceutically acceptable excipient. ### Claim 9 (depends on 1) A method of treating one or more symptoms of treating, preventing, or ameliorating one or more symptoms of a proliferative disease in a subject, comprising administering to the subject a therapeutically effective amount of the interleukin-2 polypeptide of claim 1. ### Claim 10 (depends on 1) A method of activating an immune effector cell, comprising contacting the cell with an effective amount of the IL-2 polypeptide of any one of the interleukin-2 polypeptides of claim 1. ### Claim 11 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide further comprises an amino acid substitution at position 15, 16, or 130 as set forth in SEQ ID NO: 1, 2, 3, 4, or 5. ### Claim 12 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide further comprises an amino acid substitution of E15K, E15Q, E15V, H16D, H16E, H16N, H16Q, S130A, S130E, S130F, or S130W. ### Claim 13 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide further comprises an amino acid substitution of E15K or E15Q. ### Claim 14 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide further comprises an amino acid substitution at position 130 as set forth in SEQ ID NO: 1, 2, 3, 4, or 5. ### Claim 15 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide further comprises an amino acid substitution of S130A, S130E, S130F, or S130W. ### Claim 16 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide comprises a replacement of an amino acid sequence of SEQ ID NO: 171 with an amino acid sequence of one of SEQ ID NOs: 166 to 170 and 219 to 223. ### Claim 17 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide comprises a replacement of an amino acid sequence of SEQ ID NO: 171 with an amino acid sequence of SEQ ID NO: 166. ### Claim 18 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide comprises a replacement of an amino acid sequence of SEQ ID NO: 171 with an amino acid sequence of SEQ ID NO: 167. ### Claim 19 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide comprises a replacement of an amino acid sequence of SEQ ID NO: 171 with an amino acid sequence of SEQ ID NO: 168. ### Claim 20 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide comprises a replacement of an amino acid sequence of SEQ ID NO: 171 with an amino acid sequence of SEQ ID NO: 169. ### Claim 21 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide comprises a replacement of an amino acid sequence of SEQ ID NO: 171 with an amino acid sequence of SEQ ID NO: 170. ### Claim 22 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide comprises a replacement of an amino acid sequence of SEQ ID NO: 171 with an amino acid sequence of SEQ ID NO: 219. ### Claim 23 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide comprises a replacement of an amino acid sequence of SEQ ID NO: 171 with an amino acid sequence of SEQ ID NO: 220. ### Claim 24 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide comprises a replacement of an amino acid sequence of SEQ ID NO: 171 with an amino acid sequence of SEQ ID NO: 221. ### Claim 25 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide comprises a replacement of an amino acid sequence of SEQ ID NO: 171 with an amino acid sequence of SEQ ID NO: 222. ### Claim 26 (depends on 1) The interleukin-2 polypeptide of claim 1, wherein the interleukin-2 polypeptide comprises a replacement of an amino acid sequence of SEQ ID NO: 171 with an amino acid sequence of SEQ ID NO: 223. ### Claim 27 (depends on 1) The interleukin-2 polypeptide of claim 1, comprising an amino acid sequence selected from SEQ ID NOs: 172 to 176, 184 to 188, and 224 to 234. ### Claim 28 (depends on 1) The interleukin-2 polypeptide of claim 1, comprising an amino acid sequence selected from SEQ ID NOs: 172 to 176 and 224 to 234.