# US 10,246,501 B2 · Fusion polypeptides and methods of use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,246,501 B2 - Document ID: US10246501B2 - Status: Granted - Kind: B2 - Application number: 15/107,101 - Filed: 2014-01-08 - Published: 2017-01-26 - Granted: 2019-04-02 - Earliest claimed: 2014-01-08 - Assignees: Prosit Sole Biotechnology (Beijing) Co, Ltd - Applicants: Prosit Sole Biotechnology (Beijing) Co. Ltd - Inventors: Hongyu Liu; Mingzhi Zhao; Hetong Sun - Web page: https://patentgrep.com/patent/US10246501B2 ## CPC - C07K 14/54: Interleukins [IL] - A61P 25/00: Drugs for disorders of the nervous system - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 31/12: Antivirals - A61P 31/14: for RNA viruses - A61P 31/16: for influenza or rhinoviruses - A61P 31/20: for DNA viruses - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 14/555: Interferons [IFN] - C07K 2319/00: Fusion polypeptide - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Disclosed are fusion polypeptides comprising fragments from a first and a second isoform of an interferon lambda family, nucleic acids encoding the fusion polypeptides, and vectors and host cells containing the same, and methods of making and using such compositions in treatment of interferon lambda-related diseases, disorders, and conditions. ## Claims ### Claim 1 A fusion polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 3-19. ### Claim 2 (depends on 1) The fusion polypeptide of claim 1, wherein the fusion polypeptide retains the secondary structure of a first interferon lambda isoform or a second interferon lambda isoform and is devoid of any additional B-epitope or T-epitope as compared to that of the first interferon lambda isoform or the second interferon lambda isoform. ### Claim 3 (depends on 1) The fusion polypeptide of claim 1, wherein the fusion polypeptide has a structure of formula I: (S1)-(helix A)-(S2)-(helix C)-(S3)-(helix D)-(S4)-(helix E)-(S5)-(helix F)-(S6) wherein: a. helix D comprises an amino acid sequence exhibiting at least 90% homology to a fragment having residues from about V98 to Q112 of IL28B (SEQ ID NO: 2) or from about V89 to Q103 of IL29 (SEQ ID NO: 1); b. helix E comprises an amino acid sequence exhibiting at least 90% homology to a fragment having residues from about R130 to E145 of IL28B (SEQ ID NO: 2) or from about R121 to E136 of IL29 (SEQ ID NO: 1); c. each of S1, S2, S3, S4, S5 and S6 is independently a spacer sequence having between 1 to about 50 amino acid residues; and wherein said fusion polypeptide is characterized in that: i. helix A comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about P27 to L44 of IL28B (SEQ ID NO: 2), helix C comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about R56 to A80 of IL29 (SEQ ID NO: 1), and helix F comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about G139 to A161 of IL29 (SEQ ID NO: 1); or ii. helix A comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about P20 to L37 of IL29 (SEQ ID NO: 1), helix C comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about R63 to A87 of IL28B (SEQ ID NO: 2), and helix F comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about G 148 to A170 of IL28B (SEQ ID NO: 2); or iii. helix A comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about P27 to L44 of IL28B (SEQ ID NO: 2), helix C comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about R63 to A87 of IL28B (SEQ ID NO: 2), and helix F comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about G139 to Al61 of IL29 (SEQ ID NO: 1); or iv. helix A comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about P20 to L37 of IL29 (SEQ ID NO: 1), helix C comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about R56 to A80 of IL29 (SEQ ID NO: 1), and helix F comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about G148 to A170 of IL28B (SEQ ID NO: 2); or v. helix A comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about P27 to L44 of IL28B (SEQ ID NO: 2), helix C comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about R56 to A80 of IL29 (SEQ ID NO: 1), and helix F comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about G148 to A170 of IL28B (SEQ ID NO: 2); or vi. helix. A comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about P20 to L37 of IL29 (SEQ ID NO: 1), helix C comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about R63 to A87 of IL28B (SEQ ID NO: 2), and helix F comprises an amino acid sequence exhibiting at least 95% homology to a fragment having residues from about G139 to A161 of IL29 (SEQ ID NO: 1). ### Claim 4 (depends on 3) The fusion polypeptide of claim 3, wherein helix A is identical to a fragment having residues from about P27 to L44 of IL28B (SEQ ID NO: 2). ### Claim 5 (depends on 3) The fusion polypeptide of claim 3, wherein helix A is identical to a fragment having residues from about P20 to L37 of IL29 (SEQ TD NO: 1). ### Claim 6 (depends on 3) The fusion polypeptide of claim 3, wherein helix C is identical to a fragment having residues from about R63 to A87 of IL28B (SEQ ID NO: 2). ### Claim 7 (depends on 3) The fusion polypeptide of claim 3, wherein helix C is identical to a fragment having residues from about R56 to A80 of IL29 (SEQ ID NO: 1). ### Claim 8 (depends on 3) The fusion polypeptide of claim 3, wherein helix F is identical to a fragment having residues from about G148 to A170 of IL28B (SEQ ID NO: 2). ### Claim 9 (depends on 3) The fusion polypeptide of claim 3, wherein helix F is identical to a fragment having residues from about G139 to A161 of IL29 (SEQ ID NO: 1). ### Claim 10 (depends on 1) The fusion polypeptide of claim 1, further comprising: a) at least one modification in an amino acid residue corresponding to IL28B (SEQ ID NO: 2), wherein said at least one modification in a) is selected from the group consisting of dV2, dP3, dV4, dA5, dR6, dL7, dR8, G9K, A10P, L11T, P12T, D13T, A14G , R15K, A20G, Q21R, Q31A, A32S, R35K, K37R, L45K, D48N, C49W, K50S, R52S, R54P, L55V, R58G, T59N, Q64L, T88A, dD90, dT91, D92P, G96E, R114Q, T127P, C168S, C175S, P3G, V4P, A5V, R6P, L7T and R8S; or b) at least one modification in an amino acid residue corresponding to IL29 (SEQ ID NO: 1), wherein said at least one modification in b) is selected from the group consisting of R14Q, L57Q, A81T, 82aD, 82bT, G83D, E87G, Q105R, P118T, and D162E. ### Claim 11 (depends on 1) The fusion polypeptide of claim 1, wherein the fusion polypeptide exhibits at least 90% sequence homology to IL28B (SEQ ID NO: 2) and IL29 (SEQ ID NO: 1). ### Claim 12 (depends on 1) The fusion polypeptide of claim 1, wherein the fusion polypeptide exhibits at least 95% sequence homology to IL28B (SEQ ID NO: 2) and IL29 (SEQ ID NO: 1). ### Claim 13 (depends on 1) The fusion polypeptide of claim 1, wherein the N-terminus of said fusion polypeptide is further modified by a polyethylene glycol (PEG). ### Claim 14 (depends on 1) A pharmaceutical composition comprising at least one of the fusion polypeptides of claim 1 and a pharmaceutically acceptable excipient. ### Claim 15 (depends on 1) A method of treating an infection by hepatitis B virus, hepatitis C virus and influenza virus in a mammal in need thereof, comprising administering to said mammal a therapeutically effective amount of the fusion polypeptide of claim 1. ### Claim 16 (depends on 1) A host cell expressing the fusion polypeptide of claim 1. ### Claim 17 (depends on 1) A vector comprising a polynucleotide encoding the fusion polypeptide of claim 1. ### Claim 18 (depends on 1) A method of producing the fusion polypeptide of claim 1 , comprising expressing a vector comprising a polynucleotide encoding the fusion polypeptide of claim 1 in a cell under conditions suitable for protein expression, thereby producing said fusion polypeptide.