# US 2014/0155313 A1 · Hydrogels with covalently linked polypeptides > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0155313 A1 - Document ID: US20140155313A1 - Status: Published application - Kind: A1 - Application number: 14/097,215 - Filed: 2013-12-04 - Published: 2014-06-05 - Earliest claimed: 2012-12-04 - Assignees: Susavion Biosciences, Inc. - Applicants: Susavion Biosciences, Inc. - Inventors: Laura L. Eggink; J. Kenneth Hoober - Web page: https://patentgrep.com/patent/US20140155313A1 ## CPC - A61K 47/58: obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin - A61K 38/02: Peptides of undefined number of amino acids; Derivatives thereof - A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)} - A61K 47/6903: {the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel} - A61L 15/32: Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin {(A61L15/225 takes precedence)} - C07K 1/1133: {by redox-reactions involving cystein/cystin side chains} - 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) - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - 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) ## Abstract The present invention provides methods of synthesizing hydrogels that contain covalently linked polypeptides. These polypeptides may be tetravalent peptides or polypeptides that bind to cell surface receptors. The hydrogels synthesized by the methods of the present invention may be used in wound dressings or applied directly to wounds to promote healing. ## Claims ### Claim 1 A composition comprising an acrylate polymeric scaffold covalently linked to a compound represented by formula (II): wherein X1 is a linker selected from the group consisting of polyethylene glycol (PEG) and an amino acid sequence consisting of GGGS (SEQ ID NO: 1), and each of Q1, Q2, Q3, and Q4 is independently a therapeutic polypeptide. ### Claim 2 (depends on 1) The composition of claim 1, wherein the acrylate polymeric scaffold is covalently linked to the compound represented by formula (II) at the vinyl group on the C-terminal cysteinyl amide. ### Claim 3 (depends on 1) The composition of claim 1, wherein the acrylate polymeric scaffold comprises an acrylate selected from the group consisting of 2-Hydroxyethyl Methacrylate, Methyl Methacrylate, Hydroxymethacrylate, Hydroxy Ethyl Meth Acrylate (HEMA), Poly Glucosylethyl Methacrylate (PGEMA), Poly Ethyl Methacrylate (PEMA), and Poly Methyl Methacrylate (PMMA). ### Claim 4 (depends on 1) The composition of claim 1, wherein each of Q1, Q2, Q3, and Q4 is independently a full-length polypeptide or an active peptide fragment of a polypeptide selected from the group consisting of cytokines, growth factors, cell adhesion molecules, and antibodies. ### Claim 5 (depends on 1) The composition of claim 1, wherein each of Q1, Q2, Q3, and Q4 independently comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5. ### Claim 6 A method of synthesizing a hydrogel comprising: (a) reacting a C-terminal cysteine sulfhydryl group of a first peptide polymer with a halogen on a compound represented by formula (I): wherein n is an integer between 1 and 6, R1 represents a halogen, and R2 represents a methyl, an ethyl, a hydroxymethyl, a hydroxyethyl, or a hydrogen; and (b) adding the first peptide polymer to a second polymer with a radical initiator to begin polymerization of the hydrogel. ### Claim 7 (depends on 6) The method of claim 6, wherein the first peptide polymer is a polypeptide. ### Claim 8 (depends on 7) The method of claim 7, wherein the polypeptide is a tetravalent peptide. ### Claim 9 (depends on 8) The method of claim 8, wherein the tetravalent peptide is selected from the group consisting of SVH1B, SV6D, SVD2, and SVC1. ### Claim 10 (depends on 7) The method of claim 7, wherein the polypeptide binds to cell surface receptors. ### Claim 11 (depends on 10) The method of claim 10, wherein in the polypeptide is a full-length polypeptide or an active peptide fragment of a polypeptide selected from the group consisting of cytokines, growth factors, cell adhesion molecules, and antibodies. ### Claim 12 (depends on 7) The method of claim 7, wherein the polypeptide has a molecular weight of less than 200 kilodaltons (kD). ### Claim 13 (depends on 6) The method of claim 6, wherein compound represented by formula (I) is selected from a group consisting of 3-iodo-2-methyl-1-propene and allyl-idodide. ### Claim 14 (depends on 6) The method of claim 6, wherein the second polymer is selected from the group consisting of acrylic acid, 2-hydroxyethyl methacrylate, methyl methacrylate, 2-acrylamido-2-methylpropane sulfonic acid (AMPS), and hydroxymethacrylate. ### Claim 15 (depends on 6) The method of claim 6, further comprising: (c) adding a pharmacologically-active agent to the hydrogel after polymerization is terminated. ### Claim 16 (depends on 15) The method of claim 15, wherein the pharmacologically-active agent is selected from the group consisting of vulnerary agents, hemostatic agents, antibiotics, antihelminthics, anti-fungal agents, hormones, anti-inflammatory agents, polypeptides, oligonucleotides, cytokines, antibodies, and enzymes. ### Claim 17 (depends on 6) A hydrogel synthesized with the method of claim 6. ### Claim 18 (depends on 17) A wound dressing comprising the hydrogel of claim 17. ### Claim 19 (depends on 17) A method of treating a wound in a subject comprising applying to the wound the hydrogel of claim 17.