HYDROGELS WITH COVALENTLY LINKED POLYPEPTIDES

• US 20140155313A1
• Filed: 12/04/2013
• Published: 06/05/2014
• Est. Priority Date: 12/04/2012
• Status: Active Grant

• Current Assignee: Susavion Biosciences, Inc.
• Original Assignee: Susavion Biosciences, Inc.
• Inventors: Eggink, Laura L., Hoober, J. Kenneth
• Granted Patent: US 9,155,796 B2
• Time in Patent Office: Days
• US Class Current: 514/1.1
• CPC Class Codes: A61K 38/02 Peptides of undefined number of amino acids; Derivatives thereof
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: 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
• CPC Class Codes: A61K 47/6903 the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
• CPC Class Codes: A61L 15/32 Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin A61L15/225 takes precedence
• CPC Class Codes: C07K 1/1133 by redox-reactions involving cystein/cystin side chains

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

1. A composition comprising an acrylate polymeric scaffold covalently linked to a compound represented by formula (II):

2. 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.

3. 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).

4. 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.

5. 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.

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);

7. The method of claim 6, wherein the first peptide polymer is a polypeptide.

8. The method of claim 7, wherein the polypeptide is a tetravalent peptide.

9. The method of claim 8, wherein the tetravalent peptide is selected from the group consisting of SVH1B, SV6D, SVD2, and SVC1.

10. The method of claim 7, wherein the polypeptide binds to cell surface receptors.

11. 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.

12. The method of claim 7, wherein the polypeptide has a molecular weight of less than 200 kilodaltons (kD).

13. 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.

14. 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.

15. The method of claim 6, further comprising:

(c) adding a pharmacologically-active agent to the hydrogel after polymerization is terminated.

16. 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.

17. A hydrogel synthesized with the method of claim 6.

18. A wound dressing comprising the hydrogel of claim 17.

19. A method of treating a wound in a subject comprising applying to the wound the hydrogel of claim 17.