Polyoxymethylene-oxyethylene copolymers in conjuction with biomolecules

• US 5,476,653 A
• Filed: 03/22/1995
• Issued: 12/19/1995
• Est. Priority Date: 06/17/1992
• Status: Expired due to Term

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Hendren, Wayne, Pitt, Colin G.
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US08/409,630
• Time in Patent Office: 272 Days
• Field of Search: 424/78.3, 424/78.1, 424/54.1, 424/54.2, 424/54.3, 525/410, 528/403
• US Class Current: 424/78.3
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: Y10S 530/81 Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier

Abstract

Biological factors with enhanced biological activity are prepared by covalently linking a biomolecule to one or more chains of a synthetic polymer wherein the synthetic polymer is derived from the oxymethylene-oxyethylene part structure.

Claims

1. A composition of matter comprising a first component and a second component,

the first component selected from the group consisting of a biologically active molecule and a carrier of a biologically active molecule wherein said carrier carries a biologically active molecule, and

the second component consisting of a linear polymer chain of oxymethylene and oxyethylene monomers wherein the second component is covalently linked to the first component.

2. A composition of matter according to claim 1 wherein the polymer chain containing between 10% and 90% of polymerized oxymethylene monomers by number.

3. A composition of matter according to claim 1 wherein the polymer chain contains 50% of polymerized oxymethylene monomers by number.

4. A composition of matter according to claim 1 wherein the polymer chain contains about 33% of polymerized oxymethylene monomers by number.

5. A composition of matter according to claim 1 wherein the polymer chain contains a --O--CH₂ --O--CH₂ --CH₂ --repeat.

6. A composition of matter according to claim 1 wherein the polymer chain contains a --O--CH₂ --O--CH₂ --CH₂ --O--CH₂ --CH₂ --repeat.

7. A composition of matter according to claim 1 wherein the polymer chain contains random polymers of oxymethylene and oxyethylene monomers.

8. A composition of matter according to claim 1 wherein the polymer chain contains blocks of polymerized oxymethylene monomers and polymerized oxyethylene monomers.

9. A composition of matter according to claim 1 wherein the polymer chain contains both random and block polymers of oxymethylene and oxyethylene monomers.

10. A composition of matter according to claim 1 wherein the first component is selected from the group consisting of a polypeptide, a carbohydrate, and a liposome.

11. A composition of matter according to claim 1 wherein the first component is a protein.

12. A composition of matter according to claim 11 wherein the protein is a hematopoietic growth factor.

13. A composition of matter according to claim 12 wherein the hematopoietic growth factor is selected from the group consisting of EGF, EPO, GM-CSF, G-CSF, PDGF, MI, consensus interferon and SCF.

14. A composition of matter according to claim 1 wherein the monomers of the polymer chain are selected from the group consisting of 1,3-dioxolane, 1,3,6-trioxocane, oxirane, 1,3,5-trioxane and mixtures thereof.

15. A composition of matter according to claim 1 wherein the polymer chain has a number average molecular weight between 500 and 100,000.

16. A composition of matter according to claim 15 wherein the polymer chain has a number average molecular weight between 500 and 100,000.

17. A composition of matter according to claim 1 wherein the polymer chain is attached to the first component via reaction with an active ester of a carboxylic acid or carbonate derivative of said polymer.

18. A composition of matter according to claim 1 wherein the polymer chain is attached to the first component via reaction with a member selected from the group consisting of an ester of N-hydroxysuccinimide, an ester of p-nitrophenol, and an ester 1-hydroxy-2-nitro-benzene-4-sulfonate, attached to the polymer.

19. A composition of matter according to claim 1 wherein the polymer chain is attached to the first component via reaction of one or more free sulfhydryl groups of the first component and a maleimido or haloacetyl derivative of the polymer.

20. A composition of matter according to claim 1 wherein the polymer chain is attached to the first component via reaction of a member selected from the group consisting of an amino, a carboxyl, a sulfhydryl and a hydroxyl group of the first component.

21. A composition of matter according to claim 1 wherein the polymer chain is attached to the first component via reaction with a member selected from the group consisting of an amino, a hydrazino and a hydrazido derivative of the polymer chain and one or more aldehyde groups on the first component generated by oxidation of the carbohydrate moieties of the first component.