Non-antigenic amine derived polymers and polymer conjugates

• US 6,177,087 B1
• Filed: 11/03/1998
• Issued: 01/23/2001
• Est. Priority Date: 06/24/1994
• Status: Expired due to Term

• Current Assignee: Enzon Pharmaceuticals Inc. (Icahn Associates Holding LLC)
• Original Assignee: Enzon Pharmaceuticals Inc. (Icahn Associates Holding LLC)
• Inventors: Pendri, Annapurna, Martinez, Anthony, Greenwald, Richard B.
• Primary Examiner(s): Harrison, Robert H.
• Application Number:
  US09/184,910
• Time in Patent Office: 812 Days
• Field of Search: 424/278.1, 424/78.18, 424/279.1, 424/78.17, 526/352, 526/436, 526/936, 530/402, 530/815, 546/1, 546/157
• US Class Current: 424/278.1
• 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: C07K 14/805 Haemoglobins; Myoglobins
• CPC Class Codes: C08G 65/329 with organic compounds
• CPC Class Codes: C08G 65/33303 containing amino group
• CPC Class Codes: C08G 65/3331 cyclic
• CPC Class Codes: Y10S 526/936 Physiological use, e.g. pharmaceutical, veterinary, dental
• CPC Class Codes: Y10S 530/815 Carrier is a synthetic polymer

Abstract

Substantially non-antigenic polymers containing pI and/or pH optimum modulating moieties are disclosed. The polymers are useful as intermediates for synthesis of amine-based polymers and in the formation of activated polymers for conjugation with nucleophiles. Conjugates and methods of preparation and treatment with the conjugates are also disclosed.

Claims

1. A method of treatment comprising administering to a mammal in need thereof a therapeutically effective amount of a polymer conjugate comprising the formula:

2. The method of claim 1, wherein R is a poly(alkylene oxide).

3. The method of claim 1, wherein said poly(alkylene oxide) residue is capped with a C_1-4 alkyl group distal to said covalent linkage (L¹).

4. The method of claim 2, wherein said poly(alkylene oxide) is selected from the group consisting of poly(ethylene glycol) homopolymers, alkyl-capped poly(ethylene oxides), and copolymers of block copolymers of poly(alkylene oxides).

5. The method of claim 2, wherein said poly(alkylene oxide) has a molecular weight between about 200 and about 100,000 daltons.

6. The method of claim 5, wherein said poly(alkylene oxide) has a molecular weight between 1,000 and about 50,000 daltons.

7. The method of claim 6, wherein poly(ethylene glycol) homopolymer has a molecular weight of about 2,500 and about 25,000 daltons.

8. The method of claim 1, wherein R is a poly(ethylene glycol) homopolymer.

9. The method of claim 1, where in said nucleophile is a protein.

10. The method of claim 9, wherein said protein is selected form the group consisting of polyclonal antibodies, monoclonal antibodies, fragments of antibodies and single chain antibodies.

11. The method of claim 1, wherein said nucleophile is a peptide.

12. The method of claim 1, wherein said nucleophile is an enyme.

13. The method of claim 1, wherein said nucleophile is a polypeptide.