Conjugates formed from polymer derivatives having particular atom arrangements

• US 20060275252A1
• Filed: 03/23/2006
• Published: 12/07/2006
• Est. Priority Date: 05/23/2003
• Status: Active Grant

• Current Assignee: Nektar Therapeutics
• Original Assignee: Nektar Therapeutics
• Inventors: Bentley, Michael D., Charles, Stephen A., McManus, Samuel P., Kozlowski, Antoni, Harris, J. Milton
• Granted Patent: US 7,947,261 B2
• Time in Patent Office: Days
• US Class Current: 424/78.270
• CPC Class Codes: A61K 31/357 having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; Related peptides
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61K 38/215 IFN-beta
• CPC Class Codes: A61K 38/24 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 38/37 Factors VIII
• 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: C08G 65/329 with organic compounds
• CPC Class Codes: C08G 65/33337 cyclic
• CPC Class Codes: C08G 65/33344 containing carbamate group

Abstract

Polymeric reagents are provided comprising a moiety of atoms arranged in a specific order, wherein the moiety is positioned between a water-soluble polymer and a reactive group. The polymeric reagents are useful for, among other things, forming polymer-active agent conjugates. Related methods, compositions, preparations, and so forth are also provided.

Claims

1. A conjugate comprising a water-soluble polymer, a

2. The conjugate of claim 1, wherein R¹ is H.

3. The conjugate of claim 1, wherein the water-soluble polymer portion is a poly(alkylene oxide).

4. The conjugate of claim 3, wherein the poly(alkylene oxide) is a poly(ethylene glycol).

5. The conjugate of claim 4, wherein the poly(ethylene glycol) is terminally capped with methoxy.

6. The conjugate of claim 4, wherein the poly(ethylene glycol) has a molecular weight of from about 100 Daltons to about 100,000 Daltons.

7. The conjugate of claim 6, wherein the poly(ethylene glycol) has a molecular weight of from about 1,000 Daltons to about 60,000 Daltons.

8. The conjugate of claim 7, wherein the poly(ethylene glycol) has a molecular weight of from about 2,000 Daltons to about 50,000 Daltons.

9. The conjugate of claim 1, comprising the following structure:

10. The conjugate of claim 1, comprising the following structure:

11. The conjugate of claim 10, comprising the following structure:

12. The conjugate of claim 11, comprising the following structure:

13. The conjugate of claim 11, comprising the following structure

14. The conjugate of claim 1, comprising the following structure:

15. The conjugate of claim 1, wherein the pharmacologically active agent is selected from the group consisting of erythropoietin, granulocyte-colony stimulating factor, interferon-α

, human growth hormone, interferon-β

, follicle stimulating hormone, Factor VIII, B-domain deleted Factor VIII, desmopressin, and amdoxivir.

16. The conjugate of claim 10, wherein the pharmacologically active agent is selected from the group consisting of erythropoietin, granulocyte colony stimulating factor, interferon-α

, human growth hormone, interferon-β

, follicle stimulating hormone, Factor VIII, B-domain deleted Factor VIII, desmopressin, and amdoxivir.

17. The conjugate of claim 11, wherein the pharmacologically active agent is selected from the group consisting of erythropoietin, granulocyte colony stimulating factor, interferon-α

, human growth hormone, interferon-P, follicle stimulating hormone, Factor VIII, B-domain deleted Factor VIII, desmopressin, and amdoxivir.

18. The conjugate of claim 13, wherein the pharmacologically active agent is selected from the group consisting of erythropoietin, granulocyte colony stimulating factor, interferon-α

, human growth hormone, interferon-β

, follicle stimulating hormone, Factor VIII, B-domain deleted Factor VIII, desmopressin, and amdoxivir.

19. The conjugate of claim 14, wherein the pharmacologically active agent is selected from the group consisting of human growth hormone.