Compositions comprising a polymeric reagent and a pharmacologically active agent

• US 9,399,070 B2
• Filed: 05/22/2015
• Issued: 07/26/2016
• Est. Priority Date: 05/23/2003
• Status: Expired due to Term

• Current Assignee: Nektar Therapeutics
• Original Assignee: Nektar Therapeutics
• Inventors: Harris, J. Milton, Kozlowski, Antoni, McManus, Samuel P., Bentley, Michael D., Charles, Stephen A.
• Primary Examiner(s): Fubara, Blessing M
• Application Number:
  US14/720,213
• Publication Number:
  US 20150328331A1
• Time in Patent Office: 431 Days
• Field of Search: 424/78.27, 424/85.1, 424/85.5, 424/85.7, 424/78.37, 525/54.1, 525/50
• US Class Current: 1/1
• 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

Pharmaceutical compositions of conjugates are provided. The conjugates can be prepared by (among other ways) conjugating a pharmacologically active agent with a polymeric reagent that has a particular arrangement of atoms. Related methods, preparations, and so forth are also provided.

Claims

1. A composition comprising

(i) a polymeric reagent of the following structure,

2. The composition of claim 1, wherein each R¹ is H.

3. The composition of claim 1, wherein each poly(alkylene glycol) is a poly(ethylene glycol).

4. The composition of claim 3, wherein each poly(ethylene glycol) is terminally capped with methoxy.

5. The composition of claim 4, wherein each poly(ethylene glycol) has a molecular weight of from about 100 Daltons to about 100,000 Daltons.

6. The composition of claim 5, wherein each poly(ethylene glycol) has a molecular weight of from about 1,000 Daltons to about 60,000 Daltons.

7. The composition of claim 6, wherein each poly(ethylene glycol) has a molecular weight of from about 2,000 Daltons to about 50,000 Daltons.

8. The composition of claim 1, wherein the polymeric reagent has the following structure:

9. The composition 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 delated Factor VIII, desmopressin and amdoxivir.

10. The composition of claim 1, wherein each R¹ is an organic radical and is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl and substituted aryl.

11. The composition of claim 1, wherein the polymeric reagent has as structure selected from the group consisting of

12. The composition of claim 1, wherein the polymeric reagent has a structure selected from the group consisting of

13. The composition of claim 1, wherein the polymeric reagent has a structure selected from the group consisting of

14. The composition of claim 1, wherein the polymeric reagent has the following structure:

15. The composition of claim 1, wherein the polymeric reagent has the following structure: