Pharmaceutical compositions of conjugates formed from polymer derivatives having particular atom arrangements

• US 9,044,516 B2
• Filed: 12/20/2013
• Issued: 06/02/2015
• Est. Priority Date: 05/23/2003
• Status: Active Grant

• Current Assignee: Nektar Therapeutics Incorporated
• Original Assignee: Nektar Therapeutics Incorporated
• Inventors: Harris, J. Milton, Kozlowski, Antoni, McManus, Samuel P., Bentley, Michael D., Charles, Stephen A.
• Primary Examiner(s): Fubara, Blessing M
• Application Number:
  US14/136,497
• Publication Number:
  US 20140227218A1
• Time in Patent Office: 529 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 pharmaceutical preparation comprising

(i) a conjugate of the following structure,

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

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

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

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

6. The pharmaceutical preparation 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 pharmaceutical preparation 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 pharmaceutical preparation conjugate of claim 1, wherein the conjugate has the following structure:

9. The pharmaceutical preparation of claim 1, wherein the conjugate has the following structure:

10. The pharmaceutical preparation of claim 1, wherein the conjugate has the following structure:

11. The pharmaceutical preparation of claim 1, wherein the conjugate has the following structure:

12. The pharmaceutical preparation 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.

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