Polymer derivatives having particular atom arrangements

• US 7,887,789 B2
• Filed: 05/21/2004
• Issued: 02/15/2011
• 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
• Primary Examiner(s): Landau; Sharmila Gollamudi
• Assistant Examiner(s): Love; Trevor M
• Application Number:
  US10/851,691
• Publication Number:
  US 20050009988A1
• Time in Patent Office: 2,461 Days
• Field of Search: None
• US Class Current: 424/78.08
• 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: A61P 35/00 Antineoplastic agents
• 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 polymeric reagent of the following structure

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

3. The polymeric reagent of claim 2, wherein each R¹ is an organic radical selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl and substituted aryl.

4. The polymeric reagent of claim 2, wherein each R¹ is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tent-butyl, n-pentyl, isopentyl, neopentyl, tort-pentyl, and piperidonyl.

5. The polymeric reagent of claim 1, wherein each water-soluble polymer is a poly(alkylene oxide).

6. The polymeric reagent of claim 5, wherein each poly(alkylene oxide) is a poly(ethylene glycol).

7. The polymeric reagent of claim 6, wherein each poly(ethylene glycol) is terminally capped with an end-capping moiety selected from the group consisting hydroxyl and alkoxy.

8. The polymeric reagent of claim 6, wherein each poly(ethylene glycol) is terminally capped with methoxy.

9. The polymeric reagent of claim 7, wherein each poly(ethylene glycol) has a molecular weight of from about 100 Daltons to about 100,000 Daltons.

10. The polymeric reagent of claim 9, wherein each poly(ethylene glycol) has a molecular weight of from about 1,000 Daltons to about 60,000 Daltons.

11. The polymeric reagent of claim 10, wherein each poly(ethylene glycol) has a molecular weight of from about 2,000 Daltons to about 50,000 Daltons.

12. The polymeric reagent of claim 1, wherein each nitrogen atom of each

13. The polymeric reagent of claim 1, wherein each nitrogen atom of each

14. The polymeric reagent of claim 1, wherein the reactive group is selected from the group consisting of hydroxyl, ester, orthoester, carbonate, acetal, aldehyde, aldehyde hydrate, ketone, vinyl ketone, ketone hydrate, thione, monothiohydrate, dithiohydrate, hemiketal, monothioketal hemiketal, dithiohemiketal, ketal, dithioketal, alkenyl, acrylate, methacrylate, acrylamide, sulfone, amine, hydrazide, thiol, disulfide, thiol hydrate, carboxylic acid, isocyanate, isothiocyanate, maleimide, succinimide, benzotriazole , vinylsulfone, chloroethylsulfone, dithiopyridine, vinylpyridine, iodoacetamide, epoxide, glyoxals, diones, mesylates, tosylates, thiosulfonate, tresylate, silane, —

(CH₂)_rCO₂H, —

(CH₂)_r′

—

CO₂NS, —

(CH₂)_r′

CO₂Bt, —

(CH₂)_rCH(OR)₂, —

(CH₂)_rCHO, —

(CH₂)₂—

NH₂, —

(CH₂)_rM, —

(CH₂)_r—

S—

SO₂—

R, where r is 1-5, r′

is 0-5, R is aryl or alkyl, NS is N-succinimidyl, Bt is 1-benzotriazolyl, and M is N-maleimidyl, and protected and activated forms of any of the foregoing.

15. The polymeric reagent of claim 1, comprising a structure of:

16. The polymeric reagent of claim 15, wherein (f) is 2 to 4 and (n) is 0 to 4.

17. The polymeric reagent of claim 1, comprising a structure selected from the group consisting of:

18. The polymeric reagent of claim 1, comprising a structure selected from the group consisting of

19. The polymeric reagent of claim 1, comprising a structure selected from the group consisting of

20. The polymeric reagent of claim 1, comprising a structure selected from the group consisting of