Claims
- 1. A biologically active polymer conjugate, comprising a water-soluble and non-peptidic polymer backbone having at least one terminus, said terminus being covalently bonded to the structure wherein: L is the point of bonding to the terminus of the polymer backbone; Q is O or S; m is 1 to about 20; Z is selected from the group consisting of alkyl, substituted alkyl, aryl and substituted aryl; W is a linker; and D is a biologically active agent.
- 2. The polymer conjugate of claim 1, wherein W is selected from the group consisting of —O—, —S—, and —NH—.
- 3. The polymer conjugate of claim 1, wherein D is selected from the group consisting of peptides, proteins, enzymes, small molecule drugs, dyes, lipids, nucleosides, oligonucleotides, cells, viruses, liposomes, microparticles and micelles.
- 4. The polymer conjugate of claim 1, wherein the water-soluble and non-peptidic polymer backbone is selected from the group consisting of poly(alkylene glycol), poly(oxyethylated polyol), poly(olefinic alcohol), poly(vinylpyrrolidone), poly(hydroxypropylmethacrylamide), poly(α-hydroxy acid), poly(vinyl alcohol), polyphosphazene, polyoxazoline, poly(N-acryloylmorpholine), and copolymers, terpolymers, and mixtures thereof.
- 5. The polymer conjugate of claim 1, wherein the water-soluble and non-peptidic polymer is poly(ethylene glycol).
- 6. The polymer conjugate of claim 5, wherein the poly(ethylene glycol) has an average molecular weight from about 200 Da to about 100,000 Da.
- 7. The polymer conjugate of claim 6, wherein the poly(ethylene glycol) has an average molecular weight from about 6000 Da to about 80,000 Da.
- 8. The polymer conjugate of claim 1, wherein the water-soluble and non-peptidic polymer has from about 2 to about 300 termini.
- 9. The polymer conjugate of claim 1, wherein Z is a C1-C8 alkyl or substituted alkyl.
- 10. The polymer conjugate of claim 1, wherein Z is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, and benzyl.
- 11. The polymer conjugate of claim 1, wherein m is 1 to about 10.
- 12. The polymer conjugate of claim 1, wherein the polymer has the structure: wherein: POLY is a water-soluble and non-peptidic polymer backbone; and R′ is a capping group or a functional group.
- 13. The polymer conjugate of claim 12, wherein R′ is methoxy.
- 14. The polymer conjugate of claim 12, wherein R′ is a functional group selected from the group consisting of hydroxyl, protected hydroxyl, active ester, active carbonate, acetal, aldehyde, aldehyde hydrate, alkenyl, acrylate, methacrylate, acrylamide, active sulfone, amine, protected amine, hydrazide, protected hydrazide, thiol, protected thiol, carboxylic acid, protected carboxylic acid, isocyanate, isothiocyanate, maleimide, vinylsulfone, dithiopyridine, vinylpyridine, iodoacetamide, epoxide, glyoxal, dione, mesylate, tosylate, and tresylate.
- 15. The polymer conjugate of claim 12, wherein POLY is poly(ethylene glycol).
- 16. The polymer conjugate of claim 15, wherein the poly(ethylene glycol) has an average molecular weight from about 200 Da to about 100,000 Da.
- 17. The polymer conjugate of claim 16, wherein the poly(ethylene glycol) has an average molecular weight from about 6000 Da to about 80,000 Da.
- 18. The polymer conjugate of claim 12, wherein Z is a C1-C8 alkyl or substituted alkyl.
- 19. The polymer conjugate of claim 12, wherein Z is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, and benzyl.
- 20. The polymer conjugate of claim 12, wherein m is 1 to about 10.
- 21. The polymer conjugate of claim 12, wherein W is selected from the group consisting of —O—, —S—, and —NH—.
- 22. The polymer conjugate of claim 1, wherein the polymer has the structure: wherein: POLY is a water-soluble and non-peptidic polymer backbone; R is a central core molecule; and q is an integer from 2 to about 300.
- 23. The polymer conjugate of claim 22, wherein POLY is poly(ethylene glycol).
- 24. The polymer conjugate of claim 23, wherein POLY has an average molecular weight from about 200 Da to about 100,000 Da.
- 25. The polymer conjugate of claim 24, wherein POLY has an average molecular weight from about 6000 Da to about 80,000 Da.
- 26. The polymer conjugate of claim 22, wherein Z is a C1-C8 alkyl or substituted alkyl.
- 27. The polymer conjugate of claim 22, wherein Z is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, and benzyl.
- 28. The polymer conjugate of claim 22, wherein m is 1 to about 10.
- 29. The polymer conjugate of claim 22, wherein W is selected from the group consisting of —O—, —S—, and —NH—.
- 30. The polymer conjugate of claim 1, wherein the polymer has the structure: wherein PEG is poly(ethylene glycol).
- 31. The polymer conjugate of claim 30, wherein the poly(ethylene glycol) has an average molecular weight from about 200 Da to about 100,000 Da.
- 32. The polymer conjugate of claim 31, wherein the poly(ethylene glycol) has an average molecular weight from about 6000 Da to about 80,000 Da.
- 33. The polymer conjugate of claim 30, wherein Z is a C1-C8 alkyl or substituted alkyl.
- 34. The polymer conjugate of claim 30, wherein Z is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, and benzyl.
- 35. The polymer conjugate of claim 30, wherein m is 1 to about 10.
- 36. The polymer conjugate of claim 30, wherein W is selected from the group consisting of —O—, —S—, and —NH—.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a divisional of U.S. application Ser. No. 09/741,933 filed on Dec. 20, 2000, now U.S. Pat. No. 6,495,659, which claims the benefit of U.S. Provisional Application No. 60/171,784, filed Dec. 22, 1999, both of which are herein incorporated by reference in their entirety.
US Referenced Citations (4)
Number |
Name |
Date |
Kind |
5614549 |
Greenwald et al. |
Mar 1997 |
A |
5672662 |
Harris et al. |
Sep 1997 |
A |
5840900 |
Greenwald et al. |
Nov 1998 |
A |
6495659 |
Bentley et al. |
Dec 2002 |
B2 |
Foreign Referenced Citations (3)
Number |
Date |
Country |
63097606 |
Apr 1988 |
JP |
WO 9703106 |
Jan 1997 |
WO |
WO 9945964 |
Sep 1999 |
WO |
Non-Patent Literature Citations (2)
Entry |
Topchiyeva, I.N. “Synthesis of Biologically Active Polyethylene Glycol Derivatives. A Review”, Polymer Science U.S.S.R., 1990, pp. 833-851, vol. 32, No. 5. |
Fradet, et al., “Synthesis of Monocarboxylic Polyoxyethylenes”, Polymer Bulletin, Feb. 1981, pp. 205-210, vol. 4., No. 4. |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/171784 |
Dec 1999 |
US |