Claims
- 1. A sterically hindered polymer, comprising a water-soluble and non-peptidic polymer backbone having at least one terminus, said terminus being covalently bonded to the structure
- 2. The polymer of claim 1, wherein said 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.
- 3. The polymer of claim 1, wherein the water-soluble and non-peptidic polymer is poly(ethylene glycol).
- 4. The polymer of claim 3, wherein the poly(ethylene glycol) has an average molecular weight from about 200 Da to about 100,000 Da.
- 5. The polymer of claim 1, wherein the water-soluble and non-peptidic polymer has from about 2 to about 300 termini.
- 6. The polymer of claim 1, wherein Z is a C1-C8 alkyl or substituted alkyl.
- 7. The polymer 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.
- 8. The polymer of claim 1, wherein m is 1 to about 10.
- 9. The polymer of claim 1, wherein X is selected from the group consisting of chlorine, bromine, N-succinimidyloxy, sulfo-N-succinimidyloxy, 1-benzotriazolyloxy, hydroxyl, 1-imidazolyl, and p-nitrophenyloxy.
- 10. The polymer of claim 1, wherein the polymer has the structure
- 11. The polymer of claim 10, wherein R′ is methoxy.
- 12. The polymer of claim 10, wherein R′ is a functional group selected from the group consisting of hydroxyl, protected hydroxyl, active ester, active carbonate, acetal, aldehyde, aldehyde hydrates, 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, glyoxals, diones, mesylates, tosylates, and tresylate.
- 13. The polymer of claim 10, wherein R′ is —W—D, wherein W is a linker and D is a biologically active agent.
- 14. The polymer of claim 10, wherein R′ is —Q(CH2)mCHZC(O)X, wherein Q, m, Z and X are as defined above.
- 15. The polymer of claim 10, wherein POLY is poly(ethylene glycol).
- 16. The polymer 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 of claim 10, wherein Z is a C1-C8 alkyl or substituted alkyl.
- 18. The polymer of claim 10, wherein Z is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, and benzyl.
- 19. The polymer of claim 10, wherein m is 1 to about 10.
- 20. The polymer of claim 10, wherein X is hydroxyl.
- 21. The polymer of claim 1, wherein the polymer has the structure
- 22. The polymer of claim 21, wherein POLY is poly(ethylene glycol).
- 23. The polymer of claim 22, wherein POLY has an average molecular weight from about 200 Da to about 100,000 Da.
- 24. The polymer of claim 1, wherein the polymer has the structure
- 25. The polymer of claim 24, wherein X is hydroxyl.
- 26. 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
- 27. The biologically active polymer conjugate of claim 26, wherein W is selected from the group consisting of O, S, and NH.
- 28. The biologically active polymer conjugate of claim 26, 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.
- 29. A method of preparing a biologically active polymer conjugate, comprising:
providing a water-soluble and non-peptidic polymer comprising a polymer backbone having at least one terminus, said terminus being covalently bonded to the structure 14wherein: L is the point of bonding to the terminus of the polymer backbone; Q is O or S; m is 0 to about 20; Z is selected from the group consisting of alkyl, substituted alkyl, aryl and substituted aryl; and X is a leaving group; reacting the polymer with a biologically active agent to form a biologically active polymer conjugate having at least one terminus covalently bonded to the following structure 15wherein: L is the point of bonding to the terminus of the polymer backbone; Q is O or S; m is 0 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.
- 30. The method of claim 29, wherein W is selected from the group consisting of O, S, and NH.
- 31. The method of claim 29, 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.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No. 60/171,784, filed Dec. 22, 1999, which is herein incorporated by reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60171784 |
Dec 1999 |
US |