Claims
- 1. A polymer composition, comprising a mixture of a polymer derivative having the structure R—O-POLY-R′ and a polymer derivative having the structure R—O-POLY-O—R, wherein POLY is a water-soluble and non-peptidic polymer, R is an alkyl or an aryl group, and R′ is a functional group.
- 2. The polymer composition of claim 1, wherein POLY is selected from poly(alkylene oxides), poly(acryloylmorpholine), poly(oxazoline), and poly(vinylpyrrolidine).
- 3. The polymer composition of claim 1, wherein POLY is poly(ethylene glycol).
- 4. The polymer composition of claim 3, wherein POLY has the formula —CH2CH2—O—(CH2CH2O)n—CH2CH2—, where n is from about 8 to about 4000.
- 5. The polymer composition of claim 1, wherein R is methyl.
- 6. The polymer composition of claim 1, wherein R′ is selected from the group consisting of hydroxyl, mesylate, tosylate, tresylate, —O—CO2R3 wherein R3 is H, alkyl or N-succinimidyl, —O—(CH2)n—CO2R3 wherein n is 1-6 and R3 is H, alkyl or N-succinimidyl, —NHR4 wherein R4 is H or alkyl or an amine protecting group, —O—(CH2)n—CH(ZR5)2 wherein n is 1-6, and Z is O or S, R5 is H or an alkyl group, Ar—CH═CH—CH═CH—CO2—, wherein Ar represents a moiety selected from the group consisting of phenyl, substituted phenyl, biphenyl, substituted biphenyl, polycyclic aryls, substituted polycyclic aryls, and heterocyclic aryls, —O—(CH2)n—CHO wherein n is 1-6, —O2CCH2CH2CO2R6, wherein R6 is H or N-succinimidyl, CH2═CH—CO2—, and —O—CH2—CO2CH(CH3)CH2CO2—NHS, wherein NHS is N-succinimidyl.
- 7. The polymer composition of claim 1, wherein R′ is hydroxyl.
- 8. The polymer composition of claim 1, wherein R′ is —O—CO2R3 or —O—(CH2)n—CO2R3, wherein n is 1-6 and R3 is H, alkyl or N-succinimidyl.
- 9. The polymer composition of claim 8, wherein R3 is N-succinimidyl.
- 10. The polymer composition of claim 1, wherein R′ is —O—(CH2)n—CHO wherein n is 1-6.
- 11. The polymer composition of claim 1, wherein R′ is —O—(CH2)n—CH(ZR5)2 wherein n is 1-6, Z is O or S, and R5 is H or an alkyl group.
- 12. The polymer composition of claim 1, wherein POLY is poly(ethylene glycol), R is methyl, and R′ is —O—(CH2)n—CHO wherein n is 2.
- 13. The polymer composition of claim 12, wherein POLY has the formula —CH2CH2—O—(CH2CH2O)n—CH2CH2—, where n is from about 8 to about 4000.
- 14. The polymer composition of claim 1, wherein POLY is poly(ethylene glycol), R is methyl, and R′ is hydroxyl.
- 15. The polymer composition of claim 14, wherein POLY has the formula —CH2CH2—O—(CH2CH2O)n—CH2CH2—, where n is from about 8 to about 4000.
- 16. A polymer composition, comprising a polymer derivative having the structure R—O-POLY-R′, wherein POLY is a water-soluble and non-peptidic polymer, R is an alkyl or an aryl group, and R′ is a functional group, in the absence of HO-POLY-OH.
- 17. The polymer composition of claim 16, wherein POLY is selected from poly(alkylene oxides), poly(acryloylmorpholine), poly(oxazoline), and poly(vinylpyrrolidine).
- 18. The polymer composition of claim 16, wherein POLY is poly(ethylene glycol).
- 19. The polymer composition of claim 18, wherein POLY has the formula —CH2CH2—O—(CH2CH2O)n—CH2CH2—, where n is from about 8 to about 4000.
- 20. The polymer composition of claim 16, wherein R is methyl.
- 21. The polymer composition of claim 16, wherein R′ is selected from the group consisting of hydroxyl, mesylate, tosylate, tresylate, —O—CO2R3 wherein R3 is H, alkyl or N-succinimidyl, —O—(CH2)n—CO2R3 wherein n is 1-6 and R3 is H, alkyl or N-succinimidyl, —NHR4 wherein R4 is H or alkyl or an amine protecting group, —O—(CH2)n—CH(ZR5)2 wherein n is 1-6, and Z is O or S, R5 is H or an alkyl group, Ar—CH═CH—CH═CH—CO2—, wherein Ar represents a moiety selected from the group consisting of phenyl, substituted phenyl, biphenyl, substituted biphenyl, polycyclic aryls, substituted polycyclic aryls, and heterocyclic aryls, —(CH2)n—CHO wherein n is 1-6, —O2CCH2CH2CO2R6, wherein R6 H or N-succinimidyl, CH2═CH—CO2—, and —O—CH2—CO2CH(CH3)CH2CO2—NHS, wherein NHS is N-succinimidyl.
- 22. The polymer composition of claim 16, wherein R′ is hydroxyl.
- 23. The polymer composition of claim 16, wherein R′ is —O—CO2R3 or —O—(CH2)n—CO2R3, wherein n is 1-6 and R3 is H, alkyl or N-succinimidyl.
- 24. The polymer composition of claim 23, wherein R3 is N-succinimidyl.
- 25. The polymer composition of claim 16, wherein R′ is —O—(CH2)n—CHO wherein n is 1-6.
- 26. The polymer composition of claim 16, wherein R′ is —O—(CH2)n—CH(ZR5)2 wherein n is a number of 1-6, Z is O or S, and R5 is H or an alkyl group.
- 27. The polymer composition of claim 16, wherein POLY is poly(ethylene glycol), R is methyl, and R′ is —O—(CH2)n—CHO, wherein n is 2.
- 28. The polymer composition of claim 27, wherein POLY has the formula —CH2CH2—O—(CH2CH2O)n—CH2CH2—, where n is from about 8 to about 4000.
- 29. The polymer composition of claim 16, wherein POLY is poly(ethylene glycol), R is methyl, and R′ is hydroxyl.
- 30. The polymer composition of claim 29, wherein POLY has the formula —CH2CH2—O—(CH2CH2O)n—CH2CH2—, where n is from about 8 to about 4000.
- 31. A polymer conjugate composition, comprising a mixture of a conjugated polymer having the structure R—O-POLY-M1, wherein POLY is a water-soluble and non-peptidic polymer, R is an alkyl or an aryl group, and M1 is a macromolecule, with a polymer derivative having the structure R—O-POLY-O—R, wherein R and POLY are as defined above.
- 32. The polymer conjugate composition of claim 31, wherein M1 is selected from the group consisting of proteins, peptides, lipids, drugs, and polysaccharides.
- 33. The polymer conjugate composition of claim 31, wherein POLY is selected from poly(alkylene oxides), poly(acryloylmorpholine), poly(oxazoline), and poly(vinylpyrrolidine).
- 34. The polymer conjugate composition of claim 31, wherein POLY is poly(ethylene glycol).
- 35. The polymer conjugate composition of claim 34, wherein POLY has the formula —CH2CH2—O—(CH2CH2O)n—CH2CH2—, where n is from about 8 to about 4000.
- 36. The polymer conjugate composition of claim 31, wherein R is methyl.
- 37. A method of forming a polymer conjugate composition, comprising:
providing a mixture of a polymer derivative having the structure R—O- POLY-R′, wherein POLY is a water-soluble and non-peptidic polymer, R is an alkyl or an aryl group, and R′ is a functional group, with a polymer derivative having the structure R—O-POLY-O—R, wherein R and POLY are as defined above; and reacting the functional group R′ with a macromolecule to form a mixture of a conjugated polymer having the formula R—O-POLY-M1, wherein POLY and R are as defined above and M1 is a macromolecule, and a polymer derivative having the structure R—O-POLY-O—R.
- 38. The method of claim 37, wherein POLY is selected from poly(alkylene oxides), poly(acryloylmorpholine), poly(oxazoline), and poly(vinylpyrrolidine).
- 39. The method of claim 37, wherein POLY is poly(ethylene glycol).
- 40. The method of claim 39, wherein POLY has the formula —CH2CH2—O—(CH2CH2O)n—CH2CH2—, where n is from about 8 to about 4000.
- 41. The method of claim 37, wherein R is methyl.
- 42. The method of claim 37, wherein R′ is selected from the group consisting of hydroxyl, mesylate, tosylate, tresylate, —O—CO2R3 wherein R3 is H, alkyl or N-succinimidyl, —O—(CH2)n—CO2R3 wherein n is 1-6 and R3 is H, alkyl or N-succinimidyl, —NHR4 wherein R4 is H or alkyl or an amine protecting group, —O—(CH2)n—CH(ZR5)2 wherein n is 1-6, and Z is O or S, R5 is H or an alkyl group, Ar—CH═CH—CH═CH—CO2—, wherein Ar represents a moiety selected from the group consisting of phenyl, substituted phenyl, biphenyl, substituted biphenyl, polycyclic aryls, substituted polycyclic aryls, and heterocyclic aryls, —O—(CH2)n—CHO wherein n is 1-6, —O2CCH2CH2CO2R6, wherein R6 is H or N-succinimidyl, CH2═CH—CO2—, and —O—CH2—CO2CH(CH3)CH2CO2—NHS, wherein NHS is N-succinimidyl.
- 43. The method of claim 37, wherein R′ is hydroxyl.
- 44. The method of claim 37, wherein R′ is —O—CO2R3 or —O—(CH2)n—CO2R3, wherein n is 1-6 and R3 is H, alkyl or N-succinimidyl.
- 45. The method of claim 44, wherein R3 is N-succinimidyl.
- 46. The method of claim 37, wherein R′ is —O—(CH2)n—CHO wherein n is 1-6.
- 47. The method of claim 37, wherein R′ is —O—(CH2)n—CH(ZR5)2 wherein n is a number of 1-6, Z is O or S, and R5 is H or an alkyl group.
- 48. The method of claim 37, wherein POLY is poly(ethylene glycol), R is methyl, and R′ is —O—(CH2)n—CHO wherein n is 2.
- 49. The method of claim 48, wherein POLY has the formula —CH2CH2—O—(CH2CH2O)n—CH2CH2—, where n is from about 8 to about 4000.
- 50. The method of claim 37, wherein the macromolecule is selected from the group consisting of proteins, peptides, lipids, drugs, and polysaccharides.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser. No. 09/186,759, filed Nov. 5, 1998, which claims the benefit of Provisional Application No. 60/064,600, filed Nov. 6, 1997, both of which are incorporated by reference herein in their entirety.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60064600 |
Nov 1997 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09186759 |
Nov 1998 |
US |
Child |
10071469 |
Feb 2002 |
US |