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Paramétrages

Paramétrages

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1. WO2010033216 - CONJUGUÉS POLYMÈRES DE PEPTIDES DE NESIRITIDE

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

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What is claimed is:

1. A conjugate comprising a residue of a nesiritide moiety covalently attached, either directly or through a spacer moiety of one or more atoms, to a water-soluble, non-peptidic polymer.

2. A conjugate of claim 1 , wherein the polymer is a linear polymer.

3. A conjugate of claim 1, wherein the polymer is a branched polymer.

4. The conjugate of any one of claims 1, 2 and 3, wherein the nesiritide moiety is recombinantly prepared.

5. The conjugate of any one of claims 1, 2 and 3, wherein the nesiritide moiety is prepared by chemical synthesis.

6. The conjugate of any one of claims 1 to 5, wherein the polymer is selected from the group consisting of poly(alkylene oxide), poly( vinyl pyrrolidone), poly( vinyl alcohol), polyoxazoline, and poly(acryloylmorpholine).

7. The conjugate of claim 6, wherein the polymer is a poly(alkylene oxide).

8. The conjugate of claim 7, wherein the poly(alkylene oxide) is a poly( ethylene glycol).

9. The conjugate of claim 8, wherein the poly(ethylene glycol) is terminally capped with an end-capping moiety selected from the group consisting of hydroxy, alkoxy, substituted alkoxy, alkenoxy, substituted alkenoxy, alkynoxy, substituted alkynoxy, aryloxy and substituted aryloxy.

10. The conjugate of claim 8 , wherein the the poly(ethylene glycol) has a weight-average molecular weight in a range of from about 500 Daltons to about 100,000 Daltons.

11. The conjugate of claim 10, wherein the the poly(ethylene glycol) has a weight-average molecular weight in a range of from about 2000 Daltons to about 50,000 Daltons.

12. The conjugate of claim 11, wherein the the poly(ethylene glycol) has a weight-average molecular weight in a range of from about 5000 Daltons to about 40,000 Daltons.

13. The conjugate of any of the preceding claims, wherein the water-soluble, non-peptidic polymer is conjugated at an amino-terminal amino acid of the nesiritide moiety.

14. The conjugate of any of the preceding claims, wherein the water-soluble, non-peptidic polymer is conjugated at a carboxy-terminal amino acid of the nesiritide moiety.

15. The conjugate of any of the preceding claims, wherein the water-soluble, non-peptidic polymer is conjugated at an internal cycteine amino acid of the nesiritide moiety.

16. The conjugate of any of the preceding claims, wherein the water-soluble, non-peptidic polymer is conjugated at an epsilon amino group of an internal lysine amino acid of the nesiritide moiety.

17. The conjugate of claim 8, wherein the polymeric reagent has the following structure:

O O

H3C-(OCH2CH2)n-O-C NH-(CH2CH2O)4— CH2CH2CH2CH wherein, (n) is independently an integer having a value of from about 2 to about 4000.

18. The conjugate of claim 8, wherein the polymeric reagent has the following structure:


Wherein, (n) is independently an integer having a value of from about 2 to about 4000.

19. The conjugate of claim 8, wherein the polymeric reagent has the following structure:
wherein, (n) is independently an integer having a value of from about 2 to about 4000.

20. The conjugate of any one of the preceding claims, wherein the nesiritide residue is covalently attached through a spacer moiety of one or more atoms.

21. The conjugate of claim 20, wherein the spacer moiety includes an amine linkage.

22. The conjugate of claim 20, wherein the spacer moiety includes an amide linkage.

23. The conjugate of claim 20, wherein the spacer moiety includes a disulfide linkage.

24. The compound of any one of the preceding claims, wherein the nesiritide residue is covalently attached via a stable linkage.

25. The compound of any one of the preceding claims, wherein the nesiritide residue is covalently attached via a releasable linkage.

26. A pharmaceutical composition comprising a conjugate of any one of the preceding claims and a pharmaceutically acceptable excipient.

27. A method for making a conjugate comprising contacting, under conjugation conditions, a nesiritide moiety with a polymeric reagent bearing a functional group.

28. A method of treatment comprising administering a compound of any of the preceding claims to a subject in need thereof.