Drug-oligomer conjugates

• US 20040253206A1
• Filed: 03/29/2004
• Published: 12/16/2004
• Est. Priority Date: 09/13/1999
• Status: Abandoned Application

• Current Assignee: Biocon Limited (Biocon Incorporated)
• Original Assignee: Biocon Limited (Biocon Incorporated)
• Inventors: Ekwuribe, Nnochiri N., Dyakonov, Tatyana, Price, Christopher H.
• Application Number:
  US10/811,760
• Publication Number:
  US 20040253206A1
• Time in Patent Office: Days
• US Class Current: 424/78.27
• 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: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Drug-oligomer conjugates and pharmaceutical compositions prepared therefrom. Methods of making and using the drug-oligomer conjugates and pharmaceutical compositions.

Claims

1. A conjugate comprising:

(a) at least one therapeutic compound; and

(b) one or more PEG polymers and/or oligomers, each joined to a bonding site on the therapeutic compound by a hydrolyzable bond, said PEG polymers and/or oligomers each;

(i) comprising a straight or branched PEG segment consisting of 1 to 25 polyethylene glycol units; and

(ii) comprising a salt-forming moiety.

2. The conjugate of claim 1, wherein the conjugate is a prodrug.

3. The conjugate of claim 1, wherein the straight or branched PEG segment consists of from 2 to 20 polyethylene glycol units.

4. The conjugate of claim 1, wherein the polyethylene glycol oligomer has a number of polyethylene glycol units selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, and 9.

5. The conjugate of claim 1, wherein the salt-forming moiety is selected from the group consisting of:

ammonium, carboxylate, phosphate, sulfate and mesylate.

6. The conjugate of claim 1, wherein the therapeutic compound is derivatized by from 1 up to the maximum number of sites of attachment for the polyethylene glycol oligomer(s).

7. The conjugate of claim 1, which, when delivered via the oral route of administration to treat a mammalian subject having a disease condition responsive to the therapeutic compound, provides a therapeutically effective dose of the therapeutic compound to the blood.

8. The conjugate of claim 1, wherein the therapeutic compound is a peptide.

9. The conjugate of claim 1, wherein the therapeutic compound is a protein.

10. A pharmaceutical composition comprising:

(a) a conjugate of claim 1;

and

(b) a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10, wherein the conjugate is a prodrug.

12. The pharmaceutical composition of claim 10 in a form suitable for oral administration.

13. A conjugate comprising a therapeutic compound joined by hydrolysable bond(s) to one or more PEG oligomer(s) selected from the group consisting of:

14. The conjugate of claim 13, wherein the conjugate is a prodrug.

15. The conjugate of claim 13, wherein the therapeutic compound is derivatized by from 1 up to the maximum number of sites of attachment for the polyethylene glycol oligomer(s).

16. The conjugate of claim 13, wherein the therapeutic compound is a peptide.

17. The conjugate of claim 13, wherein the therapeutic compound is a protein.

18. A pharmaceutical composition comprising:

(a) a conjugate of claim 13;

and

(b) a pharmaceutically acceptable carrier.

19. The pharmaceutical composition of claim 18, wherein the conjugate is a prodrug.

20. The pharmaceutical composition of claim 18 in a form suitable for oral administration.

21. A method of treating a mammalian subject having a disease condition responsive to a therapeutic compound, said method comprising administering to the subject of an effective disease treating amount of a conjugate comprising:

(a) at least one therapeutic compound; and

(b) one or more PEG polymers and/or oligomers, each joined to a bonding site on the therapeutic compound by a hydrolyzable bond, said PEG polymers and/or oligomers each;

(i) comprising a straight or branched PEG segment consisting of 1 to 25 polyethylene glycol units; and

(ii) comprising a salt-forming moiety.

22. The method of claim 21, wherein the conjugate is a prodrug.

23. The conjugate of claim 21, wherein the therapeutic compound is a peptide.

24. The conjugate of claim 21, wherein the therapeutic compound is a protein.

25. A method of treating a mammalian subject having a disease condition responsive to a therapeutic compound, said method comprising administering to the subject of an effective disease treating amount of a conjugate comprising the therapeutic compound joined by hydrolyzable bond(s) to one or more PEG oligomer(s) selected from the group consisting of:

26. The method of claim 25, wherein the conjugate is a prodrug.

27. The conjugate of claim 25, wherein the therapeutic compound is a peptide.

28. The conjugate of claim 25, wherein the therapeutic compound is a protein.