ENZYMATIC ANTICANCER THERAPY

• US 20090047270A1
• Filed: 04/18/2008
• Published: 02/19/2009
• Est. Priority Date: 04/20/2007
• Status: Active Grant

• Current Assignee: Unikeris Limited
• Original Assignee: Enzon Pharmaceuticals Inc. (Icahn Associates Holding LLC)
• Inventors: Sapra, Puja, Filpula, David R.
• Granted Patent: US 8,741,283 B2
• Time in Patent Office: Days
• US Class Current: 424/94.600
• CPC Class Codes: A61K 38/50 acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
• 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 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• 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: C12N 9/78 acting on carbon to nitrogen bonds other than peptide bonds (3.5)
• CPC Class Codes: C12Y 305/04004 Adenosine deaminase (3.5.4.4)

Abstract

What is provided is a method of treating a patient having a tumor comprising administering an effective amount of adenosine deaminase, preferably polyalkylene oxide conjugated, to a patient in need thereof.

Claims

1. A method of treating a patient having a tumor comprising administering an effective amount of adenosine deaminase to the patient in need thereof.

2. The method of claim 1, wherein the tumor is malignant.

3. The method of claim 1, wherein the amount of adenosine deaminase administered is effective to substantially reduce tissue levels of adenosine or deoxyadenosine in said patient, and wherein growth or spread of the tumor is inhibited by reduced tissue levels of adenosine in said patient.

4. The method of claim 1, wherein the tumor is a solid tumor.

5. The method of claim 1, wherein the tumor is selected from the group consisting of prostate tumor, ovarian cancer and colorectal cancer.

6. The method of claim 1, wherein the adenosine deaminase is conjugated to a substantially non-antigenic polymer.

7. The method of claim 6, wherein the substantially non-antigenic polymer is a polyalkylene oxide.

8. The method of claim 7, wherein the polyalkylene oxide is polyethylene glycol.

9. The method of claim 7 wherein the substantially non-antigenic polymer ranges in size from about 4,000 to about 45,000 Daltons.

10. The method of claim, 6 wherein the conjugated adenosine deaminase is administered in a dose ranging from about 10 U to about 30 U per kg.

11. The method of claim 1 wherein the conjugated adenosine deaminase is administered for a sufficient period of time to maintain inhibition of the tumor.

12. The method of claim 1 wherein the adenosine deaminase is administered for a time period ranging from 1 to about 20 days.

13. The method of claim 6, wherein the conjugate comprises two or more molecules of adenosine deaminase per substantially non-antigenic polymer.

14. The method of claim 6, wherein the adenosine deaminase comprises from about 11 to about 18 polyethylene glycol strands attached to epsilon amino groups of one or more Lys residues of the adenosine deaminase.

15. The method of claim 14, wherein the adenosine deaminase is conjugated to the polyethylene glycol via a urethane linkage.

16. The method of claim 1, wherein the adenosine deaminase is administered by a route selected from the group consisting of subcutaneous, intravenous, intramuscular, intrathecal, intraperitoneal, inhalation and transurethral.

17. The method of claim 1, wherein the adenosine deaminase is adenosine deaminase purified from a bovine source or is a recombinant adenosine deaminase.

18. The method of claim 17, wherein the recombinant adenosine deaminase is selected from the group consisting of recombinant bovine adenosine deaminase comprising SEQ ID NO:

1, recombinant human adenosine deaminase comprising SEQ ID NO;

3 and recombinant bovine adenosine deaminase comprising SEQ ID NO;

5.

19. The method of claim 18, wherein the recombinant bovine adenosine deaminase comprising SEQ ID NO:

5 comprises a Cys74 that is capped to prevent oxidation in an aqueous medium.

20. The method of claim 18T wherein the recombinant adenosine deaminase is according to SEQ ID NO:

1 or SEQ ID NO;

5, with an amino acid substitution selected from the group consisting of Gln in place of Lys₁₉₈;

Ala in place of Thr₂₄₅;

Arg in place of Gly₃₅₁, and combinations thereof.

21. A method of inhibiting tumor growth in a mammal, comprising administering an effective amount of adenosine deaminase or active fragment thereof to a mammal in need thereof.