Combinations for the treatment of cancer

• US 20090030005A1
• Filed: 07/17/2008
• Published: 01/29/2009
• Est. Priority Date: 07/19/2007
• Status: Abandoned Application

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Ruefli-Brasse, Astrid, Kamb, Alexander
• Application Number:
  US12/218,865
• Publication Number:
  US 20090030005A1
• Time in Patent Office: Days
• US Class Current: 514/249
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

This invention is in the field of pharmaceutical agents and specifically relates to combinations, compositions, uses and methods for treating cancer.

Claims

1. A pharmaceutical composition comprising a de novo purine biosynthesis inhibitor and at least one CDK inhibitor.

2. The pharmaceutical composition of claim 1 containing a CDK4 inhibitor.

3. The pharmaceutical composition of claim 1 containing a CDK6 inhibitor.

4. The pharmaceutical composition of claim 1 wherein the CDK inhibitor is selected from P-276-00, GW-491619, NU-6027, AG-12275, AG-12286, PD-0166285, PD-0332991 and Alvocidib.

5. The pharmaceutical composition of claim 1 wherein the de novo purine biosynthesis inhibitor inhibits AdSL.

6. The pharmaceutical composition of claim 1 wherein the de novo purine biosynthesis inhibitor inhibits AdSS.

7. The pharmaceutical composition of claim 1 wherein the de novo purine biosynthesis inhibitor is selected from alanosine and SDX-102.

8. The pharmaceutical composition of claim 1 wherein the de novo purine biosynthesis inhibitor is methotrexate.

9. A method of treating cancer with a combination comprising at least one de novo purine biosynthesis inhibitor and at least one CDK inhibitor.

10. The method of claim 9 comprising a rescue substrate.

11. The method of claim 10 wherein the rescue substrate is adenine, MTA or an MTA derivative.

12. The method of claim 10 wherein de novo purine biosynthesis inhibitor is administered after the CDK inhibitor.

13. A kit comprising, in one or more containers, separately or in admixture one or more de novo purine biosynthesis inhibitor and at least one CDK inhibitor.

14. A method of detecting tumors having p16 and MTAP co-inactivation, wherein the inactivation identifies a tumor that is likely to respond to a composition comprising at least one de novo purine biosynthesis inhibitor and at least one CDK inhibitor.

15. A method of treating a subject determined to have tumors with inactivation of both p16 and MTAP.

16. The method of claim 15, wherein the tumors have inactivation of both p16-related polynucleotide or polypeptide and MTAP polynucleotide or polypeptide.

17. A method for prognostic or diagnostic assessment of a neoplastic disorder in a subject, comprising:

a) preparing a sample of nucleic acids from a specimen obtained from the subject;

b) contacting the sample with a panel of nucleic acid segments consisting of at least 2 members from the group consisting of p16, CDK4, CDK6, and MTAP to detect the levels of the panel segments;

c) evaluating the sample against a reference standard to determine the magnitude of change in the amounts of the at least 2 members present in the sample; and

d) correlating the magnitude of change with the presence or resolution of the disorder.