Pharmaceutical Compositions Comprising an Anti-Teratogenic Compound and Applications of the Same

• US 20090060903A1
• Filed: 08/29/2007
• Published: 03/05/2009
• Est. Priority Date: 08/29/2007
• Status: Active Grant

• Current Assignee: Bioventures, LLC
• Original Assignee: The Board of Trustees of the University of Arkansas (University of Arkansas System)
• Inventors: Knobloch, Jurgen, Ruther, Uli, Shaughnessy, John D.
• Granted Patent: US 7,723,301 B2
• Time in Patent Office: Days
• US Class Current: 424/130.100
• 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 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 33/14 Alkali metal chlorides; Alkaline earth metal chlorides
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/74 Inducing cell proliferation
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

Pharmaceutical compositions comprising anti-teratogenic agents are disclosed. Additionally, pharmaceutical compositions comprising anti-neoplastic agents and anti-teratogenic agents are disclosed. Methods of assessing the teratogenicity of a compound are disclosed. The present invention further comprises applications of the aforementioned compositions and methods.

Claims

1. A pharmaceutical composition comprising an anti-neoplastic agent and an anti-teratogenic agent.

2. The pharmaceutical composition of claim 1 wherein said anti-neoplastic agent is selected from the group consisting of thalidomide and lenalidomide.

3. The pharmaceutical composition of claim 1 wherein said anti-teratogenic agent comprises an agent that activates the Wnt signaling pathway downstream of the Wnt ligand-receptor interaction.

4. The pharmaceutical composition of claim 3 wherein said agent that activates the Wnt signaling pathway downstream of the Wnt ligand-receptor interaction is selected from the group consisting of an inhibitor of BMP signaling, an inhibitor of Dkk1, an inhibitor of Gsk3β

, and an oxidative stress antagonist.

5. The pharmaceutical composition of claim 4 wherein said inhibitor of BMP signaling comprises Noggin.

6. The pharmaceutical composition of claim 4 wherein said inhibitor of Dkk1 comprises an anti-Dkk1 antibody.

7. The pharmaceutical composition of claim 4 wherein said inhibitor of Gsk3β

is LiCl or Gsk3-Inhibitor IX.

8. The pharmaceutical composition of claim 4 wherein said oxidative stress antagonist is PBN.

9. A pharmaceutical composition for blocking the teratogenicity of an anti-neoplastic agent comprising an agent that activates the Wnt signaling pathway downstream of the Wnt ligand-receptor interaction.

10. The pharmaceutical composition of claim 9 wherein said anti-neoplastic agent is selected from the group consisting of thalidomide and lenalidomide.

11. The pharmaceutical composition of claim 9 wherein said agent that activates the Wnt signaling pathway downstream of the Wnt ligand-receptor interaction is selected from the group consisting of an inhibitor of BMP signaling, an inhibitor of Dkk1, an inhibitor of Gsk3β

, and an oxidative stress antagonist.

12. The pharmaceutical composition of claim 11 wherein said inhibitor of BMP signaling comprises Noggin.

13. The pharmaceutical composition of claim 11 wherein said inhibitor of Dkk1 comprises an anti-Dkk1 antibody.

14. The pharmaceutical composition of claim 11 wherein said inhibitor of Gsk3β

is LiCl or Gsk3-Inhibitor IX.

15. The pharmaceutical composition of claim 11 wherein said oxidative stress antagonist is PBN.

16. A method of inhibiting the teratogenicity of an anti-neoplastic agent comprising administering a pharmaceutical composition comprising an agent that activates the Wnt signaling pathway downstream of the Wnt ligand-receptor interaction.

17. The method of claim 16 wherein said anti-neoplastic agent is selected from the group consisting of thalidomide and lenalidomide.

18. The method of claim 16 wherein said agent that activates the Wnt signaling pathway downstream of the Wnt ligand-receptor interaction is selected from the group consisting of an inhibitor of BMP signaling, an inhibitor of Dkk1, an inhibitor of Gsk3β

, and an oxidative stress antagonist.

19. The method of claim 18 wherein said inhibitor of BMP signaling comprises Noggin.

20. The method of claim 18 wherein said inhibitor of Dkk1 comprises an anti-Dkk1 antibody.

21. The method of claim 18 wherein said inhibitor of Gsk3β

is LiCl or Gsk3-Inhibitor IX.

22. The method of claim 18 wherein said oxidative stress antagonist is PBN.

23. A method of assessing the teratogenicity of a compound comprising:

(a) administering the compound to a cell; and

(b) observing whether there is activation of the Wnt signaling pathway downstream of the Wnt ligand-receptor interaction in comparison to an untreated cell.

24. A method of treating a mammalian subject comprising administering to said mammalian subject an effective amount of a pharmaceutical composition comprising an anti-neoplastic agent and an anti-teratogenic agent.

25. The method of claim 24 wherein said anti-neoplastic agent is selected from the group consisting of thalidomide and lenalidomide.

26. The method of claim 24 wherein said anti-teratogenic agent comprises an agent that activates the Wnt signaling pathway downstream of the Wnt ligand-receptor interaction.

27. The method of claim 24 wherein said agent that activates the Wnt signaling pathway downstream of the Wnt ligand-receptor interaction is selected from the group consisting of an inhibitor of BMP signaling, an inhibitor of Dkk1, an inhibitor of Gsk3β

, and an oxidative stress antagonist.

28. The method of claim 26 wherein said inhibitor of BMP signaling comprises Noggin.

29. The method of claim 26 wherein said inhibitor of Dkk1 comprises an anti-Dkk1 antibody.

30. The method of claim 26 wherein said inhibitor of Gsk3β

is LiCl or Gsk3-Inhibitor IX.

31. The method of claim 26 wherein said oxidative stress antagonist is PBN.