METHOD FOR NON-INVASIVE DETECTION AND TREATMENT OF CEREBRAL ANEURYSMS

• US 20090068097A1
• Filed: 02/06/2007
• Published: 03/12/2009
• Est. Priority Date: 02/07/2006
• Status: Active Grant

• Current Assignee: Lers Surgical, LLC
• Original Assignee: Lers Surgical, LLC
• Inventors: Sevrain, Lionel C.
• Granted Patent: US 8,501,156 B2
• Time in Patent Office: Days
• US Class Current: 424/1.490
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants

Abstract

Described herein is a method for non-invasive detection and treatment of intra-cranial aneurysms. Antibodies are provided to specifically react/bind with antigens of the cerebral aneurism wall. The antibodies may be bound to a label and/or to a therapeutic agent for diagnosis and/or for treatment purposes thereof. Intra-cranial aneurysms are thus non-invasively detected before rupture occurs and are specifically treated.

Claims

1. A compound comprising:

an antibody moiety for binding a subendothelial component of a cerebral artery; and

a label moiety or a therapeutic moiety.

2. The compound of claim 1, wherein the subendothelial component is accessible from the bloodstream upon formation of an aneurysm or once an aneurysm is formed.

3. The compound of claim 1 wherein the subendothelial component is found in at least one of a tunica intima, an internal elastic lamina, a tunica media and/or a tunica adventitia component of a cerebral artery.

4. The compound of claim 1, wherein the label moiety is a radioactive label or a near infrared fluorophore.

5. The compound of claim 1, wherein the therapeutic moiety is selected from the group consisting of a thrombogenic molecule, a compound for promoting cell growth, a polymerisable molecule, and a compound for repairing an aneurismal wall.

6. The compound of claim 1, wherein the labeling or therapeutic moiety is coupled to a macromolecule or a red blood cell.

8. The compound of claim 1, wherein the therapeutic moiety is selected from the group consisting of elastin, elastin degradation product, fibronectin, fibrinogen, a protease inhibitor, and a cell growth factor.

10. The compound of claim 8 wherein the protease inhibitor is an elastase inhibitor or is a matrix metalloproteinase inhibitor.

12. The compound of claim 1, wherein the subendothelial component is a structural protein.

13. The compound of claim 12, wherein the structural protein is selected from the group consisting of elastin, fibronectin, fibrinogen, a fibrinogen precursor, collagen, laminin, elastin microfibrillar-associated proteins, desmosine, isodesmosine and a cell surface antigen of smooth muscle cell or fibroblast.

15. The compound of claim 1, wherein the aneurysm is a saccular cerebral artery aneurysm.

16. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

34. A kit comprising a container including the compound of claim 1 or the pharmaceutical composition of claim 16.

35. The compound of claim 5, wherein the macromolecule comprises albumin, transferrin, a globulin, pectin, gelatin, dextran, or a cellulose derivative.

36. The compound of claim 12, wherein the component is expressed because of vascular wall pathological response.

37. The compound of claim 36, wherein the component expressed because of vascular wall pathological response comprises elastin degradation product, elastase, intracellular structural protein, or angiogenetic growth factor.

38. The compound of claim 37, wherein the growth factor comprises vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF).

7. (canceled)

9. (canceled)

11. (canceled)

14. (canceled)

17. A method for detecting a cerebral aneurysm, the method comprising:

administering to a mammal in need thereof a compound coupled to a macromolecule or a red blood cell, said compound comprising;

an antibody moiety for binding a subendothelial component of a cerebral artery and

a label moiety; and

detecting the presence of the label moiety at a cerebral artery site,

wherein the presence of the label moiety at the cerebral artery site is indicative of a cerebral aneurysm.

18. The method of claim 17, wherein the mammal in need has or is suspected of having a cerebral aneurysm.

19. The method of claim 17, wherein administration of the compound is performed intra-vascularly.

20. The method of claim 17, wherein the label is a radioactive label or a near infrared fluorophore.

21. The method of claim 17, wherein the cerebral aneurysm is a saccular cerebral artery aneurysm.

32. The method of claim 17, wherein the subendothelial component is a structural protein.

33. The method of claim 32, wherein the structural protein is selected from the group consisting of elastin, fibronectin, fibrinogen, a fibrinogen precursor, collagen, laminin, elastin microfibrillar-associated proteins, desmosine, isodesmosine and a cell surface antigen of smooth muscle cell or fibroblast.

39. The method of claim 32, wherein the component is expressed because of vascular wall pathological response.

40. The method of claim 39, wherein the component expressed because of vascular wall pathological response comprises elastin degradation product, elastase, intracellular structural protein, or angiogenetic growth factor.

41. The method of claim 40, wherein the growth factor comprises vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF).

22. A method for treating a cerebral aneurysm, the method comprising administering to a mammal in need thereof, a compound comprising an antibody moiety for binding a subendothelial component of a cerebral artery and a therapeutic moiety.

23. The method of claim 22, wherein the mammal in need has or is suspected of having a cerebral aneurysm.

24. The method of claim 22, wherein the therapeutic moiety is selected from the group consisting of a thrombogenic molecule, a compound for promoting cell growth, a polymerisable molecule and a compound for repairing the aneurismal wall.

25. The method of claim 24, wherein the therapeutic moiety is coupled to a macromolecule or a red blood cell.

28. The method of claim 22, wherein the therapeutic moiety is selected from the group consisting of elastin, elastin degradation fragment, fibronectin, fibrinogen, and a cell growth factor.

29. The method of claim 22, wherein the therapeutic moiety is a protease inhibitor.

30. The method of claim 29, wherein the protease inhibitor is an elastase inhibitor or a matrix metalloproteinase inhibitor.

26. (canceled)

27. (canceled)

31. (canceled)