Claims for Patent: 7,622,102

Summary for Patent: 7,622,102

Title:	Method for monitoring early treatment response
Abstract:	Disclosed is a method for monitoring early treatment response of a cancer treatment comprising measuring by magnetic resonance spectroscopy (MRS), for example, proton MRS, the amount of Choline present in the tissue adjoining or surrounding the cancerous tissue before and after treatment; the treatment comprises administration of an angiogenesis inhibitor, for example, a VEGF inhibitor, whereby a decrease in the amount of Choline after treatment is indicative of a positive response. The decrease in the amount of Choline represents the decrease in the internal cell membrane as a result of down regulation of the organelles and their secretory granules and their transport vesicles. Disclosed also is a method for determining effectiveness of an angiogenesis inhibitor in the treatment of cancer. Also disclosed are methods of monitoring early treatment response in diseases where an angiogenesis effector, i.e., an inhibitor or promoter of angiogenesis, is employed.
Inventor(s):	Norfray; Joseph F. (Glenview, IL)
Assignee:	Receptomon, LLC (Glenview, IL)
Application Number:	11/053,059
Patent Claims:	1. A method for monitoring early treatment response of a cancer treatment comprising measuring, by Magnetic Resonance Spectroscopy (MRS), the amount of Choline present in a tissue adjoining or surrounding the cancerous tissue before and after treatment, wherein said treatment comprises administration of an angiogenesis inhibitor, whereby a decrease in the amount of Choline after treatment is indicative of a positive response. 2. The method of claim 1, wherein the MRS is based on the resonance of nuclei selected from the group consisting of .sup.31P, .sup.1H, .sup.13C, and .sup.23Na, and any combination thereof. 3. The method of claim 2, wherein the MRS is based on .sup.1H resonance. 4. The method of claim 1, wherein measuring the amount of Choline comprises measuring the height of a peak corresponding to Choline. 5. The method of claim 1, wherein measuring the amount of Choline comprises measuring the area under a peak corresponding to Choline. 6. The method of claim 1, wherein measuring the amount of Choline comprises measuring the ratio of the height of a peak corresponding to Choline relative to the height of peak of an internal standard. 7. The method of claim 6, wherein the internal standard is total creatine when the MRS is based on .sup.1H resonance. 8. The method of claim 6, wherein the internal standard is adenosine triphosphate (ATP) when the MRS is based on .sup.31P resonance. 9. The method of claim 1, wherein measuring the amount of Choline comprises measuring the ratio of the area under a peak corresponding to Choline relative to the area under a peak of an internal standard. 10. The method of claim 9, wherein the MRS is based on .sup.1H resonance and the internal standard is total creatine. 11. The method of claim 1, wherein the angiogenesis inhibitor interrupts one or more pathways selected from the group consisting of a growth factor signaling pathway, an integrin/protease pathway, a coagulation/fibrinolysis pathway, and an inflammatory signaling pathway. 12. The method of claim 1, wherein measuring the amount of Choline comprises measuring the amount of choline, phosphocholine, phosphatidylcholine, lysophosphatidylcholine, or glycerophosphocholine, phosphomonoesters of choline, phosphodiesters of choline, phosphoethanolamine, glycerophosphoethanolamine, or any combination thereof. 13. The method of claim 1, wherein the amount of Choline is measured within a period of about 168 hours of said treatment. 14. The method of claim 13, wherein the amount of Choline is measured within a period of about 24 hours. 15. The method of claim 14, wherein the amount of Choline is measured within 12 hours of said treatment. 16. The method of claim 1, wherein the angiogenesis inhibitor is selected from the group consisting of VEGF receptor tyrosine kinase inhibitors, monoclonal antibodies to growth factor receptors, VEGF toxin conjugate, dominant negative VEGF-2, soluble VEGFR (VEGF-TRAP) and antisense oligonucleotides, growth factor transforming kinases, farnesyl transferase inhibitors, agents targeting tumor suppressors, agents that inhibit proliferation of endothelial cells, antibody and peptide integrin inhibitors, plasmin inhibitors, urokinase-type plasminogen activator inhibitors, matrix metalloproteinase inhibitors, cyclooxygenase inhibitors, lipoxygenase inhibitors, and inhibitors of mitogenic effects, and any combination thereof. 17. The method of claim 1, wherein the angiogenesis inhibitor is selected from the group consisting of SU5416, SU6668, cetuximab, gefitinib, erlotinib, canertinib, EKB-569, lapatinib, IMC-C225, ABX-EGF, HuMax-EGFR, DC101, suramin, gleevec, herceptin, p-53 (PRIMA-1), thalidomide, squalamine, anti-.alpha..sub.vB.sub.3 integrin antibody, anti-.alpha..sub.vB5 integrin antibody, cyclic peptide inhibitor of integrin .alpha..sub.vB.sub.3//.alpha..sub.vB.sub.5, cilengitide, fumagallin, TNP-470, EMD 121974, .alpha.2-antiplasmin, .alpha.2-macroglobulin, kininostatin, BMS275291, COL-3, marimastat, neovastat, solimastat, angiostatin, endostatin, antithrombin fragments, fibrinogen-E, fibrin-D, thrombospondin-1, platelet factor-4, low molecular weight heparins, Vioxx, Celebrex, and interferon-.alpha. and .beta., and any combination thereof. 18. The method of claim 1, wherein the cancer is selected from the group consisting of brain cancer, colorectal cancer, breast cancer, acute leukemia, lung cancer, kidney cancer, squamous cell cancer, testicular cancer, stomach cancer, melanoma, sarcomas, ovarian cancer, non-small cell lung cancer, esophageal cancer, gastric cancer, pancreatic cancer, neuroblastoma, mesothelioma, prostate cancer, bone cancer, kidney cancer, and hepatocellular cancer. 19. The method of claim 1, wherein inhibition of angiogenesis causes an interruption in an up-regulated intracellular organelle. 20. The method of claim 19, wherein the interruption in the up-regulated intracellular organelle decreases the number of secretory granules. 21. The method of claim 19, wherein the interruption in the up-regulated intracellular organelle decreases the number of transporting vesicles. 22. The method of claim 1, wherein inhibition of angiogenesis causes an interruption in a function of the Golgi apparatus. 23. The method of claim 1, wherein inhibition of angiogenesis causes an interruption in a function of the lysosomes. 24. The method of claim 1, wherein inhibition of angiogenesis causes an interruption in a function of the endoplasmic reticulum. 25. The method of claim 1, wherein inhibition of angiogenesis causes an interruption in a function of the mitochondrion. 26. The method of claim 1, wherein inhibition of angiogenesis causes an interruption in a function of the nucleus. 27. The method of claim 1, wherein inhibition of angiogenesis causes an interruption in a function of the peroxisomes. 28. A method for monitoring cancer treatment comprising: (a) localizing a tumor in a patient; (b) selecting a region of interest (ROI) of the tumor and a tissue adjoining or surrounding the tumor; (c) obtaining magnetic resonance spectra (MRS) of the ROI; (d) measuring the amount of Choline from the MRS spectra; (e) initiating treatment comprising administering an angiogenesis inhibitor; (f) obtaining MR spectra of the tumor at the same ROI within a period of 7 days of initiating treatment; (g) measuring the amount of Choline from the MR spectra; and (h) comparing the amount of Choline obtained before treatment with the amount of Choline obtained after treatment; whereby a decrease in the amount of Choline after treatment is indicative of a positive response to treatment. 29. The method of claim 28, wherein the MR spectra of the tumor is obtained within 3 days of initiating treatment. 30. The method of claim 29, wherein the MR spectra of the tumor is obtained within 1 day of initiating treatment. 31. A method for determining effectiveness of a molecule as a drug for treating cancer comprising administering an amount of the molecule to an animal having a cancerous tissue and measuring, by Magnetic Resonance Spectroscopy, the amount of Choline present in the tissue surrounding the cancerous tissue before and after administering the molecule, wherein said molecule comprises an angiogenesis inhibitor, whereby a decrease in the amount of Choline after administering said molecule is indicative of its effectiveness. 32. A method for monitoring early treatment response of an angiogenesis effector treatment in a diseased animal comprising measuring, by Magnetic Resonance Spectroscopy (MRS), the amount of Choline present in the diseased tissue before and after treatment, wherein said treatment comprises administration of an angiogenesis effector, whereby a change in the amount of Choline after treatment is indicative of a positive response. 33. The method of claim 32, wherein the angiogenesis effector is an inhibitor of angiogenesis. 34. The method of claim 32, wherein the angiogenesis effector is a promoter of angiogenesis. 35. The method of claim 33, wherein the disease is retinopathy, rheumatoid arthritis, hereditary hemorrhagic telangiecstasia, or hyperplasia. 36. The method of claim 34, wherein the disease is a stroke or cardiac disease. 37. The method of claim 33, wherein angiogenesis is inhibited by interfering with a proangiogenic signaling pathway involving a growth factor, integrin/protease, coagulation/fibrinolysis factor, or inflammatory factor. 38. The method of claim 34, wherein angiogenesis is promoted by up-regulating a proangiogenic pathway involving a growth factor, integrin/protease, coagulation/fibrinolysis factor, or inflammatory factor. 39. The method of claim 1, wherein the Choline is the total choline. 40. The method of claim 28, wherein the Choline is the total choline. 41. The method of claim 31, wherein the Choline is the total choline. 42. The method of claim 32, wherein the Choline is the total choline.

Details for Patent 7,622,102

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2039-02-26
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2039-02-26
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Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2039-02-26