Claims for Patent: 6,306,819

Summary for Patent: 6,306,819

Title:	Method for regulating size of vascularized normal tissue
Abstract:	Angiogenesis inhibitors are administered to patients in an amount effective to regulate normal, non-transformed vascularized tissue size and/or growth by regulating its vascular compartment. Examples of tissues that can be controlled include adipose tissue, intestinal polyps, muscle (including cardiac) tissue, and endometrial tissue. The response of these tissues to the angiogenesis inhibitors is dose-dependent, reversible, and common to a variety of different angiogenesis inhibitors (examples use TNP-470, angiostatin, and endostatin), based on studies in animal models of obesity, intestinal polyps, cardiac hypertrophy, and endometriosis. Initial studies conducted in an adipose tissue model (genetically obese mice and normal control mice) showed that the growth and mass of adipose tissue is under the control of microvascular endothelium. Expansion of adipose tissue was associated with endothelial cell proliferation. Inhibition of angiogenesis led to reduction in adipose tissue mass. Weight gain in animals receiving angiogenesis inhibitors was significantly restricted, in spite of increases in appetite sufficient to cause weight gain in paired-fed mice. Discontinuation of the inhibitor resulted in rapid expasion of the adipose tissue. The effect was dose-dependent, repeatedly reversible, and occurred in response to all of the inhibitors tested. Significant inhibition was also observed in both the intestinal polyp and cardiac hypertrophy animal models, using dosages of two-thirds or less than the dosages used to treat tumors. Preliminary results in an endometriosis model also show a clear trend towards decreased development of endometriosis in animals treated with angiogenesis inhibitors at a dosage of one-third the dosage used to treat tumors. No effect on normal tissue that was not proliferating, other than adipose tissue, was observed.
Inventor(s):	Rupnick; Maria (Malden, MA), Langer; Robert S. (Newton, MA), Folkman; Judah (Brookline, MA)
Assignee:	Massachusetts Institute of Technology (Cambridge, MA) Children\'s Medical Center Corporation (Boston, MA)
Application Number:	09/183,556
Patent Claims:	1. A method of decreasing the size and/or growth of tissue selected from the group consisting of adipose tissue, endometrium tissue, benign polyps, hypertrophied cardiac tissue, hypertrophied renal tissue, hypertrophied prostatic tissue and tissue containing amyloid deposits in a human or animal comprising administering an effective amount of angiogenesis inhibitor to the animal to decrease the size or growth of the vascularized normal tissue. 2. The method of claim 1 wherein the inhibitor is a collagenase inhibitor. 3. The method of claim 1 wherein the inhibitor is selected from the group consisting of TNP-470, angiostatin, endostatin, and thalidomide. 4. The method of claim 1 wherein the normal vascularized tissue is adipose tissue. 5. The method of claim 4 wherein the animal or human has a genetic defect resulting in obesity. 6. The method of claim 4 whereby the inhibitor suppresses appetite. 7. The method of claim 6 wherein the inhibitor is TNP-470 administered in an amount effective to suppress appetite. 8. The method of claim 7 wherein the TNP-470 is administered in an amount effective to reduce the vascular supply to adipose tissue. 9. The method of claim 1 wherein the tissue is selected from the group consisting of endometrium tissue, benign polyps, hypertrophied cardiac tissue, hypertrophied prostatic tissue. 10. The method of claim 9 wherein the animal or human has polypsis. 11. The method of claim 9 wherein the animal or human has endometriosis. 12. The method of claim 9 wherein the animal or human has an enlarged prostate. 13. The method of claim 9 wherein the animal or human has cardiac or renal hypertrophy.

Details for Patent 6,306,819

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2017-10-31