Claims for Patent: 8,748,379

Summary for Patent: 8,748,379

Title:	RTEF-1 variants and the use thereof for inhibition of angiogenesis
Abstract:	Dominant negative (DN) variants of transcriptional enhancer factor 1-related (RTEF-1) are described. DN RTEF-1 polypeptides may be directly targeted to cells or delivered in nucleic acid expression vectors to alter cellular transcription. Methods for inhibiting VEGF production and thereby treating angiogenic disorders such as cancer are described. For example, in certain aspects, DN RTEF-1 may be used to treat angiogenic disorders of the eye such as age related macular degeneration (AMD).
Inventor(s):	Stout; J. Timothy (Portland, OR), McFarland; Trevor J. (Portland, OR), Appukuttan; Binoy (Portland, OR)
Assignee:	Research Development Foundation (Carson City, NV)
Application Number:	12/134,626
Patent Claims:	1. An isolated polypeptide that is at least 95% identical to SEQ ID NO:2; SEQ ID NO:3 or SEQ ID NO:4. 2. The isolated polypeptide of claim 1, wherein the polypeptide consists of SEQ ID NO: 3. 3. The isolated polypeptide of claim 1, wherein the amino acid sequence is at least 95% identical to SEQ ID NO:2. 4. The isolated polypeptide of claim 3, wherein the amino acid sequence is at least 98% identical to SEQ ID NO:2. 5. The isolated polypeptide of claim 4, wherein the amino acid sequence is identical to SEQ ID NO:2. 6. The isolated polypeptide of claim 1, wherein the amino acid sequence is at least 95% identical to SEQ ID NO:3. 7. The isolated polypeptide of claim 6, wherein the amino acid sequence is at least 98% identical to SEQ ID NO:3. 8. The isolated polypeptide of claim 7, wherein the amino acid sequence is identical to SEQ ID NO:3. 9. The isolated polypeptide of claim 1, wherein the amino acid sequence is at least 95% identical to SEQ ID NO:4. 10. The isolated polypeptide of claim 9, wherein the amino acid sequence is at least 98% identical to SEQ ID NO:4. 11. The isolated polypeptide of claim 10, wherein the amino acid sequence is identical to SEQ ID NO:4. 12. The isolated polypeptide of claim 1, further comprising a secretion signal sequence. 13. The isolated polypeptide of claim 1, further comprising a cell internalization moiety. 14. The isolated polypeptide of claim 13, wherein the internalization moiety is a peptide, a polypeptide, an aptamer or an avimer. 15. The isolated polypeptide of claim 14, wherein the internalization moiety comprises internalization sequences from HIV tat, HSV-1 tegument protein VP22, or Drosophila antennopedia. 16. The isolated polypeptide of claim 14, wherein the internalization moiety comprises a poly-arginine, a poly-methionine and/or a poly-glycine peptide. 17. The isolated polypeptide of claim 13, wherein the internalization moiety comprises the amino acid sequence RMRRMRRMRR (SEQ ID NO:23). 18. The isolated polypeptide of claim 13, wherein the internalization moiety is an antibody. 19. The isolated polypeptide of claim 18, wherein the antibody is an IgA, an IgM, an IgE, an IgG, a Fab, a F(ab')2, a single chain antibody, or a paratope peptide. 20. The isolated polypeptide of claim 13, further comprising a cell secretion signal. 21. The isolated polypeptide of claim 20, wherein the cell secretion signal comprises a human IL-2 secretion signal sequence (SEQ ID NO:22). 22. The isolated polypeptide of claim 21, further defined as comprising the amino acid sequence of SEQ ID NO:3, SEQ ID NO:22 and SEQ ID NO:23. 23. A method for treating a patient with an angiogenic disorder comprising administering to the patient an effective amount of a therapeutic composition comprising the polypeptide according to claim 6. 24. The method of claim 23, wherein the angiogenic disorder is ocular neovascularization, an arterio-venous malformation, coronary restenosis, peripheral vessel restenosis, glomerulonephritis, or rheumatoid arthritis. 25. The method of claim 24, wherein the angiogenic disorder is ocular neovascularization. 26. The method of claim 23, wherein the ocular neovascularization is due to macular degeneration, corneal graft rejection, retinopathy of prematurity (ROP), or diabetic retinopathy. 27. The method of claim 26, wherein the ocular neovascularization is due to age-related macular degeneration (AMD). 28. The method of claim 23, further comprising administering a second anti-angiogenic therapy. 29. The method of claim 28, wherein the second anti-angiogenic therapy is an antibody that binds to VEGF, a VEGF receptor, FGF, or an FGF receptor. 30. The method of claim 28, wherein the second anti-angiogenic therapy is bevacizumab, ranibizumab, or pegaptanib sodium. 31. The method of claim 23, wherein the angiogenic disorder is a cancer. 32. The method of claim 31, wherein the cancer is a metastatic cancer. 33. The method of claim 31, wherein the cancer is a bladder, blood, bone, bone marrow, brain, breast, colon, esophagus, eye, gastrointestinal, gum, head, kidney, liver, lung, nasopharynx, neck, ovary, prostate, skin, stomach, testis, tongue, or uterus cancer. 34. The method of claim 33, wherein the cancer is an eye cancer that is further defined as ocular melanoma. 35. The method of claim 31, further comprising administering a second anticancer therapy. 36. The method of claim 35, wherein the second anticancer therapy is chemotherapy, surgical therapy, immunotherapy, or radiation therapy. 37. The method of claim 23, wherein the patient is a human. 38. The method of claim 23, wherein the therapeutic composition is administered systemically. 39. The method of claim 23, wherein the therapeutic composition is administered locally. 40. The method of claim 23, wherein the therapeutic composition is administered to the eye. 41. The method of claim 40, wherein the therapeutic composition is administered topically to the eye or by intraocular injection. 42. The method of claim 41, wherein the therapeutic composition is administered topically to the eye as an eye drop.

Details for Patent 8,748,379

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2027-06-06
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	06/30/2006		2027-06-06
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	08/10/2012		2027-06-06
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	10/13/2016		2027-06-06