Claims for Patent: 9,802,984

Summary for Patent: 9,802,984

Title:	Biomimetic peptide and biodegradable delivery platform for the treatment of angiogenesis- and lymphangiogenesis-dependent diseases
Abstract:	Mimetic peptides having anti-angiogenic and anti-tumorigenic properties and methods of their use for treating cancer, ocular diseases, such as age-related macular degeneration, and other-angiogenesis-dependent diseases are disclosed. More particularly, an isolated peptide comprising the amino acid sequence LRRFSTAPFAFIDINDVINF, which exhibits anti-angiogenic activity in endothelial cell proliferation, migration, adhesion, and tube formation assays, anti-migratory activity in human breast cancer cells in vitro, anti-angiogenic and anti-tumorigenic activity in vivo in breast cancer xenograft models, and age-related macular degeneration models is disclosed. The isolate peptide also exhibits anti-lymphangiogenic and directly anti-tumorigenic properties.
Inventor(s):	Popel; Aleksander S. (Lutherville-Timonium, MD), Pandey; Niranjan B. (White Marsh, MD), Lee; Esak (Windsor Mill, MD), Green; Jordan J. (Nottingham, MD), Shmueli; Ron B. (Baltimore, MD)
Assignee:	THE JOHNS HOPKINS UNIVERSITY (Baltimore, MD)
Application Number:	14/896,521
Patent Claims:	1. An isolated peptide comprising the amino acid sequence LRRFSTAPFAFIDINDVINF (SEQ ID No: 1), optionally having one or more D amino acids, wherein the peptide exhibits anti-angiogenic, anti-vascular permeability, anti-tumorigenesis and/or anti-lymphangiogenic properties. 2. A composition comprising a pharmaceutically acceptable carrier and an effective amount of the isolated peptide of claim 1. 3. A kit comprising the isolated peptide from claim 1. 4. A nanoparticle or microparticle comprising the isolated peptide from claim 1. 5. The nanoparticle or microparticle of claim 4, wherein the nanoparticle or microparticle comprises PLGA and/or PLGA-PEG. 6. The nanoparticle or microparticle of claim 5, comprising about 2% to about 5% by mass of the isolated peptide loaded onto or into PLGA and/or PLGA-PEG nanoparticles or microparticles. 7. The nanoparticle or microparticle of claim 5, comprising about 6% to about 10% by mass of the isolated peptide loaded onto or into the PLGA and/or PLGA-PEG nanoparticles or microparticles. 8. The nanoparticle or microparticle of claim 4, wherein the nanoparticle or microparticle comprises a poly(beta-amino ester) (PBAE) and/or PBAE-PEG. 9. The nanoparticle or microparticle of claim 8, comprising about 1% to about 5% by mass of the isolated peptide loaded onto or into the PBAE and/or PBAE-PEG nanoparticles or microparticles. 10. The nanoparticle or microparticle of claim 8, comprising about 6% to about 10% by mass of the isolated peptide loaded onto or into the PBAE and/or PBAE-PEG nanoparticles or microparticles. 11. The nanoparticle or microparticle of claim 4, wherein the nanoparticle or microparticle comprises a combination of a poly(beta-amino ester) (PBAE), PLGA, and PEG. 12. The nanoparticle or microparticle of claim 11, comprising about 1% to about 5% by mass of the isolated peptide loaded onto or into particles comprising a combination of a poly(beta-amino ester)(PBAE), PLGA, and PEG. 13. The nanoparticle or microparticle of claim 11, comprising about 6% to about 10% by mass of the isolated peptide loaded onto or into particles comprising a combination of a poly(beta-amino ester) (PBAE), PLGA, and PEG. 14. A method for inhibiting angiogenesis, lymphangiogenesis, vascular permeability and/or tumorigenesis involving a cell, the method comprising: contacting the cell with the isolated peptide of claim 1, in an amount sufficient to inhibit angiogenesis, lymphangiogenesis, vascular permeability and/or tumorigenesis involving the cell. 15. The method of claim 14, wherein contacting the cell results in an inhibition of adhesion, migration, proliferation, and/or tube formation involving the cell. 16. The method of claim 14, wherein the cell is selected from the group consisting of an endothelial cell, a microvascular cell, and a lymphatic cell. 17. The method of claim 14, wherein the cell is found in adipose tissue and the method reduces or prevents obesity. 18. The method of claim 14, wherein the cell is a transplanted cell and the method reduces or prevents tissue and/or organ rejection after transplantation of the cell. 19. The method of claim 14, wherein the isolated peptide is loaded onto or into a nanoparticle or microparticle before contacting the cell. 20. The method of claim 19, wherein the nanoparticle or microparticle comprises PLGA and/or PLGA-PEG. 21. The method of claim 19, wherein the nanoparticle or microparticle comprises PBAE and/or PBAE-PEG. 22. The method of claim 19, wherein the nanoparticle or microparticle comprises PBAE, PLGA, and PEG. 23. A method for treating angiogenesis, lymphangiogenesis, vascular permeability, and/or tumorigenesis in a subject, the method comprising: administering to the subject an isolated peptide of claim 1, in an amount sufficient to treat the subject. 24. The method of claim 23, wherein the subject is human. 25. The method of claim 23, wherein the subject is nonhuman. 26. The method of claim 23, wherein the subject has a disease that comprises a neoplasia. 27. The method of claim 26, wherein the neoplasia comprises a solid tumor. 28. The method of claim 26, wherein the neoplasia comprises a cancer. 29. The method of claim 28, wherein the cancer is selected from the group consisting of breast, lung, glioblastoma, ocular, renal cell, hepatic cell, head, and neck cancer. 30. The method of claim 23, wherein the method inhibits angiogenesis, lymphangiogenesis, vascular permeability, and/or tumorigenesis in or surrounding a tumor. 31. The method of claim 30, wherein the tumor is a primary tumor or an established metastasized tumor. 32. The method of claim 23, wherein the method inhibits lymphangiogenesis, angiogenesis and/or tumorigenesis perioperatively and/or postoperatively. 33. The method of claim 28, wherein the method inhibits the establishment of metastasis or inhibits further metastasis of the cancer. 34. The method of claim 28, wherein the method inhibits dissemination of tumor cells through the blood and/or lymphatic vasculature. 35. The method of claim 23, wherein the subject has a disease that is related to ocular angiogenesis or diabetic retinopathy. 36. The method of claim 35, wherein the disease related to ocular angiogenesis is selected from the group consisting of age-related macular degeneration, macular edema, neovascular glaucoma, proliferative diabetic retinopathy, and retinopathy of prematurity. 37. The method of claim 23, wherein the isolated peptide is loaded onto or into a nanoparticle or microparticle before administering to the subject. 38. The method of claim 37, wherein the nanoparticle or microparticle comprises PLGA and/or PLGA-PEG. 39. The method of claim 37, wherein the nanoparticle or microparticle comprises PBAE and/or PBAE-PEG. 40. The method of claim 37, wherein the nanoparticle or microparticle comprises PLGA, PBAE, and PEG. 41. The method of claim 38, comprising about 2% to about 5% by mass of the isolated peptide loaded onto or into the PLGA nanoparticle or microparticle comprising PLGA. 42. The method of claim 38, comprising about 1% to about 10% by mass of the isolated peptide loaded onto or into the PLGA nanoparticle or microparticle comprising PLGA. 43. The method of claim 40, comprising about 1% to about 10% by mass of the isolated peptide loaded onto or into the PBAE nanoparticle or microparticle comprising PBAE. 44. The method of claim 23, wherein the isolated peptide is administered in combination with at least one other anti-angiogenesis agent. 45. The method of claim 44, wherein the at least one other anti-angiogenesis agent is selected from the group consisting of aflibercept, ranibizumab, bevacizumab, and combinations thereof. 46. The method of claim 14, wherein the peptide consists of the amino acid sequence LRRFSTAPFAFIDINDVINF (SEQ ID No: 1). 47. The method of claim 23, wherein the peptide consists of the amino acid sequence LRRFSTAPFAFIDINDVINF (SEQ ID No: 1). 48. The method of claim 29, wherein the subject has a hepatic cell cancer. 49. The method of claim 29, wherein the subject has breast cancer. 50. The method of claim 27, wherein the peptide is administered by parenteral administration. 51. The method of claim 35, wherein the peptide is administered by intraocular injection.

Details for Patent 9,802,984

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2033-06-07
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	06/30/2006		2033-06-07
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	08/10/2012		2033-06-07
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	10/13/2016		2033-06-07
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	03/20/2018		2033-06-07