Claims for Patent: 9,527,858

Summary for Patent: 9,527,858

Title:	Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers
Abstract:	The invention relates generally to anti-angiogenesis agents and related methods of using to anti-angiogenesis agents for biomedical applications including direct monotherapy and combination therapy for treatment of an angiogenesis related condition. In an embodiment, the invention provides a class of opioid compounds and structurally related opioid derivatives exhibiting anti-VEGF activity for use in therapeutic procedures, including phototherapy. Opioid compounds and structurally related opioid derivatives of the invention may be administered alone or in combination with administration of a phototherapy agent and/or other therapeutic agent.
Inventor(s):	Cantrell; Gary L. (Hazelwood, MO), Rajagopalan; Raghavan (Hazelwood, MO), Karwa; Amolkumar (Hazelwood, MO), Dorshow; Richard B. (Hazelwood, MO)
Assignee:	Mallinckrodt LLC (Hazelwood, MO)
Application Number:	14/316,443
Patent Claims:	1. A method for treating cancer, the method comprising: administering to a patient in need of treatment an effective amount of a purified (+) enantiomer compound substantially free of a corresponding (-) enantiomer, the (+) enantiomer compound having the formula (FX1): ##STR00136## wherein: ring A is ##STR00137## X is --OH, --OCH.sub.3, or C.sub.2-C.sub.8 alkoxy; Y is --H or --OH; W is --(CR.sup.10R.sup.11)--, --(C.dbd.O)--, --(C.dbd.S)--, --(C.dbd.CR.sup.12R.sup.13)--, or --(CR.sup.14NR.sup.15R.sup.16)--; each of R.sup.1 and R.sup.2 is independently --H, --CH.sub.3, --(O.sup.-), C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.10 haloalkyl, C.sub.5-C.sub.10 aryl, C.sub.5-C.sub.10 heteroaryl, C.sub.5-C.sub.10 alkylaryl, C.sub.5-C.sub.10 alkylheteroaryl, C.sub.5-C.sub.10 carbonylalkenylaryl, or C.sub.5-C.sub.10 carbonylalkenylheteroaryl; each of R.sup.3--R.sup.5, R.sup.9--R.sup.16 and R.sup.50--R.sup.54 is independently --H, --OH, --OCH.sub.3, C.sub.1-C.sub.8 alkyl, C.sub.3-C.sub.8 cycloalkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkoxy, C.sub.5-C.sub.10 aryl, C.sub.5-C.sub.10 heteroaryl, C.sub.5-C.sub.10 alkylaryl, C.sub.5-C.sub.10 alkylheteroaryl, halo, nitrile, C.sub.1-C.sub.8 haloalkyl, C.sub.1-C.sub.10 hydroxyalkyl, or C.sub.5-C.sub.10 carbonylalkenylheteroaryl; and n is 1, and the nitrogen to which R.sup.2 is attached has a positive charge and optionally is associated with an anion. 2. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX11): ##STR00138## wherein: A.sup.-z is independently an anion; z is independently 1, 2 or 3; and m is independently 0 or 1, wherein when m is 0, A.sup.-z is not present. 3. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX15): ##STR00139## 4. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX17): ##STR00140## 5. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX20): ##STR00141## 6. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX22): ##STR00142## 7. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX24): ##STR00143## 8. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX26): ##STR00144## 9. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX28): ##STR00145## 10. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX29): ##STR00146## 11. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX31) ##STR00147## 12. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX33): ##STR00148## 13. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX35): ##STR00149## 14. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX37): ##STR00150## 15. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX40): ##STR00151## 16. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX42): ##STR00152## 17. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX44): ##STR00153## 18. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX46): ##STR00154## 19. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX48): ##STR00155## 20. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX49). ##STR00156## 21. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX51): ##STR00157## 22. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX53): ##STR00158## 23. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX55): ##STR00159## 24. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX57): ##STR00160## 25. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX59): ##STR00161## 26. The method of claim 1 wherein said (+) enantiomer compound has the formula: ##STR00162## 27. The method for treating cancer of claim 1, further comprising administering to said patient a mixture of two or more purified (+) enantiomer compounds each independently having a formula (FX1). 28. The method of claim 1, comprising a method for treating pancreatic cancer. 29. The method of claim 1, comprising a method of suppressing tumor growth or tumor metastasis. 30. The method of claim 1, further comprising administering to said patient one or more chemotherapeutic agents. 31. The method of claim 1, further comprising administering to said patient one or more VEGF inhibitors. 32. The method of claim 1, further comprising administering to said patient 5-fluorouracil, floxuridine, furtulon, capecitabine, gemcitabine, taxol, doxorubicin, cisplatin, thalidomide, paclitaxel, docetaxel or bevacizumab. 33. A method for treating cancer, the method comprising: administering to a patient in need of treatment an effective amount of a purified (+) enantiomer compound substantially free of a corresponding (-) enantiomer, the (+) enantiomer compound having the formula (FX13): ##STR00163## wherein: each of R.sup.1 and R.sup.2 is independently --H, --CH.sub.3, --(O.sup.-), C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.10 haloalkyl, C.sub.5-C.sub.10 aryl, C.sub.5-C.sub.10 heteroaryl, C.sub.5-C.sub.10 alkylaryl, C.sub.5-C.sub.10 alkylheteroaryl, C.sub.5-C.sub.10 carbonylalkenylaryl, or C.sub.5-C.sub.10 carbonylalkenylheteroaryl; and n is 1, and the nitrogen to which R.sup.2 is attached has a positive charge and optionally is associated with an anion. 34. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX72): ##STR00164## 35. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX74): ##STR00165## 36. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX80): ##STR00166## 37. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX82): ##STR00167## 38. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX84): ##STR00168## 39. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX87): ##STR00169## 40. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX100): ##STR00170## 41. The method for treating cancer of claim 33 further comprising administering to said patient a mixture of two or more purified (+) enantiomer compounds each independently having a formula (FX13). 42. The method of claim 33, comprising a method for treating pancreatic cancer. 43. The method of claim 33, comprising a method of suppressing tumor growth or tumor metastasis. 44. The method of claim 33, further comprising administering to said patient one or more chemotherapeutic agents. 45. The method of claim 33, further comprising administering to said patient one or more VEGF inhibitors. 46. The method of claim 33, further comprising administering to said patient 5-fluorouracil, floxuridine, furtulon, capecitabine, gemcitabine, taxol, doxorubicin, cisplatin, thalidomide, paclitaxel, docetaxel or bevacizumab. 47. A method for treating cancer, the method comprising: administering to a patient in need of treatment an effective amount of a purified (+) enantiomer compound substantially free of a corresponding (-) enantiomer, the (+) enantiomer compound having the formula (FX15): ##STR00171## wherein: each of R.sup.1 and R.sup.2 is independently --H, --CH.sub.3, --(O.sup.-), C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.10 haloalkyl, C.sub.5-C.sub.10 aryl, C.sub.5-C.sub.10 heteroaryl, C.sub.5-C.sub.10 alkylaryl, C.sub.5-C.sub.10 alkylheteroaryl, C.sub.5-C.sub.10 carbonylalkenylaryl, or C.sub.5-C.sub.10 carbonylalkenylheteroaryl; and n is 1, and the nitrogen to which R.sup.2 is attached has a positive charge and optionally is associated with an anion. 48. The method of claim 47, wherein said (+) enantiomer compound has the formula (FX92): ##STR00172## 49. The method of claim 47, wherein said (+) enantiomer compound has the formula (FX95): ##STR00173## 50. The method of claim 47, wherein said (+) enantiomer compound has the formula (FX106): ##STR00174## 51. The method for treating cancer of claim 47, further comprising administering to said patient a mixture of two or more purified (+) enantiomer compounds each independently having a formula (FX15). 52. The method of claim 47, comprising a method for treating pancreatic cancer. 53. The method of claim 47, comprising a method of suppressing tumor growth or tumor metastasis. 54. The method of claim 47, further comprising administering to said patient one or more chemotherapeutic agents. 55. The method of claim 47, further comprising administering to said patient one or more VEGF inhibitors. 56. The method of claim 47, further comprising administering to said patient 5-fluorouracil, floxuridine, furtulon, capecitabine, gemcitabine, taxol, doxorubicin, cisplatin, thalidomide, paclitaxel, docetaxel or bevacizumab.

Details for Patent 9,527,858

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2029-07-16