Claims for Patent: 9,026,372

Summary for Patent: 9,026,372

Title:	Methods for providing a system of care for a high-dose oxazaphosphorine drug regimen
Abstract:	The present invention provides methods of treating subjects with an oxazaphosphorines, methods of identifying subjects that are suitable for oxazaphosphorine treatment, and systems for ensuring the safety and efficacy of a treatment that includes oxazaphosphorine administration.
Inventor(s):	O\'Donnell, Jr.; Francis (Longboat Key, FL), Santos; Carlos (Tampa, FL)
Assignee:	Accentia Biopharmaceuticals, Inc. (Tampa, FL)
Application Number:	12/789,401
Patent Claims:	1. A method of providing a system of care with a high-dose oxazaphosphorine drug regimen to treat or delay the onset of transplant rejection, comprising, carrying out the following steps prior to administration of the high-dose oxazaphosphorine drug regimen: a. registering a subject and generating a unique identifier for the subject in a non-transitory computerized storage medium; b. providing counseling to the subject regarding the risks associated with the administration of the high-dose oxazaphosphorine drug regimen, and obtaining the subject's informed consent for participation in the regimen; c. registering one or more of the following items in the storage medium: 1) results of two independent pregnancy tests from the subject in the case of a female subject, 2) a measure of the level of aldehyde dehydrogenase (ALDH) enzyme in the subject's peripheral lymphocytes, 3) a measure of the level of ALDH enzyme in the subject's hematogenous stem cells, 4) a measure of the white blood cell (WBC) count of the subject prior to and after the high-dose oxazaphosphorine drug regimen, 5) result of an assay for detecting the presence of one or more viruses in the subject; 6) a measure of the QT/QTc interval of the subject, 7) a platelet count from the subject, 8) a neutrophil count from the subject, 9) a record of the subject meeting the qualifying inclusion criteria, or 10) the absence of exclusion criteria, or a combination of any of the foregoing, d. registering in the storage medium all pharmaceuticals or other substances currently being administered to the subject, and confirming in the storage medium that none of the pharmaceuticals include contraindicated pharmaceuticals or substances; e. computing an approval status code upon successful completion of steps a-d which corresponds to the subject's identifier within the storage medium; and f. transmitting to an administration facility authorization to administer the high-dose oxazaphosphorine drug regimen to the subject based on the approval status code, or transmitting to the drug manufacturer authorization to release the oxazaphosphorine of the high-dose oxazaphosphorine regimen to the administration facility based on the approval status code, causing the administration facility to administer the high-dose oxazaphosphorine drug regimen to the subject based on the approval status code, to treat or delay the onset of transplant rejection. 2. The method of claim 1, wherein transmitting of (f) comprises transmitting the approval status code to the drug manufacturer or administration facility, and wherein the approval status code is affixed to, or otherwise associated with, a container containing the oxazaphosphorine. 3. The method of claim 2, wherein the approval status code comprises a bar code or other identifier specific to the subject. 4. The method of claim 1, wherein the high-dose oxazaphosphorine drug regimen comprises administration of a first dose of the oxazaphosphorine drug to the subject, and wherein said method further comprises carrying out at least one of the following steps after administration of the first dose of the oxazaphosphorine drug to the subject: g. monitoring the QT/QTc interval in the subject to ensure cardiac safety during and following administration of the drug regimen; h. registering in the storage medium the administration of each dose of the oxazaphosphorine drug administered to the subject; i. registering in the storage medium any adverse events experienced by the subject in conjunction with the administration of the oxazaphosphorine drug; j. re-computing the approval code and transmitting the re-computed approval code to the care provider prior to administration of the next successive dose of the oxazaphosphorine drug to the subject; k. administering to the subject one or more prophylactic drugs or pharmaceuticals prior to, concurrent with, or after administration of the oxazaphosphorine regimen to the subject, and registering the administration of each of the one or more prophylactic drugs or pharmaceuticals in the storage medium; l. administering to the subject one or more biologics after administration of the oxazaphosphorine regimen to the subject, and registering the administration of each of the biologics in the storage medium; m. registering in the storage medium the administration to the subject of any necessary supportive care therapy; n. registering the results in the storage medium of one or more assays administered to the subject; or o. registering in the storage medium any adverse events potentially disqualifying the subject from receiving further treatment. 5. The method of claim 4, wherein the contraindicated pharmaceutical or other substance of (d) is one or more among: live virus vaccines, allopurinol, pentostatin, cyclosporine, St. John's Wort, etanercept, nevirapine, trastuzumab, ondansetron, succinylcholine, digoxin, chloramphenicol, and indomethacin. 6. The method of claim 1, wherein the contraindicated pharmaceutical or substance of (d) is one or more grapefruit products. 7. The method of claim 1, wherein the contraindicated pharmaceutical or other substance of (d) is one or more ALDH inhibition factors, one or more ALDH activation factors, or both. 8. The method of claim 7, wherein the one or ALDH inhibition factors includes at least one selected from the group consisting of hormonal contraceptive use, tobacco use, chronic alcohol consumption, and any combinations thereof. 9. The method of claim 7, wherein the one or more ALDH inhibition factors includes at least one ALDH inhibition agent selected from the group consisting of disulfiram, hormonal contraceptive, procarbazine, N-methyltetrazolylthiomethyl bearing beta-lactam, kudzu root product, calcium carbimide, diazepam, chlordiazepoxide, isosorbide dinitrate, nitroglycerine, chlorpropamide, tolazamide, and cephalosporin, or an ALDH inhibiting metabolite thereof. 10. The method of claim 7, wherein the one or more ALDH inhibition factors are one or more anti-cancer agents, antibiotics, or dietary supplements. 11. The method of claim 7, wherein the one or more ALDH inhibition factors are one or more irreversible inhibitors of ALDH. 12. The method of claim 7, wherein the one or more ALDH activation factors are one or more ALDH activation agents selected from the group consisting of coffee, oltipraz, Crucifera vegetable family member, Liliaceae vegetable family member, and Phenobarbital, or an ALDH activating metabolite of any of the foregoing. 13. The method of 1, wherein the authorization of (f) is selected from at least one of the following: 1) a telephonic facsimile, paper, or Internet transmission of the subject's unique identifier, 2) a telephonic facsimile, paper, or Internet transmission of the subject's unique identifier in combination with an approval code for dispensing the oxazaphosphorine drug to the subject, 3) at least one dose of the oxazaphosphorine drug in a container affixed or otherwise associated with the subject's unique identifying information, or any combination thereof. 14. The method of claim 4, wherein re-computing of (k) is based upon an algorithm considering the number of doses received, known adverse events and the successful completion of all prophylactic and supportive care. 15. The method of claim 4, wherein the one or more assays of (n) are selected from among: 1) disease-specific assays for markers of unwanted immune disease, 2) a measure of the WBC count of the subject, 3) a test for serious infectious disease, 4) a measure of hepatic function, 5) a measure of the level and/or activity of hematopoietic progenitor stem cell ALDH enzyme, 6) tests for cardiovascular disease or insufficiency, 7) PCR blood draws for assessing the need for an antiviral to prevent CMV pneumonia, 8) tests for allergy to any of the prophylactic drugs or biologics as administered, or any combination thereof. 16. The method of claim 1, wherein the transplant rejection is from a bone marrow transplant. 17. The method of claim 16, wherein the transplant rejection is graft-versus-host disease. 18. The method of claim 1, wherein the transplant is for treatment of a hereditary hemoglobinopathy. 19. The method of claim 1, wherein the high-dose oxazaphosphorine drug regimen comprises administration of 200 mg/kg oxazaphosphorine drug intravenously. 20. The method of claim 1, wherein the high-dose oxazaphosphorine drug regimen comprises intravenous administration of about 40 mg/kg to about 50 mg/kg in divided doses over a period of from about 2 to about 5 days. 21. The method of claim 1, wherein the oxazaphosphorine of the high-dose oxazaphosphorine drug regimen is selected from the group consisting of cyclophosphamide, ifosfamide, perfosfamide, trophosphamide, 4-hydroxycyclophosphamide, aldophosphamide, and a pharmaceutically acceptable salt, solvate, prodrug, or active metabolite of any of the foregoing. 22. A non-transitory computer-readable storage medium holding computer executable instructions to carry out the steps of the method of claim 1. 23. The storage medium of claim 22, wherein the storage medium is selected from an application specific integrated circuit (ASIC), a compact disc (CD), a digital video disk (DVD), a random access memory (RAM), a read only memory (ROM), a disk, memory stick, hard disk, or CD-ROM. 24. The method of claim 1, wherein the storage medium is selected from an application specific integrated circuit (ASIC), a compact disc (CD), a digital video disk (DVD), a random access memory (RAM), a read only memory (ROM), a disk, memory stick, hard disk, or CD-ROM. 25. The method of claim 1, wherein the assay for detecting the presence of one or more viruses in (c)(5) is for the detection of CMV infection, and wherein said method further comprises administering a suitable antiviral therapy for CMV if the assay in step (c)(5) is positive for CMV infection. 26. The method of claim 1, further comprising step (g) providing an amount of the oxazaphosphorine drug of the high-dose oxazaphosphorine drug regimen to the administration facility for administration to the subject. 27. The method of claim 1, wherein the high-dose oxazaphosphorine drug regimen comprises administration of 50 mg/kg/day of the oxazaphosphorine drug intravenously, for four consecutive days. 28. The method of claim 17, wherein the transplant is for treatment of a hematologic malignancy. 29. The method of claim 1, wherein the method comprises (c)(2): registering in the storage medium a measure of the level of ALDH enzyme in the subject's peripheral lymphocytes. 30. The method of claim 1, wherein the method comprises (c)(3): registering in the storage medium a measure of the level of ALDH enzyme in the subject's hematogenous stem cells. 31. The method of claim 1, wherein the method comprises (c)(4) registering in the storage medium a measure of the WBC count of the subject prior to and after the high-dose oxazaphosphorine drug regimen. 32. The method of claim 1, wherein the method comprises: (c)(2): registering in the storage medium a measure of the level of ALDH enzyme in the subject's peripheral lymphocytes; (c)(3): registering in the storage medium a measure of the level of ALDH enzyme in the subject's hematogenous stem cells; and (c)(4) registering in the storage medium a measure of the WBC count of the subject prior to and after the high-dose oxazaphosphorine drug regimen.

Details for Patent 9,026,372

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2027-11-21
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2027-11-21
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2027-11-21
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2027-11-21
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2027-11-21
Immunex Corporation	ENBREL	etanercept	Injection	103795	02/01/2007		2027-11-21
Immunex Corporation	ENBREL MINI	etanercept	Injection	103795	09/14/2017		2027-11-21