Claims for Patent: 10,292,984

Summary for Patent: 10,292,984

Title:	Methods for increasing blood plasma 2\'-deoxyuridine (dUrd) and thymidylate synthase inhibition
Abstract:	The present invention provides methods for increasing plasma dUrd levels comprising the administration of 6R-MTHF. The methods of increasing plasma dUrd increase dUrd levels compared to equimolar concentrations of LV. The present invention also provides methods for increasing TS inhibition comprising the administration of 6R-MTHF. The present invention also provides methods for increasing TS inhibition comprising the administration of 6R-MTHF.
Inventor(s):	Carlsson; Goran U. (Jonsered, SE), Gustavsson; Bengt (Vastra Froelunda, SE), Odin; Elisabeth (Goteborg, SE), Wettergren; Yvonne (Goteborg, SE), Vedin; Anders (Goteborg, SE)
Assignee:	Isofol Medical AB (Goteborg, SE)
Application Number:	15/893,235
Patent Claims:	1. A method of increasing plasma concentration of 2'-deoxyuridine (dUrd) in a human subject comprising: a. a step of administering 500 mg/m.sup.2 5-fluorouracil (5-FU) intravenously as a bolus injection to said human subject; b. following (a), a step of administering 30, 60, 120, or 240 mg/m.sup.2 [6R]-5, 10-methylene tetrahydrofolate (6R-MTHF) intravenously as one or more bolus injections to said human subject; and c. optionally administering a therapeutically effective amount of at least one anticancer agent selected from the group consisting of oxaliplatin, irinotecan, and bevacizumab; wherein said administration produces an increased plasma concentration of dUrd relative to dUrd plasma concentration in a human subject following administration of an equimolar dose of 5-formyl tetrahydrofolate (LV). 2. The method of claim 1, wherein said human subject suffers from cancer. 3. The method of claim 2, wherein said cancer is colorectal cancer. 4. A method of inhibiting thymidylate synthase (TS) in a human subject comprising: a. a step of administering 500 mg/m.sup.2 5-FU intravenously as a bolus injection to said human subject; b. following (a), a step of administering 30, 60, 120, or 240 mg/m.sup.2 6R-MTHF intravenously as one or more bolus injections to said human subject; and c. optionally administering a therapeutically effective amount of at least one anticancer agent selected from the group consisting of oxaliplatin, irinotecan, and bevacizumab; wherein said administration produces an increased inhibition of TS relative to TS inhibition in a human subject following administration of an equimolar dose of LV. 5. The method of claim 4, wherein said human subject suffers from cancer. 6. The method of claim 5, wherein said cancer is colorectal cancer. 7. The method of claim 1, wherein the 6R-MTHF is administered intravenously as more than one bolus injection to said human subject. 8. The method of claim 1, wherein the 6R-MTHF is administered intravenously as two bolus injections to said human subject. 9. The method of claim 1, wherein the 6R-MTHF is administered intravenously as a bolus injection to said human subject approximately 30 minutes following step (a). 10. The method of claim 1, where the 6R-MTHF is administered intravenously as a bolus injection to said human subject approximately 30 and 60 minutes following step (a). 11. The method of claim 4, where in the 6R-MTHF is administered intravenously as more than one bolus injection to said human subject. 12. The method of claim 4, wherein the 6R-MTHF is administered intravenously as two bolus injections to said human subject. 13. The method of claim 4 wherein the 6R-MTHF is administered intravenously as a bolus injection to said human subject approximately 30 minutes following step (a). 14. The method of claim 4, wherein the 6R-MTHF is administered intravenously as a bolus injection to said human subject approximately 30 and 60 minutes following step (a). 15. The method of claim 1, wherein the 6R-MTHF has a chemical purity greater than 90% and in 95% isomeric excess over [6S]-5, 10-methylene tetrahydrofolate (6S-MTHF). 16. The method of claim 4, wherein the 6R-MTHF has a chemical purity greater than 90% and in 95% isomeric excess over [6S]-5, 10-methylene tetrahydrofolate (6S-MTHF).

Details for Patent 10,292,984

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2037-02-14