Claims for Patent: 7,829,708

Summary for Patent: 7,829,708

Title:	Metabolically inert antifolates for treating disorders of abnormal cellular proliferation and inflammation
Abstract:	The present invention provides compositions and methods for the treatment of disorders of abnormal cell proliferation and/or inflammation, such as psoriasis and inflammatory bowel disease, in a human or other host animals.
Inventor(s):	Roberts; Michael J. (Williamsburg, VA), Pedder; Simon (Charlotte, NC)
Assignee:	Chelsea Therapeutics, Inc. (Charlotte, NC)
Application Number:	11/223,433
Patent Claims:	1. A pharmaceutical composition comprising a compound of the formula: ##STR00030## or its pharmaceutically acceptable salt, wherein: if Y.sup.1 and Y.sup.2 are both oxygen, and V.sup.1 and V.sup.2 are both oxygen, then at least two of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are not H; X is CH.sub.2, CHCH.sub.3, CH(CH.sub.2CH.sub.3), NH, NCH.sub.3, or NR.sup.7; R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.7 are independently selected from H, optionally substituted alkyl, optionally substituted alkenyl or alkynyl, acyl, --C(O)-(alkyl), --C(O)-(alkenyl), --C(O)-(alkynyl), --C(.dbd.Y.sup.3)V.sup.3, lipid, phospholipid, carbohydrate, peptide, cholesterol, an amino acid residue, or an amino acid acyl residue; R.sup.5 and R.sup.6 are independently selected from H, optionally substituted alkyl, optionally substituted alkenyl or alkynyl, lipid, phospholipid, carbohydrate, peptide, cholesterol, an amino acid residue, or other pharmaceutically acceptable leaving group that is capable of providing a --C(.dbd.Y)V.sup.-or --C(.dbd.Y)VH moiety when administered in vivo; each Y.sup.1, Y.sup.2, and Y.sup.3 independently is O, S, or NJ.sup.1; each V.sup.1 and V.sup.2 independently is O, S, or NJ.sup.1; each V.sup.3 independently is OH, OJ.sup.1, SH, SJ.sup.1, NH.sub.2, NHJ.sup.1, NJ.sup.1J.sup.2, CH.sub.3, CH.sub.2R.sup.101, CHR.sup.101R.sup.102, or CR.sup.101R.sup.102R.sup.103; each J.sup.1 and J.sup.2 independently are hydrogen, alkyl, alkenyl, alkynyl, alkaryl, cycloalkyl, aryl, cycloaryl, heteroalkyl, heterocycle, heteroaryl, hydroxyl, alkoxy, or amine; and each R.sup.101, R.sup.102, and R.sup.103 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, acyl, heteroaryl, heteroalkyl, hydroxyl, alkoxy, cyano, azido, halogen, nitro, SO.sub.2, SO.sub.3, thioalkyl, or amino; and a pharmaceutically acceptable carrier selected from microcrystalline cellulose or cyclodextrin. 2. The pharmaceutical composition of claim 1, further comprising a second therapeutic agent, the composition being provided as a single unit dose. 3. The pharmaceutical composition of claim 2, wherein the second therapeutic agent is an anti-neoplastic agent. 4. The pharmaceutical composition of claim 2, wherein the second therapeutic agent is selected from the group consisting of anti-angiogenic agents, alkylating agents, anti-metabolites, cytotoxic agents, and anti-rheumatoid arthritis agent. 5. The pharmaceutical composition of claim 2, wherein the second therapeutic agent is selected from the group consisting of non-steroidal anti-inflammatory agents, analgesics, corticosteroids and disease-modifying anti-rheumatic agents. 6. The pharmaceutical composition of claim 5, wherein the disease-modifying anti-rheumatic agent is a TNF blocker. 7. The pharmaceutical composition of claim 6, wherein the TNF blocker is selected from the group consisting of etanercept, infliximab, adalimumab, and CDP-870. 8. The pharmaceutical composition of claim 2, wherein the second therapeutic agent is an anti-autoimmune disease agent. 9. The pharmaceutical composition of claim 2, wherein the second therapeutic agent is selected from the group consisting of rituximab, abatacept, actemra, leflunomide, and methotrexate. 10. A pharmaceutical composition comprising a compound of the formula: ##STR00031## or its pharmaceutically acceptable salt, wherein: if Y.sup.1 and Y.sup.2 are both oxygen, and V.sup.1 and V.sup.2 are both oxygen, then at least two of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are not H; X is CH.sub.2, CHCH.sub.3, CH(CH.sub.2CH.sub.3), NH, NCH.sub.3, or NR.sup.7; R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.7 are independently selected from H, optionally substituted alkyl, optionally substituted alkenyl or alkynyl, acyl, --C(O)-(alkyl), --C(O)-(alkenyl), --C(O)-(alkynyl), --C(.dbd.Y.sup.3)V.sup.3, lipid, phospholipid, carbohydrate, peptide, cholesterol, an amino acid residue, or an amino acid acyl residue; R.sup.5 and R.sup.6 are independently selected from H, optionally substituted alkyl, optionally substituted alkenyl or alkynyl, lipid, phospholipid, carbohydrate, peptide, cholesterol, an amino acid residue, or other pharmaceutically acceptable leaving group that is capable of providing a --C(.dbd.Y)V.sup.-or --C(.dbd.Y)VH moiety when administered in vivo; each Y.sup.1, Y.sup.2, and Y.sup.3 independently is O, S, or NJ.sup.1; each V.sup.1 and V.sup.2 independently is O, S, or NJ.sup.1; each V.sup.3 independently is OH, OJ.sup.1, SH, SJ.sup.1, NH.sub.2, NHJ.sup.1, NJ.sup.1J.sup.2, CH.sub.3, CH.sub.2R.sup.101, CHR.sup.101R.sup.102, or CR.sup.101R.sup.102R.sup.103; each J.sup.1 and J.sup.2 independently are hydrogen, alkyl, alkenyl, alkynyl, alkaryl, cycloalkyl, aryl, cycloaryl, heteroalkyl, heterocycle, heteroaryl, hydroxyl, alkoxy, or amine; and each R.sup.101, R.sup.102, and R.sup.103 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, acyl, heteroaryl, heteroalkyl, hydroxyl, alkoxy, cyano, azido, halogen, nitro, SO.sub.2, SO.sub.3, thioalkyl, or amino; a pharmaceutically acceptable carrier; and a second therapeutic agent; the composition being provided as a single unit dose. 11. The pharmaceutical composition of claim 10, wherein the second therapeutic agent is an anti-autoimmune disease agent. 12. The pharmaceutical composition of claim 10, wherein the second therapeutic agent is selected from the group consisting of rituximab, abatacept, actemra, leflunomide, and methotrexate. 13. A compound of the formula: ##STR00032## or its pharmaceutically acceptable salt, wherein: if Y.sup.1 and Y.sup.2 are both oxygen, and V.sup.1 and V.sup.2 are both oxygen, then at least two of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are not H; X is CH.sub.2, CHCH.sub.3, CH(CH.sub.2CH.sub.3), NH, NCH.sub.3, or NR.sup.7; R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.7 are independently selected from H, optionally substituted alkyl, optionally substituted alkenyl or alkynyl, acyl, --C(O)-(alkyl), --C(O)-(alkenyl), --C(O)-(alkynyl), --C(.dbd.Y.sup.3)V.sup.3, lipid, phospholipid, carbohydrate, peptide, cholesterol, an amino acid residue, or an amino acid acyl residue; R.sup.5 and R.sup.6 are independently selected from H, optionally substituted C.sub.3-C.sub.7 alkyl, optionally substituted alkenyl or alkynyl, lipid, phospholipid, carbohydrate, peptide, cholesterol, an amino acid residue, or other pharmaceutically acceptable leaving group that is capable of providing a --C(.dbd.Y)V.sup.-or --C(.dbd.Y)VH moiety when administered in vivo; each Y.sup.1, Y.sup.2, and Y.sup.3 independently is O, S, or NJ.sup.1; each V.sup.1 and V.sup.2 independently is O, S, or NJ.sup.1; each V.sup.3 independently is OH, OJ.sup.1, SH, SJ.sup.1, NH.sub.2, NHJ.sup.1, NJ.sup.1J.sup.2, CH.sub.3, CH.sub.2R.sup.101, CHR.sup.101R.sup.102, or CR.sup.101R.sup.102R.sup.103; each J.sup.1 and J.sup.2 independently are hydrogen, alkyl, alkenyl, alkynyl, alkaryl, cycloalkyl, aryl, cycloaryl, heteroalkyl, heterocycle, heteroaryl, hydroxyl, alkoxy, or amine; and each R.sup.101, R.sup.102, and R.sup.103 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, acyl, heteroaryl, heteroalkyl, hydroxyl, alkoxy, cyano, azido, halogen, nitro, SO.sub.2, SO.sub.3, thioalkyl, or amino. 14. A pharmaceutical composition, comprising a compound according to claim 13 in combination with a pharmaceutically acceptable carrier. 15. The pharmaceutical composition of claim 14, further comprising a second therapeutic agent, the composition being provided as a single unit dose.

Details for Patent 7,829,708

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2024-09-08
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2024-09-08
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2024-09-08
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2024-09-08