Claims for Patent: 7,326,711

Summary for Patent: 7,326,711

Title:	Pyridino[1,2-a]pyrimidin-4-one compounds as anticancer agents
Abstract:	Pyridin[1,2-a]pyrimidinyl compounds, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the pyridino[1,2-a]pyrimidinyl compounds, either alone or in combination with at least one additional therapeutic agent. Methods of using the pyridino[1,2-a]pyrimidinyl compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases.
Inventor(s):	Wang; Weibo (Moraga, CA), Constantine; Ryan N. (Oakland, CA), Lagniton; Liana Marie (Berkeley, CA), Pecchi; Sabina (Oakland, CA), Burger; Matthew T. (Albany, CA), Desai; Manoj C. (Pleasant Hill, CA)
Assignee:	Chiron Corporation (Emeryville, CA)
Application Number:	10/870,707
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,326,711
Patent Claims:	1. A compound having the formula: ##STR00131## or a stereoisomer, tautomer, pharmaceutically acceptable salt, or ester thereof, wherein R.sub.1 is selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted alkyl, (3) substituted or unsubstituted alkenyl, (4) substituted or unsubstituted alkynyl, (5) substituted or unsubstituted aryl, (6) substituted or unsubstituted heteroaryl, (7) substituted or unsubstituted heterocyclyl, (8) substituted or unsubstituted alkylsulfonyl, and (9) substituted or unsubstituted arylsulfonyl; R.sub.2 is hydrogen; R.sub.3 is selected from the group consisting of (1) 2-propenyl, (2) phenyl, (3) thienyl, and (4) pyridyl; R.sub.4 is selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted alkyl, (3) substituted or unsubstituted alkenyl, (4) substituted or unsubstituted alkynyl, (5) substituted or unsubstituted aryl, (6) substituted or unsubstituted heteroaryl, (7) substituted or unsubstituted heterocyclyl, and (8) L-R.sub.13, wherein L is a C1-C10 saturated or unsaturated branched or unbranched carbon chain comprising one or more methylene groups, wherein one or more methylene groups are optionally independently replaced by O, N, or S; and wherein L is optionally substituted with one or two oxo groups and one or more C1-C10 branched or unbranched alkyl optionally substituted by one or more halogen atoms; R.sub.5 selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted alkyl, (3) substituted or unsubstituted alkenyl, (4) substituted or unsubstituted alkynyl, (5) substituted or unsubstituted aryl, (6) substituted or unsubstituted heteroaryl, (7) substituted or unsubstituted heterocyclyl, (8) COR.sub.10, (9) CO.sub.2R.sub.10, (10) CONR.sub.11R.sub.12, (11) S(O).sub.mR.sub.10, and (12) SO.sub.2NR.sub.11R.sub.12; R.sub.6, R.sub.7, R.sub.8, and R.sub.9 are independently selected from the group consisting of (1) hydrogen, (2) halogen, (3) nitro, (4) cyano, (5) hydroxy, (6) substituted or unsubstituted alkoxy, (7) substituted or unsubstituted methylenedioxy, (8) substituted or unsubstituted amino, (9) substituted or unsubstituted alkyl, (10) substituted or unsubstituted alkenyl, (11) substituted or unsubstituted alkynyl, (12) substituted or unsubstituted aryl, (13) substituted or unsubstituted heteroaryl, (14) substituted or unsubstituted alkylsulfonyl, and (15) substituted or unsubstituted arylsulfonyl; R.sub.10, R.sub.11, and R.sub.12 are independently selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted alkyl, (3) substituted or unsubstituted alkenyl, (4) substituted or unsubstituted alkynyl, (5) substituted or unsubstituted aryl, (6) substituted or unsubstituted heteroaryl, and (7) substituted or unsubstituted heterocyclyl; or R.sub.11 and R.sub.12 taken together with the nitrogen atom to which they are attached form a 3- to 7-membered heterocyclic ring; R.sub.13 selected from the group consisting of (1) substituted or unsubstituted amino, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heteroaryl, and (4) substituted or unsubstituted heterocyclyl; and m=0, 1, or 2. 2. A compound of claim 1, wherein substituted alkyl comprises arylalkyl, heteroarylalkyl, heterocyclylalkyl, aminoalkyl, alkylaminoalkyl, dialkyaminoalkyl, or sulfonamidoalkyl. 3. A compound of claim 1, wherein R.sub.1 is arylalkyl. 4. A compound of claim 1, wherein R.sub.1 is benzyl. 5. A compound of claim 1, wherein R.sub.4 is L-R.sub.13. 6. A compound of claim 5, wherein L is a C1-C10 saturated or unsaturated branched or unbranched carbon chain. 7. A compound of claim 5, wherein R.sub.13 is selected from the group consisting of amino, cycloalkyl, aryl, and heterocyclyl. 8. A compound of claim 5, wherein L-R.sub.13 is substituted or unsubstituted aminoalkyl. 9. A compound of claim 5, wherein L-R.sub.13 is aminopropyl. 10. A compound of claim 1, wherein R.sub.5 is COR.sub.10. 11. A compound of claim 10, wherein R.sub.10 is selected from the group consisting of substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. 12. A compound of claim 10, wherein R.sub.10 is substituted phenyl or substituted pyridyl. 13. A compound of claim 12, wherein the substituted phenyl is an alkyl- or halo-substituted phenyl. 14. A compound of claim 1, wherein R.sub.6, R.sub.7, R.sub.8, and R.sub.9 are independently selected from the group consisting of hydrogen, alkyl, and halo. 15. A compound of claim 1 selected from the group consisting of: N-[1-(3-benzyl-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)propyl]-4-br- omo-N-[3-(dimethylamino)propyl]benzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)eth- yl]-4-bromobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)eth- yl]-4-methylbenzamide; N-(3-aminopropyl)-N-[(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)(cycl- opropyl)methyl]-4-bromobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-tert-butylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-(trifluoromethoxy)benzamide; 4-(acetylamino)-N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]py- rimidin-2-yl)propyl]benzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-ethoxybenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-2,6-dichlorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]benzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-methylbenzenesulfonamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-2,4-difluorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]isonicotinamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-3-chloroisonicotinamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-5-methylpyrazine-2-carboxamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]pyrazine-2-carboxamide; N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)propyl]-4-methyl-N-[4- -(methylamino)butyl]benzamide; 2-(2-aminoethoxy)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-N,4-dimethylbenzamide; 2-(3-aminopropoxy)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pr- opyl]-N,4-dimethylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]thiophene-2-carboxamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-2-furamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-5-chlorothiophene-2-carboxamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]pyridine-2-carboxamide; and N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]quinoxaline-6-carboxamide. 16. A compound of claim 1 selected from the group consisting of: N-(3-aminopropyl)-N-[1-(3-benzyl-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin- -2-yl)propyl]-4-bromobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin- -2-yl)propyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-chlorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-fluorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-cyanobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-methoxybenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-2-chlorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-3-chlorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-3,5-dichlorobenzamide; 2-{1-[(3-aminopropyl)(4-methylbenzyl)amino]propyl}-3-benzyl-4H-pyrido[1,2- -a]pyrimidin-4-one; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-3,4-difluorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-3-fluorobenzamide; N-[2-(aminomethyl)prop-2-enyl]-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrim- idin-2-yl)butyl]-4-methylbenzamide; N-[2-(aminomethyl)prop-2-enyl]-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrim- idin-2-yl)but-3-enyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-2,4-dimethoxybenzamide; N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)propyl]-4-methyl-N-(p- iperidin-3-ylmethyl)benzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-2-methoxybenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-3,4-dimethoxybenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-2-chloro-4-fluorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-6-methoxynicotinamide; N-(azetidin-3-ylmethyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-- yl)propyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-2-naphthamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-3-(trifluoromethyl)benzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-3-chloro-1-benzothiophene-2-carboxamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-2-- methylpropyl]-2,3-dichlorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-2-- methylpropyl]-3,5-dichlorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]nicotinamide; and N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-(dimethylamino)benzamide. 17. A compound of claim 1 selected from the group consisting of: N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-bromobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-7-chloro-4-oxo-4H-pyrido[1,2-a]pyrimidin- -2-yl)propyl]-4-bromobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-7-chloro-4-oxo-4H-pyrido[1,2-a]pyrimidin- -2yl)propyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-(trifluoromethyl)benzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-4-ethylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-3,4-dichlorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-2,4-dichlorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-2,3-dichlorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)but- yl]-4-methylbenzamide; N-(4-aminobutyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)prop- yl]-4-methylbenzamide; N-(3-amino-2,2-dimethylpropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrim- idin-2-yl)propyl]-4-methylbenzamide; N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)propyl]-4-methyl-N-(2- -piperidin -2-ylethyl)benzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)but- -3-enyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-2-- methylpropyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-2-- methylpropyl]-4-chlorobenzamide; N-(3-aminopropyl)-N-[(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)(cycl- opropyl)methyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)(cycl- opropyl)methyl]-4-chlorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-6-chloronicotinamide; N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)propyl]-4-methyl-N-(p- yrrolidin-3-ylmethyl)benzamide; N-(3-aminopropyl)-N-[(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)(phen- yl)methyl]-4-chlorobenzamide; N-(3-aminopropyl)-N-[(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)(thie- n-2-yl)methyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)(thie- n-2-yl)methyl]-4-chlorobenzamide; N-(3-aminopropyl)-N-[(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)(pyri- din-2-yl)methyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)(pyri- din-2-yl)methyl]-4-chlorobenzamide; N-(3-aminopropyl)-N-[(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)(phen- yl)methyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-2-- methylpropyl]-6-chloronicotinamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-2-- methylpropyl]-3,4-dichlorobenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)pro- pyl]-2,2-difluoro-1,3-benzodioxole-5-carboxamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-2-- methylpropyl]-3-fluoro-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-2-- methylpropyl]-2-chloro-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-2-- methylpropyl]-3-chloro-4-methylbenzamide; N-(3-aminopropyl)-N-{1-[3-(3-chlorobenzyl)-4-oxo-4H-pyrido[1,2-a]pyrimidi- n-2-yl]-2-methylpropyl}-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin- -2-yl)-2-methylpropyl]-4-methylbenzamide; N-(3-aminopropyl)-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-2-- methylpropyl]-3,4-dimethylbenzamide; N-(3-aminopropyl)-4-methyl-N-{2-methyl-1-[3-(3-methylbenzyl)-4-oxo-4H-pyr- ido[1,2-a]pyrimidin-2-yl]propyl}benzamide; N-(3-aminopropyl)-3-fluoro-4-methyl-N-{2-methyl-1-[3-(3-methylbenzyl)-4-o- xo-4H-pyrido[1,2-a]pyrimidin-2-yl]propyl}benzamide; N-[3-(benzylamino)propyl]-N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-- 2-yl)-2-methylpropyl]-4-methylbenzamide; and N-[1-(3-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)-2-methylpropyl]-N-{3- -[(cyclohexylmethyl)amino]propyl}-4-methylbenzamide. 18. A composition, comprising a pharmaceutically acceptable carrier and an amount of a compound of claim 1 effective to inhibit KSP activity in a human or animal subject when administered thereto. 19. The composition of claim 18 further comprising at least one additional agent for the treatment of cancer. 20. The composition of claim 19, wherein the at least one additional agent for the treatment of cancer is selected from irinotecan, topotecan, gemcitabine, imatinib, 5-fluorouracil, leucovorin, carboplatin, cisplatin, docetaxel, paclitaxcl, tezacitabine, cyclophosphamide, vinca alkaloids, anthracyclines, rituximab, and trastuzumab. 21. A method for inhibiting KSP activity in a human or animal subject, comprising administering to the human or animal subject a composition comprising an amount of a compound of claim 1 effective to inhibit KSP activity the human or animal subject.

Details for Patent 7,326,711

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2023-06-20
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2023-06-20
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2023-06-20
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2023-06-20