Claims for Patent: 8,143,247

Summary for Patent: 8,143,247

Title:	Combinations for the treatment of diseases involving cell proliferation
Abstract:	Disclosed are pharmaceutical compositions for the treatment of diseases which involve cell proliferation. Also disclosed are methods for the treatment of said diseases, comprising co-administration of a compound 1 of Formula (I) ##STR00001## wherein the groups L, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 have the meanings given herein and of an effective amount of an active compound 2 and/or co-treatment with radiation therapy, in a ratio which provides an additive and synergistic effect, and to the combined use of a compound 1 of Formula (I) and of an effective amount of an active compound 2 and/or radiotherapy for the manufacture of corresponding pharmaceutical combination preparations.
Inventor(s):	Munzert; Gerd (Ulm, DE), Steegmaier; Martin (Reutlingen, DE), Baum; Anke (Vienna, AT)
Assignee:	Boehringer Ingelheim International GmbH (Ingelheim am Rhein, DE)
Application Number:	12/437,280
Patent Claims:	1. A pharmaceutical composition comprising: (i) a compound 1 of Formula (I) ##STR01026## wherein the compound (1) is selected from the group consisting of the compounds of formula shown in the following Table: TABLE-US-00003 Config. R.sup.1 R.sup.2 R.sup.1 or R.sup.2 R.sup.3 R.sup.4 L.sub.n--R.sup.5.sub.m H ##STR01027## R ##STR01028## ##STR01029## ##STR01030## H ##STR01031## R ##STR01032## ##STR01033## ##STR01034## optionally in form of its tautomers, racemates, enantiomers, diastereomers and the mixtures thereof and optionally in form of the pharmacologically acceptable acid addition salts; and (ii) at least one further chemotherapeutic or naturally occurring, semi-synthetic or synthetic therapeutic agent 2, which is selected from the group consisting of 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline, 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{[4-(homomorpholin-4-yl)-1-oxo-2-bu- ten-1-yl]amino}-7-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline, 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-a- nilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone, 3-Z-[1-(4-dimethylaminomethylanilino)-1-(4-(2-carboxyethyl)phenyl)methyle- ne]-6-fluoro-2-indolinone, irinotecan, topotecan, oxaliplatin, docetaxel, paclitaxel, gemcitabine, pemetrexed, cisplatin, carboplatin, bevacizumab, cetuximab, gefitinib, 5-fluorouracil (5-FU) and erlotinib, or a tautomer, stereoisomer or a pharmaceutically acceptable salt thereof; optionally in combination with one or more pharmaceutically acceptable excipients, and optionally for a co-treatment with radiotherapy or radio-immunotherapy, in the form of a combined preparation for simultaneous, separate or sequential administration. 2. The pharmaceutical composition according to claim 1, wherein the further chemotherapeutic or naturally occurring, semi-synthetic or synthetic therapeutic agent 2 is the di-maleic acid salt of the compound 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline. 3. The pharmaceutical combination according to claim 1, wherein the further chemotherapeutic or naturally occurring, semi-synthetic or synthetic therapeutic agent 2 is the di-maleic acid salt of the compound 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline, or 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{[4-(homomorpholin-4-yl)-1-oxo-2-bu- ten-1-yl]amino}-7-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline, or a tautomer, stereoisomer or a pharmaceutically acceptable salt thereof. 4. The pharmaceutical combination according to claim 1, wherein the further chemotherapeutic or naturally occurring, semi-synthetic or synthetic therapeutic agent 2 is 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{[4-(homomorpholin-4-yl)-1-oxo-2-bu- ten-1-yl]amino}-7-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline, or a tautomer, stereoisomer or a pharmaceutically acceptable salt thereof. 5. The pharmaceutical combination according to claim 1, wherein the further chemotherapeutic or naturally occurring, semi-synthetic or synthetic therapeutic agent 2 is 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-a- nilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone, or a pharmaceutically acceptable salt thereof. 6. The pharmaceutical combination according to claim 1, wherein the further chemotherapeutic or naturally occurring, semi-synthetic or synthetic therapeutic agent 2 is the monoethanesulfonate salt of 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-a- nilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone. 7. The pharmaceutical composition according to claim 1, wherein the further chemotherapeutic or naturally occurring, semi-synthetic or synthetic therapeutic agent 2 is selected from the group consisting of irinotecan, topotecan, oxaliplatin, docetaxel, paclitaxel, gemcitabine, pemetrexed, cisplatin, carboplatin, bevacizumab, cetuximab, gefitinib, 5-fluorouracil (5-FU) or erlotinib or a pharmaceutically acceptable salt thereof. 8. The pharmaceutical composition according to claim 1, wherein the compound 1 is: TABLE-US-00004 ##STR01035## Config. R.sup.1 R.sup.2 R.sup.1 or R.sup.2 R.sup.3 R.sup.4 L.sub.n--R.sup.5.sub.m H ##STR01036## R ##STR01037## ##STR01038## ##STR01039## wherein the abbreviations X.sub.2, X.sub.3, X.sub.4 and X.sub.5 used in the Table in each case denote a link to a position in the general Formula shown in the Table instead of the corresponding groups R.sup.1, R.sup.2, R.sup.3, R.sup.4 and L-R.sup.5. 9. The pharmaceutical composition according to claim 1, wherein the compound 1 is: TABLE-US-00005 ##STR01040## Con- fig. R.sup.1 R.sup.1 R.sup.2 or R.sup.2 R.sup.3 R.sup.4 L.sub.n--R.sup.5.sub.m H ##STR01041## R ##STR01042## ##STR01043## ##STR01044## wherein the abbreviations X.sub.2, X.sub.3, X.sub.4 and X.sub.5 used in the Table in each case denote a link to a position in the general Formula shown in the Table instead of the corresponding groups R.sup.1, R.sup.2, R.sup.3, R.sup.4 and L-R.sup.5. 10. The pharmaceutical combination according to claim 1, wherein the further chemotherapeutic or naturally occurring, semi-synthetic or synthetic therapeutic agent 2 is 3-Z-[1-(4-dimethylaminomethylanilino)-1-(4-(2-carboxyethyl)phenyl)methyle- ne]-6-fluoro-2-indolinone, or a pharmaceutically acceptable salt thereof. 11. The pharmaceutical composition according to claim 1, wherein the further chemotherapeutic or naturally occurring, semi-synthetic or synthetic therapeutic agent 2 is 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-bute- n-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline or a pharmaceutically acceptable salt thereof.

Details for Patent 8,143,247

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2024-08-14
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2024-08-14
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2024-08-14