Claims for Patent: 8,809,562

Summary for Patent: 8,809,562

Title:	Use of metallocene compounds for cancer treatment
Abstract:	Metallocene compounds and pharmaceutical compositions containing these metallocene compounds are disclosed and described. Methods of treating cancer employing such metallocene compounds and pharmaceutical compositions also are provided.
Inventor(s):	Hlavinka; Mark L. (Bartlesville, OK), Yang; Qing (Bartlesville, OK), Murph; Mandi Michelle (Watkinsville, GA)
Assignee:	Chevron Phillips Chemical Company LP (The Woodlands, TX)
Application Number:	13/488,490
Patent Claims:	1. A method of treating cancer in a subject in need thereof, comprising administering to the subject a composition comprising a therapeutically effective amount of a metallocene compound, and optionally a pharmaceutically acceptable diluent, excipient, or carrier; wherein the metallocene compound has the structure of formula CPH-1, CPH-2, CPH-3, CPH-4, CPH-5, CPH-6, CPH-7, CPH-8, CPH-9, CPH-10, CPH-11, CPH-12, CPH-13, CPH-14, or CPH-15, or a pharmaceutically acceptable salt thereof: ##STR00009## ##STR00010## ##STR00011## wherein the cancer is melanoma, lung, colon, urinary bladder, breast, renal, prostate, ovarian, cervical, or head and neck cancer. 2. A method of treating cancer in a subject in need thereof, comprising administering to the subject a composition comprising: a therapeutically effective amount of a metallocene compound having formula MET-B, or a pharmaceutically acceptable salt thereof: ##STR00012## and optionally a pharmaceutically acceptable diluent, excipient, or carrier; wherein: M is Ti, Zr, or Hf; each R.sup.X, R.sup.Y, and R.sup.Z independently is H, a halide, hydrocarbyl group, or halogenated hydrocarbyl group; E.sup.1 is C or Si; R.sup.1 and R.sup.2 are independently H or a hydrocarbyl group, or halogenated hydrocarbyl group; X.sup.1 and X.sup.2 are independently a monoanionic ligand; and q, r, and s are independently 0, 1, 2, 3, or 4; and wherein the cancer is melanoma, lung, colon, urinary bladder, breast, renal, prostate, ovarian, cervical, or head and neck cancer. 3. The method of claim 2, wherein the cancer is resistant or insensitive to treatment with one or more of alemtuzumab, aminoglutethimide, anastrozole, asparginase, bacillus calmette-guerin, bendamustine, bevacizumab, bicalutamide, bleomycin, bortezomib, brentuximab, cabazitaxel, capecitabine, carboplatin, carmustine, cervarix, cetuximab, cisplatin, cyclophosphamide, cytarabine, dacarbazine, dasatinib, daunorubicin, desarelix, dexamethasone, docetaxel, doxil, doxorubicin, epirubicin, erlotinib, etoposide, everolimus, exemestane, fadrozole, fludarabine, 5-fluorouracil, flutamide, fulvestrant, gardasil, gemcitabine, goserelin, ibritumomab, idarubicin, ifosfamide, il-2, imatinib, inlyta, interferon-alpha, ipilimumab, irinotecan, ixabepilone, lapatinib, lenalidomide, letrozole, leucovorin, leuprolide, lomustine, megestrol acetate, melphalan, methotrexate, 6-mercaptopurine, mitomycin-C, mitoxantrone, nilotinib, nilutamide, oxaliplatin, paclitaxel, panitumumab, pazopanib, pegasparginase, pemetrexed, procarbazine, raloxifene, rituximab, sorafenib, sunitinib, sylatron (Peg), tamoxifen, temozolomide, temsirolimus, thalidomide, thioguanine, thiotepa, topotecan, toremifene, tositumomab, trastuzumab, vemurafenib, vincristine, vinorelbine, vismodegib, and/or vorinostat. 4. The method of claim 2, wherein the cancer is resistant or insensitive to treatment with a platinum agent. 5. The method of claim 2, wherein the cancer is resistant or insensitive to treatment with a taxane. 6. The method of claim 1, wherein the subject is a human. 7. The method of claim 2, wherein: M is Zr or Hf; or at least one R.sup.X, R.sup.Y, or R.sup.Z is a C.sub.1 to C.sub.8 alkyl or C.sub.3 to C.sub.8 alkenyl group; or E.sup.1 is C; or at least one of R.sup.1 and R.sup.2 is an alkyl, alkenyl, or phenyl; or q, r, and s are independently 0, 1, or 2; or any combination thereof. 8. The method of claim 2, wherein: M is Zr or Hf; at least one R.sup.X, R.sup.Y, or R.sup.Z is a C.sub.1 to C.sub.8 alkyl or C.sub.3 to C.sub.8 alkenyl group; E.sup.1 is C; at least one of R.sup.1 and R.sup.2 is a phenyl group or an alkenyl group; q, r, and s are independently 0 or 1; and at least one of X.sup.1 and X.sup.2 is Cl. 9. The method of claim 2, wherein the composition is administered in combination with a therapeutically effective amount of a therapeutic agent, the therapeutic agent comprising alemtuzumab, aminoglutethimide, anastrozole, asparginase, bacillus calmette-guerin, bendamustine, bevacizumab, bicalutamide, bleomycin, bortezomib, brentuximab, cabazitaxel, capecitabine, carboplatin, carmustine, cervarix, cetuximab, cisplatin, cyclophosphamide, cytarabine, dacarbazine, dasatinib, daunorubicin, desarelix, dexamethasone, docetaxel, doxil, doxorubicin, epirubicin, erlotinib, etoposide, everolimus, exemestane, fadrozole, fludarabine, 5-fluorouracil, flutamide, fulvestrant, gardasil, gemcitabine, goserelin, ibritumomab, idarubicin, ifosfamide, il-2, imatinib, inlyta, interferon-alpha, ipilimumab, irinotecan, ixabepilone, lapatinib, lenalidomide, letrozole, leucovorin, leuprolide, lomustine, megestrol acetate, melphalan, methotrexate, 6-mercaptopurine, mitomycin-C, mitoxantrone, nilotinib, nilutamide, oxaliplatin, paclitaxel, panitumumab, pazopanib, pegasparginase, pemetrexed, procarbazine, raloxifene, rituximab, sorafenib, sunitinib, sylatron (Peg), tamoxifen, temozolomide, temsirolimus, thalidomide, thioguanine, thiotepa, topotecan, toremifene, tositumomab, trastuzumab, vemurafenib, vincristine, vinorelbine, vismodegib, vorinostat, or a mixture thereof. 10. The method of claim 9, wherein the therapeutic agent comprises bevacizumab, dacarbazine, docetaxel, 5-fluorouracil, gemcitabine, ipilimumab, paclitaxel, or a mixture thereof. 11. The method of claim 9, wherein the therapeutically effective amount of the metallocene compound administered in combination with the therapeutically effective amount of the therapeutic agent results in a synergistic increase in cytotoxicity. 12. The method of claim 6, wherein the cancer is melanoma. 13. The method of claim 6, wherein the cancer is ovarian cancer. 14. The method of claim 6, wherein the cancer is lung, colon, urinary bladder, renal, prostate, or head and neck cancer. 15. The method of claim 6, wherein the cancer is breast or cervical cancer. 16. The method of claim 2, wherein the subject is a human. 17. The method of claim 16, wherein the cancer is melanoma. 18. The method of claim 16, wherein the cancer is ovarian cancer. 19. The method of claim 16, wherein the cancer is lung, colon, urinary bladder, renal, prostate, or head and neck cancer. 20. The method of claim 16, wherein the cancer is breast or cervical cancer.

Details for Patent 8,809,562

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Teknika Llc	TICE BCG	bcg live	For Injection	102821	June 21, 1989		2032-06-05
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	November 26, 1997		2032-06-05
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	February 19, 2002		2032-06-05
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	September 25, 1998		2032-06-05