Claims for Patent: 10,195,188

Summary for Patent: 10,195,188

Title:	Method of treating pancreatic cancer
Abstract:	The present disclosure describes methods of treating pancreatic cancer and limiting over-expression of oncogenes, activating tumor suppressor genes or regulating signaling proteins in patients comprising administering compounds and pharmaceutical combinations as described herein.
Inventor(s):	Bekker; Petrus (Mountain View, CA), Miao; Shichang (Foster City, CA), Charo; Israel (Mountain View, CA), Schall; Tom (Mountain View, CA)
Assignee:	ChemoCentryx, Inc. (Mountain View, CA)
Application Number:	15/694,363
Patent Claims:	1. A pharmaceutical combination comprising a compound of Formula I: ##STR00027## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is halogen or C.sub.1-6 alkyl; R.sup.2 is hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkyl, C.sub.1-6 haloalkoxy, or --CN; R.sup.3 is hydrogen, halogen, or C.sub.1-6 alkyl; R.sup.4 is hydrogen, halogen, or C.sub.1-6 alkyl; each R.sup.5 is independently C.sub.1-6 alkyl, --OH, or --NH.sub.2; n is 0, 1, 2, or 3; each of A.sup.1, A.sup.2, and A.sup.3 is --CH-- or --N--, where at least one of A.sup.1, A.sup.2, or A.sup.3 is --N--; and one or more additional therapeutic compound, wherein the combination comprises a fixed dose combination or separate doses, wherein the one or more additional therapeutic compound is selected from one or more of a Btk tyrosine kinase inhibitor, an Erbb2 tyrosine kinase receptor inhibitor; an Erbb4 tyrosine kinase receptor inhibitor, a thymidylate synthase inhibitor, an EGFR tyrosine kinase receptor inhibitor, an Epidermal growth factor antagonist, a Fyn tyrosine kinase inhibitor, a kit tyrosine kinase inhibitor, a Lyn tyrosine kinase inhibitor, a NK cell receptor modulator, a PDGF receptor antagonist, a PARP inhibitor, a poly ADP ribose polymerase inhibitor, a poly ADP ribose polymerase 1 inhibitor, a poly ADP ribose polymerase 2 inhibitor, a poly ADP ribose polymerase 3 inhibitor, a galactosyltransferase modulator, a dihydropyrimidine dehydrogenase inhibitor, an orotate phosphoribosyltransferase inhibitor, a telomerase modulator, a mucin 1 inhibitor, a mucin inhibitor, a secretin agonist, a TNF related apoptosis inducing ligand modulator, an IL17 gene stimulator, an interleukin 17E ligand, a Neurokinin receptor agonist, a cyclin G1 inhibitor, a checkpoint inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA4 inhibitor, a topoisomerase I inhibitor, an Alk-5 protein kinase inhibitor, a connective tissue growth factor ligand inhibitor, a notch-2 receptor antagonist, a notch-3 receptor antagonist, a hyaluronidase stimulator, a MEK-1 protein kinase inhibitor; MEK-2 protein kinase inhibitor, a GM-CSF receptor modulator; TNF alpha ligand modulator, a mesothelin modulator, an asparaginase stimulator, a caspase-3 stimulator; caspase-9 stimulator, a PKN3 gene inhibitor, a hedgehog protein inhibitor; Smoothened receptor antagonist, an AKT1 gene inhibitor, a DHFR inhibitor, a thymidine kinase stimulator, a CD29 modulator, a fibronectin modulator, an interleukin-2 ligand, a serine protease inhibitor, a D40LG gene stimulator; TNFSF9 gene stimulator, a 2-oxoglutarate dehydrogenase inhibitor, a TGF-beta type II receptor antagonist, an Erbb3 tyrosine kinase receptor inhibitor, a cholecystokinin CCK2 receptor antagonist, a Wilms tumor protein modulator, a Ras GTPase modulator, an histone deacetylase inhibitor, a cyclin-dependent kinase 4 inhibitor A modulator, an estrogen receptor beta modulator, a 4-1BB inhibitor, a 4-1BBL inhibitor, a PD-L2 inhibitor, a B7-H3 inhibitor, a B7-H4 inhibitor, a BTLA inhibitor, a HVEM inhibitor, aTIM3 inhibitor, a GAL9 inhibitor, a LAG3 inhibitor, a VISTA inhibitor, a KIR inhibitor, a 2B4 inhibitor, a CD160 inhibitor and a CD66e modulator. 2. The pharmaceutical combination of claim 1, wherein the one or more additional therapeutic compound is selected from one or more of bavituximab, IMM-101, CAP1-6D, Rexin-G, genistein, CVac, MM-D37K, PCI-27483, TG-01, mocetinostat, LOAd-703, CPI-613, upamostat, CRS-207, NovaCaps, trametinib, Atu-027, sonidegib, GRASPA, trabedersen, nastorazepide, Vaccell, oregovomab, istiratumab, refametinib, regorafenib, lapatinib, selumetinib, rucaparib, pelareorep, tarextumab, PEGylated hyaluronidase, varlitinib, aglatimagene besadenovec, GBS-01, GI-4000, WF-10, galunisertib, afatinib, RX-0201, FG-3019, pertuzumab, DCVax-Direct, selinexor, glufosfamide, virulizin, yttrium (90Y) clivatuzumab tetraxetan, brivudine, nimotuzumab, algenpantucel-L, tegafur+gimeracil+oteracil potassium+calcium folinate, olaparib, ibrutinib, pirarubicin, Rh-Apo2L, tertomotide, tegafur+gimeracil+oteracil potassium, tegafur+gimeracil+oteracil potassium, masitinib, Rexin-G, mitomycin, erlotinib, adriamycin, dexamethasone, vincristine, cyclophosphamide, fluorouracil, topotecan, taxol, interferons, platinum derivatives, taxane, paclitaxel, vinca alkaloids, vinblastine, anthracyclines, doxorubicin, epipodophyllotoxins, etoposide, cisplatin, methotrexate, actinomycin D, dolastatin 10, colchicine, emetine, trimetrexate, metoprine, daunorubicin, teniposide, amphotericin, alkylating agents, chlorambucil, 5-fluorouracil, campthothecin, cisplatin, metronidazole, Gleevec, Avastin, Vectibix, abarelix, aldesleukin, alemtuzumab, alitretinoin, allopurinol, altretamine, amifostine, anastrozole, arsenic trioxide, asparaginase, azacitidine, AZD9291, BCG Live, bevacuzimab, fluorouracil, bexarotene, bleomycin, bortezomib, busulfan, calusterone, capecitabine, camptothecin, carboplatin, carmustine, celecoxib, cetuximab, chlorambucil, cladribine, clofarabine, cyclophosphamide, cytarabine, dactinomycin, darbepoetin alfa, daunorubicin, denileukin, dexrazoxane, docetaxel, doxorubicin (neutral), doxorubicin hydrochloride, dromostanolone propionate, epirubicin, epoetin alfa, estramustine, etoposide phosphate, etoposide, exemestane, filgrastim, floxuridine fludarabine, fulvestrant, gefitinib, gemcitabine, gemtuzumab, goserelin acetate, histrelin acetate, hydroxyurea, ibritumomab, idarubicin, ifosfamide, imatinib mesylate, interferon alfa-2a, interferon alfa-2b, irinotecan, lenalidomide, letrozole, leucovorin, leuprolide acetate, levamisole, lomustine, megestrol acetate, melphalan, mercaptopurine, 6-MP, mesna, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone, nelarabine, nofetumomab, oprelvekin, oxaliplatin, paclitaxel, palifermin, pamidronate, pegademase, pegaspargase, pegfilgrastim, pemetrexed disodium, pentostatin, pipobroman, plicamycin, porfimer sodium, procarbazine, quinacrine, rasburicase, rituximab, rociletinib, sargramostim, sorafenib, streptozocin, sunitinib maleate, talc, tamoxifen, temozolomide, teniposide, VM-26, testolactone, thioguanine, 6-TG, thiotepa, topotecan, toremifene, tositumomab, trastuzumab, tretinoin, ATRA, uracil mustard, valrubicin, vinblastine, vincristine, vinorelbine, zoledronate, zoledronic acid, pembrolizumab, nivolumab, IBI-308, mDX-400, BGB-108, MEDI-0680, SHR-1210, PF-06801591, PDR-001, GB-226, STI-1110, durvalumab, atezolizumab, avelumab, BMS-936559, ALN-PDL, TSR-042, KD-033, CA-170, STI-1014, FOLFIRINOX and KY-1003. 3. The pharmaceutical combination of claim 1, wherein the one or more additional therapeutic compound is FOLFIRINOX. 4. The pharmaceutical combination of claim 1, wherein the one or more additional therapeutic compounds are gemcitabine and paclitaxel. 5. The pharmaceutical combination of claim 1, wherein R.sup.1 is halogen or methyl; R.sup.2 is halogen or C.sub.1-6 haloalkyl; R.sup.3 is halogen or C.sub.1-6 alkyl; R.sup.4 is hydrogen; n is 0; A.sup.1 is --CH-- or --N--; A.sup.2 is --CH--; and A.sup.3 is --N--. 6. The pharmaceutical combination of claim 1, wherein the compound is selected from: ##STR00028## or a pharmaceutically acceptable salt thereof. 7. The pharmaceutical combination of claim 1, wherein the compound is ##STR00029## or a pharmaceutically acceptable salt thereof. 8. The pharmaceutical combination of claim 1, wherein the compound is ##STR00030## or a pharmaceutically acceptable salt thereof. 9. The pharmaceutical combination of claim 2, wherein the compound is ##STR00031## or a pharmaceutically acceptable salt thereof. 10. The pharmaceutical combination of claim 3, wherein the compound is ##STR00032## or a pharmaceutically acceptable salt thereof. 11. The pharmaceutical combination of claim 4, wherein the compound is ##STR00033## or a pharmaceutically acceptable salt thereof. 12. The pharmaceutical combination of claim 5, wherein the compound is ##STR00034## or a pharmaceutically acceptable salt thereof. 13. The pharmaceutical combination of claim 6, wherein the compound is ##STR00035## or a pharmaceutically acceptable salt thereof. 14. A pharmaceutical combination comprising a compound of Formula I: ##STR00036## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is halogen or C.sub.1-6 alkyl; R.sup.2 is hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkyl, C.sub.1-6 haloalkoxy, or --CN; R.sup.3 is hydrogen, halogen, or C.sub.1-6 alkyl; R.sup.4 is hydrogen, halogen, or C.sub.1-6 alkyl; each R5 is independently C.sub.1-6, --OH, or --NH.sub.2; n is 0, 1, 2, or 3; each of A.sup.1, A.sup.2, and A.sup.3 is --CH-- or --N--, where at least one of A.sup.1, A.sup.2, or A.sup.3 is --N--; and one or more of additional therapeutic compounds selected from the group consisting of: FOLFIRINOX, gemcitabine, and paclitaxel. 15. The pharmaceutical combination of claim 14, wherein the combination comprises a fixed dose combination or separate doses. 16. The pharmaceutical combination of claim 14, wherein R.sup.1 is halogen or methyl; R.sup.2 is halogen or C.sub.1-6 haloalkyl; R.sup.3 is halogen or C.sub.1-6 alkyl; R.sup.4 is hydrogen; n is 0; A.sup.1 is --CH-- or --N--; A.sup.2 is --CH--; and A.sup.3 is --N--. 17. The pharmaceutical combination of claim 14, wherein the compound is selected from: ##STR00037## or a pharmaceutically acceptable salt thereof. 18. The pharmaceutical combination of claim 14, wherein the compound is ##STR00038## or a pharmaceutically acceptable salt thereof.

Details for Patent 10,195,188

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	05/05/2004		2036-06-13
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	12/02/2004		2036-06-13
Amphastar Pharmaceuticals, Inc.	AMPHADASE	hyaluronidase	Injection	021665	10/26/2004		2036-06-13