Claims for Patent: 7,829,535

Summary for Patent: 7,829,535

Title:	Methods for bone treatment by modulating an arachidonic acid metabolic or signaling pathway
Abstract:	Methods for promoting osteogenesis to accelerate or enhance bone fracture healing, treat bone defects, and enhance bone formation are disclosed. The methods modulate an arachidonic acid metabolic or signaling pathway in general, and, in particular, utilize 5-lipoxygenase inhibitors. These molecules can be delivered alone or in combination with one or more agents that inhibit bone resorption, regulate calcium resorption from bone, enhance bone accumulation, enhance bone formation, induce bone formation, impair growth of microorganisms, reduce inflammation, and/or reduce pain.
Inventor(s):	O\'Connor; James Patrick (Menlo Park, CA)
Assignee:	Accelalox, Inc. (Menlo Park, CA)
Application Number:	11/995,529
Patent Claims:	1. A method for promoting osteogenesis to treat a mammalian subject in need thereof, comprising: administering to said subject a pharmaceutically effective amount of compound that reduces a 5-lipoxygenase activity, wherein said 5-lipoxygenase activity reduction promotes osteogenesis to treat a condition selected from the group consisting of a bone fracture, a bone defect, and a condition treated by inducing bone formation. 2. The method of claim 1, wherein said condition is a bone fracture. 3. The method of claim 2, wherein said bone fracture is a non-osteoporotic fracture, an osteoporotic fracture, a fracture associated with a congenital disease, a fracture associated with an acquired disease, or an osteotomic fracture. 4. The method of claim 3, wherein said bone fracture is a non-osteoporotic fracture. 5. The method of claim 3, wherein said bone fracture is an osteoporotic fracture. 6. The method of claim 3, wherein said bone fracture is an osteotomic fracture. 7. The method of claim 1, wherein said condition is a condition treated by inducing bone formation. 8. The method of claim 7, wherein said condition is a condition treated by a spine fusion, or a joint arthrodesis. 9. The method of claim 1, wherein said condition is a bone defect. 10. The method of claim 1, wherein said administration is in vivo. 11. The method of claim 1, wherein said administration is ex vivo. 12. The method of claim 1, wherein said compound reduces a 5-lipoxygenase activity by inhibiting a five lipoxygenase activating protein (FLAP). 13. The method of claim 1, wherein said compound comprises a small molecule. 14. The method of claim 13, wherein said small molecule is selected from the group consisting of 3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylp- ropanoic acid; 3-(1-(4-chlorobenzyl)-3-(1-butyl-thio)-5-(quinolin-2-yl-methoxy)-indol -2-y l)-2,2-dimethyl propanoic acid); nordihydroguaiaretic acid; 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoquinone; (N-(1-benzo(b)thien-2-ylethyl)-N-hydroxyurea); masoprocol; tenidap; flobufen; lonapalene; tagorizine; Abbott.RTM. A-121798; Abbott.RTM. A-76745; Abbott.RTM. A-78773; [(R)(+)N'-[[5-(4-fluorophenoxy) furan-2-yl]-1-methyl-2-propynyl]-N-hydroxyurea; Abbott.RTM. ABT 761; Dainippon.RTM. AL-3264; Bayer.RTM. Bay-x-1005; Biofor.RTM. BF-389; bunaprolast; Cytomed.RTM. CMI-392; Takeda.RTM. CV-6504; enazadrem phosphate; Leo Denmark.RTM. ETH-615; flezelastine hydrochloride; Merck Frosst.RTM. L-663536; Merckle.RTM. ML-3000; 3M Pharmaceuticals.RTM. R-840; rilopirox; Schering Plough.RTM. SCH-40120; tepoxalin; linazolast-; Zeneca.RTM. ZD-2138; Bristol-Myers Squibb.RTM. BU-4601A; carbazomycin C; lagunamycin; Wellcome.RTM. BW-70C; Ciba-Geigy.RTM. CGS-26529; Warner-Lambert.RTM. CI 1004; Warner-Lambert.RTM. PD-136005; Warner-Lambert.RTM. PD-145246; Elsai.RTM. E-3040; Fujirebio.RTM. F-1322; Fujisawa.RTM. FR-110302; Merck Frosst.RTM. L-699333; Merck Frosst.RTM. L-739010; Lilly.RTM. LY-269415; Lilly.RTM. LY-178002; Hoechst Roussel.RTM. P-8892; SmithKline Beecham.RTM. SB-202235; American Home Products.RTM. WAY-121520; American Home Products.RTM. WAY-125007; Zeneca.RTM. ZD-7717; Zeneca.RTM. ZM-216800; Zeneca.RTM. ZM-230487; 1,2-dihydro-n-(2-thiazolyl)-1-oxopyrrolo (3,2,1-kl)phenothiazine-1-carboxamide; Abbott.RTM. A-65260; Abbott.RTM. A-69412; Abbott.RTM. A-63162; American Home Products.RTM. AHR-5333; Bayer.RTM. Bay-q-1531; Boehringer Ingelheim.RTM. BI-L-357; Boehringer Ingelheim.RTM. BI-L-93BS; Boehringer Ingelheim.RTM. BIL 226XX; Bristol-Myers Squibb.RTM. BMY-30094; carbazomycin B; Wellcome.RTM. BW-B218C; Chauvin.RTM. CBS-1114; Ciba-Geigy.RTM. CGS-21595; Ciba-Geigy.RTM. CGS-22745; Ciba-Geigy.RTM. CGS-23885; Ciba-Geigy.RTM. CGS 24891; Ciba-Geigy.RTM. CGS-8515; Chiesi.RTM. CHF-1909; Warner-Lambert.RTM. CI-986; Warner-Lambert.RTM. CI 987; cirsiliol; docebenone; Eisai.RTM. E-5110; Eisai.RTM. E-6080; enofelast; epocarbazolin-A; eprovafen; evandamine; Fisons.RTM. FPL 62064; Zeneca.RTM. ICI-211965; Zeneca.RTM. ICI-216800; Kyowa Hakko.RTM. KF-8940; Merck.RTM. L-651392; Merck.RTM. L-651896; Merck.RTM. L-652343; Merck.RTM. L-656224; Merck.RTM. L-670630; Merck.RTM. L-674636; Lilly.RTM. LY-233569; Merck.RTM. MK-591; Merck.RTM. L-655240; nitrosoxacin-A; Ono.RTM. ONO-5349; Ono.RTM. ONO-LP-219; Ono.RTM. ONO-LP-269; Warner-Lambert.RTM. PD-127443; Purdue Frederick.RTM. PF-5901; Rhone-Poulenc Rorer.RTM. Rev-5367; Rhone-Poulenc Rorer.RTM. RG-5901-A; Rhone-Poulenc Rorer.RTM. RG-6866; Roussel-Uclaf.RTM. RU-46057; Searle.RTM. SC-41661A; Searle.RTM. SC-45662; Sandoz.RTM. SDZ-210-610; SmithKline Beecham.RTM. SK&F-104351; SmithKline Beecham.RTM. SK&F-104493; SmithKline Beecham.RTM. SK&F-105809; Synthelabo.RTM. SL-81-0433; Teijin.RTM. TEI-8005; Terumo.RTM. TMK-777; Terumo.RTM. TMK-781; Terumo.RTM. TMK-789; Terumo.RTM. TMK-919; Terumo.RTM. TMK-992; Teikoku Hormone.RTM. TZI-41127; American Home Products.RTM. WAY-120739; American Home Products.RTM. WY-47288; American Home Products.RTM. WY-48252; American Home Products.RTM. WY-50295; Yoshitomi.RTM. Y-19432; 4-{3-[4-(2-methyl-1H-imidazol-1-yl)phenylthio]}phenyl-3,4,5,6-tetrahydro-- 2H-pyran-4-carboxamide; esculetin; phenidone; Boehringer Ingelheim.RTM. BI-L-239; 5,8,11-eicosatriynoic acid; 5,8,11,14-eicosatetraynoic acid; cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate; curcumin; gossypol; caffeic acid; baicalein; 7,7-dimethyleicosadrenoic acid; Lilly.RTM. LY-311727; bromoenol lactone; methyl arachidonyl fluorophosphonate; methyl y-linolenyl fluorophosphonate; oleyoxyethyl phosphorylcholine; arachidonyl trifluoromethyl ketone; n-(p-amylcinnamoyl) anthranilic acid; mepacrine; quinacrine; atabrine; parabromophenacylbromide; aristolochic acid; cortisone; Glaxo SmithKline.RTM. SB-480848; Glaxo SmithKline.RTM. SB-659032; Glaxo SmithKline.RTM. SB-677116; Bristol-Myers Squibb.RTM. BMS-181162; Sterling-Winthrop.RTM. MJ33; and Millennium Pharmaceuticals.RTM. MLN977. 15. The method of claim 14, wherein said small molecule is selected from the group consisting of masoprocol; tenidap; (N-(1-benzo(b)thien-2-ylethyl)-N-hydroxyurea); flobufen; lonapalene; tagorizine; 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoquinone; Abbott.RTM. A-121798; Abbott.RTM. A-76745; Abbott.RTM. A-78773; [(R)(+)N'-[[5-(4-fluorophenoxy)furan-2-yl]-1-methyl-2-propynyl]-N-hydroxy- urea; Abbott.RTM. ABT 761; Dainippon.RTM. AL-3264; Bayer.RTM. Bay-x-1005; Biofor.RTM. BF-389; bunaprolast; Cytomed.RTM. CMI-392; Takeda.RTM. CV-6504; Ciba-Geigy.RTM. CGS-26529; enazadrem phosphate; Leo Denmark.RTM. ETH-615; flezelastine hydrochloride; Merck Frosst.RTM. L-663536; Merck Frosst.RTM. L-699333; Merckle.RTM. ML-3000, 3M Pharmaceuticals.RTM. R-840; rilopirox; Schering Plough.RTM. SCH-40120; tepoxalin; linazolast; Zeneca.RTM. ZD-7717; Zeneca.RTM. ZM-216800; Zeneca.RTM. ZM-230487; Zeneca.RTM. ZD-2138; and nordihydroguaiaretic acid. 16. The method of claim 15, wherein said small molecule is selected from the group consisting of tenidap; (N-(1-benzo(b)thien-2-ylethyl)-N-hydroxyurea); flobufen; lonapalene; tagorizine; 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl -1,4-benzoquinone; Abbott.RTM. A-121798; Abbott.RTM. A-76745; Abbott.RTM. A-78773; [(R)(+)N'-[[5-(4-fluorophenoxy)furan-2-yl]-1-methyl-2-propynyl]-- N-hydroxyurea; Abbott.RTM. ABT 761; Ciba-Geigy.RTM. CGS-26529; Biofor.RTM. BF-389; Cytomed.RTM. CMI-392; Leo Denmark.RTM. ETH-615;, Merck Frosst.RTM. L 699333; Merckle.RTM. ML-3000; 3M Pharmaceuticals.RTM. R-840; linazolast; Zeneca.RTM. ZD-7717; Zeneca.RTM. ZM-216800; Zeneca.RTM. ZM-230487; Zeneca.RTM. ZD-2138, and nordihydroguaiaretic acid. 17. The method of claim 11, wherein said compound comprises a nucleic acid comprising a sequence selected from the group consisting of 5'-AAC TGG GCG AGA TCC AGC TGG-3' (SEQ ID NO: 9), 5'-AAG CTC CCG GTG ACC ACG GAG-3' (SEQ ID NO: 10), 5'-AAG GAA GCC ATG GCC CGA TTC-3' (SEQ ID NO: 11), 5'-AAT CGA GAA GCG CAA GTA CTG-3' (SEQ ID NO: 12), 5'-AAG GAG TGG ACT TTG TTC TGA-3' (SEQ ID NO: 13), 5'-AAC TTC GGC CAG TAC GAC TGG-3' (SEQ ID NO: 14), 5'-AAG TTG GCC CGA GAT GAC CAA-3' (SEQ ID NO: 15), 5'-AAC ACA TCT GGT GTC TGA GGT-3' (SEQ ID NO: 16), 5'-AAC CAT GCG AGC CCC GCC ACC-3' (SEQ ID NO: 17), 5'-AAG CAA ACA TGG ATC AAG AAA-3' (SEQ ID NO: 18), 5'-AAG TTC CTG CTG CGT TTG CTG-3' (SEQ ID NO: 19), 5'-AAT TCA GCT CTT GAG AGC ATT-3' (SEQ ID NO: 20), 5'-AAT GGA TTC TTT GCC CAT AAA-3' (SEQ ID NO: 21), 5'-AAG TAC TTT GTC GGT TAC CTA-3' (SEQ ID NO: 22), 5'-AAT CTA TTG GCC ATC TGG GCT-3' (SEQ ID NO: 23), 5'-AAC CAG AAC TGT GTA GAT GCG-3' (SEQ ID NO: 24) 5'-AAG TGA CTT TGA AAA CTA CAT-3' (SEQ ID NO: 25), and 5'-AAT GAT GTC ATG TCA GCT CCG-3' (SEQ ID NO: 26). 18. The method of claim 11, wherein said compound comprises a nucleic acid comprising a sequence selected from the group consisting of 5'-GCA GGT GCT TCT CGC TGC AGC C-3' (SEQ ID NO: 27), 5'-GCC AGT ACT TGC GCT TCT CG-3' (SEQ ID NO: 28), 5'-CCA TCG ATA TTG TTT TTG CC-3' (SEQ ID NO: 29), 5'-GGA GCT TCT CGG GCA GCT CTG TGC-3' (SEQ ID NO: 30), 5'-CCA GGT TCT TAT ACA GCA AGC-3' (SEQ ID NO: 31), 5'-CCA GCA GCT TGA AAA TGG GGT GC-3' (SEQ ID NO: 32), 5'-GCC CCG GGC CTT GAT GGC C-3' (SEQ ID NO: 33), 5'-CCA CGC CCT TGG CAG TCG G-3' (SEQ ID NO: 34), 5'-GCG GAA TCG GGC CAT GGC TTC C-3' (SEQ ID NO: 35), 5'-GTT CCG GTC CTC TGG AAG CTC C-3' (SEQ ID NO: 36), 5'-CGC AGA CCA GAG CAC AGC G-3' (SEQ ID NO: 37), 5'-GCA AAC GCA GCA GGA AC-3' (SEQ ID NO: 38), 5'-CGT TTC CCA AAT ATG TAG CC-3' (SEQ ID NO: 39), 5'-GTT TTC AAA GTC ACT TCC G-3' (SEQ ID NO: 40), 5'-GGT TAA CTC AAG CTG TGA AGC-3' (SEQ ID NO: 41), 5'-GGA GCT GAC ATG ACA TC-3' (SEQ ID NO: 42), and 5'-GGC CAC GGT CAT GTT CAA GG-3' (SEQ ID NO: 43). 19. The method of claim 1, further comprising administering to said subject a pharmaceutically effective amount of a compound that reduces a COX-1 activity. 20. The method of claim 19, wherein said compound is selected from the group consisting of Searle.RTM. SC-560, 1-[(4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl]-4-methylpiperazine hydrochloride valeryl salicylate, aspirin, dexketoprofen, keterolac, flurbiprofen, and suprofen. 21. The method of claim 1, further comprising administering to said subject a pharmaceutically effective amount of a compound that increases a COX-2 activity. 22. The method of claim 21, wherein said compound is selected from the group consisting of prostaglandin E2; butaprost; sulprostone; Pfizer.RTM. CP-536,745-01; Pfizer.RTM. CP-043,305-02; Pfizer.RTM. CP-044,519-02; Pfizer.RTM. CP432; Ono Pharmaceutical.RTM. ONO-4819; Pfizer.RTM. CP-533,536; prostaglandin F.sub.2.alpha.; bimatoprost; cloprostenol; latanoprost; tafluprost; bone morphogenetic protein-2; platelet derived growth factor; interleukin-1.alpha.; interleukin-1.beta.; tumor necrosis factor-alpha; fibroblast growth factor, transforming growth factor-.beta.; epidermal growth factor; parathyroid hormone; parathyroid hormone related peptide; and teriparatide. 23. The method of claim 1, comprising administering to said subject an ultrasound therapy or exposing said subject to a pulsed electromagnetic field in an amount sufficient to increase a COX-2 activity in said subject. 24. The method of claim 16, wherein said 5-LO inhibitor is [(R)(+)N'-[[5-(4-fluorophenoxy) furan-2-yl]-1-methyl-2-propynyl]-N-hydroxyurea. 25. The method of claim 16, wherein said 5-LO inhibitor is Abbott.RTM. ABT 761.

Details for Patent 7,829,535

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2025-08-18