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(12) Patent Application Publication (10) Pub. No.: US 2011/0251158 A1 KEPLEY Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2011/0251158 A1 KEPLEY Et Al US 20110251 158A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0251158 A1 KEPLEY et al. (43) Pub. Date: Oct. 13, 2011 (54) FULLERENE THERAPES FOR (60) Provisional application No. 61/033,309, filed on Mar. NFLAMMATION AND INHIBITION OF 3, 2008, provisional application No. 61/033,336, filed BUILD-UP OF ARTERIAL PLAQUE on Mar. 3, 2008. Publication Classification (75) Inventors: Christopher L. KEPLEY, Ringgold, VA (US); Robert P. (51) Int. Cl. LENK, Danville, VA (US); Darren A63/685 (2006.01) K. MACFARLAND, Danville, VA C07C 69/76 (2006.01) (US); Zhiguo ZHOU, A63/492 (2006.01) Winston-Salem, NC (US) C07D 249/04 (2006.01) A6IP 9/02 (2006.01) (73) Assignee: Luna Innovations Incorporated, C07D 40/4 (2006.01) Roanoke, VA (US) C07F 9/10 (2006.01) A6II 3/66 (2006.01) A6IP 9/00 (2006.01) (21) Appl. No.: 12/884,076 A6II 3L/235 (2006.01) A63L/455 (2006.01) Filed: Sep. 16, 2010 (22) (52) U.S. Cl. ............. 514/78: 514/510; 560/80: 514/359; Related U.S. Application Data 548/255; 514/332:546/263:554/80; 514/107 (57) ABSTRACT (63) Continuation-in-part of application No. 12/921,049, filed on Sep. 3, 2010, filed as application No. PCT/ Described herein are methods for treating inflammatory dis US2009/001333 on Mar. 3, 2009, Continuation-in orders or for inhibiting the build-up of arterial plaque. The part of application No. 12/921,083, filed on Dec. 16, methods comprise administering to a Subject in need thereof 2010, filed as application No. PCT/US2009/001335 atherapeutically effective amount of a synthetically modified on Mar. 3, 2009. fullerene. Patent Application Publication Oct. 13, 2011 Sheet 1 of 37 US 2011/0251158A1 FIGURE 1 Patent Application Publication Oct. 13, 2011 Sheet 2 of 37 US 2011/0251158A1 Co-tetrainositol C60-ethanolamine FIGURE 2 Patent Application Publication Oct. 13, 2011 Sheet 3 of 37 US 2011/0251158A1 FIGURE 3 Patent Application Publication Oct. 13, 2011 Sheet 4 of 37 US 2011/0251158A1 7 (TGA) 5 (ALM) FIGURE 4 Patent Application Publication Oct. 13, 2011 Sheet 5 of 37 US 2011/0251158A1 A Clinical Indices 120 Ankle thickness 100 80 60 40 20 -20 -0- 200 ng/100 ul LNWOO42 -O- 2000 ng/100 ul LNW0042 -v- 200 ng/100 ul LNW0048 was a 2000 ng/100 ul LNW0048 -- 200 mg/100 ulPBS FIGURE 5 Patent Application Publication Oct. 13, 2011 Sheet 6 of 37 US 2011/0251158A1 : FIGURE 6 Patent Application Publication Oct. 13, 2011 Sheet 7 of 37 US 2011/0251158A1 Walues represent mast ceilgeries upregulated by at east 10% by FCeR stimulation that were inhibited >20% by inos (sorted most inhibited to least inhibited in column D) Gene symbol % increase (-) to (+) % inhibition by inositol LECT1 1024.5% 99.08% PTBP2 1538.29% 98.69% FIGURE 7 ABCG5 4480.00% 97.39% NIT1. 1913.64% 95.15% W.L 84.3% 88.13% MARVELD3 270.87% 84.86% CFH R5 34.99% 76.92% MER3 23.03% 72.22% DH3B 40.70% 69.26% LMX1B 35.8% 67.49% XYLT2 38.93% . 65.09% ANTXRL 43.68% 64.64% KYNU 74.87% 64.52% FAM22 29.86% 62.28% C12Orf52 36.53% 62.04% CA7 42.42% 60.63% CHST1. 33.91% 59.95% C20orf144, C20orf134 w 66.44% 59.92% VIBLAC1 359.97% 59.87% CDCA3 83.10% 59.76% OTUB1 62.69% 59.22% EIF1AD 30.98% 58.92% GNB2 29.14% 58.46% EF6 17.89% 58.35% RP5-981O7.3 473.55% 58.35% WASH1. 97.42% 58.22% RAD51L, 92.07% 58.17% C3orf62 A1.37% 58.07% SEPN1 20.10% 57.79% PHLDA1 35.31% 57.77% ADAD2 14.51% 57.47% SMOC2 18.70% 57.19% ACO98823.3 67.54% 57.10% RP11-318K123 . 10.62% 56.91% ASTN). 45.29% 56.41% PARP15 27.69% 55.63% RP11-1919.4 29.43% 55.51% ANKRD39,ANKRD23 61.60% 55.38% POU3F3 73.70% 55.28% FAT3 68.38% 55.27% C2OOrf102 20.76% 55.27% FGL2 6499.13% 54.84% RHO 92.42% 54.78% NOG 78.26% 54.62% Patent Application Publication Oct. 13, 2011 Sheet 8 of 37 US 2011/0251158A1 PLA2G16 34.38% 54.56% GNG4 62.55% 54.53% RP13-143G15.3 78.91% 54.53% FAM177B 41.68% 54.29% EFHD1 19.83% 53.96% FGURE 7 TCF4 67.42% 53.95% ACO92296.2-1. 43.21% 53.85% GPRC5C 34.63% 53.85% IF6 55.53% 53.77% AC146944.1-4AC146944.1-5, 25.81% 53.64% TMEM161A 33.21% 53.48% EIF2B5, FAM131A 165.68% 53.47% C9orf110 64.61% 53.00% MAFA 31.22% 52.94% RPPLY1. 16.62% 52.85% FGF22 18.24% 52.73% ACOO61588 50.22% 52.71% TRAF6 204.92% 52.67% MYBPC2SPIB 10.13% 52.27% AC116353.7 20.07% 52.24% AC135.457.2-3 54,47% 52.22% KREMEN1. 25.36% 51.87% PLAGL1. 33O46% 51.77% EIF4EBP2 99.24% 51.72% CPB1 45.44% 51.71% TNFRSF14 67.26% 51.70% C7orfA7 32.34% 51.68% CYP27C1 135.47% 51.64% COO.7 38.84% 51.60% AJAP1 39.30% 51.52% GFRA4 32.56% 51.50% ACOA3479.1. 186.02% 5.41% DPM3 10.38% 51.28% LSSAPOO1468.1 16.76% 50.97% AC38O281-3 37.18% 50.78% OR12 64.87% 50.75% ATP1A4 51.41% 50.65% PAPPA 359.84% 50.63% MAF 16.55% 50.46% AMPD2 67.64% 50.45% LRRC51. 140.25% 50.37% NKG7 40.70% 50.36% USE. 24.11% 50.24% TNRC6B 21.65% 50.24% CALML3 27.07% 50.18% ABCB11 32.38% 50.12% ETS1 25.62% 50.10% Patent Application Publication Oct. 13, 2011 Sheet 10 of 37 US 2011/0251158A1 HSD11B2 26.67% 45.44% SLC8A1 89.40% 45.13% C22Orf13 18.45% 45.05% APOOO354.4 49.26% 44.37% CPNE7 13.59% 44.79% IOCA 19.76% 447.9% FGURE 7 UTP23 18.42% 44.72% NTF3 15.58% 44.61% UBE2C 27.93% 44.53% RAB5C 29.92% 44.40% TNRSF14 1125.00% 44.39% CLC 80.17% 44.23% Corf143 177.35% 44.22% HSD4. 21.0% 44.18% MOBP 32.53% 44.16% SLT1. 27.55% 44.12% CD-233OK9.3 47.14% 44.08% SLC46A3 585.71% 44.05% SYNPO 20.17% 44.00% LRRCAO 36.19% 43.88% CLIC1, CLIC1, CLIC1, CLIC1, CLIC1 25.62% 43.76% PK3R3 62.54% 43.73% KRTAP20-2 67.04% 43.68% AC105345.3 91.52% 43.61% DPM2 73.59% 43.61% GPR371. 46.15% 43.61% ZFAND2A 36.18% 43.56% ACO84018.1 72.53% 43.38% RPUSD1 53.63% 43.36% LRRC56 32.15% 43.31% TSSK3 12.34% 43.28% SPRED3 20.52% 43.22% MURC 81.85% 43.21% PPARGCB 18.39% 43.11% YSK4 74.96% 43.03% HPAC009087.4-2 17.83% 42.99% RP11-343.24. 108.98% 42.69% DO1 36.59% 42.65% EPHB4 30.18% 42.59% NAT8 161.43% 42.54% ARTS-1 19.17% 42.52% DG1. 45.95% 42.52% SLC4A2 31.63% 42.49% KF2A 195.88% 42.39% RP1-212P92 10,04% 42.33% LRB3 25.55% 42.28% KREMEN2 37.37% 42.0% Patent Application Publication Oct. 13, 2011 Sheet 11 of 37 US 2011/0251158A1 CYP4F3LPAC140481.7AC132. 45.34% 42.09% SP140 46.87% 42.02% TMEM30A,COX7A2 24.85% 41.99% SGECP16 47.57% 41.96% PNCK 85.10% 41.91% ANKRD45 133.16% 41.88% a six KRTAP3-3 34.80% 41.83% FIGURE 7 ADRA1B 117.59% 41.62% TBX20 47.30% 41.55% KK10 76.71% 41.55% GUDP2 68.24% 41.54% HS3ST1. 52.04% 41.50% PDIA3P, PDIA3 14.75% 41.36% NDUFV1 16.57% 41.36% C20Orf)1 1.93% 41.22% KIAA1467 78.86% 41.19% AFG31 55.17% 41.17% TNRC6C 16,02% 41.12% ATP7B 54.89% 41.05% RAB36 62.31% 40.98% UBE22 33.89% 40.96% RX4 1767.86% 40.92% ACO254496-1. 48.79% 40.84% WBSCR17 16.59% 40.82% RUNX1. 11.65% 40.77% RAD54L 41.66% 40.73% ADAMSA 103.68% 40.73% NGN4Y 125.23% 40.60% ZNF587 155.56% 40.58% AMAC1, POLR2A,AMAC1L3 34.30% 40.51% NEK6 113.93% A-0.45% FBXL18 61.09% 40.38% SLC38A10 19.51% 40.34% CFH 3O7.64% 40.26% HS6ST3 37.89% 40.24% RPL3 42.63% 40.24% PAOR5 497.59% 40.20% ACO10536.8-2 34.93% A.O.19% SMCY 38.54% 40.14% NDUFA4 70.48% 40.06% HC1. 34.51% 39.97% KBTBD3 68.43% 39.95% A4GNT 19.32% 39.84% TNFAP1 196.99% 39.67% ART3 20.56% 39.64% UP2 62.19% 39.63% HNRNPAB 57.60% 39.36% Patent Application Publication Oct. 13, 2011 Sheet 12 of 37 US 2011/025.1158A1 ANKRD18B 19.25% 39.32% ACO93323.3 69.74% 39.32% OR1OJ8P 25.51% 39.30% CTNND2 13.59% 39.23% PSMB2 155.99% 39, 10% EDEM2 39.01% 39.10% FIGURE 7 DNASE 47.80% 39.05% AGXT22 65.83% 39.03% GPR26 27.50% 38.98% NEUROG2 64.12% 38.91% GPR172A A.O.17% 38.75% L17B 23.51% 38.73% SSTR5 63.31% 38.67% CCN 46.57% 38.59% ZNF497 33.48% 38.54% PA2G2C 31.22% 38.53% CTA 23.35% 38.52% GNA15 10.27% 38.48% BCR 22.86% 38.41% UBXN6 69.04% 38.40% PXN 29.11% 38.38% UPB1 167.67% 38.37% GPR62 22.30% 38.37% THRBAC112217.2 22.00% 38.31% ARF1.
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