Claims for Patent: 10,378,059

Summary for Patent: 10,378,059

Title:	Methods and molecular pharmacodynamic biomarkers for multiple signaling pathways in response to carboxyamidotriazole orotate
Abstract:	This invention provides methods, pharmacodynamics biomarker signatures for multiple signaling pathways in a cell sample such as anagen hair, in response to carboxyamidotriazole orotate (CTO) from a subject. CTO has demonstrated response in several cancers having different genomic mutations in clinical studies. This invention provides a diagnostic and prognostic assay for monitoring response to CTO ranging from -100 fold to +25 fold differential expression in several transcriptional signatures associated with tumor inhibition including EGFR, MEK, HDAC, RAS, GFS, WNT, HSP90 or non-voltage dependent calcium signaling, while inducing tumor suppressors signatures such as P53 or EGR1 in the anagen hair assay.
Inventor(s):	Karmali; Rashida A (Brooklyn, NY)
Assignee:	TACTICAL THERAPEUTICS, INC. (New York, NY)
Application Number:	13/957,720
Patent Claims:	1. A method for quantifying the response to carboxyamidotriazole orotate (CTO) on more than one signature pathway wherein said signature pathways are RAS, GFS, MEKi, HDAC, NOTCH, WNT.beta.-catenin, HSP90, EGFR, p53, EGR1, CEACAMI, TGF.beta. or Dystonin and on pharmacodynamic biomarkers for each of said signature pathways, said method comprising: a) obtaining a cell sample obtained from a subject and treating cultures of the cell sample with varying doses of CTO alone, and maintaining the cultures for different time periods; b) isolating the mRNA from the treated cultures of the cell sample obtained in step a), and preparing representative cDNA therefrom, and measuring the transcriptional alteration in expression in the treated cultures of the cell sample; c) calculating a signature score for each of the pharmacodynamics biomarkers of each of said signature pathways using the Ingenuity Pathway Analysis (IPA) System and quantitating the response to the varying doses of CTO, and selecting a list of overlapping genes expressing after 8 hours and 24 hours of exposure to CTO based on the calculated signature scores, from the list consisting of: TABLE-US-00011 Probeset ID Entrez Gene Gene Symbol 222450_at 56937 PMEPA1 233565_s_at 100528031///27111 FKBP1A-SDCBP2/// SDCBP2 242832_at 5187 PER1 240463_at -- -- 213039_at 23370 ARHGEF18 235072_s_at 63971 KIF13A 208926_at 4758 NEU1 237444_at -- -- 239451_at -- -- 222288_at -- -- 227579_at 2241 FER 212717_at 9842 PLEKHM1 226853_at 55589 BMP2K 214112_s_at 541578///91966 CXorf40A/// CXorf40B 209012_at 7204 TRIO 219476_at 79098 C1orf116 238086_at 100129617 LOC100129617 230721_at 730094 C16orf52 1566079_at 647190 RPS16P5 223839_s_at 6319 SCD 225671_at 124976 SPNS2 212961_x_at 541578 CXorf40B 223659_at 84000 TMPRSS13 229909_at 283358 B4GALNT3 223467_at 51655 RASD1 235146_at 57458 TMCC3 235548_at 164284 APCDD1L 206816_s_at 26206 SPAG8 242323_at 81579 PLA2G12A 224579_at 81539 SLC38A1 213315_x_at 91966 CXorf40A 227314_at 3673 ITGA2 227093_at 57602 USP36 200760_s_at 10550 ARL6IP5 201790_s_at 1717 DHCR7 1554980_a_at 467 ATF3 242255_at 22884 WDR37 219267_at 51228 GLTP 1555786_s_at 645687 LINC00520 229734_at 283174 LOC283174 242856_at -- -- 201037_at 5214 PFKP 1562970_at -- -- 201465_s_at 3725 JUN 202067_s_at 3949 LDLR 223679_at 1499 CTNNB1 201235_s_at 7832 BTG2 225662_at 51776 ZAK 204401_at 3783 KCNN4 222906_at 28982 FLVCR1 238613_at 51776 ZAK 206414_s_at 8853 ASAP2 210794_s_at 55384 MEG3 226621_at 9180 OSMR 230682_x_at 8714 ABCC3 235668_at 639 PRDM1 205483_s_at 9636 ISG15 215808_at 5655 KLK10 212281_s_at 27346 TMEM97 212282_at 27346 TMEM97 226287_at 91057 CCDC34 213618_at 116984 ARAP2 231089_at 100505664 LOC100505664 227140_at 3624 INHBA 231467_at -- -- 202967_at 2941 GSTA4 230323_s_at 120224 TMEM45B 224471_s_at 8945 BTRC 202708_s_at 8349 HIST2H2BE 242871_at 54852 PAQR5 205627_at 978 CDA 235542_at 200424 TET3 240410_at -- -- 236656_s_at 100288911 LOC100288911 206164_at 9635 CLCA2 203159_at 2744 GLS 224991_at 80790 CMIP 204258_at 1105 CHD1 228249_at 119710 C11orf74 229013_at 145783 LOC145783 211547_s_at 5048 PAFAH1B1 226863_at 642273 FAM110C 208161_s_at 8714 ABCC3 214805_at 1973 ElF4A1 229429_x_at 728855///728875 LOC728855/// LOC728875 202720_at 26136 TES 224995_at 56907 SPIRE1 214771_x_at 23164 MPRIP 201939_at 10769 PLK2 238587_at 84959 UBASH3B 232113_at -- -- 208690_s_at 9124 PDLIM1 201464_x_at 3725 JUN 236657_at 100288911 LOC100288911 215541_s_at 1729 DIAPH1 238028_at 647024 C6orf132 226893_at 27 ABL2 237576_x_at 100506480 LOC100506480 1552256_a_at 949 SCARB1 215255_at 22997 IGSF9B 1557258_a_at 8915 BCL10 240623_at -- -- 228754_at 6533 SLC6A6 217257_at 6452 SH3BP2 241036_at -- -- 242553_at 8714 ABCC3 239358_at -- -- 210868_s_at 79071 ELOVL6 200815_s_at 5048 PAFAH1B1 208436_s_at 3665 IRF7 208138_at 2520 GAST 241780_at -- -- 200730_s_at 7803 PTP4A1 219697_at 9956 HS3ST2 201693_s_at 1958 EGR1 218847_at 10644 IGF2BP2 230469_at 219790 RTKN2 209917_s_at 11257 TP53TG1 224329_s_at 84518 CNFN 212253_x_at 100652766///667 DST/// LOC100652766 238058_at 150381 LOC150381 239334_at 57488 ESYT2 222271_at -- -- 216718_at 388699 LINC00302 219076_s_at 5827 PXMP2 204475_at 4312 MMP1 221185_s_at 84223 IQCG 203586_s_at 379 ARL4D 217802_s_at 64710 NUCKS1 205767_at 2069 EREG 228360_at 130576 LYPD6B 228917_at -- -- 228748_at 966 CD59 219632_s_at 23729///7442 SHPK///TRPV1 238715_at 646014 LOC646014 218810_at 80149 ZC3H12A 225177_at 80223 RAB11FIP1 224454_at 55500 ETNK1 209498_at 634 CEACAM1 1557257_at 8915 BCL10 225133_at 51274 KLF3 202340_x_at 3164 NR4A1 1556545_at -- -- 212474_at 23080 AVL9 210241_s_at 11257 TP53TG1 243543_at -- -- 239132_at 4842 NOS1 222757_s_at 51776 ZAK 201194_at 6415 SEPW1 229874_x_at 100506687 LOC100506687 202557_at 6782 HSPA13 239669_at -- -- 231907_at 27 ABL2 229074_at 30844 EHD4 205428_s_at 794 CALB2 205822_s_at 3157 HMGCS1 210869_s_at 4162 MCAM 225665_at 51776 ZAK 212781_at 5930 RBBP6 232355_at 767579 SNORD114-3 213288_at 129642 MBOAT2 221666_s_at 29108 PYCARD 203072_at 4643 MYO1E 215465_at 26154 ABCA12 224453_s_at 55500 ETNK1 216935_at 388699 LINC00302 209086_x_at 4162 MCAM 218833_at 51776 ZAK 209377_s_at 9324 HMGN3 223519_at 51776 ZAK 210138_at 8601 RGS20 1558845_at 100506089 LOC100506089 201819_at 949 SCARB1 204310_s_at 4882 NPR2 239377_at 84285 EIF1AD 224611_s_at 80331 DNAJC5 219155_at 26207 PITPNC1 227163_at 119391 GSTO2 209633_at 5523 PPP2R3A 219681_s_at 80223 RAB11FIP1 221860_at 3191 HNRNPL 243296_at 10135 NAMPT 237133_at -- -- 1556000_s_at 55727 BTBD7 204681_s_at 9771 RAPGEF5 215726_s_at 1528 CYB5A 210886_x_at 11257 TP53TG1 226597_at 92840 REEP6 204995_at 8851 CDK5R1 236119_s_at 6706 SPRR2G 219228_at 55422 ZNF331 234971_x_at 113026 PLCD3 201127_s_at 47 ACLY 226880_at 64710 NUCKS1 209383_at 1649 DDIT3 204168_at 4258 MGST2 239670_at 65268 WNK2 208512_s_at 4301 MLLT4 213281_at 3725 JUN 218310_at 154881///27342 KCTD7///RABGEF1 205151_s_at 9865 TRIL 218217_at 59342 SCPEP1 205055_at 3682 ITGAE 215009_s_at 100499177 THAP9-AS1 227484_at 57522 SRGAP1 239769_at 1009 CDH11 230360_at 342035 GLDN 227112_at 23023 TMCC1 201482_at 5768 QS0X1 210337_s_at 47 ACLY 203911_at 5909 RAP1GAP 206683_at 7718 ZNF165 202935_s_at 6662 SOX9 218951_s_at 55344 PLCXD1 233488_at 84659 RNASE7 202562_s_at 11161 C14orf1 208745_at 10632 ATP5L 236078_at 57707 KIAA1609 226226_at 120224 TMEM45B 213854_at 9145 SYNGR1 243955_at -- -- 222111_at 54629 FAM63B 1560296_at -- -- 240038_at -- -- 211372_s_at 7850 IL1R2 202672_s_at 467 ATF3 218717_s_at 55214 LEPREL1 228366_at -- -- 230516_at 115416 MALSU1 201920_at 6574 SLC20A1 209632_at 5523 PPP2R3A 207367_at 479 ATP12A 1557256_a_at -- -- 200811_at 1153 CIRBP 205201_at 2737 GLI3 227724_at 728190 LOC728190 205403_at 7850 IL1R2 242827_x_at -- -- 228084_at 81579 PLA2G12A 209365_s_at 1893 ECM1 243279_at -- -- 224946_s_at 84317 CCDC115 218708_at 29107 NXT1 1560531_at 353132 LCE1B 207761_s_at 25840 METTL7A 206011_at 834 CASP1 213703_at 150759 LINC00342 224595_at 23446 SLC44A1 224613_s_at 80331 DNAJC5 212504_at 22982 DIP2C 213682_at 10762 NUP50 205247_at 4855 NOTCH4 228235_at 84848 MGC16121 242873_at -- -- 205960_at 5166 PDK4 230494_at 6574 SLC20A1 221260_s_at 81566 CSRNP2 224480_s_at 84803 AGPAT9 210180_s_at 6434 TRA2B 204621_s_at 4929 NR4A2 217863_at 8554 PIAS1 236423_at -- -- 223421_at 50626 CYHR1 220272_at 54796 BNC2 201791_s_at 1717 DHCR7 215574_at -- -- 224328_s_at 84648 LCE3D 211828_s_at 23043 TNIK 58367_s_at 79744 ZNF419 218950_at 64411 ARAP3 1552703_s_at 114769///834 CARD16///CASP1 219687_at 55733 HHAT 232127_at 1184 CLCN5 218377_s_at 10069 RWDD2B 210335_at 9182 RASSF9 227927_at -- -- 227224_at 55103 RALGPS2 224778_s_at 57551 TAOK1 229566_at 645638 LOC645638 202734_at 9322 TRIP10 201851_at 6455 SH3GL1 237337_at -- -- 37152_at 5467 PPARD 209687_at 6387 CXCL12 203152_at 64976 MRPL40 201627_s_at 3638 INSIG1 232593_at 93082 NEURL3 224769_at 57551 TAOK1 209702_at 79068 FTO 204546_at 9764 KIAA0513 232224_at 5648 MASP1 239930_at 2590 GALNT2 203178_at 2628 GATM 235782_at -- -- 218181_s_at 9448 MAP4K4 233520_s_at 202333 CMYA5 213456_at 25928 SOSTDC1 219528_s_at 64919 BCL11B 224945_at 55727 BTBD7 214866_at 5329 PLAUR 209941_at 8737 RIPK1 226029_at 57216 VANGL2 212596_s_at 10042 HMGXB4 229873_at 283219 KCTD21 226392_at 5922 RASA2 226005_at 7326 UBE2G1 214445_at 22936 ELL2 227680_at 284695 ZNF326 227786_at 90390 MED30 222067_x_at 3017 HIST1H2BD 1569106_s_at 55209 SETD5 231785_at 4909 NTF4 223937_at 27086 FOXP1 1558685_a_at 158960 LOC158960 211965_at 677 ZFP36L1 39549_at 4862 NPAS2 203800_s_at 63931 MRPS14 1556321_a_at -- -- 212321_at 8879 SGPL1 222154_s_at 26010 SPATS2L 218774_at 28960 DCPS 212268_at 1992 SERPINB1 213134_x_at 10950 BTG3 230669_at 5922 RASA2 1559901_s_at 388815 LINC00478 225298_at 25953 PNKD 242558_at -- -- 226043_at 26086 GPSM1 210236_at 8500 PPFIA1 214066_x_at 4882 NPR2 240024_at 23541 SEC14L2 235462_at 132864 CPEB2 1554015_a_at 1106 CHD2 235347_at 84859 LRCH3 230847_at 56897 WRNIP1 201427_s_at 6414 SEPP1 1557905_s_at 960 CD44 219084_at 64324 NSD1 206176_at 654 BMP6 219826_at 79744 ZNF419 212356_at 23351 KHNYN 218909_at 26750 RPS6KC1 230555_s_at 90390 MED30 212687_at 3987 LIMS1 203098_at 9425 CDYL 229054_at 677 ZFP36L1 236039_at 284348 LYPD5 209661_at 3801 KIFC3 209560_s_at 8788 DLK1 225812_at 619208 C6orf225 227829_at 120071 GYLTL1B 238623_at -- -- 229415_at 54205 CYCS 209222_s_at 9885 OSBPL2 1555809_at 83716 CRISPLD2 204567_s_at 9619 ABCG1 232277_at 64078 SLC28A3 237197_at -- -- 225209_s_at 118424 UBE2J2 231916_at 4842 NOS1 212279_at 27346 TMEM97 204862_s_at 4832 NME3 230483_at -- -- 212856_at 23151 GRAMD4 224650_at 114569 MAL2 202963_at 5993 RFX5 225320_at 90550 MCU 236274_at 8662 ElF3B 209780_at 57157 PHTF2 218823_s_at 54793 KCTD9 227787_s_at 90390 MED30 230296_at 730094 C16orf52 222892_s_at 55287 TMEM40 210610_at 634 CEACAM1 230031_at 3309 HSPA5 238477_at 10749 KIF1C 209409_at 2887 GRB10 217995_at 58472 SQRDL 226873_at 54629 FAM63B 1553722_s_at 220441 RNF152 204710_s_at 26100 WIPI2 212653_s_at 23301 EHBP1 203979_at 1593 CYP27A1 244350_at 4651 MYO10 223233_s_at 57530 CGN 1555967_at -- -- 214355_x_at 100128553/// CTAGE15P/// 100142659///340307/// CTAGE4/// 441294///643854 CTAGE6P/// CTAGE8///CTAGE9 214469_at 3012///8335 HIST1H2AB/// HIST1H2AE 212472_at 9645 MICAL2 228115_at 64762 FAM59A 228964_at 639 PRDM1 230027_s_at 84545 MRPL43 207318_s_at 8621 CDK13 221689_s_at 51227 PIGP 219270_at 79094 CHAC1 225299_at 4645 MYO5B 239770_at 83850 ESYT3 226399_at 79982 DNAJB14 226656_at 10491 CRTAP 228852_at 2029 ENSA 206239_s_at 6690 SPINK1 210993_s_at 4086 SMAD1 238462_at 84959 UBASH3B 211962_s_at 677 ZFP36L1 224666_at 197370 NSMCE1 239028_at 130574 LYPD6 213577_at 6713 SQLE 202011_at 7082 TJP1 212254_s_at 100652766///667 DST/// LOC100652766 221701_s_at 64220 STRA6 239576_at 57509 MTUS1 234418_x_at 960 CD44 227985_at 100506098 LOC100506098 213462_at 4862 NPAS2 224975_at 4774 NFIA 225990_at 91653 BOC 240616_at -- -- 219911_s_at 28231 SLCO4A1 224970_at 4774 NFIA 214623_at 26226 FBXW4P1 239478_x_at 55668 C14orf118 226909_at 85460 ZNF518B 208670_s_at 23741 EID1 206192_at 1041 CDSN 222173_s_at 55357 TBC1D2 228450_at 144100 PLEKHA7 1558097_at 253143 PRR14L 219373_at 54344 DPM3 230388_s_at 644246 KANSL1-AS1 207098_s_at 55669 MFN1 223484_at 84419 C15orf48 244804_at 8878 SQSTM1 229679_at 400073 C12orf76 225826_at 326625 MMAB 213352_at 23023 TMCC1 211883_x_at 634 CEACAM1 210387_at 8339///8343///8344/// HIST1H2BC/// 8346///8347 HIST1H2BE/// HIST1H2BF/// HIST1H2BG/// HIST1H2BI 210916_s_at 960 CD44 221432_s_at 81894 SLC25A28 218487_at 210 ALAD 223264_at 59274 MESDC1 206356_s_at 2774 GNAL 218097_s_at 79004 CUEDC2 228001_at 757 TMEM5OB 212441_at 9778 K1AA0232 201854_s_at 23300 ATMIN 121_at 7849 PAX8 222143_s_at 64419 MTMR14 1558002_at 11171 STRAP 226040_at -- -- 226141_at 91050 CCDC149 1556567_at 4676 NAP1L4 226263_at 154007 SNRNP48 212074_at 23353 SUN1 227387_at 54780 NSMCE4A 232795_at -- -- 203936_s_at 4318 MMP9 225033_at 6482 ST3GAL1 209109_s_at 7105 TSPAN6 213351_s_at 23023 TMCC1 203047_at 6793 STK10 220721_at 80110 ZNF614 1556127_at 23181 DIP2A 215016_x_at 100652766///667 DST/// LOC100652766 206576_s_at 634 CEACAM1 240674_at 3720 JARID2 225646_at 1075 CTSC 1554010_at 3340 NDST1 204100_at 7067 THRA 221840_at 5791 PTPRE 209078_s_at 25828 TXN2 218530_at 29109 FHOD1 235434_at -- -- 230063_at 9422 ZNF264 40420_at 6793 STK10 221027_s_at 81579 PLA2G12A 244202_at -- -- 212108_at 23197 FAF2 204294_at 275 AMT 225503_at 207063 DHRSX 212810_s_at 6509 SLC1A4 214814_at 91746 YTHDC1 228468_at 84930 MASTL 209108_at 7105 TSPAN6 220444_at 79230 ZNF557 206172_at 3598 IL13RA2 225002_s_at 25870 SUMF2 212205_at 94239 H2AFV 228851_s_at 2029 ENSA 209048_s_at 23613 ZMYND8 211846_s_at 5818 PVRL1 238909_at 6281 S100A10 205503_at 5784 PTPN14 243829_at 673 BRAF 244379_at -- -- 223251_s_at 55608 ANKRD10 202633_at 11073 TOPBP1 214502_at 8970 HIST1H2BJ 221773_at 2004 ELK3 41858_at 27315 PGAP2 212850_s_at 4038 LRP4 223408_s_at -- -- 214472_at 3013///8350///8351/// HIST1H2AD/// 8352///8353///8354/// HIST1H3A/// 8355///8356///8357 HIST1H3B/// 8358/ HIST1H3C/// HIST1H3D/// HIST1H3E/// HIST1H3F/// HIST1H3G/// HIST1H3H/// HIST1H3I/// HIST1H3J 225647_s_at 1075 CTSC 1559977_a_at 284723 SLC25A34 211347_at 8555 CDC14B 1558208_at -- -- 227570_at 144110 TMEM86A 227492_at 100506658///647859 LOC647859///OCLN 1558778_s_at 57496 MKL2 31637_s_at 7067///9572 NR1D1///THRA 229190_at 100507376 LOC100507376 236188_s_at 4676 NAP1L4 212503_s_at 22982 DIP2C 204760_s_at 7067///9572 NR1D1///THRA 212099_at 388 RHOB 214873_at 91355 LRP5L 228181_at 7779 SLC30A1 212763_at 23271 CAMSAP2 226285_at 4076 CAPRIN1 213567_at 3840 KPNA4 203927_at 4794 NFKBIE 208523_x_at 8339///8343///8344/// HIST1H2BC/// 8346///8347 HIST1H2BE/// HIST1H2BF/// HIST1H2BG/// HIST1H2BI 219389_at 55061 SUSD4 202329_at 1445 CSK 238523_at 79786 KLHL36 1565016_at 3276 PRMT1 226409_at 128637 TBC1D20 229926_at 100500850 MIR3682 208527_x_at 8339///8343///8344/// HIST1H2BC/// 8346///8347 HIST1H2BE/// HIST1H2BF/// HIST1H2BG/// HIST1H2BI 223598_at 5887 RAD23B 243797_at 9262 STK17B 203317_at 23550 PSD4 230965_at 9099 USP2 208490_x_at 8339///8343///8344/// HIST1H2BC/// 8346///8347 HIST1H2BE/// HIST1H2BF/// HIST1H2BG/// HIST1H2BI 235514_at 151516 ASPRV1 209098_s_at 182 JAG1 1554229_at 153222 CREBRF 209398_at 3006 HIST1H1C 202629_at 10513 APPBP2 203428_s_at 25842 ASF1A 238005_s_at 25942 SIN3A 214455_at 8339///8343///8344/// HIST1H2BC/// 8346///8347 HIST1H2BE/// HIST1H2BF/// HIST1H2BG/// HIST1H2BI 214073_at 2017 CTTN 203140_at 604 BCL6 232150_at -- -- 208546_x_at 8345 HIST1H2BH 243446_at 84962 AJUBA 236207_at 6744 SSFA2 212016_s_at 5725 PTBP1 232311_at 567 B2M 219711_at 54807 ZNF586 208579_x_at 54145///85236 H2BFS/// HIST1H2BK 239493_at 6129 RPL7 214074_s_at 2017 CTTN 228091_at 55014 STX17 234331_s_at 151354 FAM84A 212372_at 4628 MYH10 Probeset ID Gene Title 222450_at prostate transmembrane protein, androgen induced 1 233565_s_at FKBP1A-SDCBP2 readthrough (non-protein coding)/// syndecan binding protein (syntenin) 242832_at period homolog 1 (Drosophila) 240463_at -- 213039_at Rho/Rac guanine nucleotide exchange factor (GEF) 18 235072_s_at kinesin family member 13A 208926_at sialidase 1 (lysosomal sialidase) 237444_at -- 239451_at -- 222288_at -- 227579_at fer (fps/fes related) tyrosine kinase 212717_at pleckstrin homology domain containing, family M (with RUN domain) member 1 226853_at BMP2 inducible kinase 214112_s_at chromosome X open reading frame 40A///chromosome X open reading frame 40B 209012_at triple functional domain (PTPRF interacting) 219476_at chromosome 1 open reading frame 116 238086_at uncharacterized LOC100129617 230721_at chromosome 16 open reading frame 52 1566079_at ribosomal protein S16 pseudogene 5 223839_s_at stearoyl-CoA desaturase (delta- 9-desaturase) 225671_at spinster homolog 2 (Drosophila) 212961_x_at chromosome X open reading frame 40B 223659_at transmembrane protease, serine 13 229909_at beta-1,4-N-acetyl-galactosaminyl 223467_at transferase 3 RAS, dexamethasone- induced 1 235146_at transmembrane and coiled-coil domain family 3 235548_at adenomatosis polyposis coli down-regulated 1-like 206816_s_at sperm associated antigen 8 242323_at phospholipase A2, group XIIA 224579_at solute carrier family 38, member 1 213315_x_at chromosome X open reading frame 40A 227314_at integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) 227093_at Ubiquitin specific peptidase 36 200760_s_at ADP-ribosylation-like factor 6 interacting protein 5 201790_s_at 7-dehydrocholesterol reductase 1554980_a_at activating transcription factor 3 242255_at WD repeat domain 37 219267_at glycolipid transfer protein 1555786_s_at long intergenic non-protein coding RNA 520 229734_at uncharacterized LOC283174 242856_at -- 201037_at phosphofructokinase, platelet 1562970_at -- 201465_s_at jun proto-oncogene 202067_s_at low density lipoprotein receptor 223679_at catenin (cadherin-associated protein), beta 1, 88kDa 201235_s_at BTG family, member 2 225662_at sterile alpha motif and leucine zipper containing kinase AZK potassium intermediate/small 204401_at conductance calcium-activated channel, subfamily N, member 222906_at feline leukemia virus subgroup C cellular receptor 1 238613_at sterile alpha motif and leucine zipper containing kinase AZK ArfGAP with SH3 domain, 206414_s_at ankyrin repeat and PH domain 2 210794_s_at maternally expressed 3 (non-protein coding) 226621_at oncostatin M receptor 230682_x_at ATP-binding cassette, sub-family C (CFTR/MRP), member3 235668_at PR domain containing 1, with ZNF domain 205483_s_at ISG15 ubiquitin-like modifier 215808_at kallikrein-related peptidase 10 212281_s_at transmembrane protein 97 212282_at transmembrane protein 97 226287_at coiled-coil domain containing 34 213618_at ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2 231089_at uncharacterized LOC100505664 227140_at inhibin, beta A 231467_at -- 202967_at glutathione S-transferase alpha 4 230323_s_at transmembrane protein 45B 224471_s_at beta-transducin repeat containing E3 ubiquitin protein ligase 202708_s_at histone cluster 2, H2be 242871_at progestin and adipoQ receptor family member V 205627_at cytidine deaminase 235542_at tet methylcytosine dioxygenase 3 240410_at -- 236656_s_at uncharacterized LOC100288911 206164_at chloride channel accessory 2 203159_at glutaminase 224991_at c-Maf inducing protein 204258_at chromodomain helicase DNA binding protein 1 228249_at chromosome 11 open reading frame 74 229013_at uncharacterized LOC145783 platelet-activating factor 211547_s_at acetylhydrolase lb, regulatory subunit 1 (45kDa) 226863_at family with sequence similarity 110, member C 208161_s_at ATP-binding cassette, sub- family C (CFTR/MRP), member 3 214805_at eukaryotic translation initiation factor 4A1 229429_x_at uncharacterized LOC728855/// uncharacterized LOC728875 202720_at testis derived transcript (3 LIM domains) 224995_at spire homolog 1 (Drosophila) 214771_x_at myosin phosphatase Rho interacting protein 201939_at polo-like kinase 2 238587_at ubiquitin associated and SH3 domain containing B 232113_at -- 208690_s_at PDZ and LIM domain 1 201464_x_at jun proto-oncogene 236657_at uncharacterized LOC100288911 215541_s_at diaphanous homolog 1 (Drosophila) 238028_at chromosome 6 open reading frame 132 226893_at v-abl Abelson murine leukemia viral oncogene homolog 2 237576_x_at uncharacterized LOC100506480 1552256_a_at scavenger receptor class B, member 1 215255_at immunoglobulin superfamily, member 9B 1557258_a_at B-cell CLL/lymphoma 10 240623_at -- solute carrier family 6 228754_at (neurotransmitter transporter, taurine), member 6 217257_at SH3-domain binding protein 2 241036_at -- 242553_at ATP-binding cassette, sub- family C (CFTR/MRP), member 3 239358_at -- 210868_s_at ELOVL fatty acid elongase 6 platelet-activating factor 200815_s_at acetylhydrolase lb, regulatory subunit 1 (45kDa) 208436_s_at interferon regulatory factor 7 208138_at gastrin 241780_at -- 200730_s_at protein tyrosine phosphatase type IVA, member 1 219697_at heparan sulfate (glucosamine) 3-0-sulfotransferase 2 201693_s_at early growth response 1 218847_at insulin-like growth factor 2 mRNA binding protein 2 230469_at rhotekin 2 209917_s_at TP53 target 1 (non-protein coding) 224329_s_at cornifelin 212253_x_at dystonin///dystonin-like 238058_at uncharacterized LOC150381 239334_at Extended synaptotagmin-like protein 2 222271_at -- 216718_at long intergenic non-protein coding RNA 302 219076_s_at peroxisomal membrane protein 2, 22kDa 204475_at matrix metallopeptidase 1 (interstitial collagenase) 221185_s_at IQ motif containing G 203586_s_at ADP-ribosylation factor-like 4D nuclear casein kinase and 217802_s_at cyclin-dependent kinase substrate 1 205767_at epiregulin 228360_at LY6/PLAUR domain containing 6B 228917_at -- 228748_at CD59 molecule, complement regulatory protein 219632_s_at sedoheptulokinase///transient receptor potential cation channel, subfamily V, member 238715_at Uncharacterized LOC646014 218810_at zinc finger CCCH-type containing 12A 225177_at RAB11 family interacting protein 1 (class I) 224454_at ethanolamine kinase 1 209498_at carcinoembryonic antigen- related cell adhesion molecule 1 (biliary glycoprotein) 1557257_at B-cell CLL/lymphoma 10 225133_at Kruppel-like factor 3 (basic) 202340_x_at nuclear receptor subfamily 4, group A, member 1 1556545_at -- 212474_at AVL9 homolog (S. cerevisiase) 210241_s_at TP53 target 1 (non-protein coding) 243543_at -- 239132_at nitric oxide synthase 1 (neuronal) 222757_s_at sterile alpha motif and leucine zipper containing kinase AZK 201194_at selenoprotein W, 1 229874_x_at uncharacterized LOC100506687 202557_at heat shock protein 70kDa family, member 13 239669_at -- 231907_at v-abl Abelson murine leukemia viral oncogene homolog 2 229074_at EH-domain containing 4 205428_s_at calbindin 2 205822_s_at 3-hydroxy-3-methylglutaryl-CoA synthase 1 (soluble) 210869_s_at melanoma cell adhesion molecule 225665_at sterile alpha motif and leucine zipper containing kinase AZK 212781_at retinoblastoma binding protein 6 232355_at small nucleolar RNA, C/D box 114-3 213288_at membrane bound 0-acyltransferase domain containing 2 221666_s_at PYD and CARD domain containing 203072_at myosin IE 215465_at ATP-binding cassette, sub-family A (ABC1), member 12 224453_s_at ethanolamine kinase 1 216935_at long intergenic non-protein coding RNA 302 209086_x_at melanoma cell adhesion molecule 218833_at sterile alpha motif and leucine zipper containing kinase AZK 209377_s_at high mobility group nucleosomal binding domain 3 223519_at sterile alpha motif and leucine zipper containing kinase AZK 210138_at regulator of G-protein signaling 20 1558845_at uncharacterized LOC100506089 201819_at scavenger receptor class B, member 1 204310_s_at natriuretic peptide receptor B/guanylate cyclase B (atrionatriuretic peptide receptor B 239377_at eukaryotic translation initiation factor 1A domain containing 224611_s_at DnaJ (Hsp40) homolog, subfamily C, member 5 219155_at phosphatidylinositol transfer protein, cytoplasmic 1 227163_at glutathione S-transferase omega 2 209633_at protein phosphatase 2, regulatory subunit B'', alpha 219681_s_at RAB11 family interacting protein 1 (class I) 221860_at heterogeneous nuclear ribonucleoprotein L 243296_at Nicotinamide phosphoribosyltransferase 237133_at -- 1556000_s_at BTB (POZ) domain containing 7 204681_s_at Rap guanine nucleotide exchange factor (GEF) 5 215726_s_at cytochrome b5 type A (microsomal) 210886_x_at TP53 target 1 (non-protein coding) 226597_at receptor accessory protein 6 204995_at cyclin-dependent kinase 5, regulatory subunit 1 (p35) 236119_s_at small proline-rich protein 2G 219228_at zinc finger protein 331 234971_x_at phospholipase C, delta 3 201127_s_at ATP citrate lyase 226880_at Nuclear casein kinase and cyclin-dependent kinase substrate 1 209383_at DNA-damage-inducible transcript 3 204168_at microsomal glutathione S- transferase 2 239670_at WNK lysine deficient protein kinase 2 208512_s_at myeloid/lymphoid or mixed- lineage leukemia (trithorax homolog, Drosophila); translocate 213281_at Jun proto-oncogene 218310_at potassium channel tetramerisation domain containing 7//I RAB guanine nucleotide exchan 205151_s_at TLR4 interactor with leucine-rich repeats 218217_at serine carboxypeptidase 1 205055_at integrin, alpha E (antigen CD103, human mucosal lymphocyte antigen 1; alpha polypeptide 215009_s_at THAP9 antisense RNA 1 (non- protein coding) 227484_at SLIT-ROBO Rho GTPase activating protein 1 239769_at Cadherin 11, type 2, OB-cadherin 230360_at (osteoblast) gliomedin 227112_at transmembrane and coiled-coil domain family 1 201482_at quiescin 06 sulfhydryl oxidase 1 210337_s_at ATP citrate lyase 203911_at RAP1 GTPase activating protein 206683_at zinc finger protein 165 202935_s_at SRY (sex determining region Y)-box 9 218951_s_at phosphatidylinositol-specific phospholipase C, X domain containing 1 233488_at ribonuclease, RNase A family, 7 202562_s_at chromosome 14 open reading frame 1 208745_at ATP synthase, H+ transporting, mitochondrial Fo complex, subunit G 236078_at KIAA1609 226226_at transmembrane protein 45B 213854_at synaptogyrin 1 243955_at -- 222111_at family with sequence similarity 63, member B 1560296_at -- 240038_at -- 211372_s_at interleukin 1 receptor, type II 202672_s_at activating transcription factor 3 218717_s_at leprecan-like 1 228366_at -- 230516_at Mitochondrial assembly of ribosomal large subunit 1 201920_at solute carrier family 20 (phosphate transporter), member 1 209632_at protein phosphatase 2, regulatory subunit B'', alpha 207367_at ATPase, H+/K+ transporting, nongastric, alpha polypeptide 1557256_a_at -- 200811_at cold inducible RNA binding protein 205201_at GLI family zinc finger 3 227724_at uncharacterized LOC0728190 205403_at interleukin 1 receptor, type II 242827_x_at -- 228084_at phospholipase A2, group XIIA 209365_s_at extracellular matrix protein 1 243279_at -- 224946_s_at coiled-coil domain containing 115 218708_at NTF2-like export factor 1 1560531_at late cornified envelope 1B 207761_s_at methyltransferase like 7A 206011_at caspase 1, apoptosis-related cysteine peptidase 213703_at long intergenic non-protein coding RNA 342 224595_at solute carrier family 44, member 1 224613_s_at DnaJ (Hsp40) homolog, subfamily C, member 5 212504_at DIP2 disco-interacting protein 2 homolog C (Drosophila) 213682_at nucleoporin 50kDa 205247_at notch 4 228235_at uncharacterized protein MGC16121 242873_at -- 205960_at pyruvate dehydrogenase kinase, isozyme 4 230494_at solute carrier family 20 (phosphate transporter), member 1 221260_s_at cysteine-serine-rich nuclear protein 2 224480_s_at 1-acylglycerol-3-phosphate 0- acyltransferase 9 210180_s_at transformer 2 beta homolog (Drosophila) 204621_s_at nuclear receptor subfamily 4, group A, member 2 217863_at protein inhibitor of activated STAT, 1 236423_at -- 223421_at cysteine/histidine-rich 1 220272_at basonuclin 2 201791_s_at 7-dehydrocholesterol reductase 215574_at -- 224328_s_at late cornified envelope 3D 211828_s_at TRAF2 and NCK interacting kinase 58367_s_at zinc finger protein 419 218950_at ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3 1552703_s_at caspase recruitment domain family, member 16///caspase 1, apoptosis-related cysteine 219687_at hedgehog acyltransferase 232127_at chloride channel, voltage-sensitive 5 218377_s_at RWD domain containing 2B 210335_at Ras association (RaIGDS/AF-6) domain family (N-terminal) member 9 227927_at -- 227224_at Ral GEF with PH domain and SH3 binding motif 2 224778_s_at TAO kinase 1 229566_at WDNM1-like pseudogene 202734_at thyroid hormone receptor interactor 10 201851_at SH3-domain GRB2-like 1 237337_at -- 37152_at peroxisome proliferator-activated receptor delta 209687_at chemokine (C-X-C motif) ligand 12 203152_at mitochondrial ribosomal protein L40 201627_s_at insulin induced gene 1 232593_at neuralized homolog 3 (Drosophila) pseudogene 224769_at TAO kinase 1 209702_at fat mass and obesity associated 204546_at KIAA0513 232224_at mannan-binding lectin serine peptidase 1 (C4/C2 activating component of Ra-reactive fac 239930_at UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl- transferase 2 (Gal 203178_at glycine amidinotransferase (L-arginine: glycine amidinotransferase) 235782_at -- 218181_s_at mitogen-activated protein kinase kinase kinase kinase 4 233520_s_at cardiomyopathy associated 5 213456_at sclerostin domain containing 1 219528_s_at B-cell CLL/lymphoma 11B (zinc finger protein) 224945_at BTB (POZ) domain containing 7 214866_at plasminogen activator, urokinase receptor 209941_at receptor (TNFRSF)-interacting serine-threonine kinase 1 226029_at yang-like 2 (van gogh, Drosophila) 212596_s_at HMG box domain containing 4 229873_at potassium channel tetramerisation domain containing 21 226392_at RAS p21 protein activator 2 226005_at ubiquitin-conjugating enzyme E2G 1 214445_at elongation factor, RNA polymerase II, 2 227680_at zinc finger protein 326 227786_at mediator complex subunit 30 222067_x_at histone cluster 1, H2bd 1569106_s_at SET domain containing 5 231785_at neurotrophin 4 223937_at forkhead box P1 1558685_a_at uncharacterized protein BC009467 211965_at zinc finger protein 36, C3H type-like 1 39549_at neuronal PAS domain protein 2 203800_s_at mitochondrial ribosomal protein S14 1556321_a_at -- 212321_at sphingosine-1-phosphate lyase 1 222154_s_at spermatogenesis associated, serine-rich 2-like 218774_at decapping enzyme, scavenger 212268_at serpin peptidase inhibitor, clade B (ovalbumin), member 1 213134_x_at BTG family, member 3 230669_at RAS p21 protein activator 2 1559901_s_at long intergenic non-protein coding RNA 478 225298_at paroxysmal nonkinesigenic dyskinesia 242558_at -- 226043_at G-protein signaling modulator 1 210236_at protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein 214066_x_at natriuretic peptide receptor B/guanylate cyclase B (atrionatriuretic peptide receptor B 240024_at SEC14-like 2 (S. cerevisiae) 235462_at Cytoplasmic polyadenylation element binding protein 2 1554015_a_at chromodomain helicase DNA binding protein 2 235347_at leucine-rich repeats and calponin homology (CH) domain containing 3 230847_at Werner helicase interacting protein 1 201427_s_at selenoprotein P, plasma, 1 1557905_s_at CD44 molecule (Indian blood group) 219084_at nuclear receptor binding SET domain protein 1 206176_at bone morphogenetic protein 6 219826_at zinc finger protein 419 212356_at KH and NYN domain containing 218909_at ribosomal protein S6 kinase, 52kDa, polypeptide 1 230555_s_at Mediator complex subunit 30 212687_at LIM and senescent cell antigen- like domains 1 203098_at chromodomain protein, Y-like 229054_at zinc finger protein 36, C3H type-like 1 236039_at LY6/PLAUR domain containing 5 209661_at kinesin family member C3 209560_s_at delta-like 1 homolog (Drosophila) 225812_at chromosome 6 open reading frame 225 227829_at glycosyltransferase-like 1B 238623_at -- 229415_at cytochrome c, somatic 209222_s_at oxysterol binding protein-like 2 1555809_at cysteine-rich secretory protein LCCL domain containing 2 204567_s_at ATP-binding cassette, sub-family G (WHITE), member 1 232277_at solute carrier family 28 (sodium- coupled nucleoside transporter), member 3 237197_at -- 225209_s_at ubiquitin-conjugating enzyme E2, J2 231916_at nitric oxide synthase 1 (neuronal) 212279_at transmembrane protein 97 204862_s_at NME/NM23 nucleoside diphosphate kinase 3 230483_at -- 212856_at GRAM domain containing 4 224650_at mal, T-cell differentiation protein 2 (gene/pseudogene) 202963_at regulatory factor X, 5 (influences HLA class II expression) 225320_at mitochondrial calcium uniporter 236274_at eukaryotic translation initiation factor 3, subunit B 209780_at putative homeodomain transcription factor 2 potassium channel 218823_s_at tetramerisation domain containing 9 227787_s_at mediator complex subunit 30 230296_at chromosome 16 open reading frame 52 222892_s_at transmembrane protein 40 210610_at carcinoembryonic antigen-related cell adhesion molecule1 (biliary glycoprotein) 230031_at heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa) 238477_at kinesin family member 1C 209409_at growth factor receptor-bound protein 10 217995_at sulfide quinone reductase-like (yeast) 226873_at family with sequence similarity 63, member B 1553722_s_at ring finger protein 152 204710_s_at WD repeat domain, phosphoinositide interacting 2 212653_s_at EH domain binding protein 1 203979_at cytochrome P450, family 27, subfamily A, polypeptide 1 244350_at myosin X 223233_s_at cingulin 1555967_at -- 214355_x_at CTAGE family, member 15, pseudogene///CTAGE family, member 4///CTAGE family, member 214469_at histone cluster 1, H2ab/// histone cluster 1, H2ae 212472_at microtubule associated monoxygenase, calponin and LIM domain containing 2 228115_at family with sequence similarity 59, member A 228964_at PR domain containing 1, with ZNF domain 230027_s_at mitochondrial ribosomal protein L43 207318_s_at cyclin-dependent kinase 13 221689_s_at phosphatidylinositol glycan anchor biosynthesis, class P 219270_at ChaC, cation transport regulator homolog 1 (E. coli) 225299_at myosin VB 239770_at extended synaptotagmin-like protein 3 226399_at DnaJ (Hsp40) homolog, subfamily B, member 14 226656_at cartilage associated protein 228852_at endosulfine alpha 206239_s_at serine peptidase inhibitor, Kazal type 1 210993_s_at SMAD family member 1 238462_at ubiquitin associated and SH3 domain containing B 211962_s_at zinc finger protein 36, C3H type-like 1 224666_at non-SMC element 1 homolog (S. cerevisiae) 239028_at LY6/PLAUR domain containing 6 213577_at squalene epoxidase 202011_at tight junction protein 1 (zona occludens 1) 212254_s_at dystonin///dystonin-like 221701_s_at stimulated by retinoic acid gene 6 homolog (mouse) 239576_at microtubule associated tumor suppressor 1 234418_x_at CD44 molecule (Indian blood group) 227985_at uncharacterized LOC100506098 213462_at neuronal PAS domain protein 2 224975_at nuclear factor I/A 225990_at Boc homolog (mouse) 240616_at -- 219911_s_at solute carrier organic anion transporter family, member 4A1 224970_at nuclear factor I/A 214623_at F-box and WD repeat domain containing 4 pseudogene 1 239478_x_at chromosome 14 open reading frame 118 226909_at zinc finger protein 518B 208670_s_at EP300 interacting inhibitor of differentiation 1 206192_at corneodesmosin 222173_s_at TBC1 domain family, member 2 228450_at pleckstrin homology domain containing, family A member 7 1558097_at proline rich 14-like 219373_at dolichyl-phosphate mannosyltransferase polypeptide 3 230388_s_at KANSL1 antisense RNA 1 (non- protein coding) 207098_s_at mitofusin 1 223484_at chromosome 15 open reading frame 48 244804_at sequestosome 1 229679_at chromosome 12 open reading frame 76 225826_at methylmalonic aciduria (cobalamin deficiency) cbIB type 213352_at transmembrane and coiled-coil domain family 1 211883_x_at carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein) 210387_at histone cluster 1, H2bc/// histone cluster 1, H2be/// histone cluster 1, H2bf///his 210916_s_at CD44 molecule (Indian blood group) 221432_s_at solute carrier family 25 (mitochondrial iron transporter), member 28 218487_at aminolevulinate dehydratase 223264_at mesoderm development candidate 1 206356_s_at guanine nucleotide binding protein (G protein), alpha activating activity polypeptide, 218097_s_at CUE domain containing 2 228001_at transmembrane protein 50B 212441_at K1AA0232 201854_s_at ATM interactor 121_at paired box 8 222143_s_at myotubularin related protein 14 1558002_at Serine/threonine kinase receptor associated protein 226040_at -- 226141_at coiled-coil domain containing 149 1556567_at nucleosome assembly protein 1-like 4 226263_at small nuclear ribonucleoprotein 48kDa (U11/U12) 212074_at Sad1 and UNC84 domain containing 1 227387_at Non-SMC element 4 homolog A (S. cerevisiae) 232795_at -- 203936_s_at matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) 225033_at ST3 beta-galactoside alpha-2,3- sialyltransferase 1 209109_s_at tetraspanin 6 213351_s_at transmembrane and coiled-coil domain family 1 203047_at serine/threonine kinase 10 220721_at zinc finger protein 614 1556127_at DIP2 disco-interacting protein 2 homolog A (Drosophila) 215016_x_at dystonin///dystonin-like 206576_s_at carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein) 240674_at jumonji, AT rich interactive domain 2 225646_at cathepsin C 1554010_at N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 1 204100_at thyroid hormone receptor, alpha 221840_at protein tyrosine phosphatase, receptor type, E 209078_s_at thioredoxin 2 218530_at formin homology 2 domain containing 1 235434_at -- 230063_at zinc finger protein 264 40420_at serine/threonine kinase 10 221027_s_at phospholipase A2, group XIIA 244202_at -- 212108_at Fas associated factor family member 2 204294_at aminomethyltransferase 225503_at dehydrogenase/reductase (SDR family) X-linked 212810_s_at solute carrier family 1 (glutamate/neutral amino acid transporter), member 4 214814_at YTH domain containing 1 228468_at microtubule associated serine/threonine kinase-like 209108_at tetraspanin 6 220444_at zinc finger protein 557 206172_at interleukin 13 receptor, alpha 2 225002_s_at sulfatase modifying factor 2 212205_at H2A histone family, member V 228851_s_at endosulfine alpha 209048_s_at zinc finger, MYND-type containing 8 211846_s_at poliovirus receptor-related 1 (herpesvirus entry mediator C) 238909_at S100 calcium binding protein A10 205503_at protein tyrosine phosphatase, non-receptor type 14 243829_at v-raf murine sarcoma viral oncogene homolog B1 244379_at -- 223251_s_at ankyrin repeat domain 10 202633_at topoisomerase (DNA) II binding protein 1 214502_at histone cluster 1, H2bj 221773_at ELK3, ETS-domain protein (SRF accessory protein 2) 41858_at post-GPI attachment to proteins 2 212850_s_at low density lipoprotein receptor- related protein 4 223408_s_at -- 214472_at histone cluster 1, H2ad/// histone cluster 1, H3a/// histone cluster 1, H3b///histo 225647_s_at cathepsin C 1559977_a_at solute carrier family 25, member 34 211347_at CDC14 homolog B (S. cerevisiae) 1558208_at -- 227570_at transmembrane protein 86A 227492_at occludin pseudogene/// occludin 1558778_s_at MKL/myocardin-like 2 31637_s_at nuclear receptor subfamily 1, group D, member 1///thyroid hormone receptor, alpha 229190_at uncharacterized LOC100507376 236188_s_at Nucleosome assembly protein 1-like 4 212503_s_at DIP2 disco-interacting protein 2 homolog C (Drosophila) 204760_s_at nuclear receptor subfamily 1, group D, member 1///thyroid hormone receptor, alpha 212099_at ras homolog family member B 214873_at low density lipoprotein receptor- related protein 5-like 228181_at solute carrier family 30 (zinc transporter), member 1 212763_at calmodulin regulated spectrin- associated protein family, member 2 226285_at cell cycle associated protein 1 213567_at karyopherin alpha 4 (importin alpha 3) 203927_at nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon 208523_x_at histone cluster 1, H2bc/// histone cluster 1, H2be/// histone cluster 1, H2bf///his 219389_at sushi domain containing 4 202329_at c-src tyrosine kinase 238523_at kelch-like 36 (Drosophila) 1565016_at protein arginine methyltransferase 1 226409_at TBC1 domain family, member 20 229926_at microRNA 3682 208527_x_at histone cluster 1, H2bc/// histone cluster 1, H2be/// histone cluster 1, H2bf///his 223598_at RAD23 homolog B (S. cerevisiae) 243797_at serine/threonine kinase 17b 203317_at pleckstrin and Sec7 domain containing 4 230965_at ubiquitin specific peptidase 2 208490_x_at histone cluster 1, H2bc/// histone cluster 1, H2be/// histone cluster 1, H2bf///his 235514_at aspartic peptidase, retroviral- like 1 209098_s_at jagged 1 1554229_at CREB3 regulatory factor 209398_at histone cluster 1, H1c 202629_at amyloid beta precursor protein (cytoplasmic tail) binding protein 2 203428_s_at ASF1 anti-silencing function 1 homolog A (S. cerevisiae) 238005_s_at SIN3 transcription regulator homolog A (yeast) 214455_at histone cluster 1, H2bc/// histone cluster 1, H2be/// histone cluster 1, H2bf///his 214073_at cortactin 203140_at B-cell CLL/lymphoma 6 232150_at -- 208546_x_at histone cluster 1, H2bh 243446_at ajuba LIM protein 236207_at sperm specific antigen 2 212016_s_at polypyrimidine tract binding protein 1 232311_at Beta-2-microglobulin 219711_at zinc finger protein 586 208579_x_at H2B histone family, member S (pseudogene)///histone cluster 1, H2bk 239493_at ribosomal protein L7 214074_s_at cortactin 228091_at syntaxin 17 234331_s_at family with sequence similarity 84, member A 212372_at myosin, heavy chain 10, non-muscle Or, from genes for each of the pharmacodynamic biomarkers from the list further consisting of: TABLE-US-00012 MMP2 ESR1 FOS PCLG2 MAPK6 JUN COND1 PPAR1 MAPK1 MAPK7 CEBPA MAPK3 PCLG1 MAPK4 MAPK12 AKT2 CASP3 FOS HSP90AB1 JUN BAG3 CCND1 HASP90AA1 HSP90B1 AKT1 ARG2 CCNA1 CCND2 CCNE2 TNF BDNF CCNA2 CCNE1 CTF1 BRAF ARG2 CCND2 TNF PPP3R1 CALM3 BDNF CCNE1 PPP3CA PPP3R2 CAMK1 CCNA1 CCNE2 PPP3CB CALM1 CAMK1D CCNA2 CTF1 PPP3CC CALM2 CAMK1G BDNF CCNE1 PPP3CC ORAI3 TNF CCNA1 PPP3CB CAMK2D CCND2 CALM3 PPP3CA CACNA2D4 CHRNB3 HDAC10 PPP3CB CACNB1 CHRNB4 HDAC11 PPP3CC CACNB2 CHRND HDAC2 PPP3R1 CACNB3 CHRNE HDAC3 PPP3R2 CACNB4 CHRNG HDAC4 ATP2C1 CACNG1 GRIA1 HDAC5 CACNA1A CHRFAM7A GRIA2 HDAC6 CACNA1B CHRNA1 GRIA3 HDAC7 CACNA1C CHRNA10 GRIA4 HDAC8 CACNA1D CHRNA2 GRIK1 HDAC9 CACNA1F CHRNA3 GRIN1 HTR3A CACNA1H CHRNAS GRIN2B SLC8A1 CACNA2I CHRNA6 GRIN2C TNNC1 CACNA1G CHRNA4 GRIN2A RYR1 CACNA1S CHRNA7 GRIN2D CACNA2D1 CHRNA9 GRIN3A CACNA2D2 CHRNB1 GRIN3B CACNA2D3 CHRNB2 HDAC1 CACNA2D1 CHRNA9 GRIN3A CACNA2D2 CHRNB1 GRIN3B CACNA2D3 CHRNB2 HDACC1 MAP15 AKT1 MOS3 HSP90B1 CASP3 AKT2 HSP90AA1 Hsp84-2 HSPA8 AKT3 HSP90AB1 Hsp84-3 BAG3 CEBPA MAPK3 MAPK1 MAPK7 CA9 CALR CAMK2A CAMK4 ORAI3 TRPC3 TRPC7 CAMK2B NOS2 STIM1 TRPC4 BRAF CAMK2D ORAI2 STIM2 TRPC5 CA9 CAMK2G ORAI2 TRPC1 TRPC6 CALR CAMK1 ORAI2 BRAF CAMK2G STIM2 CALR Or, from genes for each of the pharmacodynamic biomarkers from the list further consisting of: TABLE-US-00013 ABCC5 CYHR1 HIST3H2A POU2F3 ATP6V1B1 DEPTOR HOXB13 RAMP1 ATXN3 DNAL4 ING4 SEMA3G BCAS1 EIF4A2 OVGP1 SEPP1 BCL2L11 EPHX2 PCMTD1 SIDT2 CALCOCO1 ERBB3 PCMTD2 AREG CAPN13 HIST1H2AC PDIA4 BTG3 CRBN HIST1H2BD PLEKHG4 CEBPG CORO1C IFRD1 PFKP DLEU2 IMPAD1 PNPT1 DPH3 KLK6 PSMC4 EIF5 KPNA4 RPS6KA3 ENO2 LRP8 S100A2 HN1 MALL SERPINB5 HSP90AA1 MTHFD1L SERPINB8 HSPA4L PADI1 SLC7A1 SRXN1 TIPIN; and d) identifying, using the calculated signature scores and quantitated responses, each of the pharmacodynamics biomarkers of each of the signature pathways by at least 3 or more genes listed in 1c). 2. The method of claim 1, wherein the pharmacodynamic biomarkers of each of the signature pathways further include at least 3 or more genes for which pharmacodynamics biomarkers are from the list consisting of: TABLE-US-00014 ABCC5 CYHR1 HIST3H2A POU2F3 ATP6V1B1 DEPTOR HOXB13 RAMP1 ATXN3 DNAL4 ING4 SEMA3G BCAS1 EIF4A2 OVGP1 SEPP1 BCL2L11 EPHX2 PCMTD1 SIDT2 CALC0001 ERBB3 PCMTD2 AREG CAPN13 HIST1H2AC PDIA4 BTG3 CRBN HIST1H2BD PLEKHG4 CEBPG CORO1C IFRD1 PFKP DLEU2 IMPAD1 PNPT1 DPH3 KLK6 PSMC4 EIF5 KPNA4 RPS6KA3 EN02 LRP8 S100A2 HN1 MALL SERPINB5 HSP9OAA1 MTHFD1L SERPINB8 HSPA4L PADI1 SLC7A1 SRXN1 TIPIN. 3. The method of claim 2, wherein at least one of the signature pathways is RAS. 4. The method of claim 3, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for RAS is inhibited in response to exposure to CTO. 5. The method of claim 2, wherein at least one of the signature pathways is GFS. 6. The method of claim 5, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for GFS is inhibited in response to exposure to CTO. 7. The method of claim 1, wherein at least one of the signature pathways is MEKi. 8. The method of claim 5, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for MEKi is inhibited in response to exposure to CTO. 9. The method of claim 1, wherein at least one of the signature pathways is HDAC. 10. The method of claim 9, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for HDAC is inhibited in response to exposure to CTO. 11. The method of claim 1, wherein at least one of the signature pathways is NOTCH. 12. The method of claim 11, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for NOTCH is inhibited in response to exposure to CTO. 13. The method of claim 1, wherein at least one of the signature pathways is WNT.beta.-catenin. 14. The method of claim 13, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for WNT.beta.-catenin is inhibited in response to exposure to CTO. 15. The method of claim 1, wherein at least one of the signature pathways is HSP90. 16. The method of claim 15, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for HSP90 is inhibited in response to exposure to CTO. 17. The method of claim 1, wherein at least one of the signature pathways is EGFR. 18. The method of claim 17, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for EGFR is inhibited in response to exposure to CTO. 19. The method of claim 1, wherein at least one of the signature pathways is P53. 20. The method of claim 19, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for P53 is induced in response to exposure to CTO. 21. The method of claim 1, wherein at least one of the signature pathways is EGR1. 22. The method of claim 21, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for EGR1 is stimulated in response to exposure to CTO. 23. The method of claim 1, wherein at least one of the signature is CEACAMI. 24. The method of claim 23, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for CEACAMI is stimulated in response to exposure to CTO. 25. The method of claim 1, wherein at least one of the signature pathways is TGF.beta.. 26. The method of claim 25, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for TGF.beta. is stimulated in response to exposure to CTO. 27. The method of claim 1, wherein at least one of the signature pathways is Dystonin. 28. The method of claim 27, wherein the signature score of the pharmacodynamic biomarkers of the signature pathways for Dystonin is stimulated in response to exposure to CTO.

Details for Patent 10,378,059

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2039-08-18
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2039-08-18