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1. 发明申请

US20170354651A1 Treatment Of Neurodegenerative Diseases With Combination Of Laquinimod And Fingolimod 审中-公开
公开(公告)号：US20170354651A1
公开(公告)日：2017-12-14
申请号：US15669748
申请日：2017-08-04
申请人： Michael Hayden , Liat Hayardeny , David Ladkani
发明人： Michael Hayden , Liat Hayardeny , David Ladkani
IPC分类号： A61K31/4704 , A61K9/00 , A61K31/137 , A61J1/03 , A61K47/18 , A61K47/02 , B65D81/26 , A61K47/26 , A61K9/28 , B65D1/02 , B65D65/38 , A61K9/14
CPC分类号： A61K31/4704 , A61J1/035 , A61K9/0053 , A61K9/14 , A61K9/2866 , A61K31/00 , A61K31/137 , A61K47/02 , A61K47/18 , A61K47/26 , A61P25/00 , A61P25/02 , A61P25/14 , A61P25/16 , A61P25/28 , B65D1/0215 , B65D65/38 , B65D81/266 , A61K2300/00
摘要： This invention provides a method of treating a subject afflicted with a neurodegenerative disease comprising periodic administration of an amount of laquinimod and an amount of fingolimod, wherein the amounts when taken together are effective to treat the subject. Also provided are packages and pharmaceutical compositions comprising laquinimod and fingolimod for treating a subject afflicted with a neurodegenerative disease. Also provided is a pharmaceutical composition comprising laquinimod for use as an add-on therapy or in combination with fingolimod, and a pharmaceutical composition comprising fingolimod for use as an add-on therapy or in combination with laquinimod, for treating said subject.

2. 发明申请

US20170003277A1 BIOLOGICAL CHARACTERIZATION OF A GLATIRAMER ACETATE RELATED DRUG PRODUCT USING MAMMALIAN AND HUMAN CELLS 审中-公开
标题翻译：使用马马里兰和人类细胞的乙酸银相关药物产品的生物学特性
公开(公告)号：US20170003277A1
公开(公告)日：2017-01-05
申请号：US14789833
申请日：2015-07-01
申请人： Michael Hayden , Fadi George Towfic , Sarah Elisabeth Kolitz , Benjamin James Zeskind , David Ladkani , Tal Hasson , Liat Hayardeny , Iris Grossman
发明人： Michael Hayden , Fadi George Towfic , Sarah Elisabeth Kolitz , Benjamin James Zeskind , David Ladkani , Tal Hasson , Liat Hayardeny , Iris Grossman
IPC分类号： G01N33/50 , A61K31/785 , G01N33/94
CPC分类号： G01N33/5023
摘要： The present invention provides a process for characterizing a glatiramer acetate related drug substance or drug product comprising the steps of: a) obtaining a batch of the glatiramer acetate related drug substance or drug product; b) contacting mammalian cells with an amount of the glatiramer acetate related drug substance or drug product of step a); and c) i) determining the level of expression of at least one gene selected from the group consisting of ABCF2, ABI2, ACP6, AFG3L2, ALMS1, ARPC4, CALM3, CCDC64, CD84, CDC6, CHAF1A, CLU, COX11, DLGAP1, DTX4, FAM49B, FHL1, FNTB, GYPC, HFE, IL10, LPHN1, NACA, OLAH, PATZ1, PDK1, POLI, REEP5, RPL5, RPS6KA2, SEC31A, SETBP1, SNRPA1, SYNCRIP, TNFSF9, TOMM40, TPM1, TSHZ1, TSPAN13, UBAP2, VAV3, VDAC2, and ZFAND6; ii) determining the level of expression of at least one gene selected from the group consisting of BIRC3, CCL24, CCR1, CISH, CSF1R, CX3CR1, CXCL10, HSPD1, ICAM1, IL1B, IFNGR1, IL27, IL2RG, IL7R, IL1RN, MMP1, MMP9, MMP14, PGRMC1, PRDM1, CARD15, CCL2, CCL5, CD14, IL10, THBD, and NFKBIA, wherein if IL1B, IL10, or MMP9 is the at least one gene selected in part (c)(ii), then selecting at least a second different gene from the group other than IL1B, IL10, or MMP9; iii) determining the level of expression of at least one gene selected from the group consisting of C13ORF31, C14ORF10, C1ORF51, C1ORF63, CBR4, CB36, CD9, COL6A1, DAB2, GATA2, KIAA0907, LOC100506233, MCM6, MMP1, MS4A4A, MTSS1, PCMTD1, STK4, STX7, TAF15, TARP, TIA1, TMF1, TRGC2, TXNDC11, and ZCCHC7, and ZCCHC7; iv) determining the level of expression of at least one gene selected from the group consisting of ANXA1, ARRB2, BEAN, BIN1, C1ORF63, CD44, CD9, CFP, COL6A1, CRIP2, EPB41, Fam119a, FGR, FOX03B, HSD11B1, HSPD1P6, LOC387790, MPEG1, MYB, OLIG1, PLD1, PPP4R2, PRDM1, RBM6, SNX27, 5OD2, STATH, TARP, TREM1, TRGC2, UBN2, and ZCCHC7; v) determining the level of expression of at least one gene selected from the group consisting of ADAM9, ADAMDEC1, AKR1C2, ANXA2, ANXA2P2, ARHGAP18, ARHGAP18, ARL6IP5, ARL6IP5, ATP2C1, BID, BIRC3, BTG1, CARD15, C1ORF21, C13ORF31, C5ORF13, C5ORF32, C9ORF130, CAST, CCL2, CCL5, CD14, CD300A, CD36, CD40, CD55, CD9, CENTA2, CHST11, COL6A1, CRYBB2, CXCL10, CYLD, DAB2, EBI3, EBI2, ECOP, EGF, FABP4, FXYD2, GHRL, GIMAP8, GLIPR1, G0S2, HMGB2, HNRPLL, ICAM1, ICAM2, IFIH1, IFNGR1, IL10, MORA, IL4I1, INADL, ISG20, ITGB5, KIAA1505, KYNU, LACTB, L0054103, LOC388344, LOC652751, LPAAT-THETA, LPXN, MAFB, MALT1, MFI2, MGC5618, MGLL, MITF, MLF1, MMPI, MMP9, MPEG1, MTSS1, MXD1, NT5E, NFKBIE, NFKBIA, NFE2L3, NFE2L3, OSBPL11, P2RX4, P2RY5, PLEKHO1, POPDC3, PLAUR, PRDM1, PSCDBP, PTX3, RAB27B, RCSD1, RPL13, SGIP1, SLC39A8, SNORD68, SRPX2, SRA1, SLIC1, SLAMF8, SLIC1, SOD2, STATH, STEAP1, SYNJ2, SYNJ2, TATDN3, TGM5, THBD, TNFAIP3, TNFAIP6, TNFRSF9, TNFSF13B, TPSAB1, TPSB2, TREM1, TXNL2, VPS33A, and VSNL1; vi) determining the level of expression of at least one gene selected from the group consisting of ACTN4, BTBD14A, C14ORF10, CISH, CLK1, CRLF3, FAM62A, FBX045, GAPDHS, HDAC4, HIC2, HNRPD, HSPD1, LOC648342, MYB, NAPB, OXCT2, SERPINB2, SFRS14, SPFH1, STT3B, WDFY1, ZNF250, and ZNF566; vii) determining the level of expression of at least one gene selected from the group consisting of A2M, ABCB1, ABCC3, ABHD2, ACPP, ADAMDEC1, ADFP, ADORA2B, ADORA3, AHNAK, ALCAM, ANKH, ANKRD57, ANXA2, ANXA2P2, APBB1IP, AQP1, ARHGAP18, ARHGAP20, ARHGEF3, ARID5B, ARMC9, ATF5, ATP1B1, ATP6V0D2, ATP9A, ATP10A, AYTL1, BCL2A1, BCL6, C3AR1, C13ORD31, C9ORF88, C9ORF89, C1ORF21, C1ORF21, C10ORF95, C13ORF31, C21ORF7, CARD12, CARD15, CCDC83, CCL5, CCL24, CCND1, CCR1, CD9, CD36, CD52, CD86, CD109, CD180, CD244, CDK5RAP2, CDKN1A, CENTA2, CKB, CKLF, CLEC7A, CNIH3, COL6A1, COL22A1, CRIP2, CSF1R, CSPG4, CTSL, CTSLL3, CX3CR1, CXCR7, CYBB, CYP1B1, DAB2, DAPP1, DDIT4L, DIXDC1, DOCK4, DOK2, DKFZP56400823, DKFZP686O1327, EBI2, EMP1, EMR2, ENPP2, EPAS1, EPS8, EPSTI1, EVL, FABP4, FADS3, FAM26B, FGD2, FGD2, FGD4, FGL2, FN1, FTH1, GBP2, GBP3, GBP5, GCNT1, GDPD1, GNDL, GNLY, GLIPR1, GLIS3, GPC1, GPR35, H2A/R, HAVCR2, HMCN1, HIPK2, HIST2H2AA, HIVEP1, HMOX1, HSPB7, ICAM1, ID2, ID2B, IFI30, IFI44, IFNGR1, IGFBP3, IL2RG, IL4I1, IL1ORA, IL27RA, IL7R, IL10, INA, IRF7, ITGB5, ITGB7, KIAA1505, KIAA1706, KMO, LBH, LFNG, LILRB1, LILRB2, LMNA, L0051334, LOC201895, LOC284262, L0051334, LOC643424, LOC643834, LOC643847, LOC644242, LOC645238, LOC650429, LOC650446, LOC652543, LOC653610, LOC653754, LPAAT-THETA, LPXN, MAF, MAFB, MAML2, MAML3, MARCH1, MCOLN3, MDGA1, ME1, MFI1, MFI2, MGC45491, MGLL, MITF, MMP1, MMP2, MMP9, MMP14, MMP19, MTMR11, MTSS1, MTSUl, NGEF, NME7, NPTX1, NRCAM, NRP1, NRP2, NT5E, OAS1, OLR1, P2RY5, P2RY14, PALLD, PAPSS2, PAQR5, PCDHGA1, PCDHGA2, PCDHGA3, PCDHGA4, PCDHGA5, PCDHGA6, PCDHGA7, PCDHGA8, PCDHGA9, PCDHGA10, PCDHGA11, PCDHGA12, PCDHGB1, PCDHGB2, PCDHGB3, PCDHGB4, PCDHGB5, PCDHGB7, PCDHGC3, PCDHGC4, PCDHGC5, PDK4, PDLIM7, PFKFB4, PGA5, PDLIM4, PHLDA1, PLA2G4A, PLEKHA7, PLEKHO1, POPDC3, PRDM1, PRSS23, PSCDBP, PSD3, PTAFR, PTGS1, PTPRO, PTRF, PTX3, RAB27B, RAB38, RAB7B, RAPH1, RASGRF1, RGL1, RGS13, RHBDF1, RIN2, S100A2, SART2, SERPINE2, SERTAD1, SETBP1, SGIP1, SH3TC1, SKIL, SLA, SLAMF7, SLAMF8, SLC6AS, SLC7A11, SLC12A6, SLC37A2, SLC41A2, SLC38A6, SLC43A2, SNAI3, ST3GAL5, STATH, STEAP1, SUCNR1, SYTL1, TBXAS1, TCF4, TFAP2A, THBD, TLR4, TM7SF4, TMEM39A, TMEM158, TNCRNA, TNFSF13B, TNFRSF21, TREM1, TRIM22, TRPA1, TRPM8, TRPS1, TUBB2A, UBXD5, UGCG, UPP1, VASH1, VEGF, VSNL1, and ZFP36L1; viii) determining the level of expression of at least one gene selected from the group consisting of ABCG1, ADAMTS1, ANKRD41, ANXA3, APCDD1, BCL2, BCL11A, BMP8B, C1ORF71, C1ORF76, ClORD121, C12ORF24, C16ORF73, C16ORF74, C20ORD27, C20ORF103, C20ORF112, CACNA2D3, CAMTA1, CAV1, CCDC85B, CDCA7L, CEBPD, CKAP4, CNTN4, COL8A2, CSPG5, CXCR4, DCUN1D4, DEPDC6, DMRT2, DUSP2, DZIP1, EBF3, EGR4, FAM117A, FKBP4, FL135848, FLOT2, GFI1, GMDS, GPR18, HAL, HNF4G, HSPC049, IL17D, IRX3, KBTBD11, KCNQ4, KCTD15, KIAA0146, KIAA0984, KIAA1026, KIAA1553, KLHL23, LGR4, LOC201164, LOC284454, LOC387763, LOC642083, LOC648232, MGC2408, MICAL1, MID1IP1, MSRB3, MUC19, NAPSB, NR1D2, PCDH8, PDE4B, PDGFD, PER2, PHF15, PKP2, PLK2, OAF, OSBPL1A, OSR2, OXCT2, PGM1, PMAIP1, PNMA6A, POU4F2, PSAT1, RAB33A, RASGRP2, RBM38, RET, RFTN1, SERPINB2, SERPINB10, SLAIN1, SLC1A3, SLC16A1, SLC19A1, SLC27A2, SLC29A1, SLC39A14, SLCO4A1, SNF1LK, SOX12, SPFH1, SPRY1, STEAP3, 5YDE2, SYNPO2, TARP, TEAD4, TDRD7, TMEM67, TPD52, TRGC2, TRGV2, TRGV9, TRIB3, TSPAN2, TUBA1, VIT, WDR49, WNT3, WT1, and YES1; ix) determining the level of expression of at least one gene selected from the group consisting of AHRR, CCDC36, CYP1B1, DOC1, EPB41L3, GAS7, GPR68, NPTX1, PDCD6, and TIPARP; x) determining the level of expression of at least one gene selected from the group consisting of ADRB2, COTL1, LOC285758, LOC644137, MALAT1, PRG1, RNF43, SAT1, THAP5, TIMP3, and TSC22D1; xi) determining the level of expression of at least one gene selected from the group consisting of AW011738, Bst2, Daxx, Gm16340, Hck, Herc6, Ifi202b, Ifi203, Ifi204, Ifi44, Ifi441, Ifit2, Inpp5b, LOC100044068, LOC100862473, Mx1, Oas11, Phf11d, Oyhin1, Sdc3, Setdb2, Tor3a, Usp18, and Zcchc2; xii) determining the level of expression of at least one gene selected from the group consisting of Ccdc711, D13ERTD608E, Fads2, Gm2a, Ifi2711, Ighm, Klk1, Scd2, Siglech, and Tspan2; xiii) determining the level of expression of at least one gene selected from the group consisting of Ahrr, AI607873, Atp10a, AW011738, Casp44, Cxc13, Gm9706, Ifi202b, Ifit2, Ifitm6, I118, Lcn2, LOC100044068, Ms4a6d, Mx1, Papd7, Rsad2, Slfn3, Slfn4, Tdrd7, Tiparp, and Zcchc2; xiv) determining the level of expression of at least one gene selected from the group consisting of Aldoc, Casp6, Ccdc711, Cox7a1, Egln3, Fam162a, Gfi1, Gpi1, Grhpr, Ifi2711, Ighm, Kcnq5, Klhdc2, Pgk1, Pkm, Tpi1, and Trappc6a; xv) determining the level of expression of at least one gene selected from the group consisting of 1600014C10Rik, 2810474O19Rik, 6720475J19Rik, Adam8, Adar, Agrn, Ahrr, AI607873, Amigo2, Ankfy1, Apobec1, Arf4, Asb2, Ascc3, Atp10a, Atp8b4, AW011738, B4galt5, BC147527, Bst2, Casp4, Chic1, Cmpk2, Csprs, Cxc13, Cybb, Daxx, Ddit3, Ddx24, Ddx58, Ddx60, Dpp4, Eif2ak2, Emr1, Epsti1, Evi2a, Fcgr1, Fcgr4, Ftsjd2, Gcnt1, Gm11772, Gm14446, Gm15433, Gm16340, Gm20559, Gm2666, Gm7609, Gm9706, Gpnmb, Gpr15, H2-T10, H2-T9, Hck, Helz2, Herc6, Hsh2d, Hspa1b, Ifi202b, Ifi203, Ifi204, Ifi205, Ifi2712a, Ifi35, Ifi44, Ifi441, Ifit1, Ifit1, Ifit2, Ifit3, Ifitm3, I118, I17r, Inpp5b, Ins16, Irf7, Isg20, Klrk1, Lga1s3bp, Lga1s9, LOC100041903, LOC100044068, LOC100503923, LOC100505160, LOC100862473, LOC664787, Lpar6, Ly6cl, Ly6c2, Mb21d1, Mitd1, Mlk1, Mmp8, Mnda, Mnda1, Ms4a4c, Ms4a6d, Mx1, Naa20, Nceh1, Ncoa7, Ngp, Nlrc5, Nmral1, Nqo1, Nt5c3, Oas1a, Oas2, Oas3, Oas11, Oas12, Ogfr, Papd7, Parp10, Parp11, Parp12, Parp14, Phf11d, Pik3ap1, Pla2g7, Plec, Pnpt1, Ppm1k, Pydc4, Pyhin1, Ramp3, Rnf213, Rnf8, Rsad2, Rtp4, Samd91, Scin, Sdc3, Setdb2, Sgcb, Shisa5, Slco3a1, Slfn1, Slfn3, Slfn4, Slfn5, Slfn8, Slfn9, St3ga16, Tcstv3, Tdrd7, Tiparp, Tmem140, Tmeml84b, Tnfsf10, Torlaip2, Tor3a, Trafd1, Trim25, Trim30a, Trim30d, Trim34a, Trim34b, Tspo, Uba7, Ubr4, Usp18, Wnt10a, Xaf1, Xaf1, Zc3hav1, Zcchc2, Zfyve26, Znfx1, and Zufsp; xvi) determining the level of expression of at least one gene selected from the group consisting of Ccdc711, D13ERTD608E, Fads2, Gm2a, Ifi2711, Ighm, Klk1, Scd2, Siglech, and Tspan2; xvii) determining the level of expression of at least one gene selected from the group consisting of CC12, CYBASC3, CYP1B1, FCAR, HBEGF, ID1, IL1B, IL4I1, MSC, NQO1, PPP1R15A, PRDM1, SLC7A11, SRXN1, TIPARP, TMEM138, TXNRD1, and VEGF; xviii) determining the level of expression of at least one gene selected from the group consisting of BCL2, CACNA2D3, C13ORF18, C20ORF103, C5ORF13, CDCA7, DEPDC6, GATM, HAL, HSPA1A, HSPC049, LOC645919, LRMP, OAF, POU4F2, RASGRP2, RET, SERPINB2, SERPINB8, SPFH1, and TDRD7; xix) determining the level of expression of at least one gene selected from the group consisting of ABCC1, ABHD12, ABHD5, ACPP, ACSL1, ADFP, ADORA2B, ADORA3, AHRR, AKNA, AKR1C1, AKR1C2, AKR1C3, ALAS1, ALOX5AP, ANKRD57, ANXA2, APBB1IP, APRIN, ARHGAP20, ARHGEF3, ARRB2, ARRDC4, ASB2, ATF5, ATG7, ATP6V0B, ATP6V0C, ATP9A, ATP9B, AXL, AYTL1, BCL2A1, BCL3, BCL6, BHLHB2, BTG1, BTG2, BTG3, C10ORF22, C10ORF54, C10ORF56, C12ORF35, C13ORF31, C14ORF43, C15ORF39, C17ORF32, C19ORF58, C1ORF122, C1ORF144, C1ORF162, C1ORF21, C1ORF38, C3AR1, C5ORF20, C6ORF166, C9ORF16, C9ORF88, CALN1, CARD15, CCL2, CCL5, CCND3, CCNL1, CCR1, CD109, CD244, CD300A, CD40, CD44, CD83, CD9, CDCA4, CDK5RAP2, CDKN1A, CHST11, CIDEC, CKB, CLEC5A, CLEC7A, CMTM3, CPEB2, CPEB4, CSF1R, CSGLCA-T, CSGLCA-T, CSPG2, CSPG2, CTSB, CTSH, CUTL1, CXCL1, CXCL2, CXXC5, CYBASC3, CYBB, CYLD, CYLD, CYP1B1, DDB1, DGAT2, DKFZP68601327, DOC1, DOK2, DUSP6, EBI2, ECGF1, ECOP, EFHD2, EIF1, ELL2, ELOVL1, EMP2, EMR2, EPAS1, EPB41L3, EPB41L3, EXT1, F3, FADS3, FAM100B, FCAMR, FCAR, FGD3, FGD4, FGL2, FLJ20489, FLJ20701, FLJ90013, FLRT2, FPRL1, FTH1, FUCA1, GAS7, GCNT1, GNA15, GPR35, GPR68, GSR, GSR, H2A, HBEGF, HERPUD1, HIPK2, HIST2H2AA, HIVEP1, HMOX1, HNRPLL, HPCAL1, ID1, ID2, IER5, IFI30, IFNGR1, IFNGR2, IGFBP3, MORA, IL1B, IL1R1, IL1RN, IL1RN, IL21R, IL27RA, IL27RA, IL4I1, IL4R, IRF5, ITGB7, JDP2, JUN, JUNB, JUND, KCNN4, KIAA0247, KIAA0999, KIAA1505, KIAA1706, KIAA1913, KITLG, KLF13, KLF4, KLF6, KLHL18, LACTB, LAT, LHX2, LOC113179, LOC338758, LOC440934, L0054103, LOC644242 LOC648998 LOC650429, LOC650446, LOC651816, LOC653524, LOC653361, LOC653840, LOC653361, LOC653506, LOC653610, LOC653840, LOC653626, LPAAT-THETA, LPL, LPXN, LRG1, LRP10, MAFB, MAFF, MALT1, MAML2, MAP1LC3B, MARCKSL1, MBP, MCL1, ME1, METRNL, MGAT4A, MGC13379, MGLL, MMP2, MMP9, MOBKL2A, MSC, MST150, MTF1, MTUS1, MYH10, NAB1, NCF1, NCF2, NCF4, NEU1, NFE2L3, NFKB1, NFKB2, NFKBIA, NFKBIE, NFXL1, NINJ1, NOTCH1, NOTCH2NL, NPTX1, NQO1, NRP1, NRP2, NT5E, NUAK1, P2RY5, P2RY6, PACSIN2, PDCD6, PDK4, PDLIM4, PECAM1, PEX19, PGD, PHLDA1, PHLDA2, PIK3R5, PIR, PITPNA, PKM2, PLAU, PLAUR, PLEKHO1, PNKD, POPDC3, PPIF, PPP1R15A, PRDM1, PRKCA, PSCD4, PSCDBP, PSMD1, PTAFR, PTGS1, PTPN14, PTPRE, PTX3, QPRT, RAB13, RAB27B, RAB38, RAB6IP1, RAI17, RAP2B, RAPGEF1, RCN1, RELB, RGL1, RGS1, RGS2, RIN3, RIT1, RND3, RSNL2, RSPO3, RUNX3, SAMSN1, SAP30, SASH1, SAT1, SDC4, SEMA4C, SERPINE2, SERTAD1, SFRS7, SGK, SH3GL1, SH3TC1, SLAMF8, SLC15A3, SLC16A3, SLC20A1, SLC23A2, SLC25A14, SLC25A19, SLC25A20, SLC2A1, SLC2A6, SLC37A2, SLC39A8, SLC43A2, SLC45A3, SLC4A2, SLC4A5, SLC6A6, SLC7A11, SLC7A11, SLIC1, SMOX, SNAI3, SOD2, SPRY2, SPSB1, SQRDL, SQSTM1, SRXN1, SSH1, ST3GAL5, STAT1, STK40, TFAP2A, TFDP1, TFEB, TGIF, THBD, TIPARP, TMEM138, TMTC1, TNFAIP3, TNFAIP6, TNFAIP8L1, TNFRSF10D, TNFRSF1B, TNFRSF21, TNFSF13B, TNFSF7, TP53BP2, TRAF3, TRAF3IP2, TRIB1, TRIB3, TRIM16, TRIM16L, TRPA1, TRPS1, TRPS1, TSHZ3, TTLL4, TXNRD1, UBE2S, UGCG, ULBP2, UPP1, URP2, VASH1, VEGF, VSNL1, YRDC, ZBTB24, ZCCHC10, ZFAND5, ZFP36L1, ZNF366, ZNF516, and ZNF697; xx) determining the level of expression of at least one gene selected from the group consisting of ABHD14B, ACTN1, ACY1L2, ADA, ADD2, AFF1, AIG1, AK2, AKAP1, ALS2CR13, ANKRD45, ANKRD55, APPL, ARHGEF6, ATG16L2, ATP8B3, ATP8B4, ATPBD1C, B3GNT7, BCL11A, BCL2, BMP8B, BRE, BSPRY, BTBD14A, C13ORF18, C13ORF18, C14ORF106, C15ORF41, C16ORF73, C1ORF121, C1ORF63, C1QBP, C1S, C20ORF103, C20ORF112, C20ORF12, C3ORF14, C5ORF13, C6ORF147, C7ORF24, C9ORF103, CABC1, CACNA2D3, CACYBP, CALCOCO2, CAMSAP1L1, CAMSAP1L1, CAT, CAV1, CDCA7, CERKL, CHST12, CHST5, CITED4, CLINT1, CLSTN2, CLTCL1, CNTN4, COL4A1, COL8A2, CUGBP2, CXORF21, DAB1, DENND4A, DEPDC6, DHRS9, DMRT2, DUT, EIF4A2, ESD, FLJ12078, FLJ20152, FLJ23861, FLJ36166, FOXP1, GATM, GGA2, GOLGA1, GOLGA8C, GOLGA8D, GOLGA8E, GOLGA8F, GOLGA8G, GPD1L, GPR18, HADH, HAL, HDAC9, HGF, HIG2, HISPPD1, HNRPA3, HNRPH3, HOXB3, HSPA1A, HSPA4L, HSPB1, HSPC049, ID2, ID2B, IDH1, IDH1, IHPK2, IRX3, ITGA4, KBTBD11, KCNN2, KIAA0960, KLF10, LARS, LGR4, LIMA1, LIX1L, LOC129285, LOC148203, LOC197322, LOC203274, LOC220594, LOC254559, LOC284702, LOC285084, LOC285758, LOC340061, LOC340061, LOC388189, LOC474170, LOC643458, LOC645919, LOC646456, LOC90835 LONRF1, LRMP, LYST, MACF1, MDH1, METTL7B, METTL8, MICAL1, MLSTD1, MNDA, MRPL24, MS4A3, MS4A4A, MS4A6A, MS4A7, MSRB3, MT1E, MT1H, MT1M, MTBP, MTHFD1, MTL5, MTR, MUC19, MUM1, MYADM, NAPSB, NAPSB, NAT11, NOC2L, NPAL3, OAF, OCRL, OMA1, OSBPL1A, OXCT2, PDCD4, PHACTR3, PHYH, PIGM, PIWIL4, PNMA6A, POU4F2, PRKAB2, PRLR, PSAT1, PSAT1, PTGER3, PTPLAD2, RABGAP1L, RAD17, RASGRP2, RBKS, RET, RNASEH2B, RNASET2, SELPLG, SERPINB10, SERPINB2, SERPINB8, SERPINI2, SKAP2, SLAIN1, SLC16A4, SLC22A15, SLC22A16, SLC40A1, SMARCA2, SNAPC3, SNX10, SPFH1, SPTBN1, ST3GAL3, STAR, STRBP, SYNPO2, TADA1L, TCFL5, TDRD7, THTPA, TIFA, TLE1, TMEM14A TOP2B, TPD52, TPM1, TRAF3IP3, TSPAN2, TTC9C, UBE2B, UBP1, UHRF2, VLDLR, VPS35, WASF1, WDFY1, WDR49, WDR68, WHDC1L1, WHDC1L2, ZBTB33, ZBTB44, ZF, ZNF207, ZNF519, ZNF658, and ZNF92; xxi) determining the level of expression of at least one gene selected from the group consisting of CCL2, CCL5, CXCL10, IL1RN, and MMP9; xxii) determining the level of expression of at least one gene selected from the group consisting of CCL5, CXCL10, and MMP9; xxiii) determining the level of expression of at least one gene selected from the group consisting of IL10 and CCL2; xxiv) determining the level of expression of at least one gene selected from the group consisting of IFNg, TNF, CCL3, CXCL8, and IL-10; xxv) determining the level of expression of at least one gene selected from the group consisting of MMP9, CCL2, CCL5, CXCL1, and IL1B; xxvi) determining the level of expression of at least one gene selected from the group consisting of MMP9, CXCL10, CCL2, and CCL5; xxix) determining the level of expression of at least one gene selected from the group consisting of CCL3, MMP9, CCL22, CCL24, CX3CL1, CCL20, CCL2, TNF, IL8, CCL13, CCL5, IL1B, CCL8, IL10, CXCL11, CXCL13, CXCL10, CCL7, CCL1, CXCL1, IFNg, CCL26, and MIF; or xxx) determining the level of expression of at least one gene selected from the group consisting of CCL3, MMP9, CCL22, CCL24, CX3CL1, CCL20, CCL2, TNF, IL8, CCL13, CCL5, IL1B, CCL8, IL10, CXCL11, CXCL13, CXCL10, CCL7, CCL1, CXCL1, IFNg, CCL26, MIF, IL16, IL6, CCL25, IL2, CCL19, CXCL2, CXCL9, and CXCL5, thereby characterizing the glatiramer acetate related drug substance or drug product of step a).

3. 发明申请

US20160074380A1 Treatment Of Neurodegenerative Diseases With Combination Of Laquinimod And Fingolimod 审中-公开
标题翻译：治疗组合拉喹莫德和芬戈莫德的神经退行性疾病
公开(公告)号：US20160074380A1
公开(公告)日：2016-03-17
申请号：US14854790
申请日：2015-09-15
申请人： Michael Hayden , Liat Hayardeny , David Ladkani
发明人： Michael Hayden , Liat Hayardeny , David Ladkani
IPC分类号： A61K31/4704 , A61K45/06 , A61K31/137
CPC分类号： A61K31/4704 , A61J1/035 , A61K9/0053 , A61K9/14 , A61K9/2866 , A61K31/00 , A61K31/137 , A61K47/02 , A61K47/18 , A61K47/26 , A61P25/00 , A61P25/02 , A61P25/14 , A61P25/16 , A61P25/28 , B65D1/0215 , B65D65/38 , B65D81/266 , A61K2300/00
摘要： This invention provides a method of treating a subject afflicted with a neurodegenerative disease comprising periodic administration of an amount of laquinimod and an amount of fingolimod, wherein the amounts when taken together are effective to treat the subject. Also provided are packages and pharmaceutical compositions comprising laquinimod and fingolimod for treating a subject afflicted with a neurodegenerative disease. Also provided is a pharmaceutical composition comprising laquinimod for use as an add-on therapy or in combination with fingolimod, and a pharmaceutical composition comprising fingolimod for use as an add-on therapy or in combination with laquinimod, for treating said subject.
摘要翻译：本发明提供了治疗患有神经变性疾病的受试者的方法，其包括定期给予一定量的拉喹莫德和一定量的芬戈莫德，其中所述量一起有效治疗受试者。还提供了包含用于治疗患有神经变性疾病的受试者的拉喹莫德和芬戈莫德的包装和药物组合物。还提供了包含用作附加治疗或与芬戈莫德组合的拉喹莫德的药物组合物，以及包含用于附加疗法的芬戈莫德或与拉喹莫德组合用于治疗所述受试者的药物组合物。

4. 发明申请

US20170224674A1 Treatment Of Neurodegenerative Diseases With Combination Of Laquinimod And Fingolimod 审中-公开
公开(公告)号：US20170224674A1
公开(公告)日：2017-08-10
申请号：US15493997
申请日：2017-04-21
申请人： Michael Hayden , Liat Hayardeny , David Ladkani
发明人： Michael Hayden , Liat Hayardeny , David Ladkani
IPC分类号： A61K31/4704 , A61K9/00 , A61K9/28 , A61K47/26 , B65D65/38 , A61K47/02 , A61K9/14 , A61J1/03 , B65D1/02 , B65D81/26 , A61K31/137 , A61K47/18
CPC分类号： A61K31/4704 , A61J1/035 , A61K9/0053 , A61K9/14 , A61K9/2866 , A61K31/00 , A61K31/137 , A61K47/02 , A61K47/18 , A61K47/26 , A61P25/00 , A61P25/02 , A61P25/14 , A61P25/16 , A61P25/28 , B65D1/0215 , B65D65/38 , B65D81/266 , A61K2300/00
摘要： This invention provides a method of treating a subject afflicted with a neurodegenerative disease comprising periodic administration of an amount of laquinimod and an amount of fingolimod, wherein the amounts when taken together are effective to treat the subject. Also provided are packages and pharmaceutical compositions comprising laquinimod and fingolimod for treating a subject afflicted with a neurodegenerative disease. Also provided is a pharmaceutical composition comprising laquinimod for use as an add-on therapy or in combination with fingolimod, and a pharmaceutical composition comprising fingolimod for use as an add-on therapy or in combination with laquinimod, for treating said subject.

5. 发明授权

US09702007B2 Genetic markers predictive of response to glatiramer acetate 有权
公开(公告)号：US09702007B2
公开(公告)日：2017-07-11
申请号：US14520280
申请日：2014-10-21
申请人： Amir Tchelet , Michael Hayden , Liat Hayardeny , Colin James Douglas Ross , Iris Grossman , David Ladkani
发明人： Amir Tchelet , Michael Hayden , Liat Hayardeny , Colin James Douglas Ross , Iris Grossman , David Ladkani
IPC分类号： A61K38/16 , C12Q1/68
CPC分类号： C12Q1/6883 , A61K38/02 , A61K38/16 , C12Q2600/106 , C12Q2600/156
摘要： The present invention provides a method for treating a human subject afflicted with multiple sclerosis or a single clinical attack consistent with multiple sclerosis with a pharmaceutical composition comprising glatiramer acetate and a pharmaceutically acceptable carrier, comprising the steps of: (i) determining a genotype of the subject at a location corresponding to the location of one or more single nucleotide polymorphisms (SNPs) selected from the group consisting of: Group 1, (ii) identifying the subject as a predicted responder to glatiramer acetate if the genotype of the subject contains one or more A alleles at the location of Group 2, one or more C alleles at the location of Group 3, one or more G alleles at the location of Group 4, or one or more T alleles at the location of kgp18432055, kgp279772, kgp3991733 or kgp7242489; and (iii) administering the pharmaceutical composition comprising glatiramer acetate and a pharmaceutically acceptable carrier to the subject only if the subject is identified as a predicted responder to glatiramer acetate.

6. 发明申请

US20130046008A1 SELECTIVE REDUCTION OF ALLELIC VARIANTS 有权
公开(公告)号：US20130046008A1
公开(公告)日：2013-02-21
申请号：US13577622
申请日：2011-02-08
申请人： C. Frank Bennett , Michael Hayden , Susan M. Freier , Sarah Greenlee , Jeffrey Carroll , Simon Warby , Eric E. Swayze
发明人： C. Frank Bennett , Michael Hayden , Susan M. Freier , Sarah Greenlee , Jeffrey Carroll , Simon Warby , Eric E. Swayze
IPC分类号： A61K31/7088 , A61P25/28 , A61K31/7115 , A61K31/7125 , C12N5/071 , A61K31/712
CPC分类号： C12Q1/6883 , C12N15/113 , C12N2310/11 , C12N2320/34 , C12Q1/6811 , C12Q1/6897 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , C12Q2525/207 , C12Q2535/131 , C12Q2539/107 , C12Q2521/327 , C12Q2525/121 , C12Q2525/185
摘要： Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a huntingtin gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate Huntington's Disease (HD).

7. 发明申请

US20110213010A1 METHODS AND COMPOSITIONS FOR THE TREATMENT OF HUNTINGTON'S DISEASE 有权
标题翻译：治疗亨廷顿病的方法和组合
公开(公告)号：US20110213010A1
公开(公告)日：2011-09-01
申请号：US12991883
申请日：2009-05-08
申请人： Michael Hayden , Jeffrey Carroll , Simon Warby
发明人： Michael Hayden , Jeffrey Carroll , Simon Warby
IPC分类号： A61K31/7088 , C12N5/071 , C12Q1/68 , A61P25/28
CPC分类号： C12Q1/6883 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/14 , C12N2320/34 , G01N33/5023 , G01N2800/2835
摘要： Methods and compositions for reducing expression of a mutant huntingtin (mHTT) protein in a cell are provided. Such methods include contacting the cell with an effective amount of a nucleic acid silencing agent targeting a differentiating polymorphism in RNA encoding the mHTT.
摘要翻译：提供了用于降低细胞中突变型亨廷丁蛋白（mHTT）蛋白表达的方法和组合物。这样的方法包括使细胞与有效量的靶向编码mHTT的RNA的差异多态性的核酸沉默剂接触。

8. 发明申请

US20070066953A1 Disposable absorbent article having deployable belt strips 审中-公开
标题翻译：具有可展开的带条的一次性吸收制品
公开(公告)号：US20070066953A1
公开(公告)日：2007-03-22
申请号：US11231512
申请日：2005-09-21
申请人： Gary LaVon , Kenneth Hamall , Theodora Beck , Michael Hayden , Susan Ludwig
发明人： Gary LaVon , Kenneth Hamall , Theodora Beck , Michael Hayden , Susan Ludwig
IPC分类号： A61F13/15
CPC分类号： A61F13/5622 , A61F13/64
摘要： A disposable absorbent article having laterally opposing interiorly attached side flaps and at least one deployable belt strip. Each of the side flaps has a longitudinally extending elastic gathering member attached adjacent to its proximal edge. The belt strip has a fixed end portion disposed in one of the waist regions and opposing first and second edges connecting the fixed end portion and an opposing free end portion. The belt strip is attached in the fixed end portion and is deployed by being folded laterally outward such that the first edge extends laterally outward from one end point of a diagonal fold line and the second edge extends laterally outward from the opposing end point of the diagonal fold line. The belt strip may be tied to another belt strip or may be fastened to the waist region of the article or to another belt strip.
摘要翻译：一种一次性吸收制品，其具有横向相对的内部连接的侧翼和至少一个可展开的带条。每个侧翼具有邻近其近侧边缘附接的纵向延伸的弹性聚集构件。带条具有设置在一个腰部区域中的固定端部和连接固定端部和相对的自由端部的相对的第一和第二边缘。带条附着在固定端部，并且通过横向向外折叠而展开，使得第一边缘从对角折线的一个端点横向向外延伸，并且第二边缘从对角线的相对端点横向向外延伸折线。带条可以绑在另一条带上，或者可以固定在制品的腰部区域或另一条带条上。

9. 发明申请

US20060271005A1 Side notched folded diaper 有权
标题翻译：侧面折叠尿布
公开(公告)号：US20060271005A1
公开(公告)日：2006-11-30
申请号：US11140888
申请日：2005-05-31
申请人： Gary LaVon , Kevin Smith , Michael Hayden
发明人： Gary LaVon , Kevin Smith , Michael Hayden
IPC分类号： A61F13/15
CPC分类号： A61F13/514
摘要： A disposable absorbent article includes a chassis and an absorbent assembly. The chassis includes a water-impermeable backsheet that is folded laterally inward at both of its side edges to form laterally opposing side flaps. Each side flap is attached to the interior surface of the chassis adjacent to its end edges. Each side flap has a longitudinally extending elastic gathering member attached adjacent to its proximal edge. Each side flap is also attached to the interior surface of the chassis at continuous longitudinally extending laterally opposing water-impermeable side seals. The chassis is side notched to give it an hourglass shape. The chassis may include an extensible formed web material. The absorbent assembly includes an absorbent core that may contain superabsorbent particles, which may be contained inside pockets. The absorbent assembly may be attached in a cruciform pattern to the chassis to allow portions of the chassis to extend laterally.
摘要翻译：一次性吸收制品包括底架和吸收组件。底盘包括不透水的底片，其在其两个侧边缘处横向向内折叠以形成横向相对的侧翼。每个侧翼连接到底盘的与其端缘相邻的内表面。每个侧翼具有邻近其近侧边缘附接的纵向延伸的弹性聚集构件。每个侧翼还在连续纵向延伸的横向相对的不透水侧密封件上附接到底盘的内表面。底盘是侧面凹槽，给它一个沙漏形状。底盘可以包括可伸长的成形网材料。吸收组件包括吸收芯，该吸收芯可包含超吸收颗粒，其可以包含在袋内。吸收组件可以以十字形图案附接到底架，以允许底盘的一部分横向延伸。

10. 发明申请

US20060235070A1 Compositions and methods for treating vascular, autoimmune, and inflammatory diseases 审中-公开
标题翻译：用于治疗血管，自身免疫和炎性疾病的组合物和方法
公开(公告)号：US20060235070A1
公开(公告)日：2006-10-19
申请号：US11351157
申请日：2006-02-08
申请人： Michael Hayden , Noel Hall
发明人： Michael Hayden , Noel Hall
IPC分类号： A61K31/401 , A61K31/366 , A61K31/22
CPC分类号： A61K31/505 , A61K31/22 , A61K31/343 , A61K31/366 , A61K31/40 , A61K31/404 , A61K31/405 , A61K31/47 , A61K31/5377 , A61K45/06 , A61K2300/00
摘要： The disclosure provides methods and compositions for the treatment of vascular, autoimmune and inflammatory diseases using a combination of an inosine monophosphate dehydrogenase (IMPDH) inhibitor and a HMG CoA reductase inhibitor.
摘要翻译：本公开提供了使用肌苷一磷酸脱氢酶（IMPDH）抑制剂和HMG CoA还原酶抑制剂的组合治疗血管，自身免疫和炎性疾病的方法和组合物。

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