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1. 发明申请

US20060240463A1 Markers associated with the therapeutic efficacy of glatiramer acetate 审中-公开
标题翻译：与醋酸格拉默的疗效相关的标记物
公开(公告)号：US20060240463A1
公开(公告)日：2006-10-26
申请号：US11409590
申请日：2006-04-24
申请人： Doron Lancet , Jacques Beckmann , Nili Avidan , Edna Ben-Asher , Dan Goldstaub , Liat Hayardeny , Iris Grossman , Ariel Miller , Clara Singer
发明人： Doron Lancet , Jacques Beckmann , Nili Avidan , Edna Ben-Asher , Dan Goldstaub , Liat Hayardeny , Iris Grossman , Ariel Miller , Clara Singer
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q2600/106 , C12Q2600/156 , C12Q2600/172 , Y10T436/143333
摘要： The present invention is directed to methods and kits based, at least in part, on the identification of allele-specific responsiveness or non-responsiveness to glatiramer acetate for the treatment of immune disorders, such as relapsing-remitting multiple sclerosis. The allele-specific responsiveness or non-responsiveness is based on polymorphisms in the following genes, CTSS, MBP, TCRB, CD95, CD86, IL-1R1, CD80, SCYA5, MMP9, MOG, SPP1 and IL-12RB2.
摘要翻译：本发明涉及至少部分地基于鉴定等位基因特异性应答性或对乙酸格拉默反应性的反应性，用于治疗免疫疾病如复发性多发性硬化症的方法和试剂盒。 CTSS，MBP，TCRB，CD95，CD86，IL-1R1，CD80，SCYA5，MMP9，MOG，SPP1和IL-12RB2中的多态性等位基因特异性反应性或非反应性。

2. 发明申请

US20100285600A1 Markers associated with the therapeutic efficacy of glatiramer acetate 审中-公开
标题翻译：与醋酸格拉默的疗效相关的标记物
公开(公告)号：US20100285600A1
公开(公告)日：2010-11-11
申请号：US12660258
申请日：2010-02-22
申请人： Doron Lancet , Jacques Beckmann , Nili Avidan , Edna Ben-Asher , Clara Singer , Liat Hayardeny , Dan Goldstaub , Iris Grossman , Ariel Miller
发明人： Doron Lancet , Jacques Beckmann , Nili Avidan , Edna Ben-Asher , Clara Singer , Liat Hayardeny , Dan Goldstaub , Iris Grossman , Ariel Miller
IPC分类号： G01N33/50
CPC分类号： C12Q1/6883 , C12Q1/6827 , C12Q2600/106 , C12Q2600/156 , C12Q2600/172 , Y10T436/143333
摘要： The present invention is directed to methods and kits based, at least in part, on the identification of allele-specific responsiveness or non-responsiveness to glatiramer acetate for the treatment of autoimmune disorders, such as relapsing-remitting multiple sclerosis. The allele-specific responsiveness or non-responsiveness is based on polymorphisms in the following genes, CTSS, MBP, TCRB, CD95, CD86, IL-1R1, CD80, SCYA5, MMP9, MOG, SPP1 and IL-12RB2.
摘要翻译：本发明涉及至少部分地基于鉴定等位基因特异性反应性或对醋酸格拉司他对于治疗自身免疫性疾病如复发性多发性硬化症的治疗无反应性的方法和试剂盒。 CTSS，MBP，TCRB，CD95，CD86，IL-1R1，CD80，SCYA5，MMP9，MOG，SPP1和IL-12RB2中的多态性等位基因特异性反应性或非反应性。

3. 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).

4. 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.

5. 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.

6. 发明申请

US20070244056A1 Combination Therapy With Glatiramer Acetate and Riluzole 审中-公开
标题翻译：联合治疗醋酸格列酮和利鲁唑
公开(公告)号：US20070244056A1
公开(公告)日：2007-10-18
申请号：US10591195
申请日：2005-03-03
申请人： Liat Hayardeny , Ety Klinger , Eran Blaugrund
发明人： Liat Hayardeny , Ety Klinger , Eran Blaugrund
IPC分类号： A61K38/03 , A61K38/07 , A61P25/00
CPC分类号： A61K31/785 , A23L33/10 , A61K31/428 , A61K38/02 , A61K45/06 , A61K2300/00
摘要： The subject invention provides a method of providing neuroprotection to the central or peripheral nervous system of a subject in need of such neuroprotection comprising periodically administering to the subject an amount of glatiramer acetate and an amount of 2-amino-6-trifluoromethoxybenzathiazole, wherein the amounts when taken together are effective to provide neuroprotection to the central or peripheral nervous system of the subject. The subject invention also provides a package comprising glatiramer acetate, 2-amino-6-trifluorormethoxybenzothiazole and instructions for use together to provide neuroprotection to the central or peripheral nervous system of a subject in need of such neuroprotection. Additionally, the subject invention provides a pharmaceutical composition comprising an amount of glatiramer acetate and an amount of 2-amino-6-trifluorormethoxybenzothiazole, wherein the amounts when taken together are effective to provide neuroprotection to the central or peripheral nervous system of the subject. The subject invention further provides a pharmaceutical combination comprising separate dosage forms of an amount of glatiramer acetate and an amount of 2-amino-6-trifluorormethoxybenzothiazole, which combination is useful to provide neuroprotection to the central or peripheral nervous system of the subject. In addition, the combination therapy may be used to treat a subject afflicted with multiple sclerosis or one afflicted with amyotrophic lateral sclerosis.
摘要翻译：本发明提供了对需要这种神经保护作用的受试者的中枢或周围神经系统提供神经保护作用的方法，其包括向受试者周期性施用一定量的乙酸格拉默和一定量的2-氨基-6-三氟甲氧基苯并噻唑，当它们一起被用于对受试者的中枢或周围神经系统提供神经保护时是有效的。本发明还提供了包含乙酸格拉默，2-氨基-6-三氟甲氧基苯并噻唑和用于一起为需要这种神经保护的受试者的中枢或周围神经系统提供神经保护作用的说明书。另外，本发明提供了一种药物组合物，其包含一定量的醋酸格拉司定和一定量的2-氨基-6-三氟甲氧基苯并噻唑，其中一起的量有效地为受试者的中枢或周围神经系统提供神经保护作用。本发明进一步提供了一种药物组合，其包含一定量的醋酸格拉默的单独剂型和2-氨基-6-三氟甲氧基苯并噻唑的量，该组合可用于向受试者的中枢或周围神经系统提供神经保护。此外，组合疗法可用于治疗患有多发性硬化症的受试者或患有肌萎缩性侧索硬化症的受试者。

7. 发明申请

US20140235670A1 TREATMENT OF PROGRESSIVE FORMS OF MULTIPLE SCLEROSIS WITH LAQUINIMOD 审中-公开
标题翻译：用LAQUINIMOD治疗多发性硬化症的进展形态
公开(公告)号：US20140235670A1
公开(公告)日：2014-08-21
申请号：US14180173
申请日：2014-02-13
申请人： Nora Tarcic , Dan Bar-Zohar , Liat Hayardeny , Yossi Gilgun Sherki , Tali Gorfine , Volker Knappertz , Ella Sorani
发明人： Nora Tarcic , Dan Bar-Zohar , Liat Hayardeny , Yossi Gilgun Sherki , Tali Gorfine , Volker Knappertz , Ella Sorani
IPC分类号： A61K31/4704
CPC分类号： A61K31/4704
摘要： This invention provides a method for treating a human subject afflicted with a progressive form of multiple sclerosis, comprising periodically administering to the human subject an amount of laquinimod effective to treat the human subject. This invention also provides laquinimod for use in treating a human subject afflicted with a progressive form of multiple sclerosis. This invention further provides pharmaceutical compositions and packages comprising an effective amount of laquinimod for treating a progressive form of multiple sclerosis.
摘要翻译：本发明提供了治疗患有多发性硬化症的进行性形式的人类受试者的方法，其包括向所述受试者周期性施用一定量的有效治疗所述人受试者的拉喹莫德。本发明还提供了用于治疗患有多发性硬化症的进行性形式的人类受试者的拉喹莫德。本发明进一步提供药物组合物和包装，其包含有效量的拉喹莫德以治疗多发性硬化症的进行形式。

8. 发明授权

US09585878B2 Treatment of BDNF-related disorders using laquinimod 有权
标题翻译：使用拉喹莫德治疗BDNF相关疾病
公开(公告)号：US09585878B2
公开(公告)日：2017-03-07
申请号：US12806275
申请日：2010-08-09
申请人： Liat Hayardeny
发明人： Liat Hayardeny
IPC分类号： A61K31/47 , A61K9/48 , A61K31/4704 , A61K31/138 , A61K31/428 , A61K9/00
CPC分类号： A61K31/4704 , A61K9/0053 , A61K9/20 , A61K31/138 , A61K31/428 , A61K2300/00
摘要： This application provides for a method of increasing brain-derived neurotrophic factor (BDNF) serum level in a human subject comprising periodically administering to the subject an amount of laquinimod or pharmaceutically acceptable salt thereof effective to increase BDNF serum level in the human subject. The method can further comprise periodically administering to the subject an amount of a second BDNF-increasing agent. This application also provides for a method for treating a human subject suffering from a BDNF-related disease comprising periodically administering laquinimod or a pharmaceutically acceptable salt thereof in an amount effective to treat the human subject. This application additionally provides for use of laquinimod in the manufacture of a medicament for increasing BDNF serum level in a human subject. This application further provides for a pharmaceutical composition comprising an amount of laquinimod effective for use in increasing BDNF serum level in a human subject. This application also provides for a pharmaceutical preparation comprising an amount of laquinimod and an amount of a second BDNF-increasing agent effective for use in increasing BDNF serum level in a human subject.
摘要翻译：本申请提供了增加人受试者脑源性神经营养因子（BDNF）血清水平的方法，其包括向受试者定期施用一定量的有效增加人受试者BDNF血清水平的拉喹莫德或其药学上可接受的盐。该方法可以进一步包括向受试者周期性施用一定量的第二BDNF增加剂。本申请还提供了治疗患有BDNF相关疾病的人受试者的方法，其包括以有效治疗人受试者的量定期施用拉喹莫德或其药学上可接受的盐。本申请另外提供了在制备用于增加人受试者中BDNF血清水平的药物中的用途。本申请还提供了一种药物组合物，其包含一定量的用于增加人受试者中BDNF血清水平的有效成分的拉喹莫德。本申请还提供了一种药物制剂，其包含一定量的拉喹莫德和一定量的有效用于增加人类受试者中BDNF血清水平的第二BDNF增加剂。

9. 发明申请

US20160243103A1 Treatment of BDNF-Related Disorders Using Laquinimod 审中-公开
标题翻译：使用Laquinimod治疗BDNF相关性疾病
公开(公告)号：US20160243103A1
公开(公告)日：2016-08-25
申请号：US15049942
申请日：2016-02-22
申请人： Liat Hayardeny
发明人： Liat Hayardeny
IPC分类号： A61K31/4704 , A61K9/00
CPC分类号： A61K31/4704 , A61K9/0053 , A61K9/20 , A61K31/138 , A61K31/428 , A61K2300/00
摘要： This application provides for a method of increasing brain-derived neurotrophic factor (BDNF) serum level in a human subject comprising periodically administering to the subject an amount of laquinimod or pharmaceutically acceptable salt thereof effective to increase BDNF serum level in the human subject. The method can further comprise periodically administering to the subject an amount of a second BDNF-increasing agent. This application also provides for a method for treating a human subject suffering from a BDNF-related disease comprising periodically administering laquinimod or a pharmaceutically acceptable salt thereof in an amount effective to treat the human subject. This application additionally provides for use of laquinimod in the manufacture of a medicament for increasing BDNF serum, level in a human subject. This application further provides for a pharmaceutical composition comprising an amount of laquinimod effective for use in increasing BDNF serum level in a human subject. This application also provides for a pharmaceutical preparation comprising an amount of laquinimod and an amount of a second BDNF-increasing agent effective for use in increasing BDNF serum level in a human subject.
摘要翻译：本申请提供了增加人受试者脑源性神经营养因子（BDNF）血清水平的方法，其包括向受试者定期施用一定量的有效增加人受试者BDNF血清水平的拉喹莫德或其药学上可接受的盐。该方法可以进一步包括向受试者周期性施用一定量的第二BDNF增加剂。本申请还提供了治疗患有BDNF相关疾病的人受试者的方法，其包括以有效治疗人受试者的量定期施用拉喹莫德或其药学上可接受的盐。本申请另外提供了用于制备用于增加BDNF血清，人类受试者水平的药物中的拉喹莫德的用途。本申请还提供了一种药物组合物，其包含一定量的用于增加人受试者中BDNF血清水平的有效成分的拉喹莫德。本申请还提供了一种药物制剂，其包含一定量的拉喹莫德和一定量的有效用于增加人类受试者中BDNF血清水平的第二BDNF增加剂。

10. 发明申请

US20140271532A1 COMBINATION THERAPY WITH GLATIRAMER ACETATE AND RASAGILINE FOR THE TREATMENT OF MULTIPLE SCLEROSIS 审中-公开
标题翻译：用于治疗多发性硬化症的乙酰胆碱酯酶和RASAGILINE的联合治疗
公开(公告)号：US20140271532A1
公开(公告)日：2014-09-18
申请号：US14292511
申请日：2014-05-30
申请人： Rivka Kreitman , Liat Hayardeny , Eran Blaugrund , Ruth Levy
发明人： Rivka Kreitman , Liat Hayardeny , Eran Blaugrund , Ruth Levy
IPC分类号： A61K31/78 , A61K31/137
CPC分类号： A61K31/78 , A61K31/135 , A61K31/137 , A61K31/785 , A61K38/02 , A61K45/06 , A61K2300/00
摘要： The subject invention provides a method of treating a subject afflicted with a form of multiple sclerosis comprising periodically administering to the subject an amount of glatiramer acetate and an amount of rasagiline or the pharmaceutically acceptable salt thereof, wherein the amounts when taken together are effective to alleviate a symptom of the form of multiple sclerosis in the subject so as to thereby treat the subject. The subject invention also provides a package comprising glatiramer acetate, rasagiline or the pharmaceutically acceptable salt thereof and instructions for use of the together to alleviate a symptom of a form of multiple sclerosis in a subject. The subject invention further provides a pharmaceutical combination comprising separate dosage forms of an amount of glatiramer acetate and an amount of rasagiline or the pharmaceutically acceptable salt thereof, which combination is useful to alleviate a symptom of a form of multiple sclerosis in a subject.
摘要翻译：本发明提供了治疗患有多发性硬化症形式的受试者的方法，其包括向受试者定期施用一定量的醋酸格拉司定和一定量的雷沙吉兰或其药学上可接受的盐，其中一起使用的量有效缓解在受试者中多发性硬化形式的症状，从而治疗受试者。本发明还提供了一种包含醋酸格拉默，雷沙吉兰或其药学上可接受的盐的包装，以及用于一起减轻受试者中多发性硬化症状的症状的说明书。本发明进一步提供药物组合，其包含一定量的醋酸格拉司定的单独剂量形式和一定量的雷沙吉兰或其药学上可接受的盐，该组合可用于减轻受试者中多发性硬化形式的症状。

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