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Pub. No.:    WO/2005/121370    International Application No.:    PCT/US2005/019217
Publication Date: 22.12.2005 International Filing Date: 02.06.2005
A61K 48/00 (2006.01), C12Q 1/68 (2006.01), C07H 21/04 (2006.01)
Applicants: ISIS PHARMACEUTICALS, INC. [US/US]; 1896 Rutherford Road, Carlsbad, CA 92008 (US) (For All Designated States Except US).
SWAYZE, Eric, E. [US/US]; (US) (For US Only).
BHAT, Balkrishen [IN/US]; (US) (For US Only).
GRIFFEY, Richard, H. [US/US]; (US) (For US Only).
PRAKASH, Thazha, P. [IN/US]; (US) (For US Only).
ALLERSON, Charles [US/US]; (US) (For US Only)
Inventors: SWAYZE, Eric, E.; (US).
BHAT, Balkrishen; (US).
GRIFFEY, Richard, H.; (US).
PRAKASH, Thazha, P.; (US).
ALLERSON, Charles; (US)
Agent: CALDWELL, John; Woodcock Washburn LLP, 2929 Arch Street - Suite 1200, Philadelphia, PA 19104-2891 (US)
Priority Data:
10/859,825 03.06.2004 US
PCT/US2004/17485 03.06.2004 US
PCT/US2004/17522 03.06.2004 US
60/584,045 29.06.2004 US
60/607,927 07.09.2004 US
10/946,147 20.09.2004 US
Abstract: front page image
(EN)The present invention provides double stranded compositions wherein one of the strands is useful in, for example, influencing the preferential loading the opposite strand into the RISC (or cleavage) complex. In particular, the present invention provides oligomeric compounds that comprise chemical modifications in at least one of the strands to drive loading of the opposite strand into the RISC (or cleavage) complex. Such modifications can be used to increase potency of duplex constructs that have been modified to enhance stability. Examples of chemical modifications that drive loading of the second strand include, but are not limited to, MOE (2'-O(CH2)2OCH3), 2'-O-methyl, -ethyl, -propyl, and -N-methylacetamide. Such modifications can be distributed throughout the strand, or placed at the 5' and/or 3' ends to make a gapmer motif on the sense strand. The activity of the 4'-thio gapmer RNA antisense strand can be improved by incorporating alternating MOE or MOE gapmer motif into the sense strand.
(FR)Des compositions à double brin dont un brin sert, par exemple, à influencer la charge préférentielle du brin opposé dans le complexe RISC (ou du clivage). Des composés oligomères comprenant, plus particulièrement, des modifications alchimiques dans au moins un des brins afin de charger le brin opposé dans le complexe RISC (de clivage). De telles modifications peuvent servir à augmenter l'activité thérapeutique des gène duplex modifiés pour augmenter la stabilité. Des exemples de modifications chimiques entraînant la charge du second brin comprennent, entre autres, MOE (2'-O(CH2)2OCH3), 2'-O-méthyl, -éthyl, -propyl, et -N-méthylacétamide. De telles modifications peuvent être distribuées à travers le brin ou placées au niveau des terminaisons 5' et/ou 3' afin d'obtenir un motif gapmère (gapmer) sur le brin sens. L'activité du brin antisens ARN gapmère 4'-thio peut être améliorée si on alterne le motif gapmère MOE ou MOE dans le brin sens.
Designated States: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, YU, ZA, ZM, ZW.
African Regional Intellectual Property Organization (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
European Patent Office (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HU, IE, IS, IT, LT, LU, MC, NL, PL, PT, RO, SE, SI, SK, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).
Publication Language: English (EN)
Filing Language: English (EN)