SELECTIVE ANTISENSE COMPOUNDS AND USES THEREOF
First Claim
Patent Images
1. A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides, wherein the linked nucleosides comprise at least 8 contiguous nucleobases of a nucleobase sequence recited in SEQ ID NO:
- 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, or 174-573.
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Abstract
The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount, activity, or expression of the target nucleic acid in a cell. In certain embodiments, hybridization results in selective modulation of the amount, activity, or expression of a target Huntingtin gene or Huntingtin transcript in a cell.
26 Citations
40 Claims
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1. A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides, wherein the linked nucleosides comprise at least 8 contiguous nucleobases of a nucleobase sequence recited in SEQ ID NO:
- 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, or 174-573.
- View Dependent Claims (2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)
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6. A compound comprising an oligonucleotide, wherein the oligonucleotide has a sugar motif selected from among:
- eeedk-d7-keee;
eeeedk-d7-eeee;
eeeedk-d7-keee;
eeeedk-d7-kkee;
eeeee-d9-eeeee;
eeeeedk-d7-eeeee;
an eeeeeeeek-d7-eee;
eeeeeeek-d7-eeee;
eeeeek-d7-eee;
eeeeek-d7-eeeeee;
eeeeek-d7-kee;
eeeeek-d7-kke;
eeeek-d7-eeee;
eeeek-d7-eeeeeee;
eeeek-d7-keee;
eeeek-d7-keeee;
eeeek-d7-kke;
eeeek-d7-kkee;
eeeekk-d3-k-d3-keke;
eeeekk-d7-kee;
eeeekk-d7-keke;
eeeekk-d7-kke;
eeeekk-d7-kkee;
eeek-d7-eeeeeeee;
eeek-d7-keeeee;
eeek-d7-kkee;
eeek-d7-kkeee;
eeek-d8-kee;
eeek-d9-keee;
eeek-d9-keke;
eeekk-d7-eeee;
eeekk-d7-keee;
eeekk-d7-kke;
eeekk-d7-kkee;
eeekk-d7-kkeee;
eek-d7-eeeeeeeee;
eek-d7-keeeeee;
eek-d7-kkeee;
eek-d8-kkee;
eekk-d8-kee;
eekk-d8-kkee;
eekk-d8-kkeee;
ek-d7-eeeeeeeeee;
ek-d8-kkeee;
ek-d9-kkke;
ekek-d6-k-dd-keke;
ekek-d8-kkeke;
ekek-d9-keee;
ekek-d9-keke;
ekekek-d7-keke;
ekekk-d8-keke;
ekk-d7-kkeee;
ekk-d7-kkeeeee;
ekk-d8-kkee;
ekk-d8-kkeee;
ekk-d8-kkeeee;
ekk-d8-kkke;
ekk-d9-kke;
ekkdk-d7-kke;
ekkk-d8-kke;
ekkk-d9-ke;
ekkkk-d7-kke;
ekkkk-d7-kkke;
kkekk-d9-kkekk;
kkkkk-d7-kkkkk;
ekkdk-d7-kke;
ekek-d8-kekee;
ekk-f-d8-kke;
ekk-z-d8-kke;
ekk-h-d8-kke;
ekk-d2-h-d6-kke;
ekk-d-h-d7-kke;
ekk-d3-f-d5-kke;
ekk-d3-z-d5-kke;
ekk-d3-h-d5-kke;
ekk-d4-h-d4-kke;
ekk-d5-f-d3-kke;
ekk-d5-z-d3-kke;
ekk-d5-h-d3-kke;
ekk-d6-f-d2-kke;
ekk-d6-z-d2-kke;
ekk-d6-h-d2-kke;
ekk-d7-f-d-kke;
ekk-d7-z-d-kke;
ekk-d7-h-d-kke;
ekk-d8-f-dkke;
ekk-d8-z-kke;
ekk-d8-h-kke; and
ekk-d9-kke.
- eeedk-d7-keee;
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13. An oligomeric compound having a sugar motif of:
- eeeekk-d7-kke motif and having a nucleobase sequence consisting of the nucleobase sequence of SEQ ID NO.;
24.
- eeeekk-d7-kke motif and having a nucleobase sequence consisting of the nucleobase sequence of SEQ ID NO.;
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36. The method of embodiment 35, wherein the treatment reduces at least one of restlessness, lack of coordination, unintentionally initiated motions, unintentionally uncompleted motions, unsteady gait, chorea, rigidity, writhing motions, abnormal posturing, instability, abnormal facial expressions, difficulty chewing, difficulty swallowing, difficulty speaking, seizure, sleep disturbances, impaired planning, impaired flexibility, impaired abstract thinking, impaired rule acquisition, impaired initiation of appropriate actions, impaired inhibition of inappropriate actions, impaired short-term memory, impaired long-term memory, paranoia, disorientation, confusion, hallucination, dementia, a anxiety, depression, blunted affect, egocentrisms, aggression, compulsive behavior, irritability, suicidal ideation, reduced brain mass, muscle atrophy, cardiac failure, impaired glucose tolerance, weight loss, osteoporosis, and testicular atrophy in the human.
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37. A method for reducing the rate of progression of a symptom associated with Huntington'"'"'s Disease, comprising administering to a human in need thereof ISIS 572772, and thereby reducing the rate of progression a symptom of Huntington'"'"'s disease in the human.
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38. A method for reversing degeneration indicated by a symptom associated with Huntington'"'"'s disease, comprising administering to a human in need thereof ISIS 572772, and thereby reversing degeneration indicated by a symptom of Huntington'"'"'s disease in the human.
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39. A method for treating a human with Huntington'"'"'s disease comprising identifying the human with the disease and administering to the human a therapeutically effective amount of ISIS 572772.
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40. The method of embodiment 39, wherein the treatment reduces at least one of restlessness, lack of coordination, unintentionally initiated motions, unintentionally uncompleted motions, unsteady gait, chorea, rigidity, writhing motions, abnormal posturing, instability, abnormal facial expressions, difficulty chewing, difficulty swallowing, difficulty speaking, seizure, sleep disturbances, impaired planning, impaired flexibility, impaired abstract thinking, impaired rule acquisition, impaired initiation of appropriate actions, impaired inhibition of inappropriate actions, impaired short-term memory, impaired long-term memory, paranoia, disorientation, confusion, hallucination, dementia, a anxiety, depression, blunted affect, egocentrisms, aggression, compulsive behavior, irritability, suicidal ideation, reduced brain mass, muscle atrophy, cardiac failure, impaired glucose tolerance, weight loss, osteoporosis, and testicular atrophy in the human.
Specification