Enhanced antisense modulation of ICAM-1
First Claim
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1. An antisense oligonucleotide comprising from about 8 to about 30 nucleotides connected by covalent linkages, wherein said antisense oligonucleotide comprises a nucleobase sequence specifically hybridizable with a nucleic acid encoding a human intercellular adhesion molecule-1, wherein said antisense compound modulates the expression of said human intercellular adhesion molecule-1 and wherein said oligonucleotide comprises at least one 2'"'"'-modification.
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Abstract
The present invention provides compositions and methods for detecting and modulating levels of intercellular adhesion molecule-1 (ICAM-1) proteins, including human ICAM-1.
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Citations
27 Claims
- 1. An antisense oligonucleotide comprising from about 8 to about 30 nucleotides connected by covalent linkages, wherein said antisense oligonucleotide comprises a nucleobase sequence specifically hybridizable with a nucleic acid encoding a human intercellular adhesion molecule-1, wherein said antisense compound modulates the expression of said human intercellular adhesion molecule-1 and wherein said oligonucleotide comprises at least one 2'"'"'-modification.
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10. An antisense oligonucleotide that modulates the expression of human intercellular adhesion molecule-1, wherein said oligonucleotide has the structure:
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GsCsCsCsAsAsGsCsTsGsGsCsAsTsCsGsTsCsA, wherein; "s" is a phosphorothioate linkage; "A", "C", "T" and "G" are 2'"'"'-deoxy-adenoine, cytidine, thymidine and guanosine nucleoside residues, respectively; "A" is an adenosine nucleoside residue comprising a 2'"'"' modification; "T" is a thymidine nucleoside residue comprising a 2'"'"' modification; "G" is a guanosine nucleoside residue comprising a 2'"'"' modification; and "C" is a 5-methyl-cytidine nucleoside residue comprising a 2'"'"' modification. - View Dependent Claims (11, 12, 13)
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14. An antisense oligonucleotide that modulates the expression of human intercellular adhesion molecule-1, wherein said oligonucleotide is ISIS 14725 having the structure:
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GsCsCsCsAsAsGsCsTsGsGsCsAsTsCsCsGsTsCsA, wherein; "s" is a phosphorothioate linkage; "A", "C", "T" and "G" are 2'"'"'-deoxy-adenosine, cytidine, thymidine and guanosine nucleoside residues, respectively; "A" is a 2'"'"'-methoxyethoxy adenosine nucleoside residue; "T" is a 2'"'"'-methoxyethoxy thymidine nucleoside residue; "G" is a 2'"'"'-methoxyethoxy guanosine nucleoside residue; and "C" is a 2'"'"'-methoxyethoxy 5-methyl-cytidine nucleoside residue. - View Dependent Claims (15)
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16. An antisense oligonucleotide that modulates the expression of human intercellular adhesion molecule-1, wherein said oligonucleotide is ISIS 15839 having the structure:
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GsCsCsCsAsAsGsCsTsGsGsCsAsTsCsGsTsCsA, wherein; "s" is a phosphorothioate linkage; "A", "T" and "G" are 2'"'"'-deoxy-adenosine, thymidine and guanosine nucleoside residues, respectively; "C" is a 2'"'"'-deoxy-5-methyl-cytidine nucleoside residue; "A"is a 2'"'"'-methoxyethoxy adenosine nucleoside residue; "T" is a 2'"'"'-methoxyethoxy thymidine nucleoside residue; "G" is a 2'"'"'-methoxyethoxy guanosine nucleoside residue; and "C" is a 2'"'"'-methoxyethoxy 5-methyl-cytidine nucleoside residue. - View Dependent Claims (17)
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18. An antisense oligonucleotide that modulates the expression of human intercellular adhesion molecule-1, wherein said oligonucleotide is ISIS 16824 having the structure:
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CsCsAsAsGsCsTsGsGsCsAsTsCsCsGsTsCsA, wherein; "s" is a phosphorothioate linkage; "A", "C", "T" and "G" are 2'"'"'-deoxy-adenosine, cytidine, thymidine and guanosine nucleoside residues, respectively; "A" is a 2'"'"'-methoxyethoxy adenosine nucleoside residue; "T" is a 2'"'"'-methoxyethoxy thymidine nucleoside residue; "G" is a 2'"'"'-methoxyethoxy guanosine nucleoside residue; and "C" is a 2'"'"'-methoxyethoxy 5-methyl-cytidine nucleoside residue. - View Dependent Claims (19)
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20. An antisense oligonucleotide that modulates the expression of human intercellular adhesion molecule-1, wherein said oligonucleotide is ISIS 16823 having the structure:
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AsAsGsCsTsGsGsCsAsTsCsCsGsTsCsA, wherein; "s" is a phosphorothioate linkage; "A", "C", "T" and "G" are 2'"'"'-deoxy-adenosine, cytidine, thymidine and guanosine nucleoside residues, respectively; "A" is a 2'"'"'-methoxyethoxy adenosine nucleoside residue; "T" is a 2'"'"'-methoxyethoxy thymidine nucleoside residue; "G" is a 2'"'"'-methoxyethoxy guanosine nucleoside residue; and "C" is a 2'"'"'-methoxyethoxy 5-methyl-cytidine nucleoside residue. - View Dependent Claims (21)
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22. An antisense oligonucleotide that modulates the expression of human intercellular adhesion molecule-1, wherein said oligonucleotide is ISIS 16158 having the structure:
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GsTsGsCsCsCsAsAsGsCsTsGsGsCsAsTsCsCsGsT, wherein; "s" is a phosphorothioate linkage; "A", "C", "T" and "G" are 2'"'"'-deoxy-adenosine, cytidine, thymidine and guanosine nucleoside residues, respectively; "A" is a 2'"'"'-methoxyethoxy adenosine nucleoside residue; "T" is a 2'"'"'-methoxyethoxy thymidine nucleoside residue; "G" is a 2'"'"'-methoxyethoxy guanosine nucleoside residue; and "C" is a 2'"'"'-methoxyethoxy 5-methyl-cytidine nucleoside residue. - View Dependent Claims (23)
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24. An antisense oligonucleotide that modulates the expression of human intercellular adhesion molecule-1, wherein said oligonucleotide is ISIS 16159 having the structure:
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AsGsCsAsGsTsGsTsGsCsCsCsAsAsGsCsTsGsGsCsAsT, wherein; "s" is a phosphorothioate linkage; "A", "C", "T" and "G" are 2'"'"'-deoxy-adenosine, cytidine, thymidine and guanosine nucleoside residues, respectively; "A" is a 2'"'"'-methoxyethoxy adenosine nucleoside residue; "T" is a 2'"'"'-methoxyethoxy thymidine nucleoside residue; "G" is a 2'"'"'-methoxyethoxy guanosine nucleoside residue; and "C" is a 2'"'"'-methoxyethoxy 5-methyl-cytidine nucleoside residue. - View Dependent Claims (25)
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26. An antisense oligonucleotide comprising from about 8 to about 30 nucleotides connected by covalent linkages, wherein said antisense oligonucleotide comprises at least an 8 nucleobase portion of SEQ ID NO:
- 3, 11, 20 or 22, and wherein said antisense oligonucleotide encodes a murine intercellular adhesion molecule-1 and modulates the expression of the murine intercellular adhesion molecule-1.
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27. An antisense oligonucleotide that modulates the expression of murine intercellular adhesion molecule-1, wherein said oligonucleotide is ISIS 17481 having the structure:
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TsCsCsCsAsCsAsGsCsAsGsCsTsTsGsCsAsCsGsA, wherein; "s" is a phosphorothioate linkage; "A", "T" and "G" are 2'"'"'-deoxy-adenosine, thymidine and guanosine nucleoside residues, respectively; "C" is a 2'"'"'-deoxy-5-methyl-cytidine nucleoside residue; "A" is a 2'"'"'-methoxyethoxy adenosine nucleoside residue; "T" is a 2'"'"'-methoxyethoxy thymidine nucleoside residue; "G" is a 2'"'"'-methoxyethoxy guanosine nucleoside residue; and "C" is a 2'"'"'-methoxyethoxy 5-methyl-cytidine nucleoside residue.
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Specification