Modulation of growth hormone receptor expression and insulin-like growth factor expression
AssigneesIsis Pharmaceuticals, Inc., Antisense Therapeutics Limited
InventorsGeorge Tachas, Kenneth W Dobie, Ravi Jain, Christopher I Belyea, Mark A Heffernan
Life of this patent
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Abstract
Compounds, compositions and methods are provided for modulating the expression of growth hormone receptor and/or insulin like growth factor-I (IGF-I). The compositions comprise oligonucleotides, targeted to nucleic acid encoding growth hormone receptor. Methods of using these compounds for modulation of growth hormone receptor expression and for diagnosis and treatment of disease associated with expression of growth hormone receptor and/or insulin-like growth factor-I are provided. Diagnostic methods and kits are also provided.
Claims22
A method of reducing the plasma level of insulin-like growth factor-1 in an animal comprising:
- identifying an animal in need of a reduction in said animal's plasma level of insulin-like growth factor-1;
- and
- administering to said animal in need thereof a modified oligonucleotide 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 nucleobases in length, wherein said modified oligonucleotide is fully complementary over the entirety of said modified oligonucleotide with a human growth hormone receptor RNA, wherein said modified oligonucleotide comprises at least one modified internucleoside linkage, modified sugar moiety, or modified nucleobase, and wherein the expression of growth hormone receptor in said animal is inhibited and said animal's plasma level of insulin-like growth factor-1 is reduced.
A method of reducing the plasma level of insulin-like growth factor-1 in an animal comprising:
- administering to said animal a modified oligonucleotide 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 nucleobases in length, wherein said modified oligonucleotide is fully complementary over the entirety of said modified oligonucleotide with a nucleic acid molecule having a sequence selected from the group consisting of SEQ ID NOs:
- 4 and 18, wherein said modified oligonucleotide comprises at least one modified internucleoside linkage, modified sugar moiety, or modified nucleobase, wherein the expression of growth hormone receptor in said animal is inhibited and said animal's plasma level of insulin-like growth factor-1 is reduced, and wherein said modified oligonucleotide comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 19, 22, 23, 24, 25, 28, 29, 30, 31, 32, 34, 35, 37, 40, 44, 45, 48, 51, 52, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 66, 67, 68, 69, 71, 73, 74, 75, 76, 79, 81, 82, 84, 85, 87, 88, 89, 91, 92, and 94.
A method of reducing the plasma level of insulin-like growth factor-1 in an animal comprising:
- administering to said animal a modified oligonucleotide 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 nucleobases in length, wherein said modified oligonucleotide is fully complementary over the entirety of said modified oligonucleotide with a nucleic acid molecule having a sequence selected from the group consisting of SEQ ID NOs:
- 4 and 18, wherein said modified oligonucleotide comprises at least one modified internucleoside linkage, modified sugar moiety, or modified nucleobase, wherein the expression of growth hormone receptor in said animal is inhibited and said animal's plasma level of insulin-like growth factor-1 is reduced, and wherein said modified oligonucleotide is fully complementary to a nucleotide sequence within the range of nucleotides 332 to 351 of SEQ ID NO:4.
Dependencies are inferred from the claim text.