Compositions and methods for the treatment of muscle wasting

• US 20080119426A1
• Filed: 06/30/2006
• Published: 05/22/2008
• Est. Priority Date: 06/30/2006
• Status: Active Grant

• Current Assignee: Lakewood Amedex Inc.
• Original Assignee: Lakewood Amedex Inc.
• Inventors: Dale, Roderic M.K.
• Granted Patent: US 8,097,596 B2
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1136 against growth factors, growth regulators, cytokines, lymphokines or hormones
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/351 Conjugate
• CPC Class Codes: C12N 2310/3521 Methyl

Abstract

The invention provides compositions of oligonucleotides targeted at genes involved in muscle wasting and/or muscle growth. In some embodiments, the oligonucleotides are modified. In some embodiments, the compositions contain one, or more than one, oligonucleotide. The invention also provides methods and kits using the compositions of the invention for the treatment of muscle wasting conditions and/or the promotion of muscle growth.

Claims

1. A composition suitable for administration to an animal comprising a modified oligonucleotide containing 7 to 75 contiguous ribose groups linked by achiral 5′

to 3′

internucleoside phosphate linkages, wherein the modified oligonucleotide is complementary to a region of a gene selected from the group consisting of the 5′

UTR region, translational start site, the 3′

UTR, and translational termination site, and wherein the gene codes for a gene product involved in a muscle wasting condition.

2. The composition of claim 1 wherein the modified oligonucleotide has a T_m of about 75-115°

C. at a concentration of 1 mM and a length of 10 to 26 bases, or a T_m of about 40°

C. to 85°

C. at a concentration of 1 pM and a length of 10 to 26 bases.

3. The composition of claim 1 wherein the oligonucleotide comprises a nucleotide selected from the group consisting of ribonucleotides and deoxyribonucleotides.

4. The composition of claim 1 wherein oligonucleotides comprise one or more nucleotides in which the 2′

position comprises a substituent.

5. The composition of claim 4 wherein the 2′

substituent is selected from the group consisting of hydrogen, methoxy, propoxy, methoxy-ethoxy, fluorine, chlorine, bromine and iodine.

6. The composition of claim 1 wherein the modified oligonucleotide is 3′

and/or 5′

end-modified.

7. The composition of claim 1 wherein the modified oligonucleotide is 3′

and/or 5′

end-blocked.

8. The composition of claim 1 wherein the oligonucleotide is an antisense oligonucleotide.

9. The composition of claim 8 wherein the antisense oligonucleotide is complementary to a myostatin gene

10. The composition of claim 9 wherein the myostatin gene is an animal myostatin gene.

11. The composition of claim 9 wherein the myostatin gene is a mammalian myostatin gene.

12. The composition of claim 9 wherein the myostatin gene is a human myostatin gene.

13. The composition of claim 8 wherein the oligonucleotide comprises a sequence selected from the group consisting of SEQ ID NOS 1-191.

14. The composition of claim 1 wherein the oligonucleotide comprises an RNAi, ribozyme or deoxyribozyme.

15. The composition of claims 1 further comprising a plurality of modified oligonucleotides.

16. The composition of claim 15 comprising two modified oligonucleotides.

17. A method of treating a muscle wasting condition comprising administering to an individual suffering from a muscle wasting condition an effective amount of the composition of claim 1.

18. A method of promoting muscle growth in an individual comprising administering to the individual an effective amount of the composition of claim 1.

19. The method of claim 17 or 18 wherein the individual is a mammal.

20. The method of claim 17 or 18 wherein the individual is a human.