Compositions and methods for the treatment of muscle wasting

• US 8,097,596 B2
• Filed: 06/30/2006
• Issued: 01/17/2012
• Est. Priority Date: 06/30/2006
• Status: Active Grant

• Current Assignee: Lakewood Amedex Inc.
• Original Assignee: Lakewood Amedex Inc.
• Inventors: Dale, Roderic M. K.
• Primary Examiner(s): ANGELL, JON E
• Application Number:
  US11/479,112
• Publication Number:
  US 20080119426A1
• Time in Patent Office: 2,027 Days
• Field of Search: 514/44.R
• US Class Current: 514/44.R
• 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 method of treating a muscle wasting condition comprising administering to an individual suffering from a muscle wasting condition an effective amount of 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 encodes FOXO1.

3. The method of claim 1 or 2 wherein the individual is a mammal.

4. The method of claim 1 or 2 wherein the individual is a human.

5. The method of claim 1, wherein the modified oligonucleotide comprises one or more nucleotides in which the 2′

position comprises a substituent.

6. The method of claim 5, wherein the 2′

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

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

and/or 5′

end-modified.

8. The method of claim 1, wherein the modified oligonucleotide is 3′

and/or 5′

end-blocked.

9. The method of claim 1, wherein the modified oligonucleotide is an antisense oligonucleotide.

10. The method of claims 1, further comprising a plurality of modified oligonucleotides containing 7 to 75 contiguous ribose groups linked by achiral 5′

to 3′

internucleoside phosphate linkages, wherein the plurality of modified oligonucleotides are complementary to regions 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 said gene codes for a gene product involved in a muscle wasting condition.

11. The method of claim 1, further comprising two modified oligonucleotides containing 7 to 75 contiguous ribose groups linked by achiral 5′

to 3′

internucleoside phosphate linkages, wherein said modified oligonucleotides are complementary to regions 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 said gene codes for a gene product involved in a muscle wasting condition.

12. The method of claim 1, wherein said oligonucleotide comprises one or more nucleotides in which the 2′

position comprises a substituent, and wherein the modified oligonucleotide is 3′ and

/or 5′

end-blocked.

2. A method of promoting muscle growth in an individual comprising administering to the individual an effective amount of 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 encodes FOXO1.

13. The method of claim 2, wherein said oligonucleotide comprises one or more nucleotides in which the 2′

position comprises a substituent, and wherein the modified oligonucleotide is 3′ and

5′

end-blocked.