Non-ionic, low osmolar contrast agents for delivery of antisense oligonucleotides and treatment of disease

Patent metadata

Field	Value
Publication number	US-9725716-B2
Application number	US-201214363670-A
Country	US
Kind code	B2
Filing date	Dec 6, 2012
Priority date	Dec 6, 2011
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

Abstract

Disclosed are compositions comprising an antisense oligonucleotide and a non-ionic, low-osmolar contrast agent. Also disclosed are methods of delivering an antisense oligonucleotide to a target sire comprising incorporating the antisense oligonucleotide into a composition comprising a non-ionic, low-osmolar contrast agent. Also disclosed are methods of treating a neurodegenerative disease comprising administering one or more of the compositions disclosed herein.

First claim

What is claimed is:

1. A composition comprising an antisense oligonucleotide complexed to a non-ionic, low-osmolar contrast agent.

2. The composition of claim 1 , wherein the low-osmolar contrast agent is iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol or ioxilan.

3. The composition of claim 2 , wherein the non-ionic, low-osmolar contrast agent is iohexol.

4. The composition of claim 1 , wherein the antisense oligonucleotide is a morpholino, siRNA, or shRNA.

5. The composition of claim 4 , wherein the antisense oligonucleotide disrupts translation, binds to a target nucleotide, induces exon skipping, blocks an intron splice silencer, blocks an exon splice enhancer, binds to a repeat nucleotide sequence, or blocks binding to a sequence in toxic RNA.

6. The composition of claim 1 , wherein the antisense oligonucleotide is a morpholino that binds to a survival motor neuron (SMN) gene, a mutated SOD1 gene, C9orf72 repeats, alpha-synuclein, dystrophia myotonic protein kinase gene (DMPK) repeats, Zinc Finger Protein 9 (ZNF9) repeats, a negative regulatory element in intro 6 or intron 7 of SMN2.

7. The composition of claim 1 , wherein the morpholino comprises the sequence set forth in SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7.

8. A method of delivering an antisense oligonucleotide to a tissue, organ, or system in a subject comprising administering to the subject the composition of claim 1 .

9. A method of treating a neurological disease in a patient in need thereof comprising administering to the patient the composition of claim 1 .

10. The method of claim 9 , wherein the neurological disease is selected from the group consisting of Alzheimer's disease, Spinal muscular atrophy (SMA), Myotonic dystrophy, Huntington's disease, Parkinson's disease, Spinocerebellar degeneration, Spinocerebellar ataxia, Friedreich's ataxia, Ataxia telangiectasia, amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, Vasomotor ataxia, Vestibulocerebellar, Ataxiadynamia, Ataxiophemia, Amyotrophic lateral sclerosis, and Olivopontocerebellar atrophy.

Assignees

• Ohio State Innovation Foundation
• Res Inst At Nationwide Children'S Hospital
• Ohio State Innovation Found And Res Inst At Nationwide Children'S Hospital

Inventors

• Burghes Arthur
• Porensky Paul
• Kaspar Brian

Classifications

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K9/0085

  Brain, e.g. brain implants; Spinal cord · CPC title

• A61K47/24

  containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids · CPC title

• C12N15/113 Primary

  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 title

• A61K31/711

  Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links · CPC title