Treatment of atonal homolog 1 (ATOH1) related diseases by inhibition of natural antisense transcript to ATOH1

• US 10,253,320 B2
• Filed: 04/09/2018
• Issued: 04/09/2019
• Est. Priority Date: 05/26/2010
• Status: Active Grant

• Current Assignee: CURNA, Inc. (Opko Health, Inc.)
• Original Assignee: CURNA, Inc. (Opko Health, Inc.)
• Inventors: Collard, Joseph, Khorkova Sherman, Olga
• Primary Examiner(s): Bowman, Amy H
• Application Number:
  US15/948,525
• Publication Number:
  US 20180230468A1
• Time in Patent Office: 365 Days
• CPC Class Codes: A61K 31/7125 Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 2/00 Peptides of undefined number of amino acids; Derivatives thereof
• 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 2310/11 Antisense
• CPC Class Codes: C12N 2310/111 spanning the whole gene, or a large part of it
• CPC Class Codes: C12N 2310/113 targeting other non-coding nucleic acids, e.g. antagomirs
• CPC Class Codes: C12N 2310/312 Phosphonates
• CPC Class Codes: C12N 2310/313 Phosphorodithioates
• CPC Class Codes: C12N 2310/314 : Phosphoramidates
• CPC Class Codes: C12N 2310/315 : Phosphorothioates
• CPC Class Codes: C12N 2310/321 : 2'-O-R Modification
• CPC Class Codes: C12N 2310/322 : 2'-R Modification
• CPC Class Codes: C12N 2310/3231 : having an additional ring, e.g. LNA, ENA
• CPC Class Codes: C12N 2310/3521 : Methyl
• CPC Class Codes: C12N 2310/3525 : MOE, methoxyethoxy
• CPC Class Codes: C12N 2310/3533 : Halogen
• CPC Class Codes: C12N 2330/10 : naturally occurring
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Atonal homolog 1 (ATOH1), in particular, by targeting natural antisense polynucleotides of Atonal homolog 1 (ATOH1). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of ATOH1.

Claims

1. A method of upregulating a function of and/or the expression of an Atonal homolog 1 (ATOH1) polynucleotide having SEQ ID NO:

1 in mammalian cells or tissues in vivo or in vitro comprising;

contacting said cells or tissues with at least one short interfering RNA (siRNA) oligonucleotide 19 to 30 nucleotides in length, said at least one siRNA oligonucleotide being at least 95% complementary to and specific for a natural antisense polynucleotide of an Atonal homolog 1 (ATOH1) polynucleotide having SEQ ID NO;

2 and, wherein said siRNA oligonucleotide upregulates a function of and/or the expression of Atonal homolog 1 (ATOH1) gene in mammalian cells or tissues in vivo or in vitro.

2. The method of claim 1, wherein said oligonucleotide has 100% sequence complementarity to a sequence of at least about 19 consecutive nucleic acids on a natural antisense polynucleotide of the Atonal homolog 1 (ATOH1) polynucleotide having SEQ ID NO:

2.

3. The method according to claim 2 wherein the at least one siRNA specifically hybridizes to a non-overlapping region of said natural antisense polynucleotide wherein said non-overlapping region is non-overlapping with the mRNA of said ATOH1 gene.

4. The method of claim 3 wherein the function or expression of said ATOH1 gene is increased relative to a mock-transfected control.

5. The method of claim 1 wherein the siRNA is 19-27 nucleotides in length.

6. The method according to claim 5 wherein the siRNA has a sequence selected from SEQ ID NO:

3 or 4.