IP Library Granted Patent US 8,153,606
Granted Patent B2
US 8,153,606 · App. 12/573,083 · Granted Apr 10, 2012

Treatment of apolipoprotein-A1 related diseases by inhibition of natural antisense transcript to apolipoprotein-A1

Assignee: OPKO CuRNA, LLC
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Quick Facts
Patent No.
US 8,153,606
App. No.
12/573,083
Granted
Apr 10, 2012
Kind
B2
Abstract

Oligonucleotide compounds modulate expression and/or function of an apolipoprotein (ApoA1) polynucleotides and encoded products thereof. Methods for treating diseases associated with apolipoprotein-A1 (ApoA1) comprise administering one or more Oligonucleotide compounds designed to inhibit the Apo-A1 natural antisense transcript to patients.

Claims (18)

1. A method of increasing function and/or expression of an apolipoprotein (ApoA1) polynucleotide in patient cells or tissues to treat a disease or disorder in said patient comprising:

contacting said patient cells or tissues with at least one antisense nucleotide 5 to 30 nucleotides in length that is specific for and is targeted to a 5 to 30 nucleotide region within a non-coding and/or coding sequence of a natural antisense transcript of the apolipoprotein (ApoA1) polynucleotide; thereby increasing function and/or expression of the apolipoprotein (ApoA1) polynucleotide in said patient cells or tissues and wherein the disease or disorder is selected from the group consisting of a cardiovascular disorder, a cholesterol disorder, diabetes, heart disease, arthritis, inflammation, a neurological disease or disorder, an autoimmune disease or disorder and obesity.

2. The method of claim 1 , wherein the expression and/or function of the apolipoprotein (ApoA1) is increased with respect to a control by at least 10%.

3. The method of claim 1 , wherein the at least one antisense oligonucleotide targets a region corresponding to a coding nucleic acid sequence of an apolipoprotein (ApoA1) polynucleotide.

4. The method of claim 1 , wherein the at least one antisense oligonucleotide targets a region corresponding to a non-coding nucleic acid sequence of an apolipoprotein (ApoA1) polynucleotide.

5. The method of claim 1 , wherein the at least one antisense oligonucleotide comprises one or more modifications selected from: at least one modified sugar moiety, at least one modified internucleoside linkage, at least one modified nucleotide, and combinations thereof.

6. The method of claim 5 , wherein the one or more modifications comprise at least one modified sugar moiety selected from: a 2′-O-methoxyethyl modified sugar moiety, a 2′-methoxy modified sugar moiety, a 2′-O-alkyl modified sugar moiety, a bicyclic sugar moiety, and combinations thereof.

7. The method of claim 5 , wherein the one or more modifications comprise at least one modified internucleoside linkage selected from: a phosphorothioate, 2″-O-methoxyethyl (MOE), 2″-fluoro, alkylphosphonate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethylester, and combinations thereof.

8. The method of claim 5 , wherein the one or more modifications comprise at least one modified nucleotide selected from: a peptide nucleic acid (PNA), a locked nucleic acid (LNA), an arabino-nucleic acid (FANA), analogues, derivatives, and combinations thereof.

9. The method of claim 1 wherein the at least one oligonucleotide comprises at least one oligonucleotide having at least 50% sequence identity to the oligonucleotide sequences set forth as SEQ ID NOS: 81-173.

10. A method of increasing an apolipoprotein (ApoA1) gene expression and/or function in mammalian cells or tissues in vivo or in vitro comprising:

contacting said cells or tissues with at least one antisense oligonucleotide of about 5 to 30 nucleotides in length, said at least one antisense oligonucleotide specific for noncoding and/or coding sequences of a sense and/or natural antisense strand of a polynucleotide encoding an apolipoprotein (ApoA1) molecule wherein the antisense oligonucleotide has at least 50% sequence identity to at least one of the nucleic acid sequences set forth as SEQ ID NOS: 81-173; and

Increasing an apolipoprotein (ApoA1) gene expression and/or function in mammalian cells or tissues in vivo or in vitro.

11. A method of preventing or treating a disease or disorder associated with at least one apolipoprotein (ApoA1) polynucleotide and/or at least one encoded product thereof, comprising:

administering to a patient a therapeutically effective dose of at least one antisense oligonucleotide that targets a region within a non-coding and/or coding natural antisense transcript of the ApoA1 polynucleotide thereby increasing expression of said at least on apolipoprotein (ApoA1) polynucleotide and/or expression product thereof; thereby preventing or treating a disease or disorder associated with the at least one apolipoprotein (ApoA1) polynucleotide and/or at least one encoded product thereof wherein the disease or disorder is selected from the group consisting of a cardiovascular disorder, a cholesterol disorder, diabetes, heart disease, arthritis, inflammation, a neurological disease or disorder, an autoimmune disease or disorder and obesity.

12. The method of claim 11 , wherein the disease or disorder associated with the at least one apolipoprotein (ApoA1) polynucleotide is selected from: a cardiovascular disorder, a cholesterol disorder, diabetes or heart disease, and/or obesity.

13. The method according to claim 1 wherein the oligonucleotides comprises sequences as set forth in SEQ ID NOS: 81-173.

14. The method according to claim 11 wherein the natural antisense transcript comprises a sequence set forth as SEQ ID NO: 2.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 8, 2013
From: COLLARD, JOSEPH; KHORKOVA SHERMAN, OLGA
To: CURNA, INC.
Reel/Frame 030751/0769 →
MERGER Recorded May 23, 2011
From: CURNA, INC.
To: OPKO CURNA, LLC
Reel/Frame 026324/0984 →
Continuity (4)
Provisional Application 61102681 · Oct 3, 2008
Provisional Application 61152236 · Feb 12, 2009
Provisional Application 61176267 · May 7, 2009
Related Publication 20100105760A1 · Apr 29, 2010