SERPINC1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF

Patent metadata

Field	Value
Publication number	US-2021254063-A1
Application number	US-202017129761-A
Country	US
Kind code	A1
Filing date	Dec 21, 2020
Priority date	Apr 26, 2012
Publication date	Aug 19, 2021
Grant date	—

Abstract

The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the Serpinc1 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of Serpinc1 and methods of treating subjects having a bleeding disorder, such as a hemophilia.

First claim

1 . A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of Serpinc1, wherein said dsRNA comprises a sense strand and an antisense strand, wherein said sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:1 and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:5.

2 . A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of Serpinc1, wherein said dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the antisense sequences listed in any one of Tables 3, 4, 8, 11, 12, 14, 15, 20, and 21.

3 . The dsRNA of claim 1 , wherein said dsRNA comprises at least one modified nucleotide.

4 . The dsRNA of claim 1 , wherein the dsRNA comprises a sense strand consisting of a sense strand sequence selected from the sequence of any one of Tables 3, 4, 8, 11, 12, 14, 15, 20, and 21, and an antisense strand consisting of an antisense sequence selected from the sequences of any one of Tables 3, 4, 8, 11, 12, 14, 15, 20, and 21.

5 . A cell containing the dsRNA of claim 1 .

6 . A vector encoding at least one strand of a dsRNA, wherein said dsRNA comprises a region of complementarity to at least a part of an mRNA encoding Serpinc1, wherein said dsRNA is 30 base pairs or less in length, and wherein said dsRNA targets said mRNA for cleavage.

7 . A pharmaceutical composition for inhibiting expression of a Serpinc1 gene comprising the dsRNA of claim 1 .

8 . A method of inhibiting Serpinc1 expression in a cell, the method comprising:
(a) contacting the cell with the dsRNA of claim 1 ; and (b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of a Serpinc1 gene, thereby inhibiting expression of the Serpinc1 gene in the cell.

9 . A method of treating a subject having a disorder that would benefit from reduction in Serpinc1 expression, comprising administering to the subject a therapeutically effective amount of the dsRNA of claim 1 , thereby treating said subject.

10 . A method of preventing at least one symptom in a subject having a disorder that would benefit from reduction in Serpinc1 expression, comprising administering to the subject a therapeutically effective amount of the dsRNA of claim 1 , thereby preventing at least one symptom in the subject having a disorder that would benefit from reduction in Serpinc1 expression.

11 . The method of claim 9 , wherein the disorder is a bleeding disorder.

12 . The method of claim 11 , wherein the bleeding disorder is a hemophilia.

13 . A method of inhibiting the expression of Serpinc1 in a subject, the method comprising
administering to said subject a therapeutically effective amount of the dsRNA of claim 1 , thereby inhibiting the expression of Serpinc1 in said subject.

14 . A method of making the double-stranded ribonucleic acid (dsRNA) of claim 1 , the method comprising:
(a) synthesizing a sense strand of the dsRNA; (b) synthesizing an antisense strand of the dsRNA; and (c) annealing the sense strand and the antisense strand,
thereby making the dsRNA.

15 . The method of claim 14 , wherein step (a) or step (b) comprises synthesizing a sense strand and/or an antisense strand comprising at least one modified RNA nucleotide.

16 . The method of claim 14 , wherein step (a) or step (b) comprises synthesizing a sense strand and/or an antisense strand conjugated with a ligand.

Assignees

• Genzyme Corp

Inventors

• Akinc Akin
• Sehgal Alfica
• Toudjarska Ivanka
• Foster Donald
• Milstein Stuart
• Bettencourt Brian
• Maier Martin A
• Charisse Klaus
• Kuchimanchi Satyanarayana
• Rajeev Kallanthottathil G
• Manoharan Muthiah

Classifications

• 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

• C12N2310/321

  2'-O-R Modification · CPC title

• C12N2310/315

  Phosphorothioates · CPC title

• C12N2310/3525

  MOE, methoxyethoxy · CPC title

• C12N2310/3523

  Allyl · CPC title