Means for inhibiting the expression of ANG2

Patent metadata

Field	Value
Publication number	US-9458461-B2
Application number	US-201414289916-A
Country	US
Kind code	B2
Filing date	May 29, 2014
Priority date	Feb 18, 2009
Publication date	Oct 4, 2016
Grant date	Oct 4, 2016

Abstract

The present invention is related to an siRNA comprising an antisense strand and a sense strand, wherein all or a portion of said antisense strand comprises an antisense duplex region, wherein all or a portion of said sense strand comprises a sense duplex region, wherein said antisense duplex region is at least partially complementary to said sense duplex region, wherein said siRNA comprises a duplex region consisting of said antisense duplex region and said sense duplex region, and wherein: a) said antisense strand comprises a nucleotide sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 68, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102 or 104; or b) said antisense strand comprises an antisense duplex region, all or a portion of which, is complementary to a portion of SEQ ID NO: 1 or 70.

First claim

We claim:

1. A method for treating a disease in a subject, the method comprising the administration of a therapeutically effective amount of a composition comprising an siRNA molecule to the subject, wherein the siRNA molecule comprises:
an antisense strand and a sense strand, wherein all or a portion of said antisense strand comprises an antisense duplex region and all or a portion of said sense strand comprises a sense duplex region, wherein said antisense duplex region is at least partially complementary to said sense duplex region, wherein said siRNA comprises a duplex region consisting of said antisense duplex region and said sense duplex region, and wherein:
the antisense strand is between 19 and 25 nucleotides in length and the sense strand is between 19 and 25 nucleotides in length, and said duplex region consists of 16 to 19 nucleotides and the duplex region of the sense strand and antisense strand being perfectly complementary or the duplex region contains 1 to 5 nucleotides that do not base pair, where one or more alternating nucleotides on the sense and/or antisense strands are modified, and said siRNA has the following antisense and sense strand combinations: SEQ ID NOs: 4 and 5; SEQ ID NOs: 6 and 7; SEQ ID NOs: 12 and 13; SEQ ID NOs: 14 and 15; SEQ ID NOs: 16 and 17; SEQ ID NOs: 18 and 19; and SEQ ID NOs: 22 and 23; and
the disease is selected from the group consisting of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pneumonia, pulmonary fibrosis, emphysema, or chronic obstructive pulmonary disease (COPD).

2. A method of treating pneumonia in a human, the method comprising the administration of a therapeutically effective amount of a composition comprising an siRNA molecule to the human, wherein the siRNA molecule comprises:
an antisense strand and a sense strand, wherein all or a portion of said antisense strand comprises an antisense duplex region and all or a portion of said sense strand comprises a sense duplex region, wherein said antisense duplex region is at least partially complementary to said sense duplex region, wherein said siRNA comprises a duplex region consisting of said antisense duplex region and said sense duplex region, and wherein:
the antisense strand is between 19 and 25 nucleotides in length and the sense strand is between 19 and 25 nucleotides in length, and said duplex region consists of 16 to 19 nucleotides and the duplex region of the sense strand and antisense strand being perfectly complementary or the duplex region contains 1 to 5 nucleotides that do not base pair, where one or more alternating nucleotides on the sense and/or antisense strands are modified, and said siRNA has the following antisense and sense strand combinations: SEQ ID NOs: 4 and 5; SEQ ID NOs: 6 and 7; SEQ ID NOs: 12 and 13; SEQ ID NOs: 14 and 15; SEQ ID NOs: 16 and 17; SEQ ID NOs: 18 and 19; and SEQ ID NOs: 22 and 23.

3. The method of claim 1 , wherein said duplex region is 16 nucleotides in length and has 1, 2, 3, 4 or 5 nucleotides that do not base pair.

4. The method of claim 1 , wherein said duplex region is 17 nucleotides in length and has 1, 2, 3, 4 or 5 nucleotides that do not base pair.

5. The method of claim 1 , wherein said duplex region is 18 nucleotides in length and has 1, 2, 3, 4 or 5 nucleotides that do not base pair.

6. The method of claim 1 , wherein said duplex region is 19 nucleotides in length and has 1, 2, 3, 4 or 5 nucleotides that do not base pair.

7. The method of claim 2 , wherein said duplex region is 16 nucleotides in length and has 1, 2, 3, 4 or 5 nucleotides that do not base pair.

8. The method of claim 2 , wherein said duplex region is 17 nucleotides in length and has 1, 2, 3, 4 or 5 nucleotides that do not base pair.

9. The method of claim 2 , wherein said duplex region is 18 nucleotides in length and has 1, 2, 3, 4 or 5 nucleotides that do not base pair.

10. The method of claim 2 , wherein said duplex region is 19 nucleotides in length and has 1, 2, 3, 4 or 5 nucleotides that do not base pair.

11. The method of claim 1 , wherein the disease is acute lung injury (ALI).

12. The method of claim 1 , wherein the disease is acute respiratory distress syndrome (ARDS).

13. The method of claim 1 , wherein the disease is pulmonary fibrosis.

14. The method of claim 1 , wherein the disease is emphysema.

15. The method of claim 1 , wherein the disease is chronic obstructive pulmonary disease (COPD).

Assignees

• Silence Therapeutics Gmbh

Inventors

• Santel Ansgar
• Kaufmann Jörg
• Witzenrath Martin

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title