Compositions and methods of treating muscle dystrophy

Patent metadata

Field	Value
Publication number	US-11707532-B2
Application number	US-202217818319-A
Country	US
Kind code	B2
Filing date	Aug 8, 2022
Priority date	Mar 27, 2020
Publication date	Jul 25, 2023
Grant date	Jul 25, 2023

Abstract

Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle dystrophy (DM1).

First claim

What is claimed is:

1. A method of treating muscular dystrophy in a subject comprising administering to the subject a therapeutically effective amount of a small interfering RNA (siRNA) conjugate comprising an anti-transferrin receptor antibody or antigen binding fragment thereof conjugated to an siRNA that hybridizes to a target sequence of Dystrophia Myotonica Protein Kinase (DMPK) mRNA, said siRNA comprises a sense strand and an antisense strand,
wherein the sense strand comprises a sequence selected from the group consisting of SEQ ID NOs: 3, 5, 7, 9, 11, 13, and 15, and the antisense strand comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 6, 8, 10, 12, 14, and 16; and
wherein the siRNA conjugate mediates RNA interference against DMPK, thereby treating muscular dystrophy in said subject.

2. The method of claim 1 , wherein the anti-transferrin receptor antibody or antigen binding fragment thereof comprises a humanized antibody, a chimeric antibody or an antigen binding fragment thereof.

3. The method of claim 2 , wherein the anti-transferrin receptor antibody or antigen binding fragment thereof comprises an IgG-scFv, nanobody, diabody, DART, TandAb, scDiabody, scDiabody-CH3, triple body, mini-antibody, minibody, TriBi minibody, scFv-CH3 KIH, Fab-scFv-Fc KIH, Fab-scFv, scFv-CH-CL-scFv, F(ab′)2, F(ab′)2-scFv2, scFv-KIH, Fab-scFv-Fc, tetravalent HCAb, scDiabody-Fc, diabody-Fc, tandem scFv-Fc, or intrabody.

4. The method of claim 1 , wherein the anti-transferrin receptor antibody or antigen binding fragment thereof specifically binds to human transferrin receptor (TfR).

5. The method of claim 1 , wherein the siRNA conjugate comprises a linker connecting the anti-transferrin receptor antibody or antigen binding fragment thereof to the siRNA.

6. The method of claim 1 , wherein the siRNA conjugate is administered parenterally, orally, intranasally, buccally, rectally, intrathecally, intravenously or transdermally.

7. The method of claim 6 , wherein the siRNA conjugate is administered intravenously.

8. The method of claim 1 , wherein the sense strand comprises the sequence of SEQ ID NO: 3 and the antisense strand comprises the sequence of SEQ ID NO: 4.

9. The method of claim 1 , wherein the anti-transferrin receptor antibody or antigen binding fragment thereof is conjugated to the siRNA via a linker.

10. The method of claim 9 , wherein the linker comprises a 4-(N-maleimidomethyl) cyclohexane-1-amidate linker.

11. The method of claim 9 , wherein the linker is conjugated with the sense strand.

12. The method of claim 11 , wherein the linker is conjugated with a 5′ end of the sense strand.

13. The method of claim 9 , wherein the linker comprises a 6-amino-1-hexanol linker.

14. The method of claim 1 , wherein the muscular dystrophy is myotonic dystrophy type 1 (DM1).

Assignees

• Avidity Biosciences Inc

Inventors

• Doppalapudi Venkata Ramana
• Hood Michael David
• Burke Rob
• COCHRAN Michael Caramian
• Darimont Beatrice Diana
• Shi Yunyu
• Marelius Gulin Erdogan
• Malecova Barbora

Classifications

• C12N2310/3521

  Methyl · CPC title

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · CPC title

• C12N2310/3533

  Halogen · CPC title

• C07K16/2881

  against CD71 · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title