Compositions and methods of treating muscle dystrophy

Patent metadata

Field	Value
Publication number	US-11446387-B2
Application number	US-202117214525-A
Country	US
Kind code	B2
Filing date	Mar 26, 2021
Priority date	Mar 27, 2020
Publication date	Sep 20, 2022
Grant date	Sep 20, 2022

Abstract

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

First claim

What is claimed is:

1. A small interfering RNA (siRNA) molecule conjugate comprising an anti-transferrin receptor antibody or antigen binding fragment thereof conjugated to a siRNA molecule that hybridizes to a target sequence of DMPK mRNA;
wherein the sense strand of the siRNA comprises the sequence selected from the group consisting of SEQ ID NOs: 3, 5, 7, 9, 11, 13, and 15, and the antisense strand of the siRNA comprises the sequence selected from the group consisting of SEQ ID NOs:
4, 6, 8, 10, 12, 14, and 16; and
wherein the siRNA molecule conjugate mediates RNA interference against DMPK.

2. The siRNA molecule conjugate of claim 1 , wherein the anti-transferrin receptor antibody or antigen binding fragment thereof comprises a humanized antibody or antigen binding fragment thereof, a chimeric antibody or antigen binding fragment thereof, or a multi-specific antibody or antigen binding fragment thereof.

3. The siRNA molecule conjugate of claim 2 , wherein the anti-transferrin receptor antibody or antigen binding fragment thereof comprises an IgG-scFv, nanobody, BiTE, 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 siRNA molecule conjugate of claim 1 , wherein the anti-transferrin receptor antibody or antigen binding fragment thereof specifically binds to human transferrin receptor (TfR).

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

6. A pharmaceutical composition comprising:
a. the siRNA molecule conjugate of claim 1 ; and
b. a pharmaceutically acceptable excipient.

7. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is formulated for parenteral, oral, intranasal, buccal, rectal, intrathecal, or transdermal administration.

8. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is formulated for intravenous administration.

9. The siRNA molecule conjugate of claim 1 , wherein siRNA comprises the sense strand comprising SEQ ID NO:3 and the antisense sequence comprising SEQ ID NO: 4.

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

11. The siRNA molecule conjugate of claim 10 , wherein the linker comprises a 4-(N-maleimidomethyl) cyclohexane-1-amidate linker.

12. The siRNA molecule conjugate of claim 10 , wherein the linker is conjugated with the sense strand of the siRNA molecule.

13. The siRNA molecule conjugate of claim 12 , wherein the linker is conjugated with the 5′ end of the sense strand of the siRNA molecule.

14. The siRNA molecule conjugate of claim 10 , wherein the linker comprises a 6-Amino-1-hexanol linker.

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