Granted Patent B1

US 12,648,998 · App. 19/234,136 · Granted Jun 9, 2026

Inventors: Beatrice Diana Darimont (San Diego, CA); Usue Etxaniz Irigoien (San Diego, CA); Venkata Ramana Doppalapudi (San Diego, CA); Michael Caramian Cochran (Palo Alto, CA); Isaac Marks (San Diego, CA); Tyler Albin (Encinitas, CA)

Assignee: Avidity Biosciences, Inc.

A61K47/6807A61K47/6849A61K47/6889C07K16/2881

Abstract

Claims (28)

1 . A conjugate comprising (i) an anti-transferrin receptor antibody or antigen binding fragment thereof, (ii) a phosphorodiamidate morpholino oligonucleotide (PMO), and (iii) a linker,

wherein the anti-transferrin receptor antibody or antigen binding fragment thereof comprises a variable heavy chain (VH) region, which comprises an HCDR1 comprising the sequence of SEQ ID NO: 17; an HCDR2 comprising the sequence of SEQ ID NO: 20; and an HCDR3 comprising the sequence of SEQ ID NO: 19;

wherein the anti-transferrin receptor antibody or antigen binding fragment thereof comprises a variable light chain (VL) region, which comprises a LCDR1 comprising the sequence of SEQ ID NO: 22; a LCDR2 comprising the sequence of SEQ ID NO: 23; and a LCDR3 comprising the sequence of SEQ ID NO: 24;

wherein the PMO comprises the sequence of SEQ ID NO: 118; and

wherein the linker comprises a maleimide group that conjugates the anti-transferrin receptor antibody or antigen binding fragment thereof to a terminus of the PMO.

2 . The conjugate of claim 1 , wherein the maleimide group is succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC).

3 . The conjugate of claim 1 , wherein the linker conjugates the anti-transferrin receptor antibody or antigen binding fragment thereof to the 3′ end terminus of the PMO.

4 . The conjugate of claim 1 , wherein the anti-transferrin receptor antibody or antigen binding fragment thereof is a full-length antibody.

5 . The conjugate of claim 4 , wherein the full-length antibody is a humanized antibody or a human antibody.

6 . The conjugate of claim 4 , wherein the full-length anti-transferrin receptor antibody further comprises a mutation in the heavy chain constant region selected from the group consisting of L233A, and L234A.

7 . The conjugate of claim 6 , wherein the full-length anti-transferrin receptor antibody further comprises the L233A, and L234A mutations in the heavy chain constant region.

8 . The conjugate of claim 1 , wherein the anti-transferrin receptor antibody or antigen binding fragment thereof is selected from the group consisting of monovalent Fab′, divalent Fab2, and single chain variable fragment (scFv).

9 . A conjugate comprising (i) an anti-transferrin receptor antibody or antigen binding fragment thereof, (ii) a phosphorodiamidate morpholino oligonucleotide (PMO), and (iii) a linker,

wherein the anti-transferrin receptor antibody or antigen binding fragment thereof comprises a variable heavy chain (VH) sequence of SEQ ID NO: 30 and a variable light chain (VL) sequence of SEQ ID NO: 34;

wherein the PMO comprises the sequence of SEQ ID NO: 118; and

wherein the linker comprises a maleimide group that conjugates the anti-transferrin receptor antibody or antigen binding fragment thereof to a terminus of the PMO.

10 . The conjugate of claim 9 , wherein the maleimide group is succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC).

11 . The conjugate of claim 9 , wherein the linker conjugates the anti-transferrin antibody or antigen binding fragment thereof to the 3′ end terminus of the PMO.

12 . The conjugate of claim 9 , wherein the anti-transferrin receptor antibody or antigen binding fragment thereof is a full-length anti-transferrin receptor antibody.

13 . The conjugate of claim 12 , wherein the full-length anti-transferrin receptor antibody is a humanized anti-transferrin receptor antibody or a human anti-transferrin receptor antibody.

14 . The conjugate of claim 12 , wherein the full-length anti-transferrin receptor antibody further comprises a mutation in the heavy chain constant region selected from the group consisting of L233A, and L234A.

15 . The conjugate of claim 14 , wherein the full-length anti-transferrin receptor antibody further comprises the L233A, and L234A mutations in the heavy chain constant region.

16 . The conjugate of claim 9 , wherein the anti-transferrin receptor antibody or antigen binding fragment thereof is selected from the group consisting of monovalent Fab′, divalent Fab2, and single chain variable fragment (scFv).

17 . A conjugate comprising (i) an anti-transferrin receptor antibody, (ii) a phosphorodiamidate morpholino oligonucleotide (PMO), and (iii) a linker,

wherein the anti-transferrin receptor antibody comprises (a) two heavy chains, wherein each of the two heavy chains comprises SEQ ID NO: 48, and (b) two light chains, wherein each of the two light chains comprises SEQ ID NO: 63;

wherein the PMO comprises the sequence of SEQ ID NO: 118; and

wherein the linker comprises a maleimide group that conjugates the anti-transferrin receptor antibody to the 3′ terminus of the PMO.

18 . The conjugate of claim 17 , wherein the maleimide group is succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC).

Assignments (2)

Continuity (3)

References Cited (362)