Anti-transferrin receptor antibody-PMO conjugates for inducing DMD exon 44 skipping
AssigneeAvidity Biosciences, Inc.
InventorsBeatrice Diana Darimont, Usue Etxaniz Irigoien, Venkata Ramana Doppalapudi, Michael Caramian Cochran, Isaac Marks, Tyler Albin
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Abstract
Disclosed herein are antibody oligonucleotide conjugates and pharmaceutical compositions that induce an alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping. Also described herein include methods for treating muscle dystrophy including Duchenne muscular dystrophy that comprises administering antibody oligonucleotide conjugates or a pharmaceutical composition that induces alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping.
Claims18
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.
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.
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.
Dependencies are inferred from the claim text.