Granted Patent B2

US 12,364,769 · App. 17/364,765 · Granted Jul 22, 2025

Inventors: Andrew John Geall (Carlsbad, CA); Venkata Ramana Doppalapudi (San Diego, CA); Joel Daniel Arias (San Diego, CA); David Sai-Ho Chu (San Diego, CA); Michael Caramian Cochran (La Jolla, CA); Rob Burke (Encinitas, CA); Philip Kovach (San Diego, CA); Barbora Malecova (San Diego, CA)

Assignee: AVIDITY BIOSCIENCES, INC.

A61K47/6807A61K31/713A61K47/60A61K47/64A61K47/6811A61K47/6849A61K47/6883A61P35/00C07H17/00C07K16/2863C12N15/113C12N2310/312C12N2310/3125C12N2310/315C12N2310/3513C12N2310/3515

Abstract

Claims (16)

1. A polynucleotide conjugate molecule comprising a binding moiety, a polynucleotide, a linker selected from succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) or bis-maleimide (BisMal);

wherein the polynucleotide comprises at least one 5′-vinylphosphonate modified non-natural nucleotide, and at least one modified internucleotide linkage or at least one inverted abasic moiety; and wherein the at least one 5′-vinylphosphonate modified non-natural nucleotide is

wherein B is a heterocyclic base moiety;

wherein the polynucleotide comprises a double-stranded polynucleic acid molecule comprising a guide strand and a passenger strand, wherein the at least one 5′-vinylphosphonate modified non-natural nucleotide is located at 5′-terminus of the guide strand and the binding moiety is conjugated to 5′-terminus of the passenger strand; and

wherein the binding moiety is an antibody or antigen binding fragment thereof that recognizes a cell surface protein.

2. The molecule of claim 1 , wherein the at least one modified internucleotide linkage comprises a phosphorothioate linkage, a phosphorodithioate linkage, a phosphorodiamidate linkage, a methylphosphonate linkage, or an amide linkage.

3. The molecule of claim 1 , wherein the at least one inverted abasic moiety is located at 5′-terminus of the passenger strand.

4. The molecule of claim 1 , wherein the guide strand and the passenger strand are RNA molecules.

5. The molecule of claim 1 , wherein the binding moiety is conjugated to the at least one inverted abasic moiety at the 5′-terminus of the passenger strand.

6. The molecule of claim 1 , wherein the antibody or antigen binding fragment thereof is an anti-transferrin receptor antibody or antigen binding fragment thereof.

7. The molecule of claim 1 , wherein the antibody or antigen binding fragment thereof is a human anti-transferrin receptor antibody or antigen binding fragment thereof.

8. The molecule of claim 1 , further comprising a polymer.

9. The molecule of claim 1 , wherein the antibody or antigen binding fragment thereof comprises a humanized antibody or antigen binding fragment thereof, a chimeric antibody or antigen binding fragment thereof, a monoclonal antibody or antigen binding fragment thereof, a monovalent Fab′, a divalent Fab2, a single-chain variable fragment (scFv), a diabody, a minibody, a nanobody, a single-domain antibody (sdAb), or a camelid antibody or antigen binding fragment thereof.

10. The molecule of claim 8 , wherein the polymer is polyethylene glycol.

11. The molecule of claim 8 , wherein the polymer has a molecular weight of about 1000 Da, 2000 Da, or 5000 Da.

12. The molecule of claim 1 , further comprising an endosomolytic moiety.

Assignments (3)

Continuity (3)

References Cited (215)