US 12,364,769 B2
Nucleic acid-polypeptide compositions and uses thereof
Andrew John Geall, Carlsbad, CA (US); Venkata Ramana Doppalapudi, San Diego, CA (US); Joel Daniel Arias, San Diego, CA (US); David Sai-Ho Chu, San Diego, CA (US); Michael Caramian Cochran, La Jolla, CA (US); Rob Burke, Encinitas, CA (US); Philip Kovach, San Diego, CA (US); and Barbora Malecova, San Diego, CA (US)
Assigned to AVIDITY BIOSCIENCES, INC., San Diego, CA (US)
Filed by Avidity Biosciences, Inc., La Jolla, CA (US)
Filed on Jun. 30, 2021, as Appl. No. 17/364,765.
Application 17/364,765 is a division of application No. 16/152,324, filed on Oct. 4, 2018, granted, now 11,110,180.
Claims priority of provisional application 62/568,238, filed on Oct. 4, 2017.
Prior Publication US 2022/0395580 A1, Dec. 15, 2022
Int. Cl. C07H 21/04 (2006.01); A61K 31/713 (2006.01); A61K 47/60 (2017.01); A61K 47/64 (2017.01); A61K 47/68 (2017.01); A61P 35/00 (2006.01); C07H 17/00 (2006.01); C07K 16/28 (2006.01); C12N 15/113 (2010.01)
CPC A61K 47/6807 (2017.08) [A61K 31/713 (2013.01); A61K 47/60 (2017.08); A61K 47/64 (2017.08); A61K 47/6811 (2017.08); A61K 47/6849 (2017.08); A61K 47/6883 (2017.08); A61P 35/00 (2018.01); C07H 17/00 (2013.01); C07K 16/2863 (2013.01); C12N 15/113 (2013.01); C12N 2310/312 (2013.01); C12N 2310/3125 (2013.01); C12N 2310/315 (2013.01); C12N 2310/3513 (2013.01); C12N 2310/3515 (2013.01)] 12 Claims
 
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

OG Complex Work Unit Chemistry
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.