Nucleic acid-polypeptide compositions and uses thereof

Abstract

Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

What is claimed is: 
     
         1 . A molecule of Formula (I):
   A-X-B-Y-C   Formula I
   wherein,
 A is an antibody or its binding fragments thereof; 
 B is a polynucleotide; 
 C is a polymer; 
 X is a bond or first non-polymeric linker; and 
 Y is a bond or second linker; 
   
       wherein the polynucleotide comprises at least one 2′ modified nucleotide, at least one modified internucleotide linkage, or at least one inverted abasic moiety; and
 wherein A and C are not attached to B at the same terminus. 
 
     
     
         2 . The molecule of  claim 1 , wherein the at least one 2′ modified nucleotide comprises 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl, 2′-deoxy, T-deoxy-2′-fluoro, 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), T-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), or 2′-O-N-methylacetamido (2′-O-NMA) modified nucleotide. 
     
     
         3 . The molecule of  claim 1 , wherein the at least one 2′ modified nucleotide comprises locked nucleic acid (LNA) or ethylene nucleic acid (ENA). 
     
     
         4 . The molecule of  claim 1 , wherein the at least one modified internucleotide linkage comprises a phosphorothioate linkage or a phosphorodithioate linkage. 
     
     
         5 . The molecule of  claim 1 , wherein the at least one inverted abasic moiety is at at least one terminus. 
     
     
         6 . The molecule of  claim 1 , wherein the polynucleotide comprises a single strand. 
     
     
         7 . The molecule of  claim 1 , wherein the polynucleotide comprises a first polynucleotide and a second polynucleotide hybridized to the first polynucleotide to form a double-stranded polynucleic acid molecule. 
     
     
         8 . The molecule of  claim 7 , wherein the second polynucleotide comprises at least one modification. 
     
     
         9 . The molecule of  claim 7 , wherein the first polynucleotide and the second polynucleotide are RNA molecules. 
     
     
         10 . The molecule of  claim 7 , wherein the first polynucleotide comprises a sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NOs: 16-75, 452-1955, 1956-1962, 1967-2002, 2013-2032, 2082-2109, or 2117. 
     
     
         11 . The molecule of  claim 7 , wherein the second polynucleotide comprises a sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NOs: 16-75, 452-1955, 1956-1962, 1967-2002, 2013-2032, 2082-2109, or 2117. 
     
     
         12 . The molecule of  claim 1 , wherein X and Y are independently a bond. 
     
     
         13 . The molecule of  claim 1 , wherein X and Y are independently a C 1 -C 6  alkyl group. 
     
     
         14 . The molecule of  claim 1 , wherein X is a homobifuctional linker or a heterobifunctional linker, optionally conjugated to a C 1 -C 6  alkyl group. 
     
     
         15 . The molecule of  claim 1 , wherein Y is a homobifuctional linker or a heterobifunctional linker. 
     
     
         16 . The molecule of  claim 1 , wherein the antibody or binding fragment thereof comprises a humanized antibody or binding fragment thereof, chimeric antibody or binding fragment thereof, monoclonal antibody or binding fragment thereof, monovalent Fab′, divalent Fab2, single-chain variable fragment (scFv), diabody, minibody, nanobody, single-domain antibody (sdAb), or camelid antibody or binding fragment thereof. 
     
     
         17 . The molecule of  claim 1 , wherein C is polyethylene glycol. 
     
     
         18 . The molecule of  claim 17 , wherein C has a molecular weight of about 1000 Da, 2000 Da, or 5000 Da. 
     
     
         19 . The molecule of  claim 1 , wherein A-X is conjugated to the 5′ end of B and Y-C is conjugated to the 3′ end of B, or Y-C is conjugated to the 5′ end of B and A-X is conjugated to the 3′ end of B. 
     
     
         20 . The molecule of  claim 1 , further comprising D, wherein D is an endosomolytic moiety.