Compositions and methods for the treatment of complications and disorders relating to von willebrand factor

Abstract

The present invention provides VWF protective agents, including aptamers and antibodies for the treatment and or amelioration of complications or disorders arising from aberrant binding or function of VWF.

1 . A polynucleotide comprising at least 25 contiguous nucleotides of SEQ ID NO. 1. 
     
     
         2 . The polynucleotide of  claim 1  wherein the sequence further comprises a double stranded region having 6 or more base pairs, wherein the double stranded region is formed by 6 or more of the 3′ and 5′ nucleotides at or near the termini. 
     
     
         3 . The polynucleotide of  claim 1 , comprising at least one chemical modification, wherein the chemical modification is made to one of the group selected from the sugar moiety of a nucleotide, the nucleobase of a nucleotide, or internucleoside linker of the polynucleotide. 
     
     
         4 . The polynucleotide of  claim 1 , wherein each nucleotide comprises at least one chemical modification, wherein the chemical modification is made to one of the group selected from the sugar moiety of a nucleotide, the nucleobase of a nucleotide, or internucleoside linker of the polynucleotide. 
     
     
         5 . The polynucleotide of  claim 4 , wherein the chemical modification is made to a sugar and the sugar modification consists of a 2′-O-Methyl modification. 
     
     
         6 . The polynucleotide of  claim 5  further comprising at least one other modification of a 3′ terminal cap, a 5′ terminal gap, and/or a conjugate. 
     
     
         7 . The polynucleotide of  claim 6 , wherein the 3′ and/or 5′ terminal cap is an inverted deoxythymidine, or an amino group (NH2). 
     
     
         8 . The polynucleotide of  claim 6  comprising a conjugate, wherein the conjugate is a naturally occurring substance, a protein, a ligand, a carbohydrate, a lipid, a synthetic polymer, a synthetic polyamino acid, an oligonucleotide, a dye, an intercalating agent, a cross-linker, a reporter molecule, or a targeting group. 
     
     
         9 . A pharmaceutical composition comprising an effective amount of a polynucleotide having at least 25 contiguous nucleotides of SEQ ID NO.: 1, and at least one pharmaceutical excipient. 
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein the polynucleotide comprises at least one chemical modification, wherein the chemical modification is made to one of the group selected from the sugar moiety of a nucleotide, the nucleobase of a nucleotide, or internucleoside linker of the polynucleotide. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the chemical modification is made to a sugar and the sugar modification consists of a 2′-O-Methyl modification. 
     
     
         12 . The pharmaceutical composition of  claim 10 , wherein the polynucleotide comprises at one least other modification of a 3′ terminal cap, a 5′ terminal gap, and a terminal conjugate. 
     
     
         13 . The pharmaceutical composition of  claim 9 , wherein the polynucleotide comprises a sequence selected from SEQ ID NOs.: 1-3. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the composition further comprises a complementary sequence having a sequence selected from SEQ ID NOs.: 4-5, which is capable of hybridizing with, or binds to, in whole or in part any of the synthetic polynucleotide of the composition. 
     
     
         15 . The pharmaceutical composition of  claim 13 , wherein the polynucleotide comprises the sequence of SEQ ID NO.: 3.