Patent ID: 8067571
Filing Date: 2011-11-29
Classification: A61K,A61P,C07D,C07F,C07K,C08F,C12N

Abstract:
1. A method for enhancing the antibacterial activity of an uncharged antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ exocyclic carbon of an adjacent subunit, where the oligonucleotide contains between 10-20 bases and a targeting sequence of at least 10 contiguous bases complementary to a bacterial RNA target, and where binding of the oligonucleotide to the RNA target region is effective to inhibit growth of a infectious bacterium in a mammalian host, comprising both of steps (a) and (b), or step (b) alone: (a) conjugating to the oligonucleotide, a carrier peptide (i) containing 8-14 amino acids composed of the subsequences selected from the group represented by XXY, XY, XZZ, XZ, XYX, YXX, YX, ZXZ, ZZX, and ZX, where (a) each X subunit independently represents arginine or an arginine analog, said analog being a cationic α-amino acid comprising a side chain of the structure R (b) modifying the oligonucleotide to contain at least one and up to 50% intersubunit linkages comprising an optionally substituted piperazino group.