Patent ID: 8658211

Claim:
An RNA interference polynucleotide delivery polyconjugate for delivering the RNA interference polynucleotide to a mammalian cell in vivo comprising: a membrane inactive reversibly modified amphipathic membrane active random copolymer poly(A a -co-(B b -graft-(C c ;D d ;E e ))) wherein A is a hydrophobic group-containing monomer, B is a primary amine-containing monomer, C comprises an RNA interference polynucleotide linked to a primary amine-containing monomer via a physiologically labile linkage orthogonal to maleamate, D comprises a targeting ligand linked to a primary amine-containing monomer via a maleamate linkage having the structure —NH—CO—C(R)═C(L)—COO − or —NH—CO—C(L)═C(R)—COO − , wherein the nitrogen is derived from the primary amine, L is charge neutral and comprises the targeting ligand and R is an alkyl group, E comprises a steric stabilizer linked to a primary amine-containing monomer via a maleamate linkage having the structure —NH—CO—C(R′)═C(SS)—COO − or —NH—CO—C(SS)═C(R′)—COO − , wherein the nitrogen is derived from the primary amine, SS is charge neutral and comprises the steric stabilizer and R′ is an alkyl group, a is an integer greater than zero, b is an integer greater than or equal to two, c is an integer greater than or equal to one, d is an integer greater than or equal to zero, e is an integer greater than or equal to zero, the value of d+e is greater than 50% of the value of b, and poly(A a -co-B b ) is membrane active.