US 9,808,480 B2Granted

Unit structure-type pharmaceutical composition for nucleic acid delivery

AssigneesNanocarrier Co., Ltd., The University of Tokyo

InventorsKazunori Kataoka, Kanjiro Miyata, Nobuhiro Nishiyama, Kensuke Osada, Sumiyo Watanabe, Shigeto Fukushima, Hiroyuki Chaya, Hiroyasu Takemoto, Yasuki Kato

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Abstract

A unit structure-type pharmaceutical composition includes at least one nucleic acid, such as siRNA, electrostatically bound to at least one block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment. The negative charge(s) of the nucleic acid are counterbalanced, at least substantially, by the positive charge(s) of the cationic polyamino acid segment such that the pharmaceutical composition is electrically neutral or nearly electrically neutral. Further, the nucleic acid is covered with the hydrophilic polymer chain segment(s). The at least one block copolymer thereby improves the blood retention capability of the nucleic acid(s).

Claims16

Dependent claims

A unit structure, consisting of:

a single double-stranded nucleic acid having 18 to 30 base pairs, and
two block copolymers, each having a cationic polyamino acid segment and a 2-arm branched hydrophilic polymer chain segment,
wherein:
(i) a difference between a total of positive charges derived from cationic groups of the cationic polyamino acid segments and a total of negative charges derived from the nucleic acid in the unit structure falls within a range of ±10% of the total of the negative charges derived from the nucleic acid,
(ii) the 2-arm branched hydrophilic polymer chain segment comprises two polyethylene glycol chains, each polyethylene glycol chain having a molecular weight of 20,000 Da or more,
(iii) each of the polyethylene glycol chains has a radius of inertia (Rg) equal to or longer than half the length of the nucleic acid, and
(iv) the cationic polyamino acid segments are bound to the nucleic acid via electrostatic bonds.

4 more elements

A unit structure, consisting of one siRNA and two block copolymers, wherein

(i) each block copolymer has a cationic polyamino acid segment and a 2-arm branched polyethylene glycol at one terminal of the polyamino acid chain segment,
(ii) each of the arms of the polyethylene glycol has a molecular weight of from 20,000 Da to 80,000 Da,
(iii) a difference between a total of positive charges derived from cationic groups of the cationic polyamino acid segments and a total of negative charges derived from the siRNA in the unit structure falls within a range of ±10% of the total of the negative charges derived from the siRNA, and
(iv) the cationic polyamino acid segments are bound to the siRNA via electrostatic bonds.

1 more element

Dependencies are inferred from the claim text.

Facts

Application: 14/395,745Filed 30 Apr 2013
Priority: JP 2012-10284127 Apr 2012
Published: US 2015/0080454 A119 Mar 2015
Granted: 7 Nov 2017
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

A61K 31/713
Compounds having three or more nucleosides or nucleotides: double-stranded nucleic acids or oligonucleotides
A61K 9/0019
Galenical forms characterised by the site of application: injectable compositions; Intramuscular, intravenous, arterial, subcutaneous…
A61K 47/56
The non-active ingredient being a modifying agent: the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or…
A61K 47/60
Obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes: the organic…