US 9,808,480 B2
Unit structure-type pharmaceutical composition for nucleic acid delivery
Kazunori Kataoka, Tokyo (JP); Kanjiro Miyata, Tokyo (JP); Nobuhiro Nishiyama, Tokyo (JP); Kensuke Osada, Tokyo (JP); Sumiyo Watanabe, Tokyo (JP); Shigeto Fukushima, Tokyo (JP); Hiroyuki Chaya, Tokyo (JP); Hiroyasu Takemoto, Tokyo (JP); and Yasuki Kato, Kashiwa (JP)
Assigned to NANOCARRIER CO., LTD., Kashiwa-shi (JP); and THE UNIVERSITY OF TOKYO, Tokyo (JP)
Appl. No. 14/395,745
Filed by THE UNIVERSITY OF TOKYO, Tokyo (JP); and NanoCarrier Co., Ltd., Kashiwa-shi (JP)
PCT Filed Apr. 30, 2013, PCT No. PCT/JP2013/062531
§ 371(c)(1), (2) Date Oct. 20, 2014,
PCT Pub. No. WO2013/162041, PCT Pub. Date Oct. 31, 2013.
Claims priority of application No. 2012-102841 (JP), filed on Apr. 27, 2012.
Prior Publication US 2015/0080454 A1, Mar. 19, 2015
Int. Cl. C12N 15/11 (2006.01); A61K 31/713 (2006.01); A61K 9/00 (2006.01); A61K 47/48 (2006.01)
CPC A61K 31/713 (2013.01) [A61K 9/0019 (2013.01); A61K 47/48215 (2013.01); A61K 47/48315 (2013.01)] 16 Claims
 
1. 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.