IP Library › Granted Patent US 9,303,122
Granted Patent B2
US 9,303,122 · App. 14/543,091 · Granted Apr 5, 2016

Charge conversional ternary polyplex

Inventors: Kazunori Kataoka (Tokyo, JP); Yan Lee (Tokyo, JP); Nobuhiro Nishiyama (Tokyo, JP); Kanjiro Miyata (Tokyo, JP); Makoto Oba (Tokyo, JP); Shigehiro Hiki (Tokyo, JP); Mai Sanjo (Tokyo, JP); HyunJin Kim (Tokyo, JP)
Assignee: THE UNIVERSITY OF TOKYO
C08G69/48A61K31/7084A61K31/785A61K48/0041C08G69/10C08G69/40C12N15/111C12N15/88C12N2310/14C12N2320/32
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 9,303,122
App. No.
14/543,091
Granted
Apr 5, 2016
Kind
B2
Abstract

Disclosed is a polymer composite (polyplex) that contains nucleic acid, a cationic polymer, and an anionic polymer. The anionic polymer covers the surface of the composite comprising the cationic polymer and nucleic acid, has a negative charge at neutral pH, and can change so as to have a positive charge at mildly acidic pH.

Claims (37)

1. A polymer complex comprising a nucleic acid, a cationic polymer and an anionic polymer of Formula (1):

wherein R 11 represents CH 2 CH 2 CH 2 CH 3 , R 12 represents hydrogen atom, R 13 represents a conjugate of a residue derived from an amine compound having a primary amine, and a compound selected from the group consisting of Formula (Ia)-(Ig) below:

m1 represents an integer of 10-500, and

m2 represents an integer of 1-5;

wherein the residue derived from an amine compound having a primary amine is a group of Formula (11):

—NH—(CH 2 ) r —X 11   (11)

wherein X 11 represents —NH 2 or —NH 3 + , and r represents an integer of 0-5, or a group of Formula (12):

—[NH—(CH 2 ) s1 ] t1 —X 12   (12)

wherein X 12 represents —NH 2 or —NH 3 + , and s1 and t1, independently from each other and independently between the [NH—(CH 2 ) s1 ] units, represent integers of 1-5 and 2-5, respectively.

2. The polymer complex according to claim 1 , wherein the residue derived from an amine compound having a primary amine is —NH—NH 2 or —NH—(CH 2 ) 2 —NH—(CH 2 ) 2 —NH 2 .

3. The polymer complex according to claim 1 , wherein the compound selected from the group consisting of Formula (Ia)-(Ig) is Formula (Ib) or (Ic) below:

4. The polymer complex according to claim 1 , wherein the cationic polymer is any compound selected from the group consisting of:

a compound of Formula (2):

wherein R 21 and R 22 independently represent a hydrogen atom or an optionally substituted linear or branched alkyl group with a carbon number of 1-12, R 23 represents a group of Formula (22):

—NH—(CH 2 ) r —X 21   (22)

wherein X 21 is a group selected from —NH 2 , —NH—CH 3 , —N(CH 3 ) 2 and a group represented by one of Formulas (i)-(viii):

and r represents a integer of 0-5; or a group of General Formula (23):

—[NH—(CH 2 ) s2 ] t2 —X 22   (23)

wherein X 22 has the same definition as X 21 , and s2 and t2, independently from each other and independently between the [NH—(CH 2 ) s2 ] units, represent integers of 1-5 and 2-5, respectively,

m3 represents an integer of 10-500, and m4 represents an integer of 1-5;

a compound of Formula (3):

wherein R 31 and R 32 are synonymous with R 21 and R 22 , respectively, R 33 represents an optionally substituted saturated or unsaturated linear or branched aliphatic hydrocarbon group or steroloxycarbonyl group with a carbon number of 11-27, m5 and m6 independently represent an integer of 0-500, provided that the sum of m5 and m6 is an integer of 10-500, m7 represents an integer of 1-5, m8 represents an integer of 1-5, and the sign “/” indicates that the sequential order of the (m5+m6) numbers of monomer units on both sides of the sign are arbitrary;

a compound of Formula (4):

wherein R 41 and R 42 are synonymous with R 21 and R 22 , respectively, R 43 is synonymous with R 33 , R 44 is synonymous with R 23 , m9 and m10 are synonymous with m5 and m6, respectively, m11 and m12 are synonymous with m7 and m8, respectively, and the sign “/” is synonymous with the same above; and

a compound of Formula (5):

wherein R 51 and R 52 are synonymous with R 21 and R 22 , respectively, R 53 and R 54 are synonymous with R 23 , L 1 represents NH, CO, a group of General Formula (13):

—(CH 2 ) p1 —NH—  (13)

wherein p1 represents an integer of 1-6, or a group represented by the following General Formula (14):

-L 2a -(CH 2 ) q1 -L 3a -  (14)

wherein L 2a represents OCO, OCONH, NHCO, NHCOO, NHCONH, CONH or COO, L 3a represents NH or CO, and q1 represents an integer of 1-6, m13, m14 and m15 independently represent an integer of 0-500, provided that the sum of m13, m14 and m15 is an integer of 10-500, m16 and m17 are synonymous with m7 and m8, respectively, n represents an integer of 0-500, and the sign “/” indicates that the sequential order of the (m13+m14+m15) numbers of monomer units on both sides of the sign are arbitrary.

5. A device for delivering a nucleic acid into a cell, comprising the polymer complex according to claim 1 .

6. A kit for delivering a nucleic acid into a cell, comprising the polymer complex according to claim 1 .

7. A device for delivering a nucleic acid into a cell, comprising the polymer complex according to claim 2 .

8. A kit for delivering a nucleic acid into a cell, comprising the polymer complex according to claim 2 .

9. A device for delivering a nucleic acid into a cell, comprising the polymer complex according to claim 3 .

10. A kit for delivering a nucleic acid into a cell, comprising the polymer complex according to claim 3 .

11. The polymer complex according to claim 1 , wherein the anionic polymer covers the surface of a complex comprising the cationic polymer and the nucleic acid.

Continuity (3)
Continuation 12990386
Provisional Application 61126077 · Apr 30, 2008
Related Publication 20150141575A1 · May 21, 2015