Multifunctional forms of polyoxazoline copolymers and drug compositions comprising the same

• US 8,501,899 B2
• Filed: 01/23/2012
• Issued: 08/06/2013
• Est. Priority Date: 01/11/2008
• Status: Active Grant

• Current Assignee: Serina Therapeutics, Inc.
• Original Assignee: Serina Therapeutics, Inc.
• Inventors: Yoon, Kunsang, Harris, J. Milton, Bentley, Michael David, Fang, Zhihao, Viegas, Tacey
• Primary Examiner(s): Truong, Duc
• Application Number:
  US13/356,552
• Publication Number:
  US 20120123055A1
• Time in Patent Office: 561 Days
• Field of Search: 528/321, 528/373, 528/403, 424/78.3
• US Class Current: 528/321
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C08G 73/0233 Polyamines derived from (poly)oxazolines, (poly)oxazines or having pendant acyl groups

Abstract

The present disclosure provides copolymers of 2-substituted-2-oxazolines possessing two or three reactive functional groups which are also chemically orthogonal. The copolymers described may be random copolymers, block copolymers or a mixture of random and block copolymer configurations. Furthermore, the present disclosure provides novel methods for synthesizing the above polymers and for conjugating to molecules such as targeting, diagnostic and therapeutic agents.

Claims

1. A target molecule-POZ conjugate comprising at least one target molecule linked to a heterofunctional polyoxazoline derivative of the general structure:

{R₁-{[N(COX)CH₂CH₂]_o—

[N(COR₂)CH₂—

CH₂)]_n—

[N(COY)CH₂—

CH₂)]_m}_a—

K_k—

}_d—

R-Q_q-Z

wherein;

R₁ is an initiating group;

R₂ is independently selected for each polyoxazoline chain from a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted aralkyl or a substituted or unsubstituted heterocyclylalkyl group;

X is a pendent moiety bearing a first functional group;

Y is a pendent moiety bearing a second functional group;

K is a linking moiety linking each polyoxazoline chain to a branching moiety R, K being independently selected for each polyoxazoline chain;

Q is a linking moiety linking the branching moiety R to Z;

R is a branching moiety capable of forming linkages with Z, either directly or through linking group Q, and with each polyoxazoline chain, either directly or through the linking group K;

Z is a moiety containing a third functional group or an inert group;

a independently selected for each polyoxazoline chain from ran which indicates a random copolymer or block which indicates a block copolymer;

d is an integer selected from 2-8;

k is an integer independently selected for each polyoxazoline chain from one or zero;

q is an integer selected from one or zero;

o is an integer independently selected for each polyoxazoline chain from 1-50;

m is an integer independently selected for each polyoxazoline chain from 0-50;

n is an integer selected from 0-1000;

wherein at least two of the first, second and third functional groups are chemically orthogonal to one another; and

wherein the at least one target molecule is linked to the polyoxazoline derivative through at least one of the first, second or third functional groups.