IP Library Granted Patent US 8,816,051
Granted Patent B2
US 8,816,051 · App. 13/077,980 · Granted Aug 26, 2014

Conjugated biological molecules and their preparation

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Quick Facts
Patent No.
US 8,816,051
App. No.
13/077,980
Granted
Aug 26, 2014
Kind
B2
Abstract

Novel biologically active compounds of the general formula (I) in which one of X and X′ represents a polymer, and the other represents a hydrogen atom; each Q independently represents a linking group; W represents an electron-withdrawing moiety or a moiety preparable by reduction of an electron-withdrawing moiety; or, if X′ represents a polymer, X-Q-W— together may represent an electron withdrawing group; and in addition, if X represents a polymer, X′ and electron withdrawing group W together with the interjacent atoms may form a ring; each of Z 1 and Z 2 independently represents a group derived from a biological molecule, each of which is linked to A and B via a nucleophilic moiety; or Z 1 and Z 2 together represent a single group derived from a biological molecule which is linked to A and B via two nucleophilic moieties; A is a C 1-5 alkylene or alkenylene chain; and B is a bond or a C 1-4 alkylene or alkenylene chain; are formed by conjugating a suitable polymer to a suitable biologically active molecule via nucleophilic groups in said molecule, preferably via a disulphide bridge.

Claims (19)

1. A process for the preparation of a compound of the general formula

in which one of X and X′ represents a polyethylene glycol, and the other represents a hydrogen atom;

each Q independently represents a linking group,

W represents a keto group or a CH(OH) group,

each of Z 1 and Z 2 independently represents a protein,

A is a C 1-5 alkylene or alkenylene chain, and

B is a bond or a C 1-4 alkylene or alkenylene chain;

which comprises reacting either:

(i) a compound of the general formula

in which X, X′, Q, A and B have the meanings given above;

W′ represents a keto group and

each L independently represents a leaving group; or

(ii) a compound of the general formula

in which X, X′, Q, W′, A and L have the meanings given above and m represents an integer 1 to 4;

with compounds of the general formula Z 1 SH and Z 2 SH.

2. A process as claimed in claim 1 , in which the or each leaving group L represents —SR, —SO 2 R, —OSO 2 R, —N + R 3 , —N + HR 2 , —N + H 2 R, halogen, or —Oø, in which R represents an alkyl or aryl group and ø represents a substituted aryl group containing at least one electron withdrawing substituent.

3. A process as claimed in claim 1 , in which Z 1 and Z 2 represent different proteins.

4. A process as claimed in claim 1 , carried out in an aqueous medium.

5. A process as claimed in claim 1 , in which each linking group Q independently represents a direct bond, an alkylene group, or an optionally-substituted aryl or heteroaryl group, any of which may be terminated or interrupted by one or more oxygen atoms, sulphur atoms, —NR groups in which R represents an alkyl or aryl group, keto groups, —O—CO— groups and/or —CO—O— groups.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded May 7, 2021
From: OXFORD FINANCE LLC,
To: ABZENA (UK) LIMITED (F/K/A POLYTHERICS LIMITED); ABZENA (CAMBRIDGE) LIMITED
Reel/Frame 056174/0440 →
SECURITY INTEREST Recorded Aug 15, 2019
From: ABZENA (UK) LIMITED (F/K/A POLYTHERICS LIMITED); ABZENA (CAMBRIDGE) LIMITED
To: OXFORD FINANCE LLC, AS COLLATERAL AGENT AND AS A LENDER
Reel/Frame 050071/0600 →
CHANGE OF NAME Recorded Jul 25, 2019
From: POLYTHERICS LIMITED
To: ABZENA (UK) LIMITED
Reel/Frame 049860/0743 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2014
From: BROCCHINI, STEPHEN JAMES; GODWIN, ANTONY ROBERT; PEDONE, ELISA; CHOI, JI-WON; SHAUNAK, SUNIL
To: POLYTHERICS LIMITED
Reel/Frame 032717/0911 →