Polytherics Limited

Biocompatibles UK Limited

Abzena (uk) Limited

Antony Robert Godwin

Stephen James Brocchini

Sunil Shaunak

Elisa Pedone

Ji-Won Choi

Andrew Lennard Lewis

Yiqing Tang

Nicholas Evans

Andrew Kyle

Mark Frigerio

Matthew Bird

Penny Bryant

David Morris

George Badescu

Jin-Won Choi

Keith Powell

Yuehua Cong

John Burt

A conjugate comprising a protein or peptide conjugated to a therapeutic, diagnostic or labelling agent via a linker, characterised in that the linker includes at least two ˜(CH—CH—O—)˜ units within a ring, said ring being attached via a single tethering atom within the ring to the rest of the linker, or said ring being attached via two or more tethering atoms within the ring to the rest of the linker at a single point.

Conjugates and conjugating reagents comprising a linker that includes at least two (−CH2—CH2—O—) units in a ring

A conjugate comprising a protein or peptide conjugated to a therapeutic, diagnostic or labelling agent via a linker, characterised in that the linker includes at least two &#x2dc;(CH&#x2014;CH&#x2014;O&#x2014;)&#x2dc; units within a ring, said ring being attached via a single tethering atom within the ring to the rest of the linker, or said ring being attached via two or more tethering atoms within the ring to the rest of the linker at a single point.

Conjugates and conjugating reagents comprising a linker that includes at least two (-CH2&#x2014;CH2&#x2014;O-) units in a ring

A conjugate of a protein or peptide conjugated to a therapeutic, diagnostic or labelling agent via a linker, in which the linker includes a protein or peptide bonding portion having the general formula: in which Pr represents said protein or peptide, each Nu represents a nucleophile present in or attached to the protein or peptide, each of A and B independently represents a Calkylene or alkenylene chain, and W' represents an electron withdrawing group or a group obtained by reduction of an electron withdrawing group; and in which the linker also includes a cyclodextrin. The invention also provides reagents for making such conjugates.

Conjugates and conjugating reagents

The invention relates to novel conjugating reagents capable of reaction with at least one nucleophile present in a peptide or protein, which contain at least one leaving group which is lost on reaction with said nucleophile, in which the leaving group includes a portion &#x2014;(CHCHO)&#x2014;, in which n is a number of six or more; and novel processes for the preparation of conjugates containing peptides or proteins made using such reagents.

Process for the conjugation of a peptide or protein with a reagent comprising a leaving group including a portion of PEG

The invention provides compound of the general formula: in which each X independently represents a polymer chain; n represents an integer greater than 1; Q represents a linker; Y represents an amide group; and Z represents either &#x2014;CH.(CHL)or &#x2014;C(CHL)(&#x2550;CH), in which each L independently represents a leaving group. The compounds are useful reagents for the conjugation of polymers to proteins, the resulting conjugates being novel and also forming part of the invention.

Conjugation reagents

A compound of the general formula X-[Q-W&#x2014;(CH&#x2550;CH)&#x2014;(CH)-L](I) in which X represents a polymer; Q represents a linking group; W represents an electron-withdrawing group; n represents 0 or an integer of from 1 to 4; L represents a leaving group; and m represent an integer of from 1 to 8. The compounds find use in the conjugation of biological molecules.

Reagents and method for conjugating biological molecules

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&#x2032; represents a polymer, X-Q-W&#x2014; together may represent an electron withdrawing group; and in addition, if X represents a polymer, X&#x2032; and electron withdrawing group W together with the interjacent atoms may form a ring; each of Zand Zindependently represents a group derived from a biological molecule, each of which is linked to A and B via an amine group; or Zand Ztogether represent a single group derived from a biological molecule which is linked to A and B via two amine groups; A is a Calkylene or alkenylene chain; and B is a bond or a Calkylene or alkenylene chain; are formed by conjugating a suitable polymer to a suitable biologically active molecule via amine groups in said molecule, preferably via a disulphide bridge. 

Conjugated biological molecules and their preparation

Novel compounds of the general formula: in which X represents a polymer,Q represents a linking group;W represents an electron-withdrawing moiety or a moiety preparable by reduction of an electron-withdrawing moiety;each of Rand Rindependently represents a hydrogen atom or a Calkyl group; andeither Zrepresents a protein or a peptide linked to CRvia a nucleophilic moiety, and Zrepresents a molecule linked to CRvia a nucleophilic moiety, or Zand Ztogether represent a single group derived from a protein or peptide linked to CRvia two nucleophilic moieties.

Conjugated proteins and peptides

The present disclosure relates to a new polymerisation process in which ethylenically unsaturated monomers are polymerised by a living radical polymerisation process in the presence of an initiator and a catalyst. Polymers produced by this new process are also thought to be novel and may be used to derivatise biological molecules to improve their efficacy as therapeutic treatments. A preferred polymer is of formula The polymers are particularly suitable for derivatising proteins, such as interferon-&#x3b1;.

Derivatisation of biological molecules

Novel compounds of the general formula (I): in which X represents a polymer; Q represents a linking group; W represents an electron-withdrawing moiety or a moiety preparable by reduction of an electron-withdrawing moiety; each of Rand Rindependently represents a hydrogen atom or a Calkyl group; and either Zrepresents a protein or a peptide linked to CRvia a nucleophilic moiety, and Zrepresents a molecule linked to CRvia a nucleophilic moiety, or Zand Ztogether represent a single group derived from a protein or peptide linked to CR via two nucleophilic moieties. 

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&#x2032; represents a polymer, X-Q-W&#x2014; together may represent an electron withdrawing group; and in addition, if X represents a polymer, X&#x2032; and electron withdrawing group W together with the interjacent atoms may form a ring; each of Zand Zindependently represents a group derived from a biological molecule, each of which is linked to A and B via a nucleophilic moiety; or Zand Ztogether represent a single group derived from a biological molecule which is linked to A and B via two nucleophilic moieties; A is a Calkylene or alkenylene chain; and B is a bond or a Calkylene 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.

The present disclosure relates to a new polymerization process in which ethylenically unsaturated monomers are polymerised by a living radical polymerization process in the presence of an initiator and a catalyst. Polymers produced by this new process are also thought to be novel and may be used to derivatise biological molecules to improve their efficacy as therapeutic treatments. A preferred polymer is of formula  The polymers are particularly suitable for derivatising proteins, such as interferon-&#x3b1;.

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Bristol, United Kingdom

Antony Robert Godwin