Polymer conjugates

A compound comprising a conjugate of a biologically active moiety and a polymeric group having a general formula:

• in which M1 is the divalent group formed when the compound of the general formula I is polymerized
• YBX I
• in which Y is an ethylenically unsaturated group selected from H2C═CR—CO-A-, H2C═CR—C6H4-A1-, H2C═CR—CH2A2, R2O—CO—CR═CR—CO—O, RCH═CH—CO—O—, RCH═C(COOR2)CH2—CO—O,
• A is —O— or NR1;
• Al is selected from the group consisting of a bond, (CH2)nA2 and (CH2)n SO3— in which n is 1 to 12;
• A2 is selected from the group consisting of a bond, —O—, O—CO—, CO—O, CO—NR1—, —NR1—CO, O—CO—NR1—, NR1—CO—O—;
• R is hydrogen or C1-4 alkyl;
• R1 is selected from the groups consisting of hydrogen, C1-4- alkyl or BX:
• R2 is hydrogen or C1-4 alkyl;
• B is selected from the group consisting of a bond, or a straight and branched alkanediyl, alkylene oxaalkylene, and alkylene (oligooxalkylene) groups, optionally containing one or more fluorine substituents;
• and
• X is a zwitterionic group, M2 is the divalent group formed when an ethyleneically unsaturated comonomer selected from anionic, cationic and non-ionic monomers is polymerised, and I1 is the residue of a initiator of general formula V which comprises said biologically active moiety,
• R11R12R13C—Y1 V
• where:
• Y1 is selected from the group consisting of Cl, Br, I, OR10, SR14, SeR14, OP(═O)R14, OP(═O)(OR14)2, O—N(R14)2 and S—C(═S)N(R14)2, where R10 is alkyl of from 1 to 20 carbon atoms in which each of the hydrogen atoms may be independently replaced by halide, R14 is aryl or a straight or branched C1-C20 alkyl group, and where an N(R14)2 group is present, the two R14 groups may be joined to form a 5- or 6-membered heterocyclic ring;
• R11 and R12 are each independently selected from the group consisting of H, halogen, C1-C20 alkyl, C3-C8 cycloalkyl, C(═O)R15, C(═O)NR16R17, COCl, OH, CN, C2-C20 alkenyl, oxiranyl, glycidyl, aryl, heterocyclyl, aralkyl and aralkenyl, in any of which the alkyl, alkenyl or aryl, heterocyclyl or cycloalkyl groups there may be from 1 to 3 substituents selected from the group consisting of hydrogen, hydroxy C1-C4 alkoxy, acyloxy, aryl, heterocyclyl, C(═O)R15, C(═O)NR16R17, —CR12R13Y1, CR11R12Y1, oxiranyl and glycidyl;
• where R15 is selected from the group consisting of alkyl of from 1 to 20 carbon atoms, alkoxy of from 1 to 20 carbon atoms, oligo(alkoxy) in which each alkoxy group has 1 to 3 carbon atoms, aryloxy and heterocyclyloxy groups any of which groups may have substituents selected from the group consisting of optionally substituted alkoxy, oligoalkoxy, amino (including mono-- and di-alkyl amino and trialkyl ammonium, which alkyl groups, in turn may have substiuents selected from acyl, acyloxy, alkoxy, alkoxycarbonyl, alkenoxycarbonyl, aryl and hydroxy), and hydroxyl groups;
• R16 and R17 are independently selected from the group consisting of H and alkyl of from 1 to 20 carbon atoms which alkyl groups, in turn may have substiuents selected from the group consisting of alkoxy, acyl, acyloxy, alkoxycarbonyl, alkenoxycarbonyl, aryl and hydroxy, or R16 and R17 may be joined together to form an alkanediyl group of from 2 to 5 carbon atoms, thus forming a 3- to 6-membered ring;
• and
• R13 is selected from the group consisting of biologically active group-substituted alkyl, cycloalkyl, —COR15, —CONR16R17, alkenyl, aryl, heterocyclyl, aralkyl and aralkenyl groups, in any of which the alkyl, alkenyl, aryl, heterocyclyl or cycloalkyl groups may have from 1 to 3 substituents selected from the group consisting of hydrogen, hydroxy, C1-C4 alkoxy, acyloxy, aryl, heterocyclyl, C(═O)R15, C(═O)NR16R17, —CR12R13Y1, CR11R12Y1 , oxiranyl and glycidyl where R15, R16 and R17 are groups as defined above for R11 and R12 with the biologically active group substituted on an alkyl, cycloalkyl, alkenyl, aryl or heterocyclyl group;
• and R36 is a monofunctional group or atom which terminates the polymeric group M1n, n is at least 2 and m is at least 0.