Abstract: Conjugates comprising a plurality of modulators of the Notch signalling pathway chemically bound to a support structure are described. The conjugates are useful for modulation of the Notch signalling pathway and treatment of associated conditions.

Abstract: Provided is a Notch ligand protein or polypeptide comprising a Notch ligand DSL domain; 1 to 5 (but no more than 5) Notch ligand EGF repeat domains; optionally, all or part of a Notch ligand N-terminal domain; and optionally, one or more heterologous amino acid sequences. Also provided is a homogeneous or heterogeneous multimer of the protein or polypeptide and a polynucleotide encoding the Notch ligand protein or polypeptide. An immune response can be modified in a subject by administering the Notch ligand protein or polypeptide to the subject.

Abstract: A method is disclosed for therapeutic modulation of Notch signalling by administering a construct comprising a multiplicity of bond, linked or immobilised modulators of Notch signalling.

Abstract: A polymer blend for use in a biomedical application comprising: (A) a polymer A, bearing zwitterionic pendant groups; and (B) a hydrophobic addition polymer B, selected from the group consisting silyl(alk)acrylates, alkyl(alk)acrylamides, dialkyl(alk)acrylamides, and alkyl(alk)acrylate polymers, wherein the structure of the blend exhibits phase separation forming a micro-phase segregated structure at a surface. Articles, methods of production and liquid blend compositions are also disclosed. Preferably A is a copolymer of 15 to 30 mole % 2-methacryloyloxyethy1-2-trimethylammonium ethyl phosphate inner salt and 85 to 70 mole % of a C6-18 alkyl methacrylate, and B is a homopolymer of a C4-18 alkyl(meth)acrylate, blended in weight proportions of 1:1 to 1:50.

Abstract: An inhibitor of the Notch signalling pathway is provided for use as an immunostimulant, for example as a vaccine adjuvant.

Abstract: Emulsion polymerizations are described in which the monomers include an ethylenically unsaturated ammonium phosphate ester monomer. The processes may be conducted with high total solids, to produce a polymer latex having a solids content in the range 20 to 60%, for instance in the range 25 to 50% by weight. Preferably comonomers include lower alkyl and higher alkyl methacrylate selected to give desirable glass transition temperatures and coalescing films, zwitterionic comonomers, polyethoxylated comonomers to confer desired biocompatibility and latex stability as well as good wetting for a film formed of the polymer and may contain crosslinking monomers, reactive monomers, anionic monomers and/or cationic monomers. The latexes are stable, even when the process is carried out in the substantial absence of non-polymerizable emmulsifier. Coatings formed from the latexes containing zwitterionic comonomer have good biocompatibilizing properties.

Abstract: Polymers may be made from zwitterionic monomers having controlled architectures and molecular weights, using living polymerisations such as group or atom transfer radical polymerisation. For instance polymers may be formed by atom transfer radical polymerisation using a copper chloride catalyst, a ligand which is water soluble, and a water soluble tertiary alkyl halide initiator to form homopolymers having controlled polydispersities of less than 1.5 and block copolymers with other hydrophilic or hydrophobic monomers. One suitable zwitterionic monomer is 2-methacryloyloxy-2?-trimethylammoniumethyl phosphate inner salt. The block copolymers may spontaneously form micelles, believed to have zwitterionic, for instance phosphorylcholine, groups at the external surface, which may be useful as drug delivery systems with improved biocompatibility.

Abstract: An inhibitor of the Notch signalling pathway is provided for the manufacture of a medicament for use in the treatment of cancer.

Abstract: Copolymers of zwitterionic monomer, especially 2-methacryloyloxyethyl-2?-trimethylammoniumethyl phosphate inner salt, and hydrophobic comonomer, especially dodecylmethacrylate, are made in a monomer starved polymerization process in which solutions of monomers are fed to the reaction vessel in which initiator is present over an extended period. The copolymers have improved compositional uniformity and provide better coatings on a range of substrates. The novel copolymers can be distinguished from prior art batch type bulk solution polymerization polymers of the same monomer composition by solubility characteristics especially in alcohol/water mixtures. Particularly preferred coating compositions comprise an alcohol:water mixture containing around 20 to 40% by volume alcohol.

Abstract: A zwitterion containing an adduct having the formula (I) wherein Z is a zwitterionic group; X is an electron withdrawing group selected from the group consisting of carbonyl and sulphone groups, sulphonium and phosphonium salts; R is a difunctional organic group; A is O or NR6 where R6 is hydrogen or lower alkyl; R1 and R2 are independently selected from hydrogen and C1-C12 alkyl groups; and R3 is hydrogen or an organic group; R4 is an organic group, preferably an optionally substituted alkyl group, an organopolysiloxane group, an organosilyl group or an oligo alkoxyalkyl group. The invention additionally provides processes for the production of such an adduct, polymers formed therefrom, coating processes and compositions comprising an adduct or polymers produced therefrom.

Abstract: Emulsion polymerisations are described in which the monomers include an ethylenically unsaturated ammonium phosphate ester monomer. The processes may be conducted with high total solids, to produce a polymer latex having a solids content in the range 20 to 60%, for instance in the range 25 to 50% by weight. Preferably comonomers include lower alkyl and higher alkyl methacrylate selected to give desirable glass transition temperatures and coalescing films, zwitterionic comonomers, polyethoxylated comonomers to confer desired biocompatibility and latex stability as well as good wetting for a film formed of the polymer and may contain crosslinking monomers, reactive monomers, anionic monomers and/or cationic monomers. The latexes are stable, even when the process is carried out in the substantial absence of non-polymerisable emmulsifier. Coatings formed from the latexes containing zwitterionic comonomer have good biocompatibilising properties.

Abstract: Emulsion polymerizations are described in which the monomers include an ethylenically unsaturated ammonium phosphate ester monomer. The processes may be conducted with high total solids, to produce a polymer latex having a solids content in the range 20 to 60%, for instance in the range 25 to 50% by weight. Preferably comonomers include lower alkyl and higher alkyl methacrylate selected to give desirable glass transition temperatures and coalescing films, zwitterionic comonomers, polyethoxylated comonomers to confer desired biocompatibility and latex stability as well as good wetting for a film formed of the polymer and may contain crosslinking monomers, reactive monomers, anionic monomers and/or cationic monomers. The latexes are stable, even when the process is carried out in the substantial absence of non-polymerisable emmulsifier. Coatings formed from the latexes containing zwitterionic comonomer have good biocompatibilising properties.

Abstract: A composition for chemoembolotherapy of solid tumours comprises particles of a water-insoluble water-swellable synthetic anionic polymer and, absorbed therein an anthracycline. Suitably the polymer is a poly(vinyl alcohol) based polymer and the drug is doxorubicin.

Abstract: Polymers may be made from zwitterionic monomers having controlled architectures and molecular weights, using living polymerisations such as group or atom transfer radical polymerisation. For instance polymers may be formed by atom transfer radical polymerisation using a copper chloride catalyst, a ligand which is water soluble, and a water soluble tertiary alkyl halide initiator to form homopolymers having controlled polydispersities of less than 1.5 and block copolymers with other hydrophilic or hydrophobic monomers. One suitable zwitterionic monomer is 2-methacryloyloxy-2′-trimethylammoniumethyl phosphate inner salt. The block copolymers may spontaneously form micelles, believed to have zwitterionic, for instance phosphorylcholine, groups at the external surface, which may be useful as drug delivery systems with improved biocompatibility.

Abstract: A silicon containing adduct having the formula (I) wherein X is an electron withdrawing group selected from the group consisting of carbonyl and sulphone groups, sulphonium and phosphonium salts; R is selected from the group consisting of hydrogen, linear and branched alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, alkaryl, aralkyl, alkoxyaryl, alkoxyalkyl, oligoalkoxyalkyl, di-alkylaminoalkyl, N-aryl-N-alky-laminoalkyl, hydroxyalkoxy, alkoxy, alkenyloxy, alkynyloxy, cycloalkoxy, cycloalkenyloxy, cycloalkynyloxy, aralkoxy, alkoxyaryloxy, alkoxyalkoxy, oligoalkoxyalkoxy, di-alkylaminoalkoxy, N-aryl-N-alkylamino-alkoxy, acyloxy, acyloxyalkyl, N-diacyl-iminoalkyl groups, organosilane, organosiloxane, hydroxyaryl, hydroxyalkenyl, hydroxyalkynyl and hydroxy groups and any of the above groups substituted with one or more hydroxyl or zwitterionic group Z, or R—X— is a nitrile group; R3 and R4 are individually selected from the group consisting of hydrogen, linear and branched alkyl

Abstract: A polyion complex (PIC) is formed of an anionic soluble polymer formed from ethylenically unsaturated monomers including at least one anionic or monomer and a cationic soluble polymer formed from ethylenically unsaturated monomer including at least one cationic monomer, in which the monomers used to form at lest one of the polymers comprise a switterionic monomer and in which the monomers used to form at least one of the polymers include non-ionic monomer, preferably C1-24 alkyl(meth)acrylate, in which the overall ratio of anionic groups to cationic groups in the PIC is in the range 1.5:1 to 1:1.5, and in which the polymers are combined in ratios to provide a PIC in which there are units derived from zwitterionic monomer in an amount in the range 1 to 70 mole % based on total monomer derived units in the PIC and there are units derived from non-ionic monomer in an amount in the range 0 to 60 mole % based on total monomer derived units in the PIC.

Abstract: An insoluble polymer is deposited in a body cavity for instance to embolize a vein or pack an aneurysm, the polymer having pendant zwitterionic groups to improve biocompatibility. The insoluble polymer is preferably formed by an in situ gelling step in which a charged, preferably soluble, polymer having pendant zwitterionic groups is introduced in the form of a composition in which it is soluble and is gelled by being mixed with a counterionically charged soluble polymer (polyelectrolyte), to form a polyion complex. Preferably the or each soluble polymer is formed by polymerizing ethylenically unsatured monomers including a zwitterionic monomer, for instance 2-methacryloyloxyethyl-2′-trimethylammoniumethyl phosphate inner salt, an ionic monomer such as trimethylammonium alkyl(alk)acrylate or a sulphoalkyl(alk)acrylate and optionally a diluent monomer such as an alkyl(alk)acrylate.

Abstract: A polyion complex (PIC) is formed of an anionic soluble polymer formed from ethylenically unsaturated monomers including at least one anionic or monomer and a cationic soluble polymer formed from ethylenically unsaturated monomer including at least one cationic monomer, in which the monomers used to form at least one of the polymers comprise a zwitterionic monomer and in which the monomers used to form at least one of the polymers include non-ionic monomer, preferably C1-24 alkyl(meth)acrylate, in which the overall ratio of anionic groups to cationic groups in the PIC is in the range 1.5:1 to 1:1.5, and in which the polymers are combined in ratios to provide a PIC in which there are units derived from zwitterionic monomer in an amount in the range 1 to 70 mole % based on total monomer derived units in the PIC and there are units derived from non-ionic monomer in an amount in the range 0 to 60 mole % based on total monomer derived units in the PIC. The PIC is preferably swollen in water and is a flowable gel.

Abstract: Emulsion polymerisations are described in which the monomers include an ethylenically unsaturated ammonium phosphate ester monomer. The processes may be conducted with high total solids, to produce a polymer latex having a solids content in the range 20 to 60%, for instance in the range 25 to 50% by weight. Preferably comonomers include lower alkyl and higher alkyl methacrylate selected to give desirable glass transition temperatures and coalescing films, zwitterionic comonomers, polyethoxylated comonomers to confer desired biocompatibility and latex stability as well as good wetting for a film formed of the polymer and may contain crosslinking monomers, reactive monomers, anionic monomers and/or cationic monomers. The latexes are stable, even when the process is carried out in the substantial absence of non-polymerisable emmulsifier. Coatings formed from the latexes containing zwitterionic comonomer have good biocompatibilising properties.

Abstract: A polymer characterised by the presence of ylid linkages in the main polymer chain of formula (A) where the dashed line represents the remainder of a ring system for which the N+ provides a heteroatom, and E is a strongly electron withdrawing group. Preferred polymers in accordance with the invention are characterised by the presence of linkages in the polymer main chain of formula (I). The polymers of the invention may be fabricated as membranes for use in various separation processes, e.g. ultrafiltration, nanofiltration, and reverse osmosis.