Abstract: Derivatives are synthesised of starting materials, usually polysaccharides, having sialic acid at the reducing terminal end, in which the reducing terminal unit is transformed into an aldehyde group. Where the polysaccharide has a sialic acid unit at the non-reducing end it may be passivated, for instance by converting into hydroxyl-substituted moiety. The derivatives may be reacted with substrates, for instance containing amine or hydrazine groups, to form non-cross-linked polysialylated compounds. The substrates may, for instance, be therapeutically useful drugs peptides or proteins or drug delivery systems.

Abstract: A polysialic acid compound is reacted with a hetero-bifunctional reagent to introduce a pendant functional group for site-specific conjugation to sulfhydryl groups, for instance side chains of cysteine units in drugs, drug delivery systems, proteins or peptides. The functional group is, for instance, an N-maleimide group.

Abstract: A polysialic acid compound is reacted with a hetero-bifunctional reagent to introduce a pendant functional group for site-specific conjugation to sulfhydryl groups, for instance side chains of cysteine units in drugs, drug delivery systems, proteins or peptides. The functional group is, for instance, an N-maleimide group.

Abstract: A composition comprising liposomes associated with a nucleic acid operatively encoding an antigenic protein and with an assistor protein, wherein the assistor protein shares at least one epitope with the antigenic protein, and wherein the nucleic acid and said assistor protein are associated with the same liposomes is described. The composition provides an improved immune response compared to mixtures of liposomes some of which are associated with the nucleic acid and some of which are associated with the assistor protein.

Abstract: The present invention relates to methods for producing N-terminal derivatives of proteins in which a polysaccharide, preferably having at least terminal sialic units and preferably consisting essentially only of sialic acid units, is reacted at the N-terminus of a protein or peptide under controlled conditions to produce an N-terminal derivative. The controlled conditions include use of acidic pH for the derivatisation step and a higher pH for purification. The derivatives are useful for improving pharmacokinetics and pharmacodynamics of proteins and peptides.

Abstract: The present invention relates to a compound which is a polysaccharide derivative of EPO, or of an EPO like protein, wherein the polysaccharide is anionic and comprises between 2 and 200 saccharide units. The present invention also relates to pharmaceutical compositions comprising the novel compounds, and methods for making the novel compounds.

Abstract: The present invention relates to a compound which is a polysaccharide derivative of GCSF, or of a GCSF like protein, wherein the polysaccharide is anionic and comprises between 2 and 200 saccharide units. The present invention also relates to pharmaceutical compositions comprising the novel compounds, and methods for making the novel compounds.

Abstract: A composition for the co-delivery to a cell of a nucleic acid and an assistor protein, comprising vesicles, nucleic acid and protein, wherein the nucleic acid operatively encodes an antigenic protein or portion thereof which shares at least one epitope with the assistor protein, the composition comprising said nucleic acid and said assistor protein associated with the same vesicles as one another. A preferred embodiment is a composition comprising liposomes formed from liposome forming materials and, associated with the liposomes, nucleic acid operatively encoding an antigenic protein and an assistor protein, wherein the assistor protein shares at least one epitope with the antigenic protein. The composition is for use as a vaccine and provides improved immune response compared to non-vesicular compositions, or mixtures of liposomes some of which are associated with nucleic acid and some of which are associated with assistor protein.

Abstract: We describe a conjugate comprising an antibody and antigen wherein said conjugate has low antibody valency and including methods to prepare said conjugate.

Abstract: A multivalent liposomal composition, preferably a vaccine, comprises liposomes formed of liposome forming compounds, containing coentrapped polysaccharide antigens of several serotypes and T-cell dependent protein carrier, such as tetanus toxoid. The invention is of use in the production of vaccines against Haemophilus influenzae, Streptococcus pneumoniae or Neisseria meningitidis.

Abstract: A liposomal composition, preferably a vaccine, comprising liposomes formed of liposome forming compounds, containing coentrapped polysaccharide antigen and T-cell dependent protein carrier, such as tetanus toxoid or diphtheria toxin modified to render it non-toxic. The invention is of use in the production of vaccines against Haemophilus influenzae, Streptococcus pneumoniae or Neisseria meningitidis.

Abstract: Polydisperse and charged polysaccharides are fractionated into low polydispersity fractions (preferably having pd <1.1), each containing species within a narrow range of molecular weights. An aqueous solution of the polydisperse polysaccharides is contacted with an ion exchange resin in a column and the polysaccharides are subjected to selective elution by aqueous elution buffer. The selective elution consists of at least 3 sequential elution buffers having different and constant ionic strength and/or pH and in which the subsequent buffers have ionic strength and/or pH than those of the preceding step. The new preparations are particularly suitable for the production of PSA-derivatised therapeutic agents intended for use in humans and animals.

Abstract: Derivatives are synthesised of starting materials, usually polysaccharides, having sialic acid at the reducing terminal end, in which the reducing terminal unit is transformed into an aldehyde group. Where the polysaccharide has a sialic acid unit at the non-reducing end it may be passivated, for instance by converting into hydroxyl-substituted moiety. The derivatives may be reacted with substrates, for instance containing amine or hydrazine groups, to form non-cross-linked polysialylated compounds. The substrates may, for instance, be therapeutically useful drugs peptides or proteins or drug delivery systems.

Abstract: The invention relates to a set of novel immunological adjuvants based upon so called “polyladder” proteins of nematode worms. These proteins are typified by repeating units separated by a protease cleavage motif of RX(K/R)R or RXFR where R is ariginine, X is any amino acid, K is lysine and F is phenylalanine. These motifs are preceded by a cysteine residue at around 7, 8 or 9 residues upstream. Polyladder proteins or fragments of polyladder proteins may be used as immunological adjuvants either mixed with, or conjugated to a vaccine antigen, and will strongly enhance the immune response against the antigen. Conjugation may take the form of a genetic fusion between adjuvant and antigen. Antigens may be derived from pathogens, or may be tumour antigens, autoantigens, or antigens of other kinds. Vaccines may be used for prophylaxis or therapy.

Abstract: A polysialic acid compound is reacted with a hetero-bifunctional reagent to introduce a pendant functional group for site-specific conjugation to sulfhydryl groups, for instance side chains of cysteine units in drugs, drug delivery systems, proteins or peptides. The functional group is, for instance, an N-maleimide group.

Abstract: An atomizing injector includes a metering set having a swirl chamber, a spray orifice and one or more feed slots etched in a thin plate. The swirl chamber is etched in a first side of the plate and the spray orifice is etched through a second side to the center of the swirl chamber. Fuel feed slots extend non-radially to the swirl chamber. The injector also includes integral swirler structure. The swirler structure includes a cylindrical air swirler passage, also shaped by etching, through at least one other thin plate. The cylindrical air swirler passage is located in co-axial relation to the spray orifice of the plate of the fuel metering set such that fuel directed through the spray orifice passes through the air swirler passage and swirling air is imparted to the fuel such that the fuel has a swirling component of motion. At least one air feed slot is provided in fluid communication with the air swirler passage and extends in non-radial relation thereto.

Abstract: We describe a conjugate comprising an anti-CD40 or anti-CD28 antibody and antigen wherein said conjugate has low antibody valency and including methods to prepare said conjugate.

Abstract: A composition for the co-delivery to a cell of a nucleic acid and an assistor protein, comprising vesicles, nucleic acid and protein, wherein the nucleic acid operatively encodes an antigenic protein or portion thereof which shares at least one epitope with the assistor protein, the composition comprising said nucleic acid and said assistor protein associated with the same vesicles as one another. A preferred embodiment is a composition comprising liposomes formed from liposome forming materials and, associated with the liposomes, nucleic acid operatively encoding an antigenic protein and an assistor protein, wherein the assistor protein shares at least one epitope with the antigenic protein. The composition is for use as a vaccine and provides improved immune response compared to non-vesicular compositions, or mixtures of liposomes some of which are associated with nucleic acid and some of which are associated with assistor protein.

Abstract: A gas turbine engine fuel injector conduit includes a single feed strip having a single bonded together pair of lengthwise extending plates. Each of the plates has a single row of widthwise spaced apart and lengthwise extending parallel grooves. Opposing grooves in each of the plates are aligned forming internal fuel flow passages through the strip from an inlet end to an outlet end. The feed strip includes a substantially straight middle portion between the inlet end and the outlet end. In one alternative, the middle portion has a radius of curvature greater than a length of the middle portion. The feed strip has at least one acute bend between the inlet end and the middle portion and a bend between the outlet end and the middle portion. The feed strip has fuel inlet holes in the inlet end connected to the internal fuel flow passages.

Abstract: A fuel injector assembly for dispensing fuel in the combustion chamber of a gas turbine engine, includes in one embodiment an elongated, multi-layered, convoluted nozzle feed strip having an internal passage for directing fuel through the length of the strip from the inlet end to an outlet end; and a cylindrical, multi-layered fuel dispensing nozzle unitary with the feed strip and fluidly connected to the outlet end of the feed strip for dispensing the fuel. The multi-layered feed strip and nozzle allow complex porting of fuel circuits through the injector. The internal fluid passages through the feed strip and nozzle are formed by etching. In another embodiment, the feed strip can be used for directing fuel from the manifold to one or more fuel injectors.