Abstract: A composition comprising a TLR2 antagonistic antibody or antigen binding fragment thereof for use in the treatment or prophylaxis of pancreatic cancer is provided. The antibody or antigen binding fragment may be provided for simultaneous, separate or sequential administration with a secondary chemotherapeutic agent such as gemcitabine, and optionally a tertiary chemotherapeutic agent such as abraxane for enhanced treatment. Also provided is a screening method for the identification of compounds for use in treatment or prevention of pancreatic cancer.

Abstract: The present invention relates to the identification of a TLR2 binding epitope wherein binding of a binding member to the epitope serves to inhibit TLR2 activation and/or signalling. Polypeptide fragments of TLR2 and three-dimensional structures comprising one or more amino acid residues His318, Pro320, Gln321 or Arg321, Tyr323, Lys347, Phe349, Leu371, Glu375, Tyr376 and His398 of TLR2 which define the identified epitope are provided for use in generating binding members. Also provided are binding members which bind to the identified epitope and methods of using same for the treatment and/or prevention of conditions associated with TLR2 activation and/or signalling.

Abstract: A fully humanized antibody having binding specificity to Toll-like Receptor 2 comprises a light chain and a heavy chain entirely comprised of amino acid sequence of human origin. The variable region of the light chain comprises an amino acid sequence which is substantially homologous with the sequence of SEQ ID NO:1, while the variable region of the heavy domain comprises an amino acid sequence which is substantially homologous with the sequence of SEQ ID NO:4. Also provided are nucleic acids encoding such antibodies, as well as the use of the antibodies in medicine, in particular for the treatment of inflammatory and autoimmune diseases which are mediated by Toll-like Receptor 2 activation and signalling.

Abstract: The present invention relates to compositions and methods for use in the treatment of conditions such as septicaemia and septic shock. The invention further provides compositions and methods for the suppression Toll-like Receptor 4 mediated activation of the immune system. The invention further provides screening assays to identify compounds which have utility in the foregoing compositions and methods.

Abstract: Disclosed are assays for the determination and quantification of the phosphorylation of TRAM (Trif-related adaptor molecule). TRAM is rapidly phosphorylated upon LPS stimulation by protein kinase C epsilon (PKC?) and that this phosphorylation is vital for TRAM to function normally. Assays suitable for detecting the state of phosphorylation of TRAM have utility in identifying compounds which have activity in modulating TRAM. Further disclosed are compounds which have utility in modulating the phosphorylation of TRAM to modulate signalling mediating by the Toll Like Receptor 4 (TLR4) receptor.

Abstract: A fully humanised antibody having binding specificity to Toll-like Receptor 2 comprises a light chain and a heavy chain entirely comprised of amino acid sequence of human origin. The variable region of the light chain comprises an amino acid sequence which is substantially homologous with the sequence of SEQ ID NO:1, while the variable region of the heavy domain comprises an amino acid sequence which is substantially homologous with the sequence of SEQ ID NO:4. Also provided are nucleic acids encoding such antibodies, as well as the use of the antibodies in medicine, in particular for the treatment of inflammatory and autoimmune diseases which are mediated by Toll-like Receptor 2 activation and signalling.

Abstract: The present invention relates to the identification of an epitope defined by residues of Toll-like Receptor (2). Targeting a binding compound, such as an antibody to the epitope results in antagonism of Toll-like Receptor (2). Further provided by the invention is the use of polypeptide comprising amino acid residues which form the epitope for use in screening for binding compounds which bind thereto, as well as to polypeptide compound which comprise the amino acid sequences of the epitope for use as vaccine compositions, when the generation of antagonistic antibodies which have binding specificity to Toll-like Receptor (2) are required, for example in the treatment of Toll-like Receptor (2) mediated disease conditions.