Abstract: The present invention relates to novel bispecific polypeptides, such as antibodies, and their use in the treatment of cancers, particularly cancers expressing carcinoembryonic antigen (CEA).

Abstract: The present invention provides a bispecific polypeptides, such as bispecific antibodies, comprising a first binding domain capable of specifically binding to a first T cell target, and a second binding domain capable of specifically binding to a second T cell target, wherein the first and second T cell targets are different targets. The invention further provides compositions of said bispecific polypeptides, as well as methods and uses of the same.

Abstract: The present disclosure relates to protein molecules that specifically bind to 5T4 and/or 4-1BB. The molecules may have at least one humanized 5T4-binding or 4-1BB-binding domain. Such molecules are useful for the treatment of cancer. The protein molecule binding to 5T4 or 4-1BB may have a second binding domain that binds to another target. The molecules may bind both 5T4-expressing cells and a cell-surface molecule expressed by an effector cell to enhance effector cell activation, proliferation, survival and/or effector-cell mediated cytotoxicity. The disclosure also provides pharmaceutical compositions comprising the 5T4-binding or 4-1BB-binding polypeptide or protein molecules, nucleic acid molecules encoding these polypeptides and methods of making and using these molecules.

Abstract: The present invention relates to antibodies (and fragments, variants, fusions and derivatives thereof) with binding specificity for domain 2 of human CD137 which are capable of inhibiting the binding of a reference antibody to human CD137. The antibodies and fragments have utility in the treatment of diseases such as cancer. The invention also relates to pharmaceutical compositions, uses, methods and kits comprising such antibodies.

Abstract: The present disclosure relates to protein molecules that specifically bind to 5T4 and/or 4-1BB. The molecules may have at least one humanized 5T4-binding or 4-1BB-binding domain. Such molecules are useful for the treatment of cancer. The protein molecule binding to 5T4 or 4-1BB may have a second binding domain that binds to another target. The molecules may bind both 5T4-expressing cells and a cell-surface molecule expressed by an effector cell to enhance effector cell activation, proliferation, survival and/or effector-cell mediated cytotoxicity. The disclosure also provides pharmaceutical compositions comprising the 5T4-binding or 4-1BB-binding polypeptide or protein molecules, nucleic acid molecules encoding these polypeptides and methods of making and using these molecules.

Abstract: The present invention relates to combination therapies for treating a solid tumour in a subject. The combination therapies comprise (a) an antibody, or antigen-binding portion thereof, that specifically binds to CD40, and (b) a further immunotherapeutic agent with efficacy in the treatment of cancer, which agent is not an anti-CD40 antibody or antigen-binding fragment thereof. The invention also relates to a kits and methods of using such therapies.

Abstract: The present invention provides bispecific polypeptides, such as bispecific antibodies, comprising a first binding domain capable of specifically binding to a first T cell target, and a second binding domain capable of specifically binding to a second T cell target, wherein the first and second T cell targets are different targets. The invention further provides compositions of said bispecific polypeptides, as well as methods and uses of the same. The first and/or second T cell target may be selected from the group consisting of OX40, CTLA-4, CD137, CD27, GITR and CD28.

Abstract: The present invention provides a bispecific polypeptides, such as bispecific antibodies, comprising a first binding domain capable of specifically binding to a first T cell target, and a second binding domain capable of specifically binding to a second T cell target, wherein the first and second T cell targets are different targets. The invention further provides compositions of said bispecific polypeptides, as well as methods and uses of the same.

Abstract: The present invention relates to antibodies (and fragments, variants, fusions and derivatives thereof) with binding specificity for domain 2 of human CD137 which are capable of inhibiting the binding of a reference antibody to human CD137. The antibodies and fragments have utility in the treatment of diseases such as cancer. The invention also relates to pharmaceutical compositions, uses, methods and kits comprising such antibodies.

Abstract: The present invention relates to antibodies (and fragments, variants, fusions and derivatives thereof) with multivalent binding specificity for CD40, which have a potency for dendritic cell activation which is higher than, or is equal to, the potency for B cell activation and wherein the antibody, antigen-binding fragment, or fusion, variant or derivative thereof has an affinity (KD) for CD40 of less than 1×10?10 M, which have utility in the treatment of diseases such as cancer. The invention also relates to pharmaceutical compositions, uses, methods and kits comprising such antibodies.

Abstract: The invention provides an antibody or fragment thereof that specifically binds to human CD40.

Abstract: The invention provides libraries of antibody molecules, libraries of nucleic acids encoding antibody molecules, methods of producing said libraries, and methods of using said libraries to select an antibody which specifically binds to an antigen. The libraries of antibody molecules include a plurality of different antibody variable domains generated by creating diversity in the CDR regions.

Abstract: The present disclosure relates to protein molecules that specifically bind to 5T4 and/or 4-1BB. The molecules may have at least one humanized 5T4-binding or 4-1BB-binding domain. Such molecules are useful for the treatment of cancer. The protein molecule binding to 5T4 or 4-1BB may have a second binding domain that binds to another target. The molecules may bind both 5T4-expressing cells and a cell-surface molecule expressed by an effector cell to enhance effector cell activation, proliferation, survival and/or effector-cell mediated cytotoxicity. The disclosure also provides pharmaceutical compositions comprising the 5T4-binding or 4-1BB-binding polypeptide or protein molecules, nucleic acid molecules encoding these polypeptides and methods of making and using these molecules.

Abstract: The invention provides a polypeptide that specifically binds to CTLA-4, particularly human CTLA-4.

Abstract: The present invention relates to antibodies (and fragments, variants, fusions and derivatives thereof) with multivalent binding specificity for CD40, which have a potency for dendritic cell activation which is higher than, or is equal to, the potency for B cell activation and wherein the antibody, antigen-binding fragment, or fusion, variant or derivative thereof has an affinity (KD) for CD40 of less than 1×10?10 M, which have utility in the treatment of diseases such as cancer. The invention also relates to pharmaceutical compositions, uses, methods and kits comprising such antibodies.

Abstract: The present invention provides pharmaceutical compositions comprising an immunostimulatory polypeptide and polyglutamic acid (PGA) nanoparticles, formulated in a pharmaceutically acceptable diluent, carrier or excipient. Such compositions have utility in stimulating the immune system in subjects, with the components capable of interacting synergistically. The invention further provides uses of the compositions of the invention, for example in the treatment of cancer, and kit and components for use in the same.

Abstract: The invention provides an isolated polypeptide comprising a variant amino acid sequence of SEQ ID NO: 1, or a fusion or derivative of said polypeptide, or a fusion of a said derivative thereof, wherein the polypeptide, fusion or derivative retains a biological activity of wild type IL-IRa. In one embodiment, the isolated polypeptide, fusion or derivative is or comprises a polypeptide variant of amino acid sequence SEQ ID NO: 1 comprising or consisting of substitutions at one or more of the following amino acid mutations of SEQ ID NO: 1: Q29K, P38Y, P38R, L42W, D47N, E52R, H54R, E90Y, Q129L, Q129N, M136N, M136D and Q149K. Also provided are pharmaceutical compositions of the above polypeptide, fusion or derivative, as well as uses of the same for treating a disease or condition capable of being treated by an agent which inhibits the function of IL-1 receptors.

Abstract: The present invention relates to antibodies (and fragments, variants, fusions and derivatives thereof) with multivalent binding specificity for CD40, which have a potency for dendritic cell activation which is higher than, or is equal to, the potency for B cell activation and wherein the antibody, antigen-binding fragment, or fusion, variant or derivative thereof has an affinity (KD) for CD40 of less than 1×10?10 M, which have utility in the treatment of diseases such as cancer. The invention also relates to pharmaceutical compositions, uses, methods and kits comprising such antibodies.

Abstract: The present invention provides an immunomodulatory agent for use in the local treatment of tumors, wherein the treatment comprises patient-specific optimization of the dose of the immunomodulatory agent to identify the maximum therapeutic dose that does not induce an increase in the number of local regulatory T cells (Treg cells) in the patient The invention further provides methods for the local treatment of tumors as well as methods for optimising treatments for the same.

Abstract: The present invention provides a polypeptide having a biological activity of the Chemotaxis Inhibitory Protein of Staphylococcus aureus (‘CHIPS’), the polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 2, or a fragment or variant thereof having a biological activity of CHIPS, wherein the fragment or variant retains amino acid substitutions K40E, D42V, N77H, K100R, K105R, N111 K and/or G112A relative to the wildtype CHIPS protein of SEQ ID NO:1. In one embodiment, polypeptide consists of the amino acid sequence of SEQ ID NO: 2. Related aspects of the invention provide pharmaceutical compositions comprising a polypeptide of the invention, together with methods or making and using the same.