Abstract: The invention provides bispecific polypeptides comprising a first binding domain, designated B1, which is capable of binding specifically to CD137, and a second binding domain, designated B2, which is capable of specifically binding to a tumour cell-associated antigen. Also provided are pharmaceutical compositions of such bispecific polypeptides and uses of the same in medicine.

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 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 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 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.

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 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 present invention provides an immunomodulatory agent for use in the local treatment of tumours, wherein the treatment comprises patient-specific optimisation 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 tumours as well as methods for optimising treatments for 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 provides a polypeptide having a biological activity of the Chemotaxis Inhibitory Protein of Staphylococcus aureus (‘CHIPS’), the polypeptide comprising a variant of the amino acid sequence of SEQ ID NO:1. Preferably, the polypeptide is a CHIPS variant wherein one or more of the following amino acids is modified: N31, S32, G33, L34, P35, K40, D42, R46, Y48, K50, G52, T53, K54, N55, S56, A57, Q58, K61, E67, K69, L76, N77, P79, D83, L90, K92, K100, K101, S104, K105, S107, Y108, N111 and G112. In a preferred embodiment, the polypeptide is less immunogenic hi humans than the wildtype CHIPS protein. The invention further provides methods of making and using such variant CHIPS polypeptides.

Abstract: A method to make libraries of hybrid polynucleotide molecules of two parental polynucleotide molecules utilizing single-stranded DNA was invented. Example of the method comprises several steps: (i) preparation of two single-stranded polynucleotide molecules comprising sequences containing one or more parts of homology and one or more parts of heterology, (ii) random or non-random fragmentation of said polynucleotides, (iii) hybridization of the fragmented molecules followed by de novo polynucleotide synthesis (i.e. polynucleotide chain elongation) on the hybridized molecules, (iv) separation of the chain elongation products (i.e. double-stranded polynucleotide molecules) into single-stranded polynucleotide molecules (denaturation) (v) hybridization of the resultant single-stranded polynucleotide molecules followed by de novo polynucleotide synthesis on the hybridized molecules, and (vi) repeating at least two further cycles of steps (iv) and (v).

Abstract: The invention provides a method for generating a polynucleotide sequence or population of sequences from parent single stranded polynucleotide sequences encoding one or more protein motifs, comprising the steps of a) providing single stranded DNA constituting plus and minus strands of parent polynucleotide sequences; b) digesting the single stranded polynucleotide sequences with a nuclease other than DNase I to generate populations of single stranded fragments; c) contacting the fragments generated from the plus strands with fragments generated from the minus strands and optionally, adding primer sequences that anneal to the 3? and 5? ends of at least one of the parent polynucleotides under annealing conditions; and d) amplifying the fragments that anneal to each other to generate at least one polynucleotide sequence encoding one or more protein motifs having altered characteristics as compared to the one or more protein motifs encoded by the parent polynucleotides.

Abstract: A method to make libraries of hybrid polynucleotide molecules of two parental polynucleotide molecules utilizing single-stranded DNA was invented. Example of the method comprises several steps: (i) preparation of two single-stranded polynucleotide molecules comprising sequences containing one or more parts of homology and one or more parts of heterology, (ii) random or non-random fragmentation of said polynucleotides, (iii) hybridization of the fragmented molecules followed by de novo polynucleotide synthesis (i.e. polynucleotide chain elongation) on the hybridized molecules, (iv) separation of the chain elongation products (i.e. double-stranded polynucleotide molecules) into single-stranded polynucleotide molecules (denaturation) (v) hybridization of the resultant single-stranded polynucleotide molecules followed by de novo polynucleotide synthesis on the hybridized molecules, and (vi) repeating at least two further cycles of steps (iv) and (v).

Abstract: The invention provides a method for generating a polynucleotide sequence or population of sequences from parent single stranded polynucleotide sequences encoding one or more protein motifs, comprising the steps of a) providing single stranded DNA constituting plus and minus strands of parent polynucleotide sequences; b) digesting the single stranded polynucleotide sequences with a nuclease other than DNase I to generate populations of single stranded fragments; c) contacting said fragments generated from the plus strands with fragments generated from the minus strands and optionally, adding primer sequences that anneal to the 3? and 5? ends of at least one of the parent polynucleotides under annealing conditions; d) amplifying the fragments that anneal to each other to generate at least one polynucleotide sequence encoding one or more protein motifs having altered characteristics as compared to the one or more protein motifs encoded by said parent polynucleotides.

Abstract: The present invention relates to a new protein of the bacteria Straphylococcus aureus with immunomodulating properties. The invention further relates to the manufacture of a therapeutic composition as general inflammation inhibitor and for the treatment of AIDS, and also the use of antibodies against CHIPS for the treatment of Staphylococcus infections.

Abstract: The invention relates to nucleic acid molecules encoding (poly)peptides having chemotaxis inhibiting (poly)peptides CHIPS activity, to recombinant vectors harboring such molecules, and the host cells carrying the vectors. The invention further relates to methods for preparing recombinant (poly)peptides having CHIPS activity and to the use of such recombinant (poly)peptides having CHIPS activity for diagnosis, prophylaxis and treatment, such as the treatment of inflammation reactions and HIV. In addition, the invention provides therapeutic and diagnostic compositions comprising as the active ingredient the (poly)peptide having CHIPS activity.