Abstract: The present invention provides an antibody of the class IgG4 comprising at least one heavy chain which comprises a CH1 domain and a hinge region, wherein in each heavy chain: a. the inter-chain cysteine at position 127, numbered according to the Kabat numbering system, in the CH1 domain is substituted with another amino acid; and b. one or more of the amino acids positioned in the upper hinge region is substituted with cysteine.

Abstract: The present invention relates to the use of limited amounts of cysteine and tryptophan in the cell culture medium during production of recombinant proteins, and in particular antibodies. Proteins and antibodies produced under such controlled conditions exhibit reduced heterogeneity, in particular reduced charge variants heterogeneity.

Abstract: It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.

Abstract: The present invention relates to the area of improved anti-IgE antibodies and antigen binding agents, and compositions thereof, which target IgE, for instance: for use in treating disorders caused by IgE (such as allergic responses, or certain autoimmune responses); and, in particular, disorders caused by the interaction of IgE with the Fc?RI receptor. In particular, this invention relates to improved anti-IgE antibodies and antigen binding agents related to novel mutants of omalizumab (Xolair®). The improved anti-IgE antibodies and antigen binding agents of the invention may have improved affinity for IgE and/or an improved interaction with the C?2 domain of IgE and/or an improved modified epitope on IgE (for instance further involving the C?2 domain of IgE) and/or the ability to disassociate IgE from the Fc?RI receptor for instance at pharmaceutically-relevant concentrations.

Abstract: Thiophene derivatives of formula (I) and a pharmaceutically acceptable salt thereof are provided. These compounds have utility for the treatment or prevention of disorders caused by IgE, such as allergy, type 1 hypersensitivity or familiar sinus inflammation.

Abstract: The invention relates to 9H-pyrrolo-dipyridine derivatives of formula I, processes for preparing them, pharmaceutical compositions containing them and their use as radiopharmaceuticals in particular as imaging agents for the detection of Tau aggregates.

Abstract: The present invention provides antibodies comprising a variable (V) domain and an insert polypeptide, wherein the insert polypeptide is within the framework 3 region of the V domain.

Abstract: The present invention relates to methods for the treatment of fibrosis. The invention discloses new research which demonstrates that interferon-lambda has directly acting anti-fibrotic effects both in vitro and in vivo and may be used to provide effective new therapies for the treatment of multiple types of fibrosis.

Abstract: Methods and associated apparatus involving designing a ligand ab initio that will bind to a binding site of a macromolecular target, or of identifying a modification to a ligand for improving the affinity of the ligand to a binding site of a macromolecular target, comprising using information about non-bonding, intra-molecular or inter-molecular atom to atom contacts extracted from a database of biological macromolecules to identify favoured regions adjacent to the binding site for particular atom types and modifying a candidate ligand to increase the intersection between atoms of the candidate ligand and the favoured regions. One or more steps of the methods may be performed by a computer.

Abstract: The invention relates to antibody molecules having specificity for antigenic determinants of both IL-17A and IL-17F, therapeutic uses of the antibody molecules and methods for producing said antibody molecules.

Abstract: A series of fused pentacyclic imidazole derivatives, being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders. In particular, the present invention is concerned with 6, 7-dihydro-7, 14-methanobenzimidazo[1, 2-b][2,5]benzodiazocin-5(14H)-one derivatives and analogs thereof.

Abstract: The present invention relates to a process for purification a protein comprising a semi-continuous chromatography step whereby the flow-through is collected and re-loaded onto the chromatography matrix.

Abstract: The present invention relates to a method of treating an autoimmune or inflammatory disease or a neurodegenerative disease with an antibody to CD154.

Abstract: The present invention relates to methods for the treatment of fibrosis. The invention discloses new research which demonstrates that interferon-lambda has directly acting anti-fibrotic effects both in vitro and in vivo and may be used to provide effective new therapies for the treatment of multiple types of fibrosis.

Abstract: The present invention relates to pharmaceutical compositions comprising from an antibody or a fragment thereof which binds IL-17A and IL-17F and a combination of glycine, acetate buffer at pH 4.6 to 5.5 and polysorbate 80.

Abstract: The present invention relates to methods for reducing the heterogeneity of a population of recombinant proteins produced in cell culture, said methods comprising growing host cells producing a recombinant protein in a cell culture medium wherein the cell culture medium comprises one or more cysteine/cystine analogs.

Abstract: The present invention provides method for increasing the percentage of monomer in a composition of recombinantly expressed antibody molecules characterised in that the antibody molecule comprises at least one Fv with specificity for an antigen of interest comprising one VH and one VL wherein said VH and VL are connected directly or indirectly via one or more linkers and are stabilised by a disulfide bond therebetween, said method comprises a) a thermal conversion step of holding the composition comprising the antibody molecule at a temperature in the range 30 to 60° C. for a period of at least 1 hour, wherein step a) is performed in the presence of a reducing agent or after treatment with a reducing agent.

Abstract: This invention relates to crystals of the human Gremlin-1 protein, and the human Gremlin-1 protein in complex with an inhibitory antibody. The invention also relates to the structure of human Gremlin-1 (on its own, or in complex with the antibody) and uses of these structures in screening for agents which modulate Gremlin-1 activity. The invention further provides antibodies which bind an allosteric inhibitory site on Gremlin-1, together with pharmaceutical compositions and medical uses of such antibodies and agents identified by the screening methods.

Abstract: The present invention provides method of increasing the percentage of monomer in a composition of recombinantly expressed antibody molecules characterised in that the antibody molecule comprises at least one Fv with specificity for an antigen of interest comprising one VH and one VL wherein said VH and VL are connected directly or indirectly via one or more linkers and are stabilised by a disulfide bond therebetween, said method comprises: a) a conversion step of treating the composition with a denaturant selected from urea and/or Guanidine hydrochloride; b) wherein step a) is performed in the presence of a reducing agent or after treatment with a reducing agent.

Abstract: CDR-grafted antibody heavy and light chains comprise acceptor framework and donor antigen binding regions, the heavy chains comprising donor residues at at least one of positions (6, 23) and/or (24, 48) and/or (49, 71) and/or (73, 75) and/or (76) and/or (78) and (88) and/or (91). The CDR-grafted light chains comprise donor residues at at least one of positions (1) and/or (3) and (46) and/or (47) or at at least one of positions (46, 48, 58) and (71). The CDR-grafted antibodies are preferably humanized antibodies, having non human, e.g. rodent, donor and human acceptor frameworks, and may be used for in vivo therapy and diagnosis. A generally applicable protocol is disclosed for obtaining CDR-grafted antibodies.