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Cambridge Enterprise Limited

Peter Alexander Smethurst

Willem Ouwehand

Richard William Farndale

Richard Willam Farndale

Specific binding members directed to human glycoprotein VI (GPVI), in particular human antibodies, may employ the antibody VH and/or VL domain of the scFv fragment herein termed 10B12 or one or more complementarity determining regions (CDRs) of the 10B12 heavy chain variable (VH) and/or light chain variable (VL) domains, especially VH CDR3 in other antibody framework regions. Antibody molecules are provided with advantageous and unexpected properties, especially ability to inhibit collagen-induced platelet aggregation and the adhesion of platelets to Collagen-Related Peptide (CRP). Domain 1 of human GPVI is a primary target for the 10B12 antibody with these properties, and the epitope includes lysine 59.

Human antibodies against human glycoprotein VI and their use

Methods of diagnosis of abnormal blood conditions associated with an increased risk of bleeding are described. Subjects homozygous or heterozygous for the GPVIallele are at considered to be at increased risk of bleeding. Kits for carrying out the methods of diagnosis, and use of the methods and kits for determining the GPVI allelotype of subjects in need of surgery, with a low platelet count, with an acquired bleeding disorder, on blood thinning drugs, or of blood donors is also described.

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Cambridge, United Kingdom

Peter Alexander Smethurst