Other

Cambridge Enterprise Limited

Schuh, Andre

Willem Ouwehand

Andre Schuh

Peter Alexander Smethurst

Roger Pedersen

Richard William Farndale

Richard Willam Farndale

Matthew Trotter

Thomas Moreau

Cedric Ghevaert

This invention relates to the forward programming of pluripotent stem cells (PSCs) into megakaryocyte (MK) progenitor cells using the transcription factors GATA1, FLI1 and TAL1. Methods of producing megakaryocyte (MK) progenitor cells and subsequently differentiating them into mature megakaryocytes are provided.

Transcription factor mediated programming towards megakaryocytes

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

Based on the discovery of the nucleotide and amino acid differences which distinguish the Govand Govallelic forms of the membrane glycoprotein CD109, and which comprise the biallelic Gov platelet alloantigen system, compositions and methods are provided for determining the Gov genotype and phenotype of individuals. Also provided, on the basis of this discovery, are compositions and methods for treating disorders associated with Gov alloantigen incompatibility, such as the bleeding disorders post-transfusion purpura, post-transfusion platelet refractoriness, and neonatal alloimmune thrombocytopenia. The two allelic forms of CD109 differ by a single amino acid. The Govallelic form has Tyr at amino acid position 703 in the CD109 sequence. The Govallelic form has Ser at the same position. This amino acid difference is due to a single change, from A for the Govallele to C for the Govallele, in the CD109 gene.

Antibodies for diagnosis and treatment of blood platelet alloimmune disorders

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.

Diagnosis of abnormal blood conditions based on polymorphisms in the glycoprotein VI gene

Diagnosis and treatment of blood disorders

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Cambridge, United Kingdom

Willem Ouwehand