Medimmune Limited

Daniel Ramsay Higazi

Ross Anthony Stewart

Nicholas Durham

Diane Hatton

Monika Anna Papworth

Sudharsan Sridharan

Suzanne J Gibson

Thomas Vincent Murray

Natalie Jo Tigue

Lesley Lynn Young

Nicholas J Bond

Sarah Milne

Lisa Bamber

Katarzyna Anna Kozakowska

Mariana Alessia Sheriff

Rebecca Leyland

Emmanuel Rossy

Adam Tibbles

The present invention relates to recombinant polypeptide therapeutics having an engineered O-linked amino acid (AA) glycosylation sequence (motif), which is covalently linked to O-glycan(s) (tag). Recombinant O-glycosylated polypeptides may be produced in mammalian cells to present natural or un-natural O-glycan structures through metabolic labelling.

Engineered O-glycosylation in recombinant polypeptides and uses thereof

We discovered that recombinant antibody light chains having a murine secretory leader sequence and an SYE motif at the N-terminus are truncated during post-translational processing. This disclosure provides two protein engineering solutions: to alter the SYE amino acid sequence of the Lc N-terminus to other alternatives; or to change the secretory leader peptide sequence. We have shown that both of these solutions are effective for preventing N-terminal light chain truncation.

Prevention of N-terminal truncation in IgG light chains

The disclosure provides GITRL fusion polypeptide subunits comprising an IgG Fc domain, a trimerization domain, and the receptor binding domain of GITR ligand, where the fusion polypeptide subunits can self-assemble into hexameric proteins. Also provided are methods of making fusion polypeptide subunits and hexameric proteins, and methods of use, e.g., treatment of cancer.

GITRL fusion proteins comprising a human coronin 1a derived trimerization domain

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Cambridge, United Kingdom

Daniel Ramsay Higazi