Improved heparan sulfate and methods of making the same
AssigneeUniversity of Copenhagen
InventorsRebecca Louise Miller, Richard Karlsson, Zhang Yang, Jeremy E. Turnbull, Henrik Clausen
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Abstract
According to the invention there is provided methods for making heparan sulfate with increased anticoagulant activity wherein the resulting product has a lower heterogeneity and presents an improved safety profile compared to conventional animal-sourced heparin.
Claims21
A method of using a polypeptide having heparan sulfate glucosamine 3-O-sulfotransferase 4 (HS3ST4) activity to increase the anti-coagulant activity of heparan sulfate;
- the method comprising providing a heparan sulfate and treating the heparan sulfate with said polypeptide to produce a heparan sulfate having increased anticoagulant activity compared to heparan sulfate which is not treated with said polypeptide;
- wherein said polypeptide comprises a sequence with at least 80% identity to SEQ ID NO:1.
2-20. (canceled)
A genetically modified mammalian cell comprising a gene encoding a polypeptide comprising:
- an amino acid sequence represented by SEQ ID NO:1, or
- an amino acid sequence with at least 80% sequence identity to SEQ ID NO:1, such as at least 90% sequence identity to SEQ ID NO:1, such as at least 95% sequence identity to SEQ ID NO:1, such as at least 99% sequence identity to SEQ ID NO:1.
Heparan sulfate having anticoagulant activity and having no binding affinity for PF4, or reduced binding affinity for PF4 compared to heparan sulfate produced by one or more 3-O-sulfotransferases selected from HS3ST1, 2, 3A, 3B, 5 and/or 6.
Dependencies are inferred from the claim text.