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Targeting tissue factor to activated platelets

a technology of activated platelets and tissue factors, which is applied in the direction of fusions for specific cell targeting, peptides/protein ingredients, peptides, etc., can solve the problems of insufficient production at this point, insufficient blood coagulation, and potentially life-threatening bleeding

Inactive Publication Date: 2012-07-12
NOVO NORDISK AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a fusion protein that targets activated platelets to promote blood clotting. The fusion protein comprises a tissue factor polypeptide and a ligand that binds to a receptor on the surface of activated platelets. The ligand can be a monoclonal antibody or an isolated complementarity determining region. The fusion protein can be used as a medicament for the treatment of coagulopathies. The technical effect of the invention is to provide a novel approach for promoting blood clotting and treating coagulopathies.

Problems solved by technology

Although fibrin is produced during the primary hemostatic response, via the so-called coagulation initiation (independent of FIX / FVIIIa), the amount produced at this point is insufficient for a strong coagel.
Such dysfunction of one part of coagulation results in insufficient blood coagulation and potentially lifethreatening bleeding.

Method used

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  • Targeting tissue factor to activated platelets
  • Targeting tissue factor to activated platelets
  • Targeting tissue factor to activated platelets

Examples

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embodiment 1

[0303]A fusion protein comprising (i) at least one tissue factor polypeptide, or biologically functional variant(s) or fragment(s) thereof, and (ii) a ligand that is capable of binding (iii) a receptor, and / or a fragment or variant thereof, wherein the receptor is present only on the surface of activated platelets.

embodiment 2

[0304]The fusion protein according to embodiment 1, wherein (iii) is TLT-1 or a fragment or variant thereof.

embodiment 3

[0305]The fusion protein according to embodiment 2, wherein (iii) is TLT-1 (16-162).

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Abstract

The current invention relates to procoagulant fusion proteins, polynucleotides that encode said fusion proteins and cells that expresses said fusion proteins. Furthermore, the current invention relates to fusion proteins for use as a medicament. Individuals that have a coagulopathy, such as haemophilia A and B with or without inhibitors, may be treated with fusions proteins of the current invention.

Description

FIELD OF THE INVENTION[0001]The current invention relates to procoagulant fusion proteins, a polynucleotides that encode said procoagulant fusion proteins, cells that expresses said procoagulant fusion protein and uses thereof.BACKGROUND OF THE INVENTION[0002]Tissue factor (TF), a transmembrane glycoprotein, is the primary cellular initiator of blood coagulation. It is predominantly expressed on the surface of sub-endothelial cells, such as smooth muscle cells and fibroblasts, and binds both zymogen coagulation Factor VII (FVII) and the activated form, Factor VIIa (FVIIa) when the integrity of the endothelium is interrupted, such as when blood vessels are severed. When TF binds FVII, it promotes FVII to FVIIa activation. TF also greatly enhances the proteolytic activity of Factor VIIa towards its physiologic substrates, Factors IX and X. FVIIa retains a zymogen-like state in solution, acting as a relatively poor enzyme. TF provides a scaffold for optimal macromolecular exosite inter...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K19/00C07K16/28
CPCA61K38/00C07K14/745C07K16/2803C07K2319/33C07K2317/34C07K2317/55C07K2317/64C07K2317/31C07K2317/21C07K2317/24C07K2317/51C07K2317/515C07K2317/524C07K2317/526C07K2317/53C07K2317/56C07K2317/92
Inventor HILDEN, IDAPETERSEN, LARS CHRISTIANBREINHOLT, JENSANDERSEN, METTE DAHLBJEIKE, JAIS ROSEEGEBJERG, THOMAS
Owner NOVO NORDISK AS