Procoagulant compounds
First Claim
1. A procoagulant compound comprising a formula Pep2-Zy-Bx-Pep1, whereinPep2 is a light chain of FVII;
- Zy is a synthetic thrombin substrate;
Bx is a self-immolative spacer; and
Pep1 is a heavy chain of FVII.
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Accused Products
Abstract
The present disclosure provides protease-activatable procoagulant compounds comprising a procoagulant polypeptide, e.g., a procoagulant peptide and/or clotting factor, and a linker comprising a protease-cleavable substrate (e.g., a synthetic thrombin substrate) and a self-immolative spacer (e.g., p-amino benzyl carbamate). Upon cleavage of the protease-cleavable substrate by a protease (e.g., thrombin), the self-immolative spacer cleaves itself from the procoagulant polypeptide such that the polypeptide is in an underivatized and active form. Also provided are pharmaceutical compositions, methods for treating bleeding disorders using the disclosed compounds, methods of enhancing in vivo efficacy of procoagulant polypeptides, methods of increasing the efficacy of proteolytic cleavage of compounds comprising procoagulant polypeptides, methods of activating procoagulant polypeptides, and methods of releasing a procoagulant polypeptide from a heterologous moiety such as PEG.
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Citations
11 Claims
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1. A procoagulant compound comprising a formula Pep2-Zy-Bx-Pep1, wherein
Pep2 is a light chain of FVII; -
Zy is a synthetic thrombin substrate; Bx is a self-immolative spacer; and Pep1 is a heavy chain of FVII. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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Specification