Thrombin C-Terminal Polypeptides for Excessive Coagulation Treatment
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Solution Overview
Problem
Current treatments lack effective agents for preventing or treating excessive blood coagulation, which can lead to conditions such as thrombosis and disseminated intravascular coagulation (DIC), especially in response to injury or foreign material contact.
Innovation Solution
Development of specific polypeptides derived from the C-terminal region of thrombin, which exhibit anti-inflammatory and anti-coagulant activities, potentially released during wounding or physiological challenges, comprising sequences like GKYGFYTHVFRLKKWIQKVIDQFGE, to inhibit coagulation processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If thrombin is used to promote coagulation, then clot formation is improved, but excessive coagulation and thrombosis occur
Solution Approach 1:
The thrombin molecule is segmented into two functional parts: the N-terminal region (residues 1-254) that promotes coagulation, and the C-terminal region (residues 255-577) that prevents excessive coagulation. By isolating and administering the C-terminal polypeptide separately, the patent achieves segmentation of thrombin's dual functions, allowing selective anti-coagulant therapy without interfering with normal clot formation processes.
Solution Approach 2:
The C-terminal polypeptide (residues 255-577) is extracted from the complete thrombin molecule and administered as a separate therapeutic agent. This extraction allows the anti-coagulant properties of the C-terminal region to be utilized independently, providing a targeted treatment for excessive coagulation disorders while leaving the N-terminal coagulation-promoting function intact in the body.
2Object-generated harmful factors
If conventional anti-coagulant treatments are used, then excessive coagulation is reduced, but effective therapeutic agents are lacking
Solution Approach 1:
The invention changes the molecular parameter by using a different structural region of thrombin (the C-terminal polypeptide residues 255-577) compared to conventional treatments. This parameter change in molecular structure provides a novel therapeutic agent with specific anti-coagulant properties that overcomes the limitations of existing treatments.
Solution Approach 2:
The C-terminal polypeptide is synthesized as a recombinant copy of the natural thrombin C-terminal region. This copying approach allows production of the therapeutic agent through recombinant DNA technology, making it manufacturable while retaining the exact amino acid sequence (residues 255-577) that provides the anti-coagulant activity.
Data Source
Figure 1A~1B
Figure 2A~2F
Figure 3A~3D
AI summary
The present invention provides polypeptides comprising or consisting of an amino acid sequence from thrombin, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant or derivative thereof, for use in the treatment or prevention of inflammation and/or excessive coagulation of the blood. Related aspects of the invention provide isolated polypeptides comprising or consisting of an amino acid sequence of any one of SEQ ID NOs: 1 to 7, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant or derivative thereof, which exhibit an anti-inflammatory activity, together with isolated nucleic acid molecules, vectors and host cells for making the same. Additionally provided are pharmaceutical compositions comprising a polypeptide of the invention, as well as methods of use of the same in the treatment and/or prevention of inflammation and/or excessive coagulation.