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Publication Number
US-9913876-B2
Publication Date
2018-03-13
Expiration Date
Abstract
A biogel, and kits, agents, and methods for formation of the biogel are described. The biogel can be used for a variety of applications, including haemostasis, wound sealing, tissue engineering or localized drug delivery.
Core Innovation
The invention provides a soluble agent for formation of a biogel. The agent comprises one or more soluble carriers, each having a plurality of fibrinogen binding moieties covalently immobilized, and each carrier comprises at least one of a protein and a biocompatible polymer. The agent is configured so that when contacted with a plurality of fibrinogen molecules when thrombin is absent, a biogel is formed comprising fibrinogen molecules and a plurality of carriers.
In the biogel, each fibrinogen molecule binds at least two fibrinogen binding moieties. This links the fibrinogen molecules together via the carriers by non-covalent bonds between the fibrinogen binding moieties and the fibrinogen molecules. The fibrinogen binding moiety is a peptide comprising an amino acid sequence NH2-G(P,H)RX- as set forth in SEQ ID NO: 15 at its amino terminal end, where X is any amino acid and either proline or histidine is present at position (P,H) in the amino acid sequence.
The invention also provides a biogel comprising fibrinogen molecules and a plurality of soluble carriers. Each soluble carrier has a plurality of fibrinogen binding moieties covalently immobilized, and each fibrinogen molecule is bound to at least two fibrinogen binding moieties, linking the fibrinogen molecules together via the soluble carriers by non-covalent bonds. The biogel is formed by contacting the soluble carriers with a plurality of fibrinogen molecules when thrombin is absent.
Claims Coverage
The document provides two independent claims: a soluble agent for forming a fibrinogen-based biogel without thrombin, and the corresponding biogel itself formed by contacting fibrinogen with thrombin-absent carriers. Across these claims, the core coverage is built around multiple covalently immobilized fibrinogen binding moieties on soluble carriers that non-covalently link fibrinogen molecules via at least two moieties per fibrinogen molecule, using the NH2-G(P,H)RX- peptide motif (SEQ ID NO:15).
Thrombin-absent soluble agent with multi-immobilized fibrinogen binding moieties
A soluble agent for formation of a biogel comprising one or more soluble carriers, each having a plurality of fibrinogen binding moieties covalently immobilized, where each carrier comprises at least one of a protein and a biocompatible polymer, and where each fibrinogen binding moiety is a peptide comprising NH2-G(P,H)RX- as set forth in SEQ ID NO:15 at its amino terminal end; upon being contacted with a plurality of fibrinogen molecules when thrombin is absent, the agent forms a biogel comprising fibrinogen molecules and a plurality of carriers such that each fibrinogen molecule binds at least two fibrinogen binding moieties and fibrinogen molecules are linked via non-covalent bonds between the moieties and fibrinogen molecules.
Thrombin-absent fibrinogen biogel linked by carriers via non-covalent bonds
A biogel comprising fibrinogen molecules and a plurality of soluble carriers, wherein each soluble carrier has a plurality of fibrinogen binding moieties covalently immobilized and each fibrinogen molecule is bound to at least two fibrinogen binding moieties so that fibrinogen molecules are linked together via the soluble carriers by non-covalent bonds between the fibrinogen binding moieties and the fibrinogen molecules, where each soluble carrier comprises at least one of a protein and a biocompatible polymer, and wherein each fibrinogen binding moiety is a peptide comprising NH2-G(P,H)RX- as set forth in SEQ ID NO:15 at its amino terminal end, wherein the biogel is formed by contacting the soluble carriers with fibrinogen molecules when thrombin is absent.
Overall claim coverage centers on thrombin-absent assembly of a fibrinogen-based biogel through multivalent, covalently immobilized peptide fibrinogen binding moieties on soluble carriers. In both independent claims, fibrinogen molecules bind at least two moieties and are linked together through carriers by non-covalent bonds, using the NH2-G(P,H)RX- peptide motif defined by SEQ ID NO:15.
Stated Advantages
Provides biogel formation comprising fibrinogen molecules when thrombin is absent.
Links fibrinogen molecules together via the carriers by non-covalent bonds between fibrinogen binding moieties and fibrinogen molecules.
Avoids forming the biogel by contacting fibrinogen with thrombin (thrombin is absent).
Documented Applications
Controlling bleeding by topically administering the biogel to a bleeding site.
Treating or sealing a wound by topically administering the biogel to a wound site.
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