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Publication Number
US-9339584-B2
Publication Date
2016-05-17
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 relates to a soluble agent for formation of a biogel comprising one or more soluble carriers on each of which a plurality of fibrinogen binding moieties are covalently immobilized. When the agent is contacted with a plurality of fibrinogen molecules in the absence of thrombin, it forms a biogel comprising fibrinogen molecules and a plurality of carriers.
In the biogel, each fibrinogen molecule binds at least two fibrinogen binding moieties, and fibrinogen molecules are linked together via the carriers by non-covalent bonds between the fibrinogen binding moieties and the fibrinogen molecules. The concept is centered on fibrinogen-mediated gel formation using immobilized fibrinogen-binding sites rather than thrombin-driven fibrin formation.
The document further describes optional thrombin and Factor XIII and their roles, including enabling fibrin formation and covalent crosslinking, while still emphasizing that the biogel can form when thrombin is absent. Carriers are described with options including human serum albumin and albumin microparticles, and covalently immobilized peptide or thrombin-cleavable fibrinogen-binding precursors are described as fibrinogen-binding moieties.
Claims Coverage
The document indicates one independent claim defining a thrombin-absent biogel formation mechanism using covalently immobilized fibrinogen-binding moieties on soluble carriers, followed by dependent claims that refine the agent by structural and formulation features.
Thrombin-absent biogel formation via covalently immobilized fibrinogen-binding moieties on carriers
A soluble agent for formation of a biogel comprising one or more soluble carriers with covalently immobilized a plurality of fibrinogen binding moieties, wherein upon contacting a plurality of fibrinogen molecules when thrombin is absent, a biogel is formed that comprises fibrinogen molecules and carriers such that each fibrinogen molecule binds at least two fibrinogen binding moieties and the fibrinogen molecules are linked together via the carriers by non-covalent bonds between the fibrinogen binding moieties and the fibrinogen molecules.
Peptide fibrinogen binding moiety motif with an NH2-G(P,H)RX- sequence
The agent of the soluble biogel formation where each fibrinogen binding moiety is a peptide containing an amino-terminal sequence NH2-G(P,H)RX-(SEQ ID NO: 15), where X is any amino acid and either proline or histidine is present at the (P,H) position.
Covalent immobilization of binding moiety through a non-peptide spacer
The agent where each fibrinogen binding moiety is immobilized to a carrier through a non-peptide spacer.
Polyethylene glycol as the non-peptide spacer
The agent where the spacer comprises polyethylene glycol.
Recombinant human albumin as the carrier
The agent where the carrier comprises recombinant human albumin.
At least four fibrinogen binding moieties per carrier on average
The agent where each carrier has on average at least four fibrinogen binding moieties per carrier.
Overall claim coverage focuses on a thrombin-absent biogel that forms through fibrinogen bridging: covalently immobilized fibrinogen binding moieties on carriers bind fibrinogen molecules at at least two sites per molecule, linking fibrinogen together via non-covalent bonds between the binding moieties and fibrinogen. Dependent refinements specify a peptide motif (NH2-G(P,H)RX-), immobilization via a non-peptide spacer (including polyethylene glycol), a recombinant human albumin carrier, and a quantitative binding-moiety density constraint.
Stated Advantages
Storage stability.
Reduced allergy/toxicity.
Documented Applications
Wound sealing and haemostasis, including localized drug delivery.
Topical administration, including topical sprayable powders and administration via topical spray.
Intravenous administration.
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