Methods and compositions for regenerating tissues
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Publication Number
US-10752663-B2
Publication Date
2020-08-25
Expiration Date
Abstract
Provided are methods for promoting the healing of injuries to tendons and ligaments by administering a NELL1 protein or a nucleic acid encoding a NELL1 protein to a subject in need thereof. Also provided are NELL1 compositions and methods for promoting tissue regeneration, promoting the healing of wounds, and enhancing fibroblast migration, proliferation, or both migration and proliferation.
Core Innovation
The invention describes a NELL1 peptide fragment or variant thereof that has at least 95% sequence identity to SEQ ID NO: 17 or 18 and lacks the carboxy-terminal 179 amino acid residues of the respective full-length NELL1 protein. The described concept addresses wound healing and tissue regeneration, with full-length NELL1 protein showing limited or no significant benefit while the NELL1 fragment or variant is associated with improved tissue regeneration or wound healing.
The document further characterizes NELL1 variants as peptide fragments or variants lacking one or both carboxy-terminal VWC domains. It also describes the fragment or variant in relation to easier purification, higher yield, and less aggregate formation compared to the corresponding full-length NELL1 protein.
The invention further includes incorporation into pharmaceutical compositions and local administration formats such as hydrogel, calcium alginate wound dressing or matrix, drug-eluting device, scaffold, matrix, and sutures. It also describes a horse body wound healing model and regenerating injured tissues, particularly tendon and ligament injuries, by administering NELL1 protein or nucleic acid encoding NELL1.
Claims Coverage
The independent claim coverage centers on a truncated NELL1 peptide fragment or variant with at least 95% sequence identity to SEQ ID NO: 17 or 18 and absence of the carboxy-terminal 179 amino acid residues. The claim set includes one or more stated properties relative to full-length NELL1 protein, together with pharmaceutical composition and kit embodiments.
High-identity NELL1 fragment or variant to SEQ ID NO: 17 or 18
A NELL1 peptide fragment or variant thereof having at least 95% sequence identity to SEQ ID NO: 17 or 18.
Carboxy-terminal deletion of 179 amino acid residues
The NELL1 peptide fragment or variant thereof lacks the carboxy-terminal 179 amino acid residues of the fragment's respective full-length NELL1 protein.
Improved properties versus full-length NELL1
The NELL1 peptide fragment or variant thereof has at least one of enhanced efficacy in tissue regeneration, enhanced promotion of wound healing, easier purification, higher yield, or less aggregate formation, when compared to the corresponding full-length NELL1 protein.
Pharmaceutical composition containing the claimed peptide or variant
A pharmaceutical composition that includes the NELL1 peptide fragment or a variant thereof as defined in the claims.
Drug-eluting or structural delivery format
The NELL1 peptide fragment or a variant is incorporated into a drug-eluting device, scaffold, matrix, or sutures.
Hydrogel or calcium alginate delivery format
The pharmaceutical composition includes a NELL1 peptide fragment or variant incorporated into a hydrogel, calcium alginate wound dressing, or calcium alginate matrix.
Kit containing the claimed peptide or variant
A kit that includes the NELL1 peptide fragment or a variant of it as defined in the claims.
Across the claim set, the core coverage is a carboxy-terminally truncated NELL1 peptide fragment or variant with at least 95% identity to SEQ ID NO: 17 or 18, with stated benefits relative to full-length NELL1 protein. Dependent claims further specify composition, delivery format, and kit embodiments.
Stated Advantages
Enhanced efficacy in tissue regeneration.
Enhanced promotion of wound healing.
Easier purification.
Higher yield.
Less aggregate formation.
Documented Applications
Wound healing in a horse body wound model, with delivery via calcium alginate dressings and comparison between full-length NELL1 and a domain-specific variant.
Regenerating injured tissues, particularly tendon and ligament injuries, by administering NELL1 protein or nucleic acid encoding NELL1.
Local administration formats using pharmaceutical compositions, including matrices and devices such as wound dressings, hydrogels, calcium alginate, scaffolds, drug-eluting devices, and sutures.
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