Methods and compositions for regenerating tissues
Inventors
Assignees
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Publication Number
US-11034741-B2
Publication Date
2021-06-15
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 relates to administering an effective amount of a NELL1 peptide fragment or variant thereof to a subject in need. The peptide fragment or variant has at least 95% sequence identity to SEQ ID NO: 17 or 18 and lacks the carboxy-terminal 179 amino acid residues of the fragment's respective full-length NELL1 protein.
The disclosure includes regenerating injured tissue and promoting the healing of an injury to a tissue by administering the same class of NELL1 peptide fragment or variant. The injured tissue comprises at least one tissue type selected from heart muscle, skeletal muscle, cartilage, bone, and skin, and the treatment is applied to a subject in need thereof.
The patent further discloses contacting a progenitor cell in an injured tissue with an effective amount of the same NELL1 peptide fragment or variant to promote maturation of the progenitor cell. The invention also states that truncated variants provide improved manufacturing characteristics, including higher yield, easier purification, and less aggregation, together with enhanced tissue regeneration and wound healing.
Claims Coverage
The independent claims share three core inventive requirements: a NELL1 peptide fragment or variant with at least 95% sequence identity to SEQ ID NO: 17 or 18, a truncation that lacks the carboxy-terminal 179 amino acid residues of the fragment’s respective full-length NELL1 protein, and application to injured tissue comprising heart muscle, skeletal muscle, cartilage, bone, and/or skin.
NELL1 peptide fragment with defined sequence identity
Administering an effective amount of a NELL1 peptide fragment or variant thereof to a subject, wherein the NELL1 peptide fragment or variant thereof has at least 95% sequence identity to SEQ ID NO: 17 or 18.
Carboxy-terminal truncation of full-length NELL1
Administering or contacting the subject with a NELL1 peptide fragment or variant thereof wherein the fragment or variant lacks the carboxy-terminal 179 amino acid residues of the respective full-length NELL1 protein.
Treatment targeted to heart muscle, skeletal muscle, cartilage, bone, or skin
Using the NELL1 peptide fragment or variant to regenerate injured tissue, promote healing of an injury, or promote maturation of a progenitor cell in injured tissue, wherein the injured tissue comprises at least one tissue type selected from heart muscle, skeletal muscle, cartilage, bone, and skin.
Across the independent claims, the inventive scope centers on using a specifically defined NELL1 peptide fragment or variant in methods for regenerating injured tissue, promoting healing of an injury, and promoting maturation of a progenitor cell in injured tissue, with the relevant injured tissue types limited to heart muscle, skeletal muscle, cartilage, bone, and skin.
Stated Advantages
Improved manufacturing characteristics, including higher yield, easier purification, and less aggregation.
Enhanced biological efficacy, including enhanced tissue regeneration and wound healing.
Increased fibroblast migration.
Increased fibroblast proliferation.
Documented Applications
Regenerating injured tissue in a subject, with injured tissue comprising at least one of heart muscle, skeletal muscle, cartilage, bone, and skin.
Promoting the healing of an injury to tissue in a subject, with tissue comprising at least one of heart muscle, skeletal muscle, cartilage, bone, and skin.
Promoting maturation of a progenitor cell in injured tissue in a subject.
Local administration and delivery in formats including wound dressings, calcium alginate matrices, scaffolds, drug-eluting devices, patches, hydrogels, and sutures.
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