Methods and compositions for regenerating tissues
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Publication Number
US-12281144-B2
Publication Date
2025-04-22
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 provides complementary DNA (cDNA) encoding a NELL1 peptide fragment or variant thereof. The encoded fragment or variant is defined by sequence identity to SEQ ID NO: 17 or 18 and is distinguished from the respective full-length NELL1 protein by lacking the carboxy-terminal 179 amino acid residues.
The cDNA encoding the NELL1 peptide fragment or variant is characterized by selected properties relative to the fragment’s respective full-length NELL1 protein, including enhanced efficacy in tissue regeneration, enhanced promotion of wound healing, easier purification, higher yield, and less aggregate formation. In another aspect, the fragment or variant is characterized specifically by enhanced promotion of wound healing when compared to the fragment’s respective full-length NELL1 protein.
The invention also encompasses host cells comprising heterologous nucleic acid sequences encoding the NELL1 peptide fragments or variants. Further embodiments include pharmaceutical compositions in which the cDNA or host cell is incorporated into a matrix, and cDNA embodiments include delivery formulation via liposomes or nanoparticles.
Claims Coverage
The independent claims cover cDNA encoding NELL1 peptide fragments or variants, and host cells comprising heterologous nucleic acid sequences encoding the same. Across the set, there are four independent claim areas: cDNA with selected properties and truncation, cDNA with higher sequence identity and wound-healing enhancement, host cell with selected properties and truncation, and host cell with higher sequence identity and wound-healing enhancement.
Cdna encoding truncated NELL1 fragments with sequence identity to seq id no: 17 or 18 and selected properties
A complementary DNA (cDNA) encoding a NELL1 peptide fragment or variant thereof, having at least 95% sequence identity to SEQ ID NO: 17 or 18, wherein the NELL1 peptide fragment or variant thereof has at least one property selected from enhanced efficacy in tissue regeneration, enhanced promotion of wound healing, easier purification, higher yield, and less aggregate formation when compared to the fragment's respective full-length NELL1 protein; and wherein the NELL1 peptide fragment or variant thereof lacks the carboxy-terminal 179 amino acid residues of the fragment's respective full-length NELL1 protein.
Cdna encoding NELL1 fragments with higher sequence identity to seq id no: 17 or 18 and wound-healing enhancement
A complementary DNA (cDNA) encoding a NELL1 peptide fragment or variant thereof having at least 99% sequence identity to SEQ ID NO: 17 or 18, wherein the NELL1 peptide fragment or variant thereof exhibits enhanced promotion of wound healing when compared to the fragment's respective full-length NELL1 protein.
Host cell with truncated NELL1 fragment cDNA and selected properties
A host cell comprising a heterologous nucleic acid sequence encoding a NELL1 peptide fragment or variant thereof, having at least 95% sequence identity to SEQ ID NO: 17 or 18, wherein the NELL1 peptide fragment or variant thereof has at least one property selected from enhanced efficacy in tissue regeneration, enhanced promotion of wound healing, easier purification, higher yield, and less aggregate formation when compared to the fragment's respective full-length NELL1 protein; and wherein the NELL1 peptide fragment or variant thereof lacks the carboxy-terminal 179 amino acid residues of the fragment's respective full-length NELL1 protein.
Host cell with NELL1 fragment cDNA and higher sequence identity for wound-healing enhancement
A host cell comprising a heterologous nucleic acid sequence encoding a NELL1 peptide fragment or variant thereof having at least 99% sequence identity to SEQ ID NO: 17 or 18, wherein the NELL1 peptide fragment or variant thereof exhibits enhanced promotion of wound healing when compared to the fragment's respective full-length NELL1 protein.
Across the independent claims, coverage centers on cDNA and host cells containing it, with sequence identity to SEQ ID NO: 17 or 18 and comparison to the corresponding full-length NELL1 protein. Where recited, the fragment lacks the carboxy-terminal 179 amino acid residues and is defined by selected properties or by enhanced wound-healing promotion alone.
Stated Advantages
Enhanced efficacy in tissue regeneration.
Enhanced promotion of wound healing.
Easier purification.
Higher yield.
Less aggregate formation.
Documented Applications
Wound healing, including enhanced promotion of wound healing compared to full-length NELL1 protein.
Tissue regeneration, including enhanced efficacy in tissue regeneration.
Pharmaceutical compositions containing the recited cDNA or host cell, including embodiments with delivery formulation via liposomes or nanoparticles and embodiments with the host cell incorporated into a matrix.
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