Polypeptides including a beta-tricalcium phosphate-binding sequence and uses thereof
Inventors
Assignees
Publication Number
US-11192923-B2
Publication Date
2021-12-07
Expiration Date
2039-10-11
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Abstract
Provided herein are beta-TCP binding sequences and chimeric polypeptides that include one or more beta-TCP binding sequences and a mammalian growth factor, compositions comprising any of these chimeric polypeptides (and optionally, beta-TCP), and methods of promoting bone or cartilage formulation, methods of replacing and/or repairing bone or cartilage, and methods of treating a bone fraction or bone loss that include administration of any of these compositions.
Core Innovation
The present invention provides chimeric polypeptides that include one or more beta-tricalcium phosphate (β-TCP)-binding sequences and a mammalian growth factor. These polypeptides are capable of binding β-TCP, allowing for their targeted delivery and sustained presence at sites of bone or cartilage injury. The beta-TCP-binding sequences can be selected from specified amino acid sequences or designed according to a defined formula, and the mammalian growth factor may be selected from a wide array of proteins known to promote bone and cartilage formation, including but not limited to BMP-2.
The invention addresses the problem that current approaches for repairing critical and complex bone and cartilage defects are often limited by poor tissue regrowth on orthopedic substrates. Challenges include loss or scarcity of implanted progenitor cells and insufficient tissue regeneration due to the failure of existing orthopedic substrates in retaining growth factors at the site of injury.
By combining β-TCP-binding sequences with mammalian growth factors, the disclosed chimeric polypeptides and their compositions aim to increase and sustain the presence of progenitor cells, enhance stem cell capture, and promote effective regeneration at the injury site. The invention also encompasses compositions containing these polypeptides and β-TCP in various formulations, as well as methods for their use in promoting bone or cartilage formation, repairing or replacing bone or cartilage, and treating bone fractures or bone loss.
Claims Coverage
The patent claims cover polypeptides comprising specific beta-TCP-binding sequences, either alone or in combination, as well as variants having substantial sequence identity to those sequences. There is one independent claim focusing on these features.
Polypeptides comprising beta-TCP-binding sequences with at least 80% identity to SEQ ID NOs: 2, 4, 6, or 7
A polypeptide defined by inclusion of at least one sequence that is at least 80% identical to the following beta-tricalcium phosphate-binding sequences: - SEQ ID NO: 2 (VIGESTHHRPWS) - SEQ ID NO: 4 (ILAESTHHKPWT) - SEQ ID NO: 6 (IIGESSHHKPFT) - SEQ ID NO: 7 (GLGDTTHHRPWG) or any combination comprising two or more of these sequences. The claim also expressly includes polypeptides comprising combinations of these sequences with each other, or with a sequence at least 80% identical to SEQ ID NO: 1 (LLADTTHHRPWT).
In summary, the claims focus on the composition of polypeptides defined by specific beta-TCP-binding sequence identities, optionally as combinations, as the core inventive concept.
Stated Advantages
The compositions can vastly improve bone healing and accelerate tissue regrowth.
They increase and sustain the number of progenitor cells at sites of bone and/or cartilage injury through stem cell capture.
The compositions allow targeted delivery and longer persistence times of growth factors at implant sites.
Use of these polypeptides allows for lower doses of growth factors compared to non-tethered forms.
The invention leads to superior bone healing outcomes, as demonstrated by greater bone mineralization and mechanical strength in treated specimens.
Documented Applications
Methods of promoting bone or cartilage formation in a subject in need thereof.
Methods of replacing and/or repairing bone or cartilage in a subject in need thereof.
Methods of treating a bone fracture or bone loss in a subject in need thereof.
Methods of repairing soft tissue in a subject in need thereof.
Methods of localized delivery of a therapeutic to a subject in need thereof.
Surgical implantation into bone defects for the purpose of bone repair.
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