Polypeptides including a beta-tricalcium phosphate-binding sequence and uses thereof
Inventors
Assignees
Publication Number
US-11773138-B2
Publication Date
2023-10-03
Expiration Date
2039-10-11
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Abstract
Provided herein are polypeptides that include one or more β-tricalcium phosphate (βTCP)-binding sequence(s) and uses thereof.
Core Innovation
The invention provides chimeric polypeptides that include one or more β-tricalcium phosphate (β-TCP)-binding sequences and a mammalian growth factor. These chimeric polypeptides can be formulated into compositions, optionally with β-TCP, for local delivery. The polypeptides are engineered so the β-TCP-binding sequences, selected from a defined group or designed by a consensus sequence (Formula I), enable strong specific binding to β-TCP or related orthopedic substrates.
This approach addresses the problem of inadequate healing and regeneration in critical-sized bone and cartilage defects, which often do not heal spontaneously or are poorly addressed by existing grafting methods. Current challenges include donor site pain, rejection, limited donor supply, risk of infection, loss of progenitor cells after implantation, and orthopedic substrates failing to facilitate sufficient tissue regeneration.
The compositions and methods can increase and sustain progenitor cells at the site of bone or cartilage injury by enhancing stem cell capture and offering local, targeted delivery of growth factors via β-TCP anchoring. The chimeric polypeptides promote bone or cartilage formation, repair, and replacement, and can also support soft tissue repair and localized therapeutic delivery. Additionally, nucleic acids encoding these polypeptides and kits comprising the compositions are provided.
Claims Coverage
The independent claim presents several main inventive features centered on the delivery of therapeutic agents to bone or cartilage using specific chimeric polypeptides featuring β-TCP-binding sequences.
Chimeric polypeptide with defined β-TCP-binding sequences for therapeutic delivery to bone or cartilage
A method of delivering a therapeutic agent to bone or cartilage in a subject, the method comprising delivering to the bone or cartilage a chimeric polypeptide comprising: - the therapeutic agent; - one or more binding polypeptides, wherein the binding polypeptides comprise: - a sequence at least 80% identical to SEQ ID NO: 2 (VIGESTHHRPWS), - a sequence at least 80% identical to SEQ ID NO: 4 (ILAESTHHKPWT), - a sequence at least 80% identical to SEQ ID NO: 6 (IIGESSHHKPFT), - a sequence at least 80% identical to SEQ ID NO: 7 (GLGDTTHHRPWG), - or a combination comprising two or more sequences of the above. The claim further explicitly covers delivery to promote bone or cartilage formation or repair, and encompasses specific application to bone defects, bone fractures, bone loss, and cartilage defects.
The claim coverage centers on the use of specifically defined chimeric polypeptides, comprising characterized β-TCP-binding sequences, to deliver therapeutic agents to bone or cartilage sites, thereby enabling targeted tissue repair and regeneration.
Stated Advantages
The compositions increase and sustain the number of progenitor cells at sites of bone and/or cartilage injury through stem cell capture.
The compositions can vastly improve bone healing and accelerate tissue regrowth when compared to standard treatments.
The approach allows for targeted delivery and longer persistence of growth factors at implant sites, which enables lower doses and is expected to produce superior outcomes.
The chimeric polypeptides are osteo-conductive, promote bone mineralization, are easily resorbed, and are useful as bone void fillers and for bone reconstruction.
Compositions can be formulated for various delivery formats (e.g., putty, paste, scaffold) to adapt to clinical needs.
Documented Applications
Promotion of bone or cartilage formation in subjects in need thereof.
Replacement and/or repair of bone or cartilage defects, including those caused by infection, tumor, trauma, or treatment adverse events.
Treatment of bone fractures.
Treatment of bone loss.
Promotion of cartilage formation and/or cartilage repair, including defects caused by disease, osteochondritis, osteonecrosis, or trauma.
Soft tissue repair.
Localized delivery of a therapeutic agent to bone or cartilage in a subject.
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