Noggin inhibitory compositions for ossification and methods related thereto
Inventors
Boden, Scott D. • Sangadala, Sreedhara
Assignees
Emory University • US Department of Veterans Affairs
Publication Number
US-9295754-B2
Publication Date
2016-03-29
Expiration Date
2032-02-23
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
This disclosure relates to compounds and compositions for forming bone and methods related thereto. In certain embodiments, the disclosure relates to methods of forming bone comprising implanting a bone graft composition comprising a growth factor such as BMP in a subject at a site of desired bone growth or enhancement in combination with a Noggin blocker.
Core Innovation
This disclosure relates to compounds and compositions for forming bone and methods related thereto. The invention provides compounds, compositions, and methods of use of these compounds to improve bone grafting or to induce bone formation in a subject. Specifically, it relates to methods of forming bone or cartilage by implanting a bone graft composition comprising a growth factor, such as BMP, in combination with a Noggin blocker at a site of desired bone or cartilage growth or enhancement. The Noggin blocker can also be used alone without exogenous BMPs.
The invention also contemplates implanting bone grafts comprising a Noggin blocker with or without growth factors, and administering pharmaceutical compositions comprising the Noggin blocker to the subject. It includes uses of disclosed compounds and derivatives for cartilage regeneration, including oral, intravenous administration, or direct injection. Typical Noggin blockers include N-(pyridin-2-yl)benzo[b]thiophene-2-carboxamide derivatives and (3-phenyl)-2-(pyridin-2-yl)acrylonitrile derivatives or their salts, which may be combined with a graft matrix like collagen sponges or hydrogels, optionally covalently linked to the matrix.
The problem addressed is the need for effective materials and methods to form bone without requiring harvesting bone from remote donor sites, which causes complications like pain and nerve damage. Current synthetic bone grafts using BMPs like BMP-2 are effective but costly and require high concentrations, limiting routine clinical use. Noggin is a BMP-specific antagonist that limits BMP activity, and blocking Noggin can potentiate BMP-induced bone growth. This disclosure aims to provide compositions that inhibit Noggin, thereby improving bone induction and reducing the need for high BMP concentrations.
Claims Coverage
The claims define four main inventive features relating to bone graft compositions, kits, and methods for forming bone using compounds of formula IA and optional growth factors.
Bone graft composition comprising compound of formula IA
A bone graft composition that includes a compound of formula IA, optionally covalently linked to a graft matrix, and optionally containing growth factors such as bone morphogenetic proteins (BMPs) including BMP-2, BMP-6, BMP-7, or BMP-9. The composition may further comprise calcium phosphates like hydroxyapatite and tricalcium phosphate, and a collagen or hydrogel matrix.
Kit comprising compound of formula IA and bone graft composition
A kit containing a compound of formula IA or its salt, and a bone graft composition, optionally including a bone morphogenetic protein or other growth factor.
Method of forming bone by implanting bone graft composition comprising compound of formula IA
A method of forming bone by implanting a bone graft composition comprising a compound of formula IA, optionally including a growth factor such as bone morphogenetic proteins (BMP-2, BMP-6, BMP-7, or BMP-9), in a subject at a site of desired bone growth. The method details the specific compounds of formula IA usable for this purpose.
Method involving implanting bone graft compositions optionally comprising compound of formula IA
A method of forming bone that includes implanting a bone graft composition optionally comprising a compound of formula IA and optionally a growth factor, focusing on the versatility and inclusion of the compound in bone formation approaches.
The claims cover the design and use of bone graft compositions containing novel compounds of formula IA, their use in kits, and methods of bone formation using these compounds optionally combined with growth factors, particularly bone morphogenetic proteins, with compositions incorporating various matrices and calcium phosphates.
Stated Advantages
The Noggin blockers enhance the activity of bone morphogenetic proteins (BMPs) by inhibiting Noggin, which typically antagonizes BMP signaling, thereby allowing improved bone formation with possibly reduced BMP dosage.
The compositions and methods potentially eliminate the need to harvest autologous bone grafts, avoiding associated complications such as pain, nerve damage, and cosmetic deformity.
The technology could reduce the cost and concentration requirements of BMPs in bone grafting, enabling more routine clinical applications.
Documented Applications
Bone grafting in spinal fusion, cancerous bone removal, plastic surgery, and filling bone voids in extremities, maxilla, mandible, pelvis, spine, and cranium.
Use in bone fracture prevention and treatment, including long bone shaft fractures like tibia or femur.
Cartilage regeneration and repair such as articular cartilage repair, intervertebral disc repair, and joint cartilage repair including the elbow, knee, ankle, wrist, and hip joints.
Use in bone degenerative diseases treatment, including osteoporosis, osteitis deformans, bone metastasis, multiple myeloma, primary hyperparathyroidism, and osteogenesis imperfecta.
Use in preparing and enhancing integration of prosthetic devices and anchors into bone tissue.
Interested in licensing this patent?