Drug – bio-affecting and body treating compositions – Dentifrices
Reexamination Certificate
1995-01-27
2003-09-16
Gitomer, Ralph (Department: 1623)
Drug, bio-affecting and body treating compositions
Dentifrices
C435S252300
Reexamination Certificate
active
06620406
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the field of tissue repair, specifically, the regeneration of a functional periodontal attachment apparatus destroyed by periodontitis. Specifically, the present invention relates to methods and compositions useful for the repair of periodontal defects, such as lesions involving the alveolar bone, periodontal ligament, and for the regeneration of cementum.
BACKGROUND OF THE INVENTION
Periodontal disease is a bacterially induced, host mediated, inflammatory disease that results in a loss of connective tissue attachment to the tooth and loss of alveolar bone. It is estimated that upwards of twenty-five percent of the population from 18 to 65 years old has some significant loss of connective tissue support at one or more sites. It is projected that nearly 10% of this population has attachment loss at multiple locations consistent with a diagnosis of moderate periodontitis.
Current periodontal disease therapies are directed at control of the inflammatory disease with the goal of preventing future disease. It is also desirable to seek to regenerate a functional periodontal attachment. To date, autogenous and allogeneic bone grafting has been the method most often used for defect filling and regeneration. However, other reconstructive surgical procedures, using synthetic alloplastic grafts or guided tissue regeneration with physical barriers are also performed.
Autogenous bone grafts are disadvantageous mainly in that they require surgery at a second site in order to obtain sufficient graft material, resulting in patient morbidity. Bone allograft may be obtained from tissue banks either fresh frozen or freeze-dried. Fresh tissue may be antigenic and is subject to limitations of current supply. Freeze-drying markedly reduces antigenicity of bone allograft, but may also decrease the osteogenic potential of the graft as well. Demineralization of the allograft may enhance osteogenic potential, but it decreases the structural integrity of the graft. In addition, the source is human donor bone which creates a risk of transmission of disease.
Alloplastic bone substitutes which have been tried include synthetic or natural hydroxyapatite, which is non-resorbable, beta tricalcium phosphate (resorbable) and polymer of polymethacrylate beads coated with polyhema bovine bone products. These materials tend to be encapsulated with minimal or no bone formation and also may cause root resorption. These bone substitutes may also cause ankylosis, and may not be suitable for regeneration of the cementum and of the periodontal ligament.
Guided tissue regeneration provides a physical barrier between the gum flap and the tooth surface to enhance the potential for wound healing. This procedure retards the apical migration of epithelium, excludes gingival connective tissue from the wound and favors healing from the periodontal ligament space. However, this procedure is technique- and site-sensitive, may leave space between the gum flap and tooth surface and does not reproducibly lead to repair of the periodontal defect.
Accordingly, despite substantial endeavors in this field, there remains a need for an effective method of repair of periodontal defects.
SUMMARY OF THE INVENTION
The present invention provides methods and compositions for regenerating periodontal tissue. In a particular embodiment, the present invention comprises methods of treating supraalveolar lesions, which have historically been difficult to treat because they involve both vertical and horizontal lesions of the alveolar bone. The methods and compositions of the present invention are advantageous in that they utilize osteogenic proteins and/or ligament-inducing proteins, which may be produced via recombinant DNA technology, and therefore are of potentially unlimited supply, and are not subject to the same concerns of contaminated source as are bone grafts. The methods and compositions of the present invention are further advantageous in that regeneration is begun of all three tissues comprising the periodontal attachment apparatus: alveolar bone, periodontal ligament space and cementum; which minimizes the occurrence of potentially undesirable conditions such as ankylosis and root resorption.
DETAILED DESCRIPTION OF THE INVENTION
According to the present invention, methods and compositions are provided for treatment of periodontal disease and for repair of periodontal lesions to the alveolar bone, particularly supraalveolar lesions which involve both vertical and horizontal lesions of the alveolar bone. Supraalveolar defects may affect areas in which the teet remain intact, in which case it is desirable to regenerate the entire periodontal attachment apparatus between alveolar bone and tooth. Alternatively, supraalveolar defects may affect areas in which the teeth have been lost, in which case it is desirable to augment the alveolar bone in order to allow more effective implantation of substitute teeth. In addition to supraalveolar defects, the methods and compositions of the present invention are useful for the treatment of mandibular and maxillary class II and III furcation and interproximal defects with and without bacterial involvement from periodontitis, as well as for ridge augmentation of both the mandibular and maxillary structures. Class II and III furcations and interproximal defects are subclasses of supraalveolar defects in which the teeth remain present. Ridge augmentation is often necessary when a patient has experienced substantial resorption of the mandibular and/or maxillary structures. This often occurs in patients who have been missing one or more teeth for an extended period of time.
The methods comprise applying to the site of a supraalveolar lesion, or to the site of a class II or class III furcation or interproximal defect, or to the mandibular or maxillary ridge requiring augmentation, an amount of a composition comprising one or more purified osteogenic and/or ligament-inducing proteins, which is effective to regenerate the alveolar mandibular and/or maxillary bone in both a vertical and horizontal direction. The methods and compositions are advantageous in that regeneration of the mandibular and/or maxillary bone in both a vertical and horizontal direction often results in bone which is better able to support dental implants. The methods and composition are further advantageous in that repair or improvement may be obtained of the entire periodontal attachment apparatus: the alveolar bone, the periodontal ligament space and the cementum layer. The method may further comprise the administration of a composition comprising a purified osteogenic and/or ligament-inducing protein to a site of periodontal lesion or defect in a suitable carrier such that the alveolar bone, the periodontal ligament apparatus, and the cementum layer are regenerated, without significant ankylosis and/or root resorption appearing. The composition is preferably administered in combination with an effective carrier. One of the key advantages of the method of the present invention is that it allows for the controlled regeneration of alveolar bone, periodontal ligament and cementum tissue in a manner which minimizes the occurrences of undesirable ankylosis and root resorption.
OSTEOGENIC OR LIGAMENT-INDUCING PROTEIN
The osteogenic protein is preferably from the subclass of proteins known generally as bone morphogenetic proteins (BMP), which have been disclosed to have osteogenic activity. These BMPs include BMP-2, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10 and BMP-11 and may also include other members of the TGF-,&bgr; superfamily of proteins. The structures of a number of BMP proteins are disclosed in U.S. Pat. Nos. 4,877,864; 5,108,922; 5,013,649; 5,116,738; 5,106,748; 5,187,076; 5,141,905; and in PCT applications WO 91/18098; WO 93/00432; W094/26893; and W094/26892, the disclosures of which are hereby incorporated by reference. The preferred osteogenic protein is BMP-2, the sequence of which is disclosed in U.S. Pat. No. 5,013,649, the disclosure of which is hereby incorporated b
Turek Thomas J.
Wozney John M.
Finnegan Henderson Farabow Garrett & Dunner, LLP.
Genetics Institute, LLC.
Gitomer Ralph
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