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U.S. Patent for Bone- and Cartilage-Regeneration Technology Issues to RCT Technologies

12.19.2000

Tucson, AZ – Dec 19, 2000

U.S. Patent No. 6,143,878 issued recently to Research Corporation Technologies (RCT) for use of an early osteogenic differentiation factor that appears to play a role in mammalian skeletal development.

The patent claims cover the use of isolated DNA sequences of the Sox9 gene, which is used in the treatment of diseases involving bone or cartilage deficiency. Claims further include the recombinant protein encoded by the gene. The particular DNA sequences and their protein products have therapeutic potential in promoting or suppressing bone and cartilage differentiation or growth.

Dr. Peter Koopman and colleagues at the University of Queensland first discovered the mouse Sox9 gene in 1995 during their ongoing investigations into the molecular genetics of mammalian development. Sox9 is related to the SRY gene, which is located on the Y chromosome and plays a role in sex determination. It appears to act downstream from SRY in the sex-determining pathway and is implicated as a fundamental testis-determining gene common to all vertebrates.

Koopman’s group isolated, sequenced and characterized both the complementary DNA and genomic Sox9 gene. The isolated gene encodes a 509 amino acid transcription factor that binds to DNA. The inventors noted Sox9 activity in all sites where the skeleton was about to develop in the mouse embryo. They found that Sox9 controls the synthesis of type II collagen, the major component of cartilage. In the embryonic phase, cartilage is established and later mineralizes to become bone.

Colleagues in the United Kingdom and Germany mapped the human equivalent of the Sox9 gene to chromosome 17 in the same region containing the locus for Campomelic Dysplasia (CD), a congenital and fatal genetic disorder. The disease, which arises when the Sox9 gene is damaged or mutated, occurs in 0.05 to 2.2 per 10,000 live births and is characterized by various skeletal defects. Most newborns with CD die within the first four weeks of life.

Further investigations into Sox9 activity show that the gene is able to “turn on” again after its primary job in early human development is finished. Researchers found Sox9-specific mRNA and Sox9 proteins present in adult patients with bone fractures, which suggests the gene may play a role in bone healing.

Of the more than 30 Sox genes known to date, those studied by Koopman’s group are important for proper development of the skeleton, central nervous system and blood vessels.

Contact

The Sox9 technology is available for licensing from RCT. Contact Bennett N. Cohen, Director, Commercialization, (520) 748-4443, fax (520) 748-0025.