Drug Discovery: An old mistake led two companies to pursue patenting and developing the same promising anticancer compound
A long-standing chemical structure error threatened the validity of a patent on an anticancer drug candidate about to enter human clinical trials this year.
The compound, called TRAIL-inducing compound 10 (TIC10), is being developed under the identifier ONC201 by the biotech firm Oncoceutics, which licensed the patent for it (US 8673923) from Pennsylvania State University. But Kim D. Janda and coworkers at Scripps Research Institute, in La Jolla, Calif., discovered this year that the reported structure of the compound on which the patent is based is wrong (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201402133).
Scripps subsequently applied for a patent on TIC10 using the correct structure and has licensed it to another company, Sorrento Therapeutics. In effect, both companies are claiming the same molecule with the intent of developing it into a commercial drug.
The error originated when chemists misassigned TIC10’s structure when it was first synthesized in the 1970s. The molecule ended up in a publicly available National Cancer Institute (NCI) library of chemical compounds—and researchers working with the compound, including those at Penn State, took for granted the structure was correct. Janda and his colleagues synthesized the library structure but found it to be biologically inactive. When they obtained a sample from NCI, which was bioactive, the researchers investigated further and discovered the structural discrepancy.
Oncoceutics believes the structural mistake is irrelevant to its licensed patent, whereas Scripps believes the error puts that patent on shaky ground. Patent attorneys C&EN asked to comment on the controversy generally consider Oncoceutics to hold the upper hand. Meanwhile, Oncoceutics is moving forward as if nothing had happened, receiving government and private foundation research grants and closing on a private-investor funding round to support development of ONC201 and its analogs. Sorrento has not yet announced its plans for TIC10.