Intellectual property strategy is fundamental to the successful development and commercialization of a personalized therapeutic and its companion diagnostic. In personalized therapy, healthcare professionals often use genetically-guided diagnostic tests to identify which medical treatments will be the safest and most effective for each patient. As the pharmaceutical industry transitions from the age of one-size-fits-all drugs to the age of personalized therapeutics, companion diagnostics will become indispensable in disease treatment and prevention. According to the Personalized Medicine Coalition, new personalized therapeutic drugs approved by the FDA are on an upward trajectory. They have risen from about 5% of all new drugs in 2005 to over 25% in 2015 and 2016.

The era of personalized therapeutics is highlighted by the success of Merck’s Keytruda (pembrolizumab), a humanized antibody used in cancer immunotherapy which targets the programmed cell death 1 (PD-1) receptor. Keytruda was initially approved for the treatment of unresectable or metastatic melanoma as a second-line therapy. Dako, in partnership with Merck, developed “PD-L1 IHC 22C3 pharmDx.” This is a companion diagnostic that detects the level of programmed death-ligand 1 (PD-L1) protein, a binding partner of PD-1. With the aid of this companion diagnostic, clinical trials were carried out to find and treat patients who are most likely to benefit from Keytruda, i.e. patients who have high expression level of PD-L1 proteins on their tumor tissues. This targeted strategy has realized its goals, by helping the drug obtain its approval. In October 2015, the FDA approved expanding the indication for Keytruda for the treatment of metastatic non-small cell lung cancer (NSCLC) in patients whose tumors express PD-L1 and who have failed treatment with other chemotherapeutic agents. In October 2016, Keytruda was approved as a first-line treatment for metastatic NSCLC in patients with high-levels of PD-L1. In the U.S., Keytruda is protected by U.S. Patents 8,354,509 and 8,900,587 which disclose the therapeutic PD-1 specific antibody and its pharmaceutical composition.

While most companion diagnostics are used in conjunction with one particular therapeutic drug, others are more versatile. They can help select an effective treatment from a range of options, based on the results of the test and the patient’s treatment history. A case in point is “cobas EGFR Mutation Test v2” developed by Roche, which is a companion diagnostic test for Tarceva (erlotinib) and Tagrisso (osimertinib), both of which are small molecule EGFR inhibitors used for NSCLC treatment. Tarceva is marketed in the U.S. by OSI Pharmaceuticals and Genentech (a subsidiary of Roche), whereas Tagrisso is marketed in the U.S. by AstraZeneca. The diagnostic uses a real-time PCR test. If the tested tumor tissue from a patient was determined to harbor exon 19 deletions and L858R mutation in EGFR, then the patient is most likely to benefit from Tarceva as a first-line treatment. If the EGFR was determined to have the mutation T790M, then the patient is most likely to benefit from Tagrisso in second and subsequent lines of therapy. In the U.S., Tarceva is protected by U.S. Patents 5,747,498, 6,900,221, 7,087,613, and RE41065, which cover the molecule, its pharmaceutical use and methods of production. Tagrisso is protected by U.S. Patent 8,946,235, which discloses the molecule, its pharmaceutical composition, and method for treatment related to the molecule. The cobas EGFR Mutation Test v2 itself is protected by U.S. Patent 7,687,247 related to the reaction mixture and DNA amplification composition, and U.S. Patent 7,964,349 that claims for a method for determining pharmacological effectiveness of treatment by erlotinib. The 7,964,349 patent is licensed to Roche by the General Hospital Corp and the Dana-Farber Cancer Institute. This is an example of how academically-driven inventions protected by patents are valued by industry and play a role in the development and commercialization of personalized medicine.

In another example, Venetoclax (Venclexta) is a small molecule oral treatment for chronic lymphocytic leukemia (CLL) marketed by Abbvie and Genentech in the U.S. This drug was granted “Breakthrough Therapy Designation” and later received accelerated FDA approval for CLL patients who have been refractory to previous treatment and have chromosomal deletion at Locus Specific Identifier (LSI) TP53. Venetoclax is linked to U.S. Patents 8,546,399 and 9,174,982 which claim the small molecule and the method of cancer treatment with the small molecule. The companion diagnostic for Venetoclax is the “Vysis CLL FISH Probe Kit” manufactured by Abbott Molecular which detects the deletion of LSI TP53 in blood specimens from patients. In addition to its prescribed use for detecting LSI TP53 deletion as an aid in identifying those patients with CLL who might benefit with Venetoclax treatment, the kit could also detect deletion of LSI ATM and LSI D13S319, and gain of the D12Z3 sequence. These additional features provide the potential for expanded use in the future. The direct-label fluorescence probes in the kit are covered by U.S. Patents 6,607,877, 7,115,709 and RE40,494, which are exclusively licensed to Abbott Molecular by The Regents of the University of California. The methods utilized by the kit in detecting multiple hybridization signals simultaneously are covered by U.S. Patent 6,203,977. This patent is exclusively licensed to Abbott Molecular by Yale University.

The rapid pace of personalized medicine development will gain momentum with advances in chemogenomics, high-throughput production of interactome data, and the coming of age of next-generation sequencing technologies. This trend is not lost on the FDA. The agency has recently provided draft guidance on the “Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product”. The diagnostic is regulated as a medical device. Competition in this space will intensify, so intellectual property protection strategies are key to support company commercialization, as well as opening up collaborative and licensing opportunities for academic institutions. In all, bringing safe and effective personalized medicine to the market serves the ultimate goal of matching the right drug with the right patient in need.