Combination therapies are often used to treat a variety of medical conditions that have proved difficult to cure with single-agent therapies including tuberculosis, leprosy, cancer, malaria, and AIDS. In cancer therapy, it is now believed that cytotoxic drugs are most effective when given in combination to achieve additive or synergistic effects.
The rationale for combination chemotherapy is that co-administering drugs that work by different molecular mechanisms can increase cancer cell killing, while reducing the likelihood of drug resistance, and minimizing overlapping toxicity.
Patent protection is vital for the development of any new drug, including new combination therapies, because creating a new therapy often requires years of extremely costly research and clinical testing for drug developers. The Federal Circuit’s decision in Novo Nordisk A/S v. Caraco Pharmaceutical Labs. Ltd., however, indicates that patent protection for combination therapies will likely be significantly more difficult to obtain in the future.
The patent at issue in Novo Nordisk was directed at the treatment of noninsulin-dependent diabetes mellitus using a novel combination of repaglinide (marketed as Prandinlin in the United States) and metformin (sold under the trade name Glucophage). Repaglinide is an “insulin secretagogue,” which works by stimulating insulin release from pancreatic beta cells. Metformin is an “insulin sensitizer” that reduces insulin resistance by acting on the liver to reduce glucose production, thereby improving insulin sensitivity in muscle and fat tissues.
Novo Nordisk scientists discovered that the combination of the two drugs was significantly more effective than their “hypothetical additive effect,” that is, the combination has a synergistic effect. However, the Federal Circuit held that the combination was obvious despite evidence of synergistic effect of the two drugs.