Patent infringement can also occur by submitting an Abbreviated New Drug Application (ANDA) to the Food and Drug Administration (FDA)

Patent infringement can also occur by submitting an Abbreviated New Drug Application (ANDA) to the Food and Drug Administration (FDA)



The most familiar type of patent infringement is that which arises from the manufacture, use, sale, or offer for sale of a product falling within the scope of a patent. Patent infringement can also occur however by the simple act of submitting an Abbreviated New Drug Application (ANDA) to the Food and Drug Administration (FDA). A lawsuit that was recently resolved on appeal demonstrates how this can happen.

The Drug Price Competition and Patent Term Restoration Act of 1984 (the Waxman-Hatch Act) contained provisions that amended both the Food and Drugs statute and the patent statute, and the effect of these provisions is seen when an ANDA is filed for a new formulation of a known drug.

The FDA provisions require an ANDA applicant to list all patents that claim the drug in some form and to certify that the new formulation raises no infringement liability under any of those patents. The applicant must also notify the owner of each listed patent and explain why the new formulation is believed to not infringe the patent.

The patent provisions state that if someone submits an ANDA with the intention of manufacturing, selling or using a drug while a patent is in force that covers the manufacture, sale or use, the submission of the ANDA will itself constitute infringement.

Thus, under the FDA statute, the patent owner is notified that a competitor intends to market the drug and is told why the competitor believes it can do so without infringing the patent, while under the patent statute the patent owner can sue the competitor immediately if the patent owner disagrees with the competitor's reasons for noninfringement.

This is exactly what happened with a new drug formulation developed by Mylan Pharmaceuticals Inc. The drug is glyburide, which is known to be effective in reducing the level of glucose in serum and is useful for treating Type II diabetes. The effectiveness of the drug is limited, however, by its low bioavailability (rate of entry into the bloodstream), and various solutions have been proposed. One of these is to prepare the drug in micronized form, i.e., as micronized particles compressed into a tablet, since micronized particles have a high surface area which helps them dissolve faster. Tabletted drugs contain large amounts of excipients (inert substances that form a vehicle for the active ingredients), however, and particle size of both the drug and the excipients must be carefully controlled so that the tablet will have a uniform consistency and a uniform drug loading.

The excipient used with glyburide is lactose. Unfortunately, the formation of lactose particles with sufficient size control for use with micronized glyburide has been a cumbersome and costly process involving wet granulation, drying, and sizing or milling. A cheaper way was the subject of U.S. Patent No. 4,916,163, owned by Pharmacia & Upjohn Company, which was based on the discovery that lactose particles with a high degree of size control can be obtained directly by spray-drying. The patent therefore claims a micronized glyburide composition with "spray-dried lactose as the preponderant excipient."

The lactose in Mylan's glyburide formulation was not spray-dried but instead anhydrous, thereby differing both in its method of preparation and in its absence of the water of hydration present in spray-dried lactose. When Mylan submitted its ANDA, it listed the Pharmacia & Upjohn patent, notified Pharmacia & Upjohn, and explained that the formulation would not infringe the patent since the formulation did not contain spray-dried lactose. Pharmacia & Upjohn did not dispute the distinction but claimed that the two forms of lactose were equivalent and that the Mylan formulation infringed under the "doctrine of equivalents." (Chemical Engineering Progress, Nov. 1997, p. 26).

Patent law states that the doctrine of equivalents will not be applied if applying it would be contrary to positions taken by the inventor or the inventor's attorney while the patent application was pending. Before the '163 patent issued, it had been rejected over earlier patents on lactose-containing glyburide formulations. In response to that rejection, Pharmacia & Upjohn stated that the lactose in the earlier patents was not spray-dried, and that spray-dried lactose was a critical feature of the invention and provided test data showing the manufacturing advantages of the spray-dried form. This was sufficiently convincing that the patent was granted.

The argument and the test data, however, prevented Pharmacia & Upjohn from later extending the scope of the patent to any form of lactose other than spray-dried. The question of whether anhydrous lactose and spray-dried lactose were equivalents in the suit against Mylan was, therefore, never reached, and the patent was deemed uninfringed.