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Mar 1, 2005 (Vol. 25, No. 5)

Strengthening Pharma and Biotech Patents

Taking Steps Toward More Effective Protection of Intellectual Property

  • All innovative companies recognize the vital interest they have in obtaining patents to protect their intellectual property. However, many companies do not realize that filing a patent application and securing a patent are only the first steps toward effective protection of intellectual property.

    A recent court decision has shown that patent owners can take proactive steps to strengthen their patents and make them less vulnerable to legal challenges after the patents have issued. This decision carries important implications for all patent holders, especially pharmaceutical and biotechnology companies faced with mounting patent challenges from competitors such as generic manufacturers.

  • Legal Challenges to Patent Validity

    One common attack on a patents validity is an allegation that the patented invention was obvious at the time of the invention. Under this theory, a competitor can invalidate a patent by showing that skilled artisans would have found it obvious to combine the existing technology to create the patented invention. To succeed with this theory, the competitor must prove obviousness with clear and convincing evidence.

    To rebut an obviousness challenge, the patent owner can rely on several different types of evidence. For example, a patentee can show nonobviousness by proving that other individuals previously had tried and failed to solve the same problem solved by the claimed invention.

    The logic is that if the claimed invention had really been obvious other individuals would have come up with the same answer as a solution to the recognized problem. This evidence is especially compelling if the patentee can also show that the claimed invention is a commercial success, thus demonstrating that other individuals had a powerful financial motive to solve the same problem solved by the patented invention, but were never able to do so.

  • New Evidence of Unexpected Benefits

    Another way to prove nonobviousness is by showing that the claimed invention has unexpected benefits. If, for example, a patentee can show that the invention has beneficial properties that were unpredictable or unforeseen, the very unpredictability of the benefits supports the nonobviousness of the invention.

    This rationale provides opportunities for patentees to develop new evidence supporting the nonobviousness of the invention long after the patent has issued.

    Recently, in Knoll Pharmaceutical Co. v. Teva Pharmaceuticals USA, the Court of Appeals for the Federal Circuit approved a technique that enables a patent owner to take proactive steps to strengthen a patent against an obviousness challenge. In that decision, the Federal Circuit held that a patent owner can rebut an obviousness challenge by using evidence of unexpected benefits discovered after the patent had issued.

    The patent in that case covered a combination of hydrocodone (a narcotic) and ibuprofen (a non-steroidal anti-inflammatory drug, or NSAID). The application for the patent was filed in 1984, and the patent issued in 1986. At about the same time, other companies had developed other analgesics that combined narcotics with non-NSAIDs such as acetaminophen.

    Knoll obtained a license to the patent in 1988 and then sponsored a series of clinical trials to demonstrate the safety and efficacy of the hydrocodone-ibuprofen combination specified by the patent. In 1997, Knoll received FDA approval to market the analgesic, which was called Vicoprofen.

    Vicoprofen was the first analgesic approved by the FDA that combined a narcotic with an NSAID. In 2000, a generic manufacturer filed an Abbreviated New Drug Application (ANDA) to obtain FDA approval to market a generic version. Pursuant to the Hatch-Waxman Act, the generic company asserted in its ANDA that Knolls patent was invalid on obviousness grounds.

    Accordingly, under the Hatch-Waxman Act, Knoll sued the generic company for patent infringement. In the ensuing litigation, the generic company claimed that Knolls patented analgesic combination was obvious because others had created similar combinations at the time the patent application was filed.

  • Sponsored Studies

    In response to the obviousness challenge, Knoll sponsored several studies at three of the nations most prestigious medical research institutions: the Memorial Sloan-Kettering Cancer Center in New York, Stanford University School of Medicine in Palo Alto, and the University of California School of Medicine in San Diego.

    In the Sloan-Kettering study, investigators found that the hydrocodone-ibuprofen combination, when administered in the ratios claimed in the patent, showed greater than additive effects and strongly suggested a synergistic interaction between the ibuprofen and hydrocodone.

    In the Stanford study, investigators found that the hydrocodone-ibuprofen combination, when administered in the dose ratios specified in the patent, produced a synergistic effect that was much greater than the predicted effect based on the potency of the individual drugs.

    In the University of California study, investigators found that the hydrocodone-ibuprofen combination produced a synergistic effect that would require at least an approximate 4- to 15-fold increase in the dose of either ibuprofen or hydrocodone delivered alone.

    The Stanford investigators presented their findings to the Society for Neuroscience in November 2002, while the University of California investigators presented their findings to the American Pain Society in March 2003.

    Accordingly, in studies conducted at three preeminent research institutions, independent teams of investigators who were not aware of each others workand who each used different protocols and methodologiesall reached the same conclusion: When hydrocodone and ibuprofen are administered in the ratios specified in the patent, they have an unexpectedly synergistic analgesic effecti.e., an analgesic effect greater than the sum of the analgesic effects of the hydrocodone and ibuprofen doses alone.

    In the litigation, Knoll offered this evidence of unexpected benefits to rebut the obviousness challenge to the patent. The trial court refused to consider the evidence on the ground that these unexpected benefits or results were discovered after the patent had been issued.

    The trial court believed that such unexpected results must have been known by the inventor at the time the patent was issued in order to be relevant. As a result, the trial court ignored Knolls new data showing unexpected benefits and held that the patent was invalid on obviousness grounds.

    On appeal, Knoll argued that the trial court erred in excluding the new evidence of unexpected benefits. To support the claim, Knoll stressed that several of the other accepted ways to show non-obviousness (such as commercial success) relied on evidence obtained after the patent had issued. Therefore, by the same logic, the new evidence of unexpected benefits should also be considered.

    The Federal Circuit agreed. In endorsing Knolls use of the new data, the Court held that a patentee could conduct new tests after the patent had issued to demonstrate the unique properties of the claimed invention. In so doing, the Court emphasized that the full range of an invention is not always understood at the time a patent application is filed.

    The court explained, Evidence developed after the patent grant is not excluded from consideration, for understanding of the full range of an invention is not always achieved at the time of filing the patent application. It is not improper to obtain additional support consistent with the patented invention, to respond to litigation attacks on validity.

    There is no requirement that an inventions properties and advantages were fully known before the patent application was filed, or that the patent application contains all of the work done in studying the invention, in order for that work to be introduced into evidence in response to litigation attack. Nor is it improper to conduct additional experiments and provide later-obtained data in support of patent validity.

    On this basis, the Federal Circuit reversed the trial courts decision holding the patent to be invalid (Knoll Pharmaceutical Co. v. Teva Pharmaceuticals USA, 367 F.3d 1381, 1385; Fed. Cir. 2004).

  • Affirmative Steps to Strengthen Patents

    The Federal Circuits endorsement of evidence developed after a patent has issued opens up new opportunities for pharmaceutical and biotechnology companies to strengthen their existing patent portfolios by conducting tests to demonstrate the unexpected benefits of the claimed invention.

    If a patent owner can obtain new evidence showing that its invention has unexpected benefits, even benefits not fully known to the inventor, it can then use this evidence to defend the validity of the patent against legal challenges by competitors.



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