Patents For Human Therapies: Too Little, Too Late?

Without a patent, a university or small company may struggle to obtain financial support for expensive animal or human studies needed to develop a drug. But the way to a patent may be blocked by a United States Patent and Trademark Office (USPTO) unwilling to accept in vitro data as predictive of human therapeutic usefulness. It is the public who suffers from this dilemma as promising therapies for deadly diseases may never reach the market. During the early 1990s, USPTO sharply limited the issuance of patents for claims that were supported by in vitro, not in vivo, data. Now that legal standards for resolving such claims have been clarified, the number of granted patents is rising. USPTO controls the breadth of issued patents through the legal requirements of utility and enablement. According to the statute that spells out utility requirements for issuing a patent, an invention must work for its intended purpose. The statute, 35 United States Code (U.S.C.) 101, says: "Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent. . . ." Under 35 U.S.C. 112, the statute that defines enablement, an application must contain "a written description of the invention . . . in such full, clear, concise and exact terms as to enable any person skilled in the art . . . to make and use" the invention. Scientists routinely make claims for human therapeutic efficacy based on in vitro models. However, USPTO has used utility and enablement requirements to challenge the sufficiency of in vitro data to predict human therapeutic value. In some cases, USPTO even rejected in vivo data, questioning the validity of some animal systems as models of human disease. For example, Jan Balzarini and colleagues at Stichting Rega VZW, a research institute in Leuven, Belgium, were denied a patent in 1991 for compositions and methods that used specific nucleoside analogs in HIV treatment. Other drugs, such as suramin, which were active against HIV in vitro, proved ineffective in clinical trials. The application detailed in vitro studies on the cytopathogenic effect of the compounds on HIV in human T lymphocyte cells as well as inhibitory effects on HIV antigen expression in infected human cells. The in vitro tests were not, in the patent examiner's view, predictive of therapeutic efficacy against HIV in view of suramin's clinical failure. Hence, the examiner ruled that Balzarini's application failed to satisfy the utility and enablement requirements. The USPTO Board of Appeals upheld the rejection, finding that Balzarini's tests were "screening tools" to identify candidates for further in vivo testing. The in vitro tests were not, in the board's view, predictive of therapeutic efficacy against HIV. Without human data to support anti-HIV therapy claims, subsequent patent applications were effectively blocked by the ruling. USPTO would not accept in vitro data, and there was no accessible animal model of HIV. Fortunately, a USPTO policy shift and recent court decisions have opened the way for broader patent protection in human therapeutics. In July 1995, USPTO released its "Utility Examination Guidelines" for biotechnology and human therapy. The guidelines, along with USPTO's "Legal Analysis Supporting Utility Examination Guidelines," clarify that evidence of actual success in treating humans is not necessary for patentability. The guidelines force an examiner to articulate a specific reason, based on the data presented in the application, why an invention does not meet utility requirements. This position was echoed by the Court of Appeals for the federal circuit, which overturned USPTO's rejection of an application for antitumor compounds invented by Miguel Brana and others at Knoll AG, part of the BASF group. Brana and colleagues found that the compounds reduced tumors in National Cancer Institute-recognized in vivo mouse models. The commissioner of patents, however, asserted that the mouse studies were nothing more than preclinical screening tests to determine whether the compounds were suitable for further testing in humans. The Court of Appeals reversed USPTO's rejection, claiming the commissioner "confused the requirements under the law for obtaining a patent with the requirements for obtaining governmental approval to market a particular drug for human consumption." Taking a cue from the Court of Appeals' decision, USPTO now allows patent claims for anti-HIV therapeutic methods based on in vitro data. Patent applicants who persevered through the dark days of the early 1990s are now obtaining their just rewards in the form of patents for anti-HIV and anti-cancer therapies. Unfortunately, however, USPTO's about-face may come too late for inventors who abandoned their applications in the face of seeming insurmountable rejections, as intervening scientific publications block their ability to reapply for patents. With drug-development costs measured in millions of dollars, the exclusivity provided by a patent is essential to attracting the capital needed to bring a drug to market. Hopefully, USPTO will continue a policy that fosters investment in promising new therapies. Daniel A. Monaco is a registered patent attorney at Seidel, Gonda, Lavorgna, and Monaco, P.C. The Philadelphia-based intellectual property law firm is a sponsor of BIO'96, the 10th International Biotechnology Meeting and Exposition, scheduled for June 9-13 in Philadelphia. The firm is also an exhibitor at the meeting.

Patents For Human Therapies: Too Little, Too Late?

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