The biotechnology and pharmaceutical industries, as well as academia, eagerly awaited a recent Federal Circuit U.S. Court of Appeals decision in which the court held that the University of Rochester's patent claims to methods for blocking the action of the enzyme called cyclooxygenase-2 (COX-2) — and that covered by implication the sales of the blockbuster drugs Celebrex and Bextra — were invalid.
At first blush, University of Rochester v. G.D. Searle, 358 F.3d 916, appears to be a solid victory for pharmaceutical companies fearing the specter of paying reach-through royalties for access to screening targets. However, although the court held that Rochester did not have an enforceable claim on these blockbuster drugs, the court's February opinion leaves many questions unanswered and even provides some guidance for inventors wanting a bigger slice of the blockbuster pie.
Patent attorneys often must draft their clients' patent applications with one eye on the present and the other on the future. Inventions arising from basic scientific research, such as performed in academic and biotechnological industry laboratories, often have little or no immediate significant commercial value. Rather, the value of these inventions lies in their use to derive still other inventions — often in scientific disciplines apart from that practiced to discover the initial invention.
Such inventions thus have value by virtue of their ability to enable other researchers to make these downstream inventions, which can be quite valuable. Patents on these sorts of enabling inventions often are referred to as tool patents. Holders of tool patents typically derive revenues from licensing the rights to practice their inventions (i.e., to use the tool) to users seeking to bring a downstream invention to market. Typically, the licensee pays the patent owner a relatively small initial fee followed by milestone payments and royalties on sales of any marketed product.
In the case of pharmaceutical research, the downstream invention typically is a drug and the tool is an enzyme, or target (or a gene that encodes the target), having an action that the drug maker seeks to modify by finding an appropriate chemical substance. Drug development, however, even with the benefit of tool patents, is a long and risky endeavor: Recent estimates from the Tufts Center for the Study of Drug Development place the time and monetary investment for a new drug as high as 15 years and $800 million (along with staggeringly high failure rates). Not surprisingly, negotiations between pharmaceutical developers — who bear most of that cost and risk — and holders of tool patents to inventions that are relevant to only the very early phases of the drug discovery process are very contentious indeed.
To complicate matters, patent attorneys try to draft tool patents that are applicable to pharmaceutical research with an eye to claiming any drug or method for treating a disease that conceivably could flow from the invention. The holder of a tool patent with these sorts of claims thus has tremendous bargaining leverage over a drug developer who wants access to the patented tool: The developer must either take a license or risk potentially devastating patent litigation on the eve of launching the drug.
Pharmaceutical developers have long objected to such patent claims as a perversion of the patent system that provides maximal rewards to those who accept little or no risk. They often complain that such patents fail two of the requirements for obtaining a patent as set out in the first paragraph of 35 U.S.C. [SECTION SYMBOL]112: (1) a patentee must describe the invention in detail sufficient that a person of ordinary skill in the field of the invention would understand that the patentee possessed the invention when the application was filed; and (2) such a skilled person must find enough information in the patent's description to make and use the invention. The first requirement is referred to as the written description requirement. The second is called the enablement requirement.
Often, however, the inventor of a tool patent does not have an idea of what the downstream product looks like or how anyone would make the product once a starting point was identified by the tool patent. To attempt to satisfy these requirements, patent attorneys and inventors work to define the downstream invention as a prophetic invention. The language describing such prophetic inventions attempts to convince the patent office that persons of skill will recognize the downstream product by its function; and the process of reaching that product is just a matter of applying standard, known practices. In other words, all one really needs is the tool to traverse the mountains and reach the final product. Needless to say, the biotech and genomics patent literature is filled with such boilerplate.
The University of Rochester received U.S. patent 6,048,850 in 2000, which claimed methods for inhibiting selectively COX-2 in a host. (COX-1 is expressed in normal gut tissue, while COX-2 is expressed only by inflamed tissues. Thus COX-2 is a better target to identify a pain-relieving drug than COX-1, because COX-2 production is associated largely with disease.) The discovery of the functions of COX-1 and COX-2 and their corresponding genes led eventually to a new class of non-steroidal anti-inflammatory compounds that provide pain relief with reduced unwanted gastrointestinal side effects — the multibillion-dollar drugs Celebrex and Bextra.
The patent arose from an application that was filed in 1992, but that only described in detail the gene for COX-2. In fact, the patent did not describe a new COX-2-specific drug or a specific method for inhibiting COX-2: Those inventions were prophetic and based on work that would presumably follow from the use of Rochester's tool. In fact, the patent describes COX-2-inhibiting compounds only generally as compounds that "will demonstrate the ability to selectively modulate the expression of [COX]-2. These compounds include but are not limited to nucleic acid encoding [COX]-2 and homologues, analogues and deletions thereof, as well as antisense, ribozyme, triple helix, antibody and polypeptide molecules and small inorganic molecules." Given that level of detail, should Rochester be entitled to a piece of the of the blockbuster pie?
Apparently not. The district court held on summary judgment that the patent was invalid for failing to meet the written description and enablement requirements. In particular, the district court found that Rochester's patent neither disclosed COX-2-inhibiting compounds nor provided any methods for identifying such compounds absent trial and error. Over Rochester's objections, the Federal Circuit agreed with the district court, explaining at length the history of the written description and enablement requirements as separate and distinct elements of the requirements for obtaining a patent. As for Rochester's attempt to describe COX-2-inhibiting compounds, the court noted that:
"Even with the three-dimensional structures of enzymes such as COX-1 and COX-2 in hand, it may even now not be within the ordinary skill in the art to predict what compounds might bind to and inhibit them, let alone have been within the purview of one of ordinary skill in the art in the 1993-1995 period in which the applications that led to the '850 patent were filed. … As the district court observed, the claimed method depends upon finding a compound that selectively inhibits [COX]-2 activity. Without such a compound, it is impossible to practice the claimed method of treatment."
The court, however, stopped short of requiring a literal description of the final drug (quoting Hyatt v. Boone, 146 F.3d 1348, 1353 (Fed. Cir. 1998)):
"We of course do not mean to suggest that the written description requirement can be satisfied only by providing a description of an actual reduction to practice. Constructive reduction to practice is an established method of disclosure, but the application must nonetheless ‘describe the claimed subject matter in terms that establish that [the applicant] was in possession of the … claimed invention, including all of the elements and limitations.'"
As for Rochester's and the amici curiae's arguments that such a standard for the written description would defeat the purpose of the Bayh-Dole Act and prevent universities from bringing "pioneering" inventions to the public, the court responded: "That argument is unsound. The Bayh-Dole Act was intended to enable universities to profit from their federally funded research. It was not intended to relax the statutory requirements for patentability."
Thus, the Federal Circuit's interpretation of the written description requirement appears to have placed a seemingly insurmountable obstacle in the path of Rochester and other holders of tool patents seeking to obtain a place at the blockbuster table. How could Rochester ever have met such stringent requirements?
Ironically, the existence of COX-2 had been hypothesized since the late 1960s as a vast amount of pharmacological and medicinal chemical research identified a large number of chemical substances having patterns of similarities and differences that could be explained by the existence of two forms of the enzyme cyclooxygenase. In 1990 scientists at DuPont reported DuP697, a compound having analgesic properties with reduced ulcerogenic effects. Thus, even as early as 1990 reports had been published of a compound having the earmarks of a selective COX-2 inhibitor. Indeed, Searle's (now Pharmacia's) scientists quickly extended the observations on DuP697 in combination with the discovery of COX-2 and several later-published compounds to create Celebrex, whose structure bears a strong familial resemblance to DuP697. Surprisingly, none of this historical information appears to have been included in the '850 patent.
How could this information have helped Rochester? The existence of DuP697 may have prevented Rochester from obtaining claims to any COX-2-inhibiting compound or method for inhibiting selectively COX-2 using any COX-2-inhibiting compound, since arguably one example of such a compound was known prior to Rochester's invention (a concept in patent law known as "accidental anticipation"). Nevertheless, had Rochester or Rochester's patent attorneys identified this publication and the long history of work in that area, Rochester could have been the first to demonstrate the usefulness of their assay using DuP697 and could have either taken an active role in drug discovery (possibly with a pharma partner) or identified prophetically a class of structures that — maybe — would have encompassed Celebrex and obviated the written description ground for invalidating the '850 patent. In either case, Rochester would have been in a better position to provide the missing descriptive details required by the Federal Circuit.
Of course, the enablement issue would have remained. (The Federal Circuit declined to rule on that question since the '850 patent was invalidated on the written description deficiency alone.) That question, when it arrives at the Federal Circuit, will be another watershed decision for the chemical and biotechnological patent bar. But, had that point been reached, Rochester arguably would have been in a stronger position since it could have pointed to having played a more direct role in the identification of the marketed product.
Thus, Rochester leaves one important question for another day. But, the decision does provide some important guidance to research tool inventors seeking a stake in a future product. Generic, boilerplate descriptions of downstream inventions are not likely to curry favor at the U.S. Patent and Trademark Office or in the courts. Rather, patent practitioners would do better to explain to their clients who want claims covering downstream inventions that they should take care to develop as detailed a prophetic description of the downstream invention as possible.
For pharmaceutical research tool inventions, this can be facilitated by working closely with someone experienced in patenting pharmaceutical inventions. Then, having set their sights on the future, the patent practitioner and inventor should take a long look at the past.
David P. Lentini joined Foley & Lardner’s San Francisco office a year ago as part of Foley’s Chemical and Pharmaceutical IP Group after holding in-house patent counsel positions for Kosan Biosciences and Chiron Corp. The views expressed by Lentini do not necessarily represent the opinion of Foley & Lardner.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.
