Classen v. Biogen: The Federal Circuit Applies Bilski to the Life Sciences

In a non-precedential opinion, a panel of the Federal Circuit affirmed a lower court’s decision in Classen v. Biogen to invalidate Dr. Classen’s process claims for encompassing patent-ineligible subject matter. I have previously discussed the district court decision in posts to this blog and Patently-O. The claims are directed to methods for determining an optimal immunization schedule based on comparing the observed incidence of immune-mediated disorders in treatment groups subjected to different vaccination schedules.

The decision, in its entirety, states as follows: “In light of our decision in In re Bilski, 545 F.3d 943 (Fed. Cir. 2008) (en banc), we affirm the district court’s grant of summary judgment that these claims are invalid under 35 U.S.C. § 101. Dr. Classen’s claims are neither “tied to a particular machine or apparatus” nor do they ‘transform[] a particular article into a different state or thing.’ Bilski, 545 F.3d at 954. Therefore we affirm.”

The opinion ducks important issues. Contrary to the holding, the claims do in fact involve a transformation, e.g., claim 1 of 5,723,283 recites a ‘method . . . which comprises immunizing mammals in the treatment group of mammals with one or more doses of one or more immunogens . . ..” The immunization of a mammal clearly effects a transformation of a particular article [a mammal] into a different state [a state of induced immunity]. It is inconceivable that this does not constitute a transformation; if that were the case, it would logically follow that all method of treatment claims are patent-ineligible. Rather, the court implicitly must have determined that, in the context of the claims at issue, immunization of a mammal constitutes an “insubstantial extra-solution activity.” In Bilski, the court held that an otherwise patent-ineligible process is not rendered patentable by tagging on an insubstantial additional step. The court could have provided some needed guidance by explaining its basis for determining that the immunization step is insubstantial, but instead the court decided to punt on the issue.

The lower courts decision was less than fully coherent on the basis for its determination that claims are patent-ineligible, at times asserting that the claims are invalid for claiming a mental process, while at other times complaining that that the claims encompass a natural phenomenon. The district court concluded that “[c]learly, the correlation between vaccination schedules and the incidence of immune mediated disorders that Dr. Classen claims to have discovered is a natural phenomenon.” The court provided absolutely no reasoning to support this conclusion. To my mind, it is not at all clear that it can be so blithely assumed that vaccination is a natural phenomenon. That would depend upon how vaccination is defined, but clearly immunization using human-generated vaccines is not something that occurs absent human intervention.

As I discussed in my previous post to Patently-O, to my mind the Bilski machine-transformation test is inappropriate in some cases involving natural phenomena. For example, a claim encompassing photosynthesis in a plant involves a transformation of a particular article [carbon dioxide and water] into a different thing [sugar and oxygen], so it passes the Bilski test. But it cannot be patentable under Supreme Court precedent, since it encompasses a natural phenomenon. I think the Federal Circuit needs to be careful in blinding applying the Bilski test to a claim arguably directed to a natural phenomenon.

A similar case is currently pending before the Federal Circuit, Prometheus v. Mayo, discussed in my earlier posts. The district court in Prometheus also found that the claims at issue encompass an unpatentable natural phenomenon, i.e., the correlation between the amount of a drug metabolite in a patient’s body with the optimal dosage of the drug. Unlike vaccination, which arguably encompasses the natural introduction of an immunogen into a patient’s body, the correlation at issue in Prometheus is entirely the results of the introduction of a non-naturally occurring drug into the patient. While the vaccination in Classen arguably can be interpreted so as to encompass a natural phenomenon, the correlation in Prometheus is not what I would consider to be a natural phenomenon. To hold otherwise would establish dangerous precedent, but the Federal Circuit might never even address the issue if it proceeds to simply apply the Bilski test in a reflexive manner, as appears to have to been the case in Classen.

I would also point out that the Classen decision does not bode well for a host of issued patent claims, particularly genetic diagnostic method claims which purport to broadly encompass any method of identifying a mutation.

WARF Unable to Persuade EPO Enlarged Board of Appeal to Allow Human Embryonic Stem Cell Claims

On November 25, 2008, the European Patent Office (EPO) Enlarged Board of Appeal (EBA) affirmed a Technical Board of Appeal (TBA) decision refusing a Wisconsin Alumni Research Foundation (WARF) patent application claiming cultured primate embryonic stem cells. (The EBA can be analogized to the Supreme Court of the EPO.) The corresponding US patent, No. 5, 843,780, has been the subject of controversy in the US, but nonetheless recently survived an ex parte reexamination challenge. The inter partes reexamination of a related WARF stem cell patent was discussed in a previous post. An appeal of that decision is currently pending.

In its decision, the EBA held that WARF’s stem cell claims violate Rule 28(c) of the Implementing Regulations to the European Patent Convention, which states “[u]nder Article 53(a), European patents shall not be granted in respect of biotechnological inventions which [uses] human embryos for industrial or commercial purposes.” The EBA based its decision on the fact that, at the time the application was filed, production of the claimed stem cells necessarily entailed the use and destruction of a human embryo, which the Board characterized as an industrial purpose within the meaning of Rule 28 (c). WARF argued that the claims are directed to cells, not embryos, but the EBA found that Rule 28(c) applies not only to subject matter of the claims but rather to the invention as a whole, which includes the methodology required to make the claimed invention.

WARF argued that the claimed embryonic stem cells could be used for research purposes, and that research is not “industrial or commercial” in nature. However, the EBA pointed out that Article 28(c) traces its origin to Article 6(c) of the Directive 98/44/EC of 6 July 1998. As originally drafted, Article 6(c) would have banned the patenting of any method in which human embryos are used. However, in order to allow the patenting of inventions which could be used to treat human embryos, i.e., procedures designed to benefit a human embryo, the Article 6(c) was amended to recite “uses of human embryos for industrial or commercial purposes.” In other words, the industrial or commercial purposes limitation was intended to allow for the patenting of inventions intended to benefit a human embryo, not to permit the patenting of inventions which exploit (let alone destroy) human embryos for research purposes. The EBA found that European legislators were concerned with preventing misuse in the sense of a commodification of human embryos, and that one of thire essential objectives was the protection of human dignity. The Board also pointed out that, consistent with its interpretation of legislative intent, the European Community excludes funding for research which results in the destruction of human embryos, including for the procurement of stem cells.

WARF further argued that the term “embryo” as used in Rule 28(c) should be interpreted as limited to embryos of 14 days or older. However, the EBA found that this narrow interpretation would be inconsistent with the intent of European legislators, pointing out that under German law an embryo is defined as including a fertilized egg, and UK law defines an embryo so as to encompass a two cell zygote and an egg in the process of fertilization. The EBA rejected also characterized WARF’s proposed narrow definition of embryo as inconsistent with a legislative intent to protect human dignity and prevent the commercialization of embryos.

WARF, and other interested parties who voiced their opinions in the case, urged the EBA to find the invention patentable based on “balancing the benefits of the invention for humanity against the prejudice to the embryo.” However, the EBA found that it was not the proper forum to decide such policy issues, particularly given the clear legislative intent to exclude inventions such as the one at issue from patentability.

Finally, WARF argued that the claims should be patentable because today the claimed human embryonic stem cells could be derived directly from other human embryonic cell lines, thereby avoiding the necessity for further destruction of human embryos. But the EBA rejected this argument also, finding that when assessing whether a claim contravenes Rule 28(c), technical developments which became publicly available only after the filing date cannot be taken into consideration. To hold otherwise, according to the EBA, could unduly prejudice the rights of a third party who might later provide an innocuous way to carry out the invention (presumably a method not involving the destruction of human embryos).

Genomics-Based Patents: Are Prophetic Assertions of Utility Enough?

During the late 1990s and early 2000s large-scale gene sequencing projects led to a wealth of newly identified human gene sequences, and a flood of patent applications attempting to lay claim to them. With so many laboratories cranking out newly discovered gene sequences every day there was huge pressure to file patent applications early, in many cases before the biological role of the gene or gene product had been assessed experimentally. In an attempt to satisfy the utility requirement, which essentially requires a patent applicant to disclose a practical use of a genetic sequence that is specific, substantial and credible, patent applicants resorted to the disclosure of “prophetic utilities.” Often times these predictions were based on sequence similarity (i.e., homology) between the sequence of the newly discovered gene product and a protein or family of proteins of known function, or identification of tissue or disease state-specific expression of the gene. In many cases this limited information was supplemented by providing essentially a laundry list of potential uses of the gene, typically involving use of the gene or genes product as a drug or diagnostic, or in the development of a drug or diagnostic. The hope was that at least one of the proposed uses would actually pan out, and the patent applicant would be able to point to the disclosure of the utility in the patent application as evidence that the utility was disclosed at the time of filing.

Although many of these applications resulted in the issuance of patents directed to the gene, the protein product of the gene, antibodies specific for the protein product, etc., it is not at all clear whether these patents would withstand a determined validity challenge during litigation. I am not aware of any case where one of these patents has actually been successfully asserted in court, either in the US or abroad. In my recent survey of human gene patent litigation in the US (“Trend in Human Gene Patent Litigation,” Science, 322:198-99 (2008)), I identified only one lawsuit in which a genomic-based patent was asserted. The lawsuit was filed by Incyte (a leading genomics company during the peak of the gene patenting frenzy, and one of the leading holders of human gene patents) against Invitrogen. Incyte appears to have filed the lawsuit in retaliation for a patent lawsuit that Invitrogen had previously filed against Incyte. Incyte and Invitrogen settled prior to any substantive briefing by the parties, so there is no indication from this lawsuit as to how Incyte's gene patents would have fared against a validity challenge.

Other major genomic companies that patented many genes based on prophetic assertions of utility, such as Human Genome Sciences, Lexicon Genetics and Millenium Pharmaceuticals, have apparently never asserted any of these patents in court. Many of these turn-of-the- century genomic companies have in recent years sought to reposition themselves as pharmaceutical companies, as the genomic-based business models have lost much of their appeal. They have also chosen not to pay maintenance fees on many of these patents, allowing them to enter the public domain. New patent filings on genes have also reportedly dropped off in recent years (see cite in my Science article).

On a number of occasions, the US Patent Office’s Board of Patent Appeals and Interferences (BPAI) has affirmed rejections of genomic-based patent claims under 35 USC 101 and 112 for lack of utility. For example, in Ex Parte Lee (2004 WL 1967421) claims to a newly discovered gene, and the corresponding protein, were rejected for failure to identify a specific utility in the application as filed. On appeal, the applicant attempted to establish utility based on post-filing date gene knockout experiments that allegedly showed that at least one of the predicted utilities actually panned out. However, the Board rejected this argument and affirmed the rejection of both the protein and DNA claims, finding that the predicted utilities were only speculative at the time the application was filed, and there was no evidence that the utility had been adequately demonstrated as of the filing date of the application.

For another example, see Ex Parte Lal, 2007 WL 1878008, an unsuccessful appeal by Incyte of a rejection based on lack of utility. The application as filed disclosed that the most similar prior art sequence the applicant could find to the protein product of the claimed gene sequence was a taste receptor, and Incyte argued that this constituted a sufficient assertion of utility. The BPAI rejected this argument, and found that post-filing date evidence that the protein actually was a taste receptor was insufficient, since the utility had not been established as of the date of filing.

On July 31, 2008 the British Royal Courts of Justice revoked a Human Genome Sciences (HGS) genomic patent claiming a member of the TNF ligand superfamily, which HGS identified as “Neutrokine-alpha.” (Eli Lilly v. Human Genome Sciences [2008] EWHC 1903 (Pat)). HGS knew at the time it filed its patent application that the newly discovered gene appeared to be a member of the TNF ligand superfamily, based on sequence similarity. The patent application discloses this fact, and includes a host of predicted utilities, many of them based on the known diverse activities of other members of the TNF superfamily. The British court found the claims to be invalid based on lack of industrial applicability (utility), insufficiency (enablement) and obviousness. In particular, the Court found that by disclosing a huge number of speculative (and often contradictory) utilities, the application in effect failed to provide any real teaching of utility and thus fail to solve any technical problem. The court was highly critical of this laundry list approach to satisfying the industrial applicability requirement. The decision cites a number of EPO Technical Board of Appeals decisions relating to patent applications disclosing prophetic utilities for biological molecules and arriving at a similar outcome.

One aspect of the British decision I found interesting, and quite different from US practice, was the Court’s ruling on obviousness. Lilly raised a number of obviousness challenges to the patent, based on prior art disclosures of clones containing partial sequences of the claimed gene, e.g., EST sequences, but the Court held that these partial sequences were insufficient to render HGS’s successful cloning of the full-length gene obvious. However, the Court held that since the specification contains more no more than a range of speculative applications of the gene, which the Court characterized as implausible, it fails to teach a person skilled in the art how to solve any technical problem. In essence, the court finds that because the applicant failed to meaningfully identify a use for the gene, the patent was invalid not only for lack of industrial activity, but also for lack of inventive step, i.e., obviousness.