Orange Book Blog

Federal Circuit Confines 271(e)(1) Safe Harbor to Pre-Approval Activities

Classen Immunotherapies v. Biogen IDEC et al., Nos. 2006-1634, -1649 (Fed. Cir. 2011)

In a 2-1 opinion today, the Federal Circuit held that the Section 271(e)(1) safe harbor "does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained."

35 U.S.C. § 271(e)(1) states:

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States . . . a patented invention . . . solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs . . . .

The law was passed as part of the Hatch-Waxman Act in 1984, and while the purpose of the law was to shield generic drug makers from claims of patent infringement during the generic drug development process, the Supreme Court has interpreted the law much more broadly.

For instance, in Eli Lilly v. Medtronic, 496 U.S. 661 (1990), the Court held that the safe harbor applies not only to pharmaceutical development, but also to medical device development.  More recently, in Merck v. Integra, 545 U.S. 193 (2005), the Court held that the safe harbor applies not only to generic pharmaceutical development, but rather to "all uses of patented inventions that are reasonably related to the development and submission of any information under the FDCA."  In addition, the Court stated, "there is simply no room in the statute for excluding certain information from the exemption on the basis of the phase of research in which it is developed or the particular submission in which it could be included."  In both Lilly and Merck, the Supreme Court reached its conclusions based on the plain language of the statute, which is intentionally broad.

In this case, Classen accused Biogen IDEC and GlaxoSmithKline of infringing its patents claiming methods of immunization on the ground that both companies participated in post-approval studies "to evaluate suggested associations between childhood vaccinations, particularly against hepatitis B and Haemophilus influenza . . . and risk of developing type 1 diabetes; and to determine whether timing of vaccinations influences risk."  The district court granted summary judgment that these activities are within the Section 271(e)(1) safe harbor.

On appeal, Classen argued "that this statute, as enacted and intended, and as judicially interpreted, is limited to activities conducted to obtain pre-marketing approval of generic counterparts of patented inventions, before patent expiration."  Biogen and GSK argued, on the other hand, that their participation in studies evaluating risks associated with different vaccination schedules is reasonably related to their requirement under, e.g., 21 C.F.R. § 601.70 and 21 C.F.R. § 600.80, to review and report adverse events to the FDA.

The majority opinion, authored by J. Newman and joined by J. Rader, found in favor of Classen, stating:

Classen is correct, for § 271(e)(1) provides an exception to the law of infringement in order to expedite development of information for regulatory approval of generic counterparts of patented products.  The statute does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained.

The majority opinion then proceeds to review the legislative history of the Hatch-Waxman Act, which obviously focused on the then-new abbreviated approval process for generic drugs.  While the majority opinion quotes from both Eli Lilly v. Medtronic and Merck v. Integra, it ignores how broadly the Supreme Court interpreted the safe harbor in those cases.  Rather, according to the majority opinion, "every decision examining the statute has appreciated that § 271(e)(1) is directed to premarketing approval of generic counterparts before patent expiration."

But as the dissent by J. Moore notes, regardless of what the statute "is directed to" (whatever that means), there was no dispute in this case that the safe harbor applies to pre-approval activities.  J. Moore wrote:

The majority cites extensively from the legislative history in an attempt to justify its construction.  But these citations miss the point entirely.  There is no dispute that § 271(e)(1) covers pre-approval studies, as the legislative history indicates.  None of the legislative history cited by the majority, nor the cases it references, speak to the question at issue here -- whether the statute as enacted also covers post-approval activities.  The question is not whether Congress intended to protect pre-approval activity -- but whether the enacted legislation covers more than just pre-approval activity.  The language Congress chose to enact and that was signed by the President is plain on its face.  There is no "pre-approval" limitation.

The other main issue addressed in the opinion concerns the patent-eligibility of Classen's claims under 35 U.S.C. § 101.  Patently-O has an excellent discussion of that portion of the opinion.

Federal Circuit Confirms that Isolated DNA May Be Patented

Assoc. for Molecular Pathology v. Myriad Genetics, No. 2010-1426 (Fed. Cir. 2011)

    by Nabeela Rasheed

In a decision last Friday, the Federal Circuit confirmed that isolated DNA may be patented.  Judge Lourie brought his considerable chemistry background to bear in writing the court's opinion in a case presenting the question of whether isolated DNA is patent-eligible subject matter.

Myriad appealed a district court decision that held, on summary judgment, that the claims of a number of patents relating to the breast and ovarian cancer genes BRCA1 and BRCA2 were invalid because the gene sequences were products of nature and therefore unpatentable.  The Federal Circuit addressed this question, and it also addressed whether the plethora of plaintiffs had standing to challenge the patents.  The following précis discusses the merits of the patent eligibility of isolated DNA molecules and methods of diagnosis.  The opinion clearly answered the first question in the affirmative for isolated DNA molecules and provided a "maybe" for diagnostic methods, but not in the form presented by Myriad.

In reviewing the patent eligibility of DNA-related claims, the court reverted to the reasoning from the Supreme Court's decision in Chakrobarty, 447 US 1981, the ancestor of most biotechnology decisions in the area of 35 U.S.C. 101.  The test fashioned since that decision focuses on whether a man-made composition is patent-eligible subject matter and answers that it is if the claimed subject matter is a non-naturally occurring composition of matter having a distinct name, character and use.

Applying the test to isolated DNAs, the Federal Circuit concluded here that the challenged claims are drawn to patentable subject matter because the claims cover molecules that are markedly different–-they have distinctive chemical identity and nature--from molecules that exist in nature.  The DNA molecules claimed by Myriad are in an isolated state: they are not the same molecules as those existing in the body.  It took human intervention in cleaving or synthesizing these new chemicals and this human intervention imparts on that isolated DNA a distinctive chemical identify from that possessed by such a chemical within native DNA.

The court took pains to explain that isolated DNA is not merely purified DNA but rather it is a distinct chemical entity defined by separate molecular species joined together by an all-important chemical bond.  In addressing the patent eligibility of the underlying DNA claims, the court dismissed the argument that the DNA should not be patent-eligible because it does not have markedly different characteristics from the characteristics of the DNA in native form.  The court again reiterated that the subject matter is a distinct chemical entity and that focusing on the properties or use of that chemical entity improperly conflates the patent eligibility inquiry with an obviousness inquiry.

In the same vein, the Federal Circuit dismissed the middle-ground arguments advanced by the Patent Office: that isolated DNAs should not be patentable because they can be seen using a "magic microscope" whereas cDNAs cannot.  The court rejected the Patent Office’s argument as it fails to understand the difference between science and invention and fails to recognize that the DNA molecules are separate chemical entities regardless of whether they are cDNA molecules or isolated genomic DNA molecules.  The court noted that the ability to visualize a DNA molecule is "worlds apart" from possession of an isolated DNA.  Noting that this is the difference between knowledge of nature and a reduction of that knowledge to a concrete form, the latter activity being the very ingenuity that the patent laws seek to encourage through protection, the court provided its imprimatur to DNA composition-of-matter claims regardless of whether they are cDNA claims or isolated genomic DNA claims.

The court was not so forthcoming with the same endorsement for the diagnostic method claims as presented in the patents.  All but one of the method claims at issue covered "analyzing" or "comparing" a patient's DNA sequence with the DNA sequence from wild-type or normal patients that do not have cancer to effectively correlate a difference in the DNAs with a cancer.  The court noted that the "analyzing" or "comparing" step is the entire process claimed, and can in fact be a mental step without being tied to some additional transformative test--and hence these method claims fail the test of patent eligibility.  However, that is not to say that Myriad provides the death knell for diagnostic method claims.  Rather, the court stated that "isolating genes to provide useful diagnostic tools and medicines is surely what the patent laws are intended to encourage and protect."

With the above encouragement in mind, it is still possible to obtain claims to methods of diagnosis of a disease as long as the diagnostic methods that involve analysis or comparison of a diseased state with a wild-type or normal state are crafted to include a physical step such as "extraction" or other manipulation of the underlying chemical to be analyzed or compared in the diagnostic step.  Crafting the appropriate language for this additional element in diagnostic method claims will become ever more important with the dawning of the age of personalized medicine and the need for protection of underlying intellectual property focused on personalized medicine.

The court seems to have applied well-established law under 35 U.S.C. 101, including the recent guidance provided by the Supreme Court in Bilski, making it a more remote possibility that the Supreme Court would accept the case review.