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Navigating  Gene Patent Minefields 

Strategic Insights 
· Genes & Liens 
· After the Gene Rush
· Patently More Difficult
· Navigating Gene Patent Minefields
· Are Gene Patents in the Public Interest?
Nov. 12, 2002 | Scientists working with gene sequences must avoid making, using, or selling gene sequences that are covered by a patent, since a finding of infringement will at a minimum result in the court assessing damages — and possibly a devastating injunction. Following is practical advice to identify and potentially avoid being a defendant in a patent infringement lawsuit.

A critical first step to avoiding patent infringement is identifying relevant patents, which can be accomplished through effective database searching. Patents identified early in the development process may be "designed around," or licensed on more commercially advantageous terms than those available as an infringing product approaches launch.

However, to determine whether design-arounds are possible or licenses are necessary, the patent claims must be construed as a court would construe them to determine their meaning and scope. This is known as "claim construction." In construing the claims, the court considers the claims themselves, the description of the claim language as provided by the patent specification, and the patent file history — the representations made to the U.S. Patent and Trademark Office (PTO) to obtain issuance of the claims. The court may also consider the "ordinary meaning" of particular terms — what one of skill in the art would understand the term to mean.

To determine infringement, the properly construed claims must be compared to the potentially infringing product or process to determine whether any patent claims are infringed. Literal infringement of a claim exists when every limitation recited in the claim is found in the accused product or process.

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Even if a claim is not literally infringed, a court may decide it has been infringed under the "doctrine of equivalents" if an equivalent for each claim limitation is found in the accused product or process. The representations made to the PTO in obtaining issuance of the patent (the patent's prosecution history, or "file wrapper") may limit the doctrine of equivalents by denying equivalency to a claim limitation that was introduced during prosecution. So far, the doctrine of equivalents has not been applied by a court to expand the scope of a gene patent beyond what is literally claimed.


Exceptions and Exemptions 
Making or using a gene " ... 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 or veterinary biological products," is exempted from infringement under Section 202 of the Hatch-Waxman Act, codified as 35 U.S.C. § 271(e)(1). Making and using a patented gene in clinical studies for a therapeutic is exempted from infringement until such time as the Abbreviated New Drug Application (ANDA) is submitted. Also exempted is the use of a gene in studies to gain FDA approval of a genetic diagnostic or susceptibility test.

Less clear is whether use of a gene "target" to identify a therapeutic would be exempted. Recent cases, however, have broadened the scope of the 271(e)(1) exemption to include activities seemingly ancillary to the generation of data for FDA approval, as well as early research activities resulting in a regulated product.

In addition to the Hatch-Waxman exemption, some think that the common-law "experimental use exception" should apply to excuse academic research using patented genes and encoded proteins, and even use of the patented sequences in drug screening assays, from infringement, given the short time the "target" is used. However, a court has yet to recognize this exception. Indeed, in a recent federal circuit case, a concurring justice ruled that there is really no need for such an exception, as in situations where there is only minor infringement that doesn't result in a commercial product, the patentee wouldn't bother to sue. In other words, although use of a patented gene sequence in purely academic research may technically amount to an infringement, it's probably not worth it for the patentee to file suit — unless the research results in identification or validation of a billion-dollar drug.


The Best Defense? A Good Offense 
If you're infringing on a gene patent, can't develop an effective design-around, and are unwilling or unable to obtain a license, the best strategy may be to lie low. A patent holder will need evidence of infringement in order to enforce patent rights. It's difficult for a patentee to understand exactly what's being done with its patented gene in other labs — unless, of course, the lab advertises its use in an article or at a conference.

If you're clearly infringing a gene patent, can't develop an effective design-around, and are unwilling or unable to obtain a license under the patent, the best strategy is to lie low. 
In addition, a dead-on infringer should determine whether the infringed patent claims are indeed valid and enforceable. In order to invalidate patent claims, the court must be satisfied that the claims fail to comply with any of the patentability requirements. Since issued patent claims are entitled to a "presumption of validity," the court must be provided with "clear and convincing evidence" otherwise. Gene patent claims are particularly vulnerable in the following three areas:

Lack of novelty: The disclosure in a patent of a novel, full-length nucleic acid sequence may suffice to support a broad range of claims, not only to the particular nucleic acid or protein, but also to related molecules, including homologous full-length sequences or fragments, complementary nucleic acid sequences, and encoded proteins to the extent that such sequences have not already been described in prior art (any publication or material that shows a patented item is obvious or not new).

Claims to nucleic acids that "hybridize to a designated sequence under a specified hybridization condition," are being issued by patent examiners, as are claims that point out nucleic acid sequences with a 90 percent identity to a designated nucleic acid. Further, in spite of the "isolated" limitation, required to distinguish the sequence from those that exist in nature (e.g., in a genome), claims to nucleic acid sequences can, in theory, be broadly drafted to cover any nucleic acid that it "comprises." For example, claims to a gene fragment can be drafted to encompass the full-length gene.

Although the breadth of these claims increases the likelihood of infringement, it also increases the probability that the claim will be ruled invalid for encompassing gene sequences that were known before the effective filing date of the patent.

Insufficient written description: Gene patent claims may also be invalidated for insufficient written description. Patent specifications must convey to one of skill in the art at the time the patent was filed that the patentee had possession of the claimed subject matter. In Regents of California v. Eli Lilly and Co., the court invalidated claims to "human insulin cDNA," and "vertebrate" and "mammalian" encoding insulin, where the only nucleic acid sequence specifically described in the patent specification was obtained from a rat. Eli Lilly and the PTO's Written Description Guidelines require that the gene sequence actually be disclosed, as opposed to being described functionally.

Lack of utility: A "specific," "substantial," and "credible" utility of a gene is required for the gene to be considered patentable. A "throw-away" utility, such as "used as a probe" is insufficient. Although a court has not as yet followed the PTO's Utility Guidelines to invalidate a patent on a gene sequence for lack of utility, where the usefulness of the sequence is clearly unknown, it is only a matter of time.

Beth E. Arnold is a partner at Foley Hoag LLP in Boston with more than 15 years of experience in worldwide patent protection on pharmaceuticals and biotechnologies. She may be reached at bea@foleyhoag.com. 





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