July 22, 2013
Law360
By Jessica L.A. Marks; Jeffrey M. Jacobstein; L. Scott Burwell
Authored by L. Scott Burwell, Jeffrey M. Jacobstein, and Jessica L.A. Marks
On June 13, 2013, the U.S. Supreme Court issued its decision in Association for Molecular Pathology v. Myriad Genetics Inc.1 The question before the court was: Are human genes patentable?2 The resounding unanimous answer given will change the practice of gene patenting from now on: Although complementary DNA ("cDNA") may be patent-eligible under 35 U.S.C. § 101, isolated genomic DNA is not. The decision to deny patent eligibility for an isolated nucleic acid reversed the U.S. Patent and Trademark Office's long history of granting such patents. Although the ultimate impact of Myriad is yet to be determined, some of the likely effects can already be predicted.
As with all inventions, there are two primary paths available to inventors seeking to protect their nucleic acid discoveries: patents and trade secrets. Now that the court has held that at least certain types of isolated DNA are not patent-eligible, inventors may be tempted to rely more heavily on trade secrets to protect their inventions. But that approach is not without risk.
At a basic level, the grant of a patent represents an exchange of benefits between the inventors and the public. Patents are granted as an incentive for inventors to disclose their inventions to the public, and, although the inventor receives a period of exclusivity, the public benefits in exchange for the disclosed information. While the patent is in force, competitors may learn from the inventor's disclosure and develop further innovations. And, after the patent expires, anyone may freely practice the claimed invention.
The alternative to patent protection is trade secret protection. As long as an inventor is able to keep an invention a secret, the inventor can retain exclusive rights to the invention indefinitely. Because the invention is kept a secret, it is often difficult for others to use it to develop further innovations. Of course, trade secret protection does not prevent others from independently making the invention. But independent creation of the invention is often much more difficult than simply learning how to make the invention from the original inventor's own disclosure.
Now that the patent path has been restricted for isolated nucleic acid claims, companies may be reconsidering the feasibility of the trade secret path. But the economic viability of trade secret protection for isolated nucleic acids is questionable. As noted above, if a competitor independently develops the same invention, for example a diagnostic assay relying on the same nucleic acid markers, then the original inventor would lack legal tools to prevent that competitor from making, using or selling the invention.
Trade secret protection is most effective in those fields where an invention is difficult to access or reverse engineer. But as admitted by both sides in the Myriad case, the techniques for determining the locations and sequences of genes are known and becoming increasingly routine. Thus, it will be difficult for companies to keep newly discovered sequences secret indefinitely, particularly once products based on those sequences are commercialized.
Moreover, if a company does decide to pursue trade secret protection in the United States, it must de facto forgo patent protection throughout the rest of the world. Isolated DNA may not be patent-eligible in the United States, but it remains patent-eligible, at least in some form, in most developed countries.
Given this patent eligibility in other countries, a company must weigh the potential benefits of the time it will have exclusive control by maintaining the invention as a trade secret against the potential that a competitor will independently discover the sequence and pursue patent protection in other countries.
In a worst-case scenario, soon after an inventor discovers the nucleic acid sequence, a competitor could independently discover the same sequence and patent it throughout the rest of the world, simultaneously preventing the original inventor from practicing the invention outside the United States and robbing the original inventor of any trade secret protection in the United States.
The claims that were deemed patent ineligible in Myriad were relatively straightforward claims to isolated genomic DNA sequences. Myriad's patents contained many other types of claims directed to different aspects of the BRCA genes and their uses, but many of these claims were not found patent ineligible. By pursuing these and other types of claims, patent applicants can attempt to approximate the coverage previously afforded by claims directed to isolated nucleic acids. Especially given the risks associated with trade secrets, as discussed above, the remaining scope of patent eligibility for nucleic acids may minimize the effect of loss of patent scope resulting from the Myriad decision.
One of the more common alternatives to claiming an isolated genomic DNA sequence (which include exons and introns) is a claim to a cDNA sequence. cDNA can be created in the laboratory by reverse transcribing messenger RNA, thereby producing DNA sequences containing only the exons—those parts of genomic DNA that are primarily responsible for encoding the amino acid sequences of proteins.
cDNA claims themselves are useful forms of patent protection because, in practice, cDNA is often used when synthesizing proteins or in making probes for diagnostic assays. cDNA used for proteins often contains relatively long sequences that usually cover several exons, and omits the introns of the genomic DNA, thereby complying with the Supreme Court's distinction between genomic DNA and constructs that do not occur in nature.3 Therefore, particularly for inventors developing recombinant and modified proteins, claims to the cDNA sequences encoding those proteins should be less open to attack on patent eligibility grounds.
While claims to cDNA used to synthesize proteins should remain patent-eligible, the scope of protection of cDNA used in diagnostic testing may be more limited. This is because the cDNA used in diagnostic applications often comprises short sequences, potentially entirely within a single exon, thereby reading on a genomic sequence. As the court stated, cDNA "is not naturally occurring," so it "does not present the same obstacles to patentability as naturally occurring, isolated DNA segments."4 But the sequence of a short cDNA sequence, such as those used for diagnostic testing, may or may not occur in nature, depending on whether the sequence is contained entirely with a single exon or whether it contains sequences spanning all or parts of two or more exons.
Likewise, claims to other types of nucleic acids, such as claims to messenger RNA, short interfering RNA, microRNA, and their DNA complements, may also run afoul of the court's focus on the sequence similarity between a segment of genomic DNA and a claimed nucleic acid. Indeed, the court appeared to recognize this possibility, stating that "very short series of DNA may have no intervening introns to remove when creating cDNA," thereby rendering such sequences "indistinguishable from natural DNA."5 Thus, although the court acknowledged that a lab technician creates something new when making cDNA, it cast doubt on the patent eligibility of cDNA sequences created from a single exon due to the sequence similarity between the cDNA construct and a stretch of genomic DNA.
Of course, until it is clear that only cDNA containing non-naturally occurring sequences is patent-eligible, a prudent patent practitioner should continue to draft claims to cDNA sequences as usual, including claims to relatively small segments of cDNA that may be congruous to the original genomic DNA. But, in drafting cDNA claims, patent practitioners will also want to be alert for the opportunity to include claims directed to cDNA segments that are not identical to any naturally occurring DNA sequences. That is, at least some of the claimed cDNA sequences should span at least parts of two exons of the genomic DNA sequence in order to ensure that the two sequences are not identical.
Such exon-spanning cDNA claims, while likely patent-eligible, may prove of less practical significance for applicants in diagnostic fields. If, going forward, only non-naturally occurring cDNA will be patent-eligible, an enterprising competitor may be able to design around a two-exon cDNA claim, for example by using a smaller cDNA fragment from within a single exon as a probe for genetic testing.
Likewise, for those inventors working in other nucleic acid fields where the products of interest are short or are not naturally spliced to remove introns before translation into proteins, there may not be a way to claim the isolated nucleic acids directly or through their cDNA sequences, since they map on those in nature. For example, companies working with microRNA and other short nucleic acid sequences may find it difficult to claim cDNA sequences as the short sequences are likely to read on stretches of genomic DNA. Thus, although claims to cDNA sequences are one way to obtain patent protection after Myriad, they may not provide the same level of protection as claims to isolated DNA previously offered.
The Myriad decision did not directly implicate claims to specific applications of isolated nucleic acids. In drafting such claims, however, practitioners should be cognizant of the limitations imposed by another recent Supreme Court case, Mayo Collaborative Services v. Prometheus Inc., 132 S. Ct. 1289 (2012). Prometheus involved a method for determining the optimal dosage of a drug by administering the drug and checking the effect of a dose of the drug on a particular metabolite level, wherein the level of the metabolite indicated that the dose should be increased or decreased. Importantly, the claims in Prometheus did not involve any particular administration or other active steps once the metabolite level was determined. The Supreme Court found the claim to be patent ineligible because it was directed to a law of nature rather than a specific application.
While the Prometheus decision further limits the scope of what can be claimed for methods employing isolated nucleic acids that relate to natural principles, method claims may still represent a viable route to pursue for practitioners. As noted by the court, "[m]any of [Myriad's] unchallenged claims are limited to such applications."6 These specific applications could cover, for example, methods of using particular nucleic acid sequences to create polypeptides or to screen for therapies, which are concrete method steps that are more likely to satisfy the newly tightened requirements for patentable subject matter.7
For example, in the '282 patent, Myriad's unchallenged claims included a "method of producing BRCA1 polypeptide" using a host cell containing a vector with isolated BRCA1 DNA. The '282 patent also included claim 20, directed to a "method for screening potential cancer therapeutics comprising growing" a host cell containing the altered BRCA1 gene in the presence of a suspected cancer therapeutic.
Importantly, claim 20 of the '282 was not part of the appeal heard by the Supreme Court, and the Federal Circuit found it patent-eligible in light of Prometheus. The Federal Circuit held that the method involved the use of a transformed host cell, "which is made by man, in contrast to a natural material."8 Thus, if diagnostic method claims involve physical processing steps, a host cell transformed by isolated genomic DNA, modified isolated genomic DNA, or some other alteration to the isolated genomic DNA so that it can be considered a man-made product and different from DNA found in nature, the claims should be patent-eligible in light of both Prometheus and Myriad. The key will be to recite in the claims the physical steps that harness or otherwise modify a nucleic acid so that it is no longer identical to the naturally occurring genomic DNA.
Patent practitioners may wish to increase their use of such method claims. In general, method of use claims were previously considered secondary to composition claims because the claim to the isolated DNA itself would cover any use of the isolated DNA. Claims directly to the isolated DNA sequence were also preferred because infringement was generally easier to detect and prove. But without the availability of certain types of direct composition claims, a multitude of separate method of use claims may be needed to cover all, or at least the most important, uses of an isolated nucleic acid. From now on, more emphasis will likely be placed on drafting method of use claims that cover the current and expected uses of the isolated DNA.9
The Myriad decision also left open the door to claims reciting compositions similar to the patent-ineligible isolated nucleic acid claims but including manmade alterations. For example, several of the unchallenged claims in Myriad's U.S. Patent No. 5,693,473 were directed to nucleic acid probes, which are nucleic acids attached to detectable labels. As such probes are not found in nature, these claims appear to be patent-eligible.
Since many diagnostic methods involve the use of some type of probe, claims that include modifications to a nucleic acid to render it usable as a probe may have value, even when the modifications are recited generically, such as claims to a particular nucleic acid sequence joined to or otherwise carrying a detectable label. Moreover, many patents and applications relating to diagnostic inventions already include such claims, providing an accessible fallback position. Practitioners will need to place increased emphasis on making sure that future applications both contain support for such probe claims, and that the wide range of possible probes are adequately disclosed to avoid design-around by competitors.
Similar reasoning would follow for claims to isolated nucleic acids having unnatural base substitutions. Since unnatural bases do not exist in nature, such claims should be patent-eligible. But, although it is possible to include unnatural base pair substitutions in a claim, the value of these sequences to patent applicants is unclear. And, of course, the obvious design-around product would be the naturally occurring or alternatively modified nucleic acid sequences.
The patent-eligibility of isolated nucleic acids with mutated base substitutions is a bit more difficult to discern. Genetic mutations can occur in nature, but they can also be created in the laboratory. Myriad does not provide guidance as to the showing required to prove that a mutation occurring in a particular percentage of the population qualifies as "naturally occurring." In view of the potential value of rare mutations that may occur only extremely infrequently, applicants should continue to pursue such claims until their patent eligibility is clear. Of course, isolated nucleic acids having mutations that do not occur in nature appear to remain patent-eligible. Although such mutated sequences may be of little value for diagnostic applications, such sequences may still be valuable in many other commercial applications (e.g., sequences for creating genetically modified crops).
Although the Supreme Court struck a blow to isolated genomic DNA claims, gene patents are unlikely to disappear in favor of trade secrets. Even though isolated genomic DNA claims are no longer patent-eligible, there is still a fairly large amount of coverage available to applicants. Claims to cDNA, methods of production and use of isolated DNA claims, and probe/DNA modification claims will satisfy the protection requirements for many applicants. Most of these claim types were already being pursued by many applicants, but the added importance of these claims will require that patent practitioners increase their attention to these types of claims when drafting applications. With some ingenuity, the remaining types of patent-eligible claims should provide substantial protection for applicants going forward.
Endnotes
1 No. 12-398 (S. Ct. June 13, 2013).
2 Ass'n for Molecular Pathology v. Myriad Genetics Inc., 133 S. Ct. 694 (Nov. 30, 2012); Petition for a Writ of Certiorari, 133 S. Ct. 694 (Sept. 25, 2012) (No. 12-398).
3 The Court acknowledged that cDNA sequences devoid of introns could occur naturally, for example as a result of reverse transcription by certain viruses, but the Court emphasized that "[t]he possibility that an unusual and rare phenomenon might randomly create a molecule similar to one created synthetically through human ingenuity does not render a composition of matter nonpatentable." Myriad, slip op. at 16, n. 8 (emphasis in original).
4 Myriad, slip op. at 16.
5 Id., at 17.
6 Id., at 17-18.
7 PerkinElmer Inc. v. Intema Ltd., No. 2011-1577, 2012 WL 5861658 (Fed. Cir. Nov. 20, 2012).
8 Assoc. for Molecular Pathology et al. v. U.S. Patent & Trademark Office et al., No. 2010-1406, Slip op. at 55-56 (Fed. Cir. Aug. 16, 2012).
9 Practitioners will also need to place increased emphasis on providing support in the specification for the increased number and type of method of use claims.
Originally printed in Law360 (www.law360.com). Reprinted with permission. This article is for informational purposes, is not intended to constitute legal advice, and may be considered advertising under applicable state laws. This article is only the opinion of the authors and is not attributable to Finnegan, Henderson, Farabow, Garrett & Dunner, LLP, or the firm's clients.
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