By Kevin E. Noonan --
Judge Giles Sutherland Rich famously said that, in patent law, "the name of the game is the claim." One of the weaknesses in the "gene patenting" debate, as well as in the District Court's opinion in AMP v. USPTO (the Myriad case), is the lack of clarity about the scope and meaning of the claims of the challenged patents. The District Court did not bother to hold a Markman hearing to construe the claims, and thus neither that Court nor the Federal Circuit in reviewing Judge Sweet's decision brought any clarity to what the parties were arguing about, instead drawing generally inapt analogies to what other claims in other patents might claim. The type and number of claims at issue are sufficiently similar, having generally the same structure and using the same language that claim construction might help, and the language used is certainly no more arcane than in any other patent case.
Construing claim language to determine the scope and meaning of the claims is a matter of law for the district court in the first instance (Markman v. Westview Instruments, Inc., 52 F.3d 1321 (Fed. Cir. 1995) (en banc), aff'd 517 U.S. 370 (1996)). The Federal Circuit reviews claim construction de novo, giving no deference to either the district court's ultimate construction of claim terms or any factual determinations underlying the court's legal determination of claim scope (Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448 (Fed. Cir. 1998) (en banc)). The way courts are to perform claim construction was set forth (most recently) by the en banc Federal Circuit in Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005) (en banc). This procedure can be summarized in a few simple rules. First, claim terms are to be given their "ordinary and customary" meaning as understood by those with skill in the art. Id. at 1313. Next, the specification is consulted to determine whether the patent applicant has acted as his or her own lexicographer, a capacity recognized as black letter patent law (see Autogiro Co. Amer. v. U.S., 384 F.2d 391 (Ct. Claims 1967). This ability to define terms is limited only insofar as the applicant attempts to define a commonly accepted term in a way that is "repugnant" to its meaning in the art. In re Hill, 161 F.2d 367 (CCPA 1947). In the event that there is any ambiguity about the "ordinary and customary" meaning of a claim term, resort to the specification is preferred under Phillips as "the single best guide to the meaning of a disputed term." Id. at 1315 (citing Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996). Finally, the prosecution file history should be consulted to ensure that a patentee cannot advance a narrow construction of a term during patent prosecution, only to argue a broader construction in an infringement action. Phillips at 1317.
With these concepts and principles in mind, generally two types of claims were at issue in the Myriad case:
1. Isolated DNA claims (as well as claims to oligonucleotides); and
2. Diagnostic method claims.
(The one other claim at issue, claim 20 of U.S. Patent No. 5,474,282, is in some ways sui generis to the other claims, being directed to methods for screening chemical compounds for anti-cancer properties.) Claim 1 of U.S. Patent No. 5,837,492 is representative of the first type of claim:
An isolated DNA molecule coding for a BRCA2 polypeptide, said DNA molecule comprising a nucleic acid sequence encoding the amino acid sequence set forth in SEQ ID NO:2.
(Claims 1 and 7 of the '282 patent; claims 6 and 7 of the '492 patent; and claim 1 of U.S. Patent No. 5,693,473 are variants of this general claim type.) The italicized words and phrases in the exemplary claim need construing, the other terms being expressly defined with regard to other terms in the claims (e.g., the amino acid sequence of the BRCA2 polypeptide is defined as SEQ ID NO: 2; as a consequence, any ambiguity in the meaning of this term devolves to any ambiguity in the nature of the expressly recited sequence).
Of the italicized terms, the parties and the Federal Circuit focused most attention on the term "isolated." This term has a meaning accepted by the Patent Office (and in the biotechnology arts) with regard to nucleic acids, wherein the term means "isolated from its natural state and processed through purifying steps that separate the gene from other molecules naturally associated with it." Utility Examination Guidelines, 66 Fed. Reg. 1094 (2001). An associated definition is found in the specification of the patents in suit:
"Isolated" or "substantially pure". An "isolated" or "substantially pure" nucleic acid (e.g., an RNA, DNA or a mixed polymer) is one which is substantially separated from other cellular components which naturally accompany a native human sequence or protein, e.g., ribosomes, polymerases, many other human genome sequences and proteins. The term embraces a nucleic acid sequence or protein which has been removed from its naturally occurring environment, and includes recombinant or cloned DNA isolates and chemically synthesized analogs or analogs biologically synthesized by heterologous systems.
Some in the gene patenting debate have characterized this meaning as encompassing isolation of total genomic DNA as falling within the scope of the claim; indeed this interpretation is one of the bases for the argument that Myriad's claims may inhibit "whole genome sequencing" methods, as Chris Hansen of the ACLU argued during oral argument in Myriad (see "AMP v. USPTO: Oral Argument at the Federal Circuit"). This interpretation is only persuasive, however, if the phrase "many other human genome sequences" is eliminated from the list of cellular components from which the BRCA-encoding DNA is separated. Thus, the ordinary and customary meaning of the term "isolated" is reinforced by the express meaning of the term as recited in the specification. And as interpreted using this meaning, the distinctions drawn in the majority and concurring opinions in Myriad, between what is isolated and what is "merely" purified, become less relevant, since DNA is understood both to be "purified" from other cellular components and "isolated" from other human genome sequences.
In addition, since claims must be construed as a whole, giving each limitation meaning and avoiding surplusage, what is "isolated" is a nucleic acid encoding an amino acid sequence "set forth" in the specification as SEQ ID NO: 2. Thus, properly interpreted, the claim is limited to DNA molecules that encode the BRCA 2 polypeptide. The only other claim term that could expand the scope of these claims to extend to nucleic acids other than those encoding the BRCA proteins (and only those having the specifically recited amino acid sequences) is the word "comprising." However, using another well-recognized rubric of claim construction, this word cannot be used to expand the scope of the claim to extend to human genomic DNA per se: first, because "claims should be so construed, if possible, as to sustain their validity," Rhine v. Casio, Inc., 183 F.3d 1342, 1345 (Fed Cir. 1999); see also Klein v. Russell, 86 U.S. (19 Wall.) 433, 466, 22 L. Ed. 116 (1873), but also because claims are interpreted in light of the specification, United States v. Adams, 383 U.S. 39, 49, 15 L. Ed. 2d 572, 86 S. Ct. 708, 174 Ct. Cl. 1293 (1966). The specification of the Myriad patents claiming DNA encoding BRCA1 and BRCA2 disclose the patentees' efforts to identify, isolate, and purify BRCA-encoding DNA. Thus, the proper interpretation of these claims is directed to DNA (and in particular, cDNA) encoding the BRCA proteins.
Turning to the diagnostic method claims, claim 1 of U.S. Patent No. 5,753,441 is representative:
A method for screening germline of a human subject for an alteration of a BRCA1 gene which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an alteration in the BRCA1 gene in said subject.
(Claims 1 of U.S. Patent No. 5,709,999; claim 1 of U.S. Patent No. 5,710,001; and claims 1 and 2 of U.S. Patent No. 6,033,857 are variants of this general claim type.) Here, the claim term "comparing" has no specific definition in the specification; however, Example 9, entitled "Analysis of BRCA 1 Mutations" sets forth the general method for extracting DNA from blood or tumor samples from patients with breast or ovarian cancer to detect mutations. The relevant claim term to be construed is thus from a tissue sample from said subject, and whether this implies a necessary transformation step to ascertain the individual patient's BRCA gene sequence. Both the District Court and the Federal Circuit treated this claim as if it had been construed to encompass mere inspection of and comparison between two sequences (i.e., printouts of the germline and patient sample sequences) that did not require a patient sample to be assayed to obtain the sequence. While not a necessarily unreasonable interpretation (since these claims do not expressly recite limitations drawn to obtaining a sample and determining the BRCA gene sequence therefrom), it is not the only interpretation. What is missing from any judicial analysis of the diagnostic method claims at issue is whether the skilled worker would understand the claim not to require these steps, and whether the specification mandates interpretation of the claim to include these steps. (The prosecution file history may also be informative as to what the patentee understood the invention to be and, more importantly, represented that understanding to the patent examiner, with regard to the scope of these claims.)
The danger in ignoring and failing to perform the fundamental and threshold exercise of construing the claims at issue in patent litigation is clearly illustrated in the briefs (both from the parties and the amici) and the decisions of both the District Court and the Federal Circuit. The Courts' analyses are understandably adrift without the anchor of having decided what the claims mean, turning them into a "nose of wax" to be susceptible to whatever argument is being advanced. Although it is perhaps too late to do so now, if the Federal Circuit grants rehearing or en banc review, it would be well if the Court mandated that the parties provide the equivalent of their Markman briefs, to enable the Court as a threshold matter to determine what the claims mean as a matter of law. Without that, it is hard to see how the Federal Circuit, or the Supreme Court if it grants certiorari, will have any reasoned basis for coming to a decision as to whether these claims recite patent-eligible subject matter. That outcome may be good for arguments based on emotion and rhetoric, but it won't be good for deciding this fundamental question of patent law.