The Patent-Ineligibility trend continues to be infectious…
| October 29, 2018
Roche Molecular Systems, Inc. v. Cepheid
October 9, 2018
Before O’Malley, Reyna and Hughes. Opinion by Reyna. Concurring opinion by O’Malley.
Summary:
The contended patent, U.S. Patent No. 5,643,723 (‘723 patent), owned by Roche is directed to methods for detecting the pathogenic bacterium Mycobacterium tuberculosis (MTB). Prior to the priority date, the general methods of detection were slow (could take three to eight weeks), and they had limitations in that they could not identify if a patient has an antibiotic-resistant strain. The standard of care at the time was treatment with the antibiotic rifampin. However, outbreaks resulted due to delays in diagnosing and reporting of the rifampin-resistant tuberculosis. In 1994, rpoB became a prime candidate for studying rifampin resistance in MTB.
The inventors of the ‘723 patent sequenced the rpoB gene in MTB and discovered that that the rpoB gene in MTB contains eleven “position-specific” “signature nucleotides” (i.e., naturally occurring single nucleotide mutations) that are only present in MTB but not in other bacteria. Based on these eleven MTB-specific signature nucleotides, the Roche inventors devised a diagnostic test that could (1) identify whether or not a biological sample contains MTB, and (2) if MTB is present, predict whether that MTB is a strain that is resistant to rifampin treatment.
Representative claims at issue are as follows:
1. A method for detecting Mycobacterium tuberculosis in a biological sample suspected of containing M. tuberculosis comprising:
(a) subjecting DNA from the biological sample to polymerase chain reaction [PCR] using a plurality of primers under reaction conditions sufficient to simplify a portion of a M. tuberculosis rpoB [gene] to produce an amplification product, wherein the plurality of primers comprises at least one primer that hybridizes under hybridizing conditions to the amplified portion of the [gene] at a site comprising at least one position-specific M. tuberculosis signature nucleotide selected, with reference to FIG. 3 (SEQ ID NO: 1), from the group consisting
a G at nucleotide position 2312,
a T at nucleotide position 2313,
an A at nucleotide position 2373,
a G at nucleotide position 2374,
an A at nucleotide position 2378,
a G at nucleotide position 2408,
a T at nucleotide position 2409,
an A at nucleotide position 2426,
a G at nucleotide position 2441,
an A at nucleotide position 2456, and
a T at nucleotide position 2465; and
(b) detecting the presence or absence of an amplification product, wherein the presence of an amplification product is indicative of the presence of M. tuberculosis in the biological sample and wherein the absence of the amplification product is indicative of the absence of M. tuberculosis in the biological sample.
- A primer having 14–50 nucleotides that hybridizes under hybridizing conditions to an M. tuberculosis rpoB [gene] at a site comprising at least one position-specific M. tuberculosis signature nucleotide selected, with reference to FIG. 3 (SEQ ID NO: 1), from the group consisting of [the same 11 nucleotides at the positions disclosed in claim 1].
Roche brought a patent infringement case against Cepheid asserting their product infringed on the ‘723 patent. Cepheid filed a motion for summary judgment, arguing that all of the asserted claims are directed to patent ineligible subject matter. The district court granted the motion, and found the claims to be indeed directed to patent ineligible subject matter. CAFC affirmed.
A. The Primer Claims:
Roche argued the primer claims are eligible because they are directed to artificial, man-made primers that differ from the naturally occurring DNA. Specifically, that the primers have both a 3-prime end and a 3-prime hydroxyl group, while the naturally occurring does not. The district court rejected Roche’s arguments and held that “the primer claims in this case, which have genetic sequences identical to those found in nature, are indistinguishable from those held to be directed to nonpatentable subject matter in In Re BRCA1.” Id. at *14 (citing In re BRCA1- & BRCA2-Based Hereditary Cancer Test Patent Litig., 774 F.3d 755, 760 (Fed. Cir. 2014) (“BRCA1”)). The CAFC agreed.
Roche further argued that BRCA1 is distinguishable because, as a bacterium, MTB has “a circular chromosome, which has neither a 3-prime end nor a 3-prime hydroxyl [group],” while “[t]he primers at issue in BRCA1 were derived from human DNA, in which each chromosome occurs as a linear molecule.” The CAFC were not persuaded, noting that “[T]he shape of MTB’s chromosomes is not relevant to the inquiry on the subject matter eligibility of the claimed primers. As this court determined in BRCA1, the subject matter eligibility inquiry of primer claims hinges on comparing a claimed primer to its corresponding DNA segment on the chromosome—not the whole chromosome.
B. The Method Claims
The CAFC held that based on the plain language of the asserted claims and the written description in the specification, the methods claims were directed to a diagnostic test based on the observation that the presence of the eleven position-specific signature nucleotides of the naturally occurring MTB rpoB gene indicates the presence of MTB in a biological sample. The detecting step of claim 1 was decided to be a mental determination step. The CAFC further held that claim 1 establishes that the method claims are directed to a relationship between the eleven naturally occurring position-specific signature nucleotides and the presence of MTB in a sample. “In other words, the method claims assert that if an investigator detects a signature nucleotide from a sample, she knows the sample contains MTB. This relationship between the signature nucleotides and MTB is a phenomenon that exists in nature apart from any human action, meaning the method claims are directed to a natural phenomenon, which itself is ineligible for patenting.”
The CAFC pulled support from the written description in concluding that the method claims of the ’723 patent are directed to a patent-ineligible natural phenomenon. Specifically, in the Summary of the Invention, the patent states:
This invention involves a comparative analysis of the rpoB sequences in MTB, other mycobacteria and related . . . bacteria . . . demonstrating the heretofore undiscovered presence of a set of MTB-specific position-specific “signature nucleotides” that permits unequivocal identification of MTB
Since the asserted claims failed Mayo step 2A, they were subjected to analysis under step 2B. The CAFC held that the claims do not contain “an inventive concept that transforms” the claim into patent-eligible subject matter. The CAFC held that “PCR amplification of DNA is the main action step of the method claims” but “PCR amplification and detection were ‘routine’ when the patent application was filed in 1994.”
Roche argued that the “method claims constitute more than a patent-ineligible natural phenomenon. Roche argues that at the time of the invention, it was “not routine or conventional to use PCR (or any other genetic test) to detect the presence of MTB in a biological sample” and “unprecedented to perform PCR using the type of primer specified in claims 1 through 13.”
The CAFC disagreed, arguing that “While it may be true that Roche inventors were the first to use PCR to detect MTB in a biological sample, being the first to discover a previously unknown naturally occurring phenomenon or a law of nature alone is not enough to confer patent eligibility.”
O’Malley’s Concurring Opinion:
Although O’Malley agreed with the decision, she wrote separately to express her belief that the court should revisit its holding in BRCA1 at least with respect to the primer claims. Specifically, she asserted that she believes that the courts holding were unduly broad for two reasons:
(1) the question raised in BRCA1 was narrower than the holding in that case; and,
(2) the interpretation of the nature and function of DNA primers lacked the benefit of certain arguments and evidence that the patent owner presents in this case.
O’Malley further stated that “unlike the appellants in Myriad and in BRCA1, here, Roche submitted evidence of record that, at the very least, raises genuine issues of material fact as to whether there exists anything in nature that both has the structure and performs the function of the claimed primers.”
O’Malley concluded that “while I agree with the majority that the broad language of our holding in BRCA1 compels the conclusion that the primer claims in this case are ineligible under 35 U.S.C. § 101, I believe that holding exceeded the confines of the issue raised on appeal and was the result of an underdeveloped record in that case. I believe, accordingly, that we should revisit our conclusion in BRCA1 en banc.”
Takeaway:
- Since the U.S. PTO guideline examples on 101 include a “method of detecting” claim as patent-eligible (Life Sciences Example 29), it will be interesting to see how the PTO interprets this case in view of their own guidelines.
- If the full court agrees with O’Malley to revisit BRCA1, this may result in a favorable outcome for certain biotech inventions.
USPTO Life Sicence 101 Example 29
