Takeaway: Petitioner’s anticipation argument based on inherency failed because Petitioner did not establish that the allegedly inherent feature is necessarily present in the anticipating reference while Patent Owner presented evidence that the allegedly inherent feature is not necessarily produced each and every time by Petitioner’s reference.

In its Decision, the Board denied institution of inter partes review of claims 1-13 and 17-20 of the ’723 patent, because Petitioner did not demonstrate a reasonable likelihood of prevailing with respect to any of the challenged claims.

The ’723 patent relates to use of polymerase chain reaction (PCR) for detection of Mycobacterium tuberculosis (MTB) and determination of its drug susceptibility. The ’723 patent discloses a set of MTB-specific position-specific “signature nucleotides” that unequivocally identify MTB strains. The ’723 patent also discloses primers that hybridize to signature nucleotides under hybridizing conditions.

Petitioner asserted (1) anticipation of claims 17-19 by Telenti, (2) obviousness of claims 1-6, 9-13, and 17-20 over Telenti, Hunt, and Marconi, and (3) obviousness of claims 7-8 over Telenti, Hunt, Marconi, and White. Petitioner also relied on a Declaration of Dr. Richard T. Marconi.

Claims 1 and 17 recite the term “hybridizing conditions.” Petitioner argued that hybridizing conditions should be construed to include an annealing temperature 42-75ºC in the presence of 5-15% glycerol by volume, about 50 mM KCl, and about 1.5 mM MgCl2. Patent Owner argued that hybridizing conditions must refer to PCR conditions, particularly the hybridization or annealing step in relation to the cited primer. The Board agreed with Patent Owner because the Petitioner’s construction relied upon a portion of the specification related to a Southern blot. The Board declined to construe “is indicative of” as requested by Petitioner.

Patent Owner requested the Board to construe “primer” and “amplification product.” Dr. Marconi asserted that a primer is an oligonucleotide that is capable of being extended by a polymerase. Patent Owner argued that a primer is used to initiate amplification and produce an amplification product. Patent Owner argues that a primer is a single stranded oligonucleotide that can be extended during PCR amplification to form an amplification product and an amplification product is an oligonucleotide produced via extension of a primer during PCR amplification. The Board agreed with Patent Owner.

Petitioner argued that Telenti anticipates claims 17-19, but stated that Telenti does not expressly state that any of its primers hybridized to a site comprising at least one of the listed signature nucleotides recited in claim 17. Petitioner argued that a primer, TR8, is downstream of a signature nucleotide. Relying on an inherency theory, Petitioner argued that if a primer in a PCR produces the correct amplification product, the primer is necessarily extended one base at a time. Thus, an oligonucleotide corresponding to the extended TR8 primer would briefly, but necessarily, produce the signature nucleotide. Patent Owner argued that Taq polymerase has low fidelity and, therefore, is not guaranteed to incorporate the correct base each and every time. Consequently, Petitioner cannot demonstrate that the correct amplification product is generated all the time. Thus, the Petitioner fails to meet the inherency threshold.

Petitioner argued claims 1-6, 9-13, and 17-20 are obvious over Telenti, Hunt, and Marconi. According to Petitioner, Telenti discloses amplifying a portion of MTB rpoB gene using PCR to produce an amplification product and detecting the presence of an amplification product. Petitioner admits that Telenti did not expressly mention that the method achieved species-specific amplification using a primer that hybridized at a site comprising at least one position-specific MTB signature nucleotide recited in claim 1 of the ’723 patent. Petitioner alleges a person of ordinary skill would have been motivated to modify Telenti’s method to do so and have a reasonable expectation of success. Given Petitioner’s failure to identify a reason that would have prompted a person of ordinary skill in the relevant field to modify or combine prior art teachings, the Board disagreed with Petitioner. The Board noted that all samples evaluated in Telenti were clinical isolates of MTB from tuberculosis (TB) patients. Thus, it was unnecessary to identify the bacterium as MTB. The Board also dismissed statements from Dr. Marconi as unsupported by evidence.

Petitioner next argued that Hunt’s disclosure of expected sequence variation amongst related bacteria in the rifampin resistance region of rpoB would have motivated a person of ordinary skill to modify Telenti’s method by using species-specific primers. The Board noted that Hunt utilized degenerate primers based on highly-conserved regions of rpoB to amplify a region containing most mutations conferring rifampin resistance in TB. Petitioner alleged that one of ordinary skill would have expected sequence variation occurring in and around the rifampin resistance region of rpoB could be used to distinguish MTB from related bacteria. The Board found that Hunt’s degenerate primers corresponded to rifampin resistance specificity, not species specificity. Further, the Board concluded that one of ordinary skill would not have been motivated to modify Telenti’s method to one that can identify MTB through signature nucleotides in MTB rpoB.

The Board also concluded that Petition failed to explain adequately why one of ordinary skill would modify the teachings of Marconi with those of Hunt and Telenti. Petitioner argued that Marconi is not limited to a particular gene or organism. Petitioner alleged that because Telenti and Hunt describe the rpoB region as highly conserved that it would have been an attractive target for Marconi’s species-specific amplification method. The Board disagreed because Petitioner did not argue that rpoB is the only or one of a finite number of conserved genes in MTB. Thus, there is no evidence to show why one of ordinary skill would have chosen rpoB instead of any other conserved gene. Thus, Petitioner did not establish a reasonable likelihood that it would prevail in showing claim 1 would have been obvious over Telenti, Hunt, and Marconi.

Regarding Petitioner’s argument of obviousness of claims 7 and 8 over Telenti, Hunt, Marconi, and White, the Board concluded that White failed to remedy the defect of Telenti, Hunt, and Marconi above. Thus, Petitioner has not established a reasonable likelihood it would prevail in showing that claims 7 and 8 would have been obvious over Telenti, Hunt, Marconi, and White.

CEPHEID v. ROCHE MOLECULAR SYSTEMS, INC. and MAYO FOUNDATION FOR EDUCATION AND MEDICAL RESEARCH IPR2015-00255

Paper 8: Decision Denying Institution of Inter Partes Review

Dated: June 11, 2015

Patents: 5,643,723

Before: Jaqueline Wright Bonilla, Susan L. C. Mitchell, and Zhenyu Yang

Written by: Yang

Related proceedings: Patent Owner asserted the ’723 patent against Petitioner inRoche Molecular SystemsInc. v. Cepheid, No. 3:14-cv-03228 (N.D. Cal filed July 14, 2014)