On June 11, 2015, the PTAB denied institution of Cepheid’s petition seeking inter partes review of Patent No. 5,643,723 directed to methods of detecting tuberculosis in humans (IPR2015-00255). To defeat institution, the patent owner successfully used its preliminary response to persuade the Board to (a) narrowly construe claim terms (despite the broadest-reasonable-construction standard), and (b) reject inherent anticipation and obviousness arguments offered by the petitioner’s expert witness.
The claims of the ’723 patent are “directed to methods based on the polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis (MTB) and concurrent determination of its drug susceptibility, utilizing the appropriate oligonucleotide primers.” The method can be used to detect resistance to Rifampin, an antibiotic used to treat tuberculosis.
The claims of the patent require use of PCR with specific oligonucleotide primers capable of hybridizing to “at least one position-specific M. tuberculosis signature nucleotide selected” from a list of nucleotide sequences disclosed in the patent.
Despite applying the “broadest-reasonable-construction” standard for claim construction, the Board ruled in favor of the patent owner in construing “hybridizing conditions” and “primer.” Curiously, although the Board adopted the patent owner’s proposed constructions, it applied the “broadest reasonable construction” standard, which is the standard it applies for unexpired patents, despite the fact that the ’723 patent expired on July 1, 2014.
The petitioner sought a construction of “hybridizing conditions” that would have encompassed a wide range of conditions. The patent owner convinced the Board, however, that hybridizing conditions in the context of the patent are limited to the conditions necessary for a primer to hybridize in connection with a PCR reaction. The Board concluded that “hybridizing conditions” means “the conditions under which a primer hybridizes to the target DNA during the PCR annealing step.”
The petitioner sought to construe “primer” as “an oligonucleotide that is capable of being extended by a polymerase.” The patent owner objected that this construction would conflate the meaning of a primer and an amplification product, which may also be capable of extension by a polymerase. The Board ruled that “a primer is a single stranded oligonucleotide used to initiate the amplification in a PCR reaction, whereas an amplification product is the result of the primer extension.”
Inherent Anticipation Argument Rejected
The petitioner argued that certain claims of the ’723 were inherently anticipated by a reference (“Telenti”) that taught the use of certain primers for detecting rifampicin resistance but that did not state that any of those primers would hybridize to any of the claimed MTB signature nucleotides. Instead, the petitioner argued that the prior-art primer would hybridize to a region of the MTB sequence disclosed in the patent and be extended by polymerization to eventually include one of the claimed signature nucleotides, briefly creating a “primer” incorporating the signature nucleotide and anticipating the claimed primer.
Inherent anticipation requires that a prior art reference must “necessarily” encompass every element of the claimed invention.
The Board rejected this argument because the Telenti reference taught use of a Taq polymerase, which is known to have low fidelity. When the Telenti primer is extended by Taq polymerase, it does not necessarily result in an extended sequence that encompasses the claimed signature nucleotide due the possibility of errors during polymerization. Because inherent anticipation requires that a prior art reference must “necessarily” encompass every element of the claimed invention, the Board found no anticipation.
The Board also relied on its construction of “primer.” Because that construction requires a “single stranded oligonucleotide,” the Board found no anticipation because at the point when the extended primer in Telenti arguably incorporated the claimed signature nucleotide, it was no longer single stranded, but double stranded (and therefore an amplification product, not a primer, under the Board’s construction).
The Board further rejected several obviousness arguments leading to denial of Cepheid’s entire petition.