Hologic Inc v. bioMerieux Inc

1. Case Identification

• Case #: IPR2018-00568
• Patent #: 8,697,352
• Filed: February 6, 2018
• Petitioner(s): Hologic, Inc.
• Patent Owner(s): bioMerieux, Inc.
• Challenged Claims: 1-6

2. Patent Overview

• Title: Method for Amplifying HIV-1 Nucleic Acid
• Brief Description: The ’352 patent discloses methods and oligonucleotide primer pairs for amplifying Human Immunodeficiency Virus 1 (HIV-1) nucleic acid. The claimed primers are designed to amplify a target sequence located within the Long Terminal Repeat (LTR) region of the HIV-1 genome.

3. Grounds for Unpatentability

Ground 1: Obviousness over Sooknanan and Myers - Claims 1-6 are obvious over Sooknanan in view of Myers under 35 U.S.C. §103.

• Prior Art Relied Upon: Sooknanan (a 1995 article, "Nucleic Acid Sequence-Based Amplification," in Molecular Methods for Virus Detection), and Myers (excerpts from the 1995 compendium Human Retroviruses and AIDS).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the prior art combination teaches every limitation of the challenged claims. Sooknanan disclosed the Nucleic Acid Sequence-Based Amplification (NASBA) method, including its application to amplify HIV-1 using a pair of primers, one of which is operably linked to a T7 promoter. However, Sooknanan’s example targeted the gag region of the HIV-1 genome. Myers disclosed a comprehensive analysis of the HIV-1 genome, identifying specific regions that were highly conserved across various viral subtypes. Critically, Myers showed that the LTR region contained four sequences of 10 or more nucleotides that were 100% conserved, while the gag region contained none.
    • Petitioner asserted that a person of ordinary skill in the art (POSITA), following Sooknanan’s general NASBA method for HIV-1 detection, would have consulted Myers to identify the most suitable target sequences for designing primers capable of detecting multiple HIV-1 subtypes. Myers directed a POSITA away from the less-conserved gag region and toward the highly conserved LTR region. The petition detailed how a POSITA would select the LTR second (20 nucleotides) and fourth (29 nucleotides) conserved sequences from Myers as optimal targets for designing a primer pair, as they fall within the preferred length for NASBA primers taught by Sooknanan (17-30 nucleotides). The resulting primers, designed according to Sooknanan's guidelines, would have the specific sequences and properties required by claims 1-6.
  • Motivation to Combine: A POSITA would combine Sooknanan and Myers to create a more effective HIV-1 detection assay. The primary motivation was to design a single primer pair capable of amplifying nucleic acid from all known HIV-1 subtypes, a well-established goal in the field. Sooknanan provided the amplification technique (NASBA), while Myers provided an essential "roadmap" to the most conserved, and therefore most effective, target sequences in the HIV-1 genome. Replacing Sooknanan's gag region primers with primers targeting the LTR region identified by Myers was a predictable step to improve the assay’s breadth and reliability.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success. Sooknanan provided detailed, established guidelines for designing functional NASBA primers, including optimal length, GC content, and rules for avoiding primer dimerization and abortive cycling. Applying these routine design principles to the specific, highly conserved LTR sequences identified in Myers was a straightforward and predictable modification, not an inventive leap. The limited number of highly conserved regions identified by Myers made the choice of the LTR region a predictable design choice.

4. Key Claim Construction Positions

• "oligonucleotide" vs. "hybridizing oligonucleotide": Petitioner argued there is no meaningful difference between these terms as used in the claims. Independent claims 3 and 5 use "hybridizing oligonucleotide," while claim 1 uses "oligonucleotide." Petitioner contended that for the claimed method to work, any "oligonucleotide" must necessarily bind, or "hybridize," to its target sequence, making the modifier "hybridizing" redundant and not a patentable distinction.
• "pair of...primers" vs. "primer set": Petitioner argued that "a primer set consisting of a first primer and a second primer" (claim 3) is functionally and structurally identical to "a pair of oligonucleotide primers" (claims 1 and 5). Both terms describe two primers used together for amplification, and this linguistic difference does not alter the scope of the claims relative to the prior art.
• "fully complementary": Petitioner proposed this term means a sequence of nucleotides in one strand completely matches the corresponding sequence in the opposite strand (G with C, A with T/U), with no mismatches. This established definition was central to demonstrating how primers designed from the 100% conserved sequences in Myers would meet the claim limitations.

5. Key Technical Contentions (Beyond Claim Construction)

• Rebuttal of Secondary Considerations (Unexpected Results): Petitioner dedicated significant argument to refuting the Patent Owner's evidence of nonobviousness, which was based on alleged "unexpected results" in the Laayoun Declaration submitted during prosecution.
  • Petitioner contended this evidence was flawed and insufficient. First, the Patent Owner’s comparative tests did not use the closest prior art. The tests compared the claimed primers to primers from a reference by Bell, but Petitioner argued that primers disclosed in a reference by Backus were structurally closer to the claimed invention and should have been used as the baseline for comparison.
  • Second, the test data was not commensurate with the full scope of the claims. The Patent Owner tested only a single primer pair (or a very narrow range of lengths and sequences), whereas the claims cover a much broader range of primer lengths (e.g., 15-26 nucleotides for the first primer). Petitioner argued that success with one specific embodiment does not prove nonobviousness across the entire claimed range.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-6 of the ’352 patent as unpatentable.