Hologic Inc v. bioMerieux Inc

1. Case Identification

• Case #: IPR2018-00569
• 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: Primer Pairs for Amplifying HIV-1 Sequences, and Use Thereof
• Brief Description: The ’352 patent discloses pairs of oligonucleotide primers for amplifying Human Immunodeficiency Virus Type 1 (HIV-1) nucleic acid sequences. The primers are designed to target conserved sequences within the long terminal repeat (LTR) region of the HIV-1 genome.

3. Grounds for Unpatentability

Ground 1: Claims 1-6 are obvious over Backus in view of Sooknanan and Myers.

• Prior Art Relied Upon: Backus (Patent 6,001,558), Sooknanan (a 1995 book chapter on Nucleic Acid Sequence-Based Amplification), and Myers (the 1995 Human Retroviruses and AIDS compendium).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Backus disclosed nearly all limitations of claim 1. Backus taught a pair of primers (SEQ ID NO:4 and SEQ ID NO:2) for amplifying the HIV-1 LTR region using Polymerase Chain Reaction (PCR). Backus’s first primer (SEQ ID NO:4) met the length and sequence requirements of claim 1 but was not operably linked to a promoter. Backus’s second primer (SEQ ID NO:2) was slightly longer than the claimed range but otherwise met the sequence requirements.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would have been motivated to modify the successful PCR primers from Backus for use in a Nucleic Acid Sequence-Based Amplification (NASBA) assay. Sooknanan taught that NASBA had significant advantages over PCR (e.g., working directly on RNA analytes without thermocycling) and provided explicit guidelines for primer design, including operably linking a T7 promoter to the first primer. A POSITA would combine Backus’s primer sequences with Sooknanan’s NASBA method to gain its advantages. Furthermore, a POSITA would consult Myers, a standard reference for conserved HIV-1 sequences, to optimize Backus’s primers. This review would reveal that the 5’-end of Backus’s second primer extended beyond the 100% conserved LTR sequence. To maximize amplification across HIV-1 subtypes, a POSITA would have been motivated to truncate this non-conserved portion, bringing the primer within the claimed length range.
  • Expectation of Success: Because the Backus primers were proven effective for amplifying the target HIV-1 LTR sequence via PCR, a POSITA would have a reasonable expectation of success in adapting them for NASBA. The proposed modifications—adding a standard promoter as taught by Sooknanan and truncating a non-conserved sequence based on data from Myers—were routine optimizations based on well-established principles.

Ground 2: Claims 1-6 are obvious over Bell in view of Sooknanan and Myers.

• Prior Art Relied Upon: Bell (a 1989 article in AIDS Research and Human Retroviruses), Sooknanan (a 1995 book chapter), and Myers (the 1995 compendium).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Bell disclosed a primer pair (P3 and P4) that amplified the HIV-1 LTR region using PCR. Bell's P3 primer was within the claimed length range for the first primer but failed to include the required "at least 15 sequential nucleotides" of the claimed sequence (SEQ ID NO:1) and was not linked to a promoter. Bell's P4 primer, intended as the second primer, was slightly longer than the claimed length range.
  • Motivation to Combine: The motivation is parallel to Ground 1. A POSITA, knowing of the advantages of NASBA from Sooknanan, would seek to adapt Bell's PCR primers for that method. A POSITA would first consult a modern reference like the 1995 Myers compendium to verify the conservation of Bell’s primer sequences, which were designed using the 1988 version of Myers. This comparison would show that portions of both the P3 and P4 primers were not 100% conserved across known HIV-1 subtypes. To improve performance, a POSITA would be motivated to modify Bell’s primers by removing the non-conserved nucleotides and extending them based on the 100% conserved sequences identified in Myers, bringing them into compliance with the claimed sequence and length limitations. Sooknanan would then provide the motivation and know-how to operably link a promoter to the modified P3 primer for use in NASBA.
  • Expectation of Success: A POSITA would have reasonably expected success. Bell’s primers already successfully amplified the correct target region. The proposed modifications involved routine techniques: consulting a standard sequence database (Myers) to optimize primer design for conservation and applying established guidelines (Sooknanan) to adapt primers from PCR to the advantageous NASBA platform.

4. Key Claim Construction Positions

• "amplification": Petitioner proposed this term means "increasing the copy number of a target nucleic acid sequence," consistent with its use in the patent and the function of techniques like NASBA.
• "fully complementary": Petitioner argued this means "the sequence of nucleotides in one strand of an oligonucleotide completely matches a sequence of nucleotides in the opposite strand such that guanines align with cytosines and adenines align with thymines (or uracils)." This construction is based on the plain meaning and the patent's warning that mispairing hampers amplification.
• "operably linked to a promoter": Based on the patent’s definition of "promoter sequence," Petitioner proposed this means the first oligonucleotide includes a nucleic acid sequence that can be recognized and bound by an RNA polymerase to initiate transcription.

5. Relief Requested

• Petitioner requests the institution of an inter partes review and the cancellation of claims 1-6 of Patent 8,697,352 as unpatentable.