PTAB

IPR2016-00820

Hologic, Inc. v. Enzo Life Sciences, Inc.

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1. Case Identification

  • Patent #: 7,064,197
  • Filed: March 30, 2016
  • Petitioner(s): Hologic, Inc.
  • Patent Owner(s): Enzo Life Sciences, Inc.
  • Challenged Claims: 1, 6, 8, 9, 12-16, 27, 31-34, 38, 41, 61-64, 68-70, 72-74, 78, 79, 100, 101, 191-195, 212, 213, 218, 219, 222, 225-227, 230, 233, and 236

2. Patent Overview

  • Title: System, Array and Non-Porous Solid Support Comprising Fixed or Immobilized Nucleic Acids
  • Brief Description: The ’197 patent discloses systems and methods for immobilizing nucleic acids on non-porous solid supports, such as glass or plastic microtiter plates. The core of the claimed invention is the use of specific chemical groups—one or more amine(s), hydroxyl(s), or epoxide(s)—on the support surface to fix or immobilize single-stranded nucleic acids in a hybridizable form.

3. Grounds for Unpatentability

Ground 1: Anticipation by Fish - Numerous claims, including independent claims 1, 6, 8, 9, 12-15, and 27, are anticipated under 35 U.S.C. §102(b) by Fish.

  • Prior Art Relied Upon: Fish (Falk Fish et al., "A Sensitive Solid Phase Microradioimmunoassay For Anti-Double Stranded DNA Antibodies," Arthritis and Rheumatism, Mar. 1981).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Fish, a 1981 publication, discloses every limitation of the independent claims. Fish describes an assay using non-porous polyvinyl microtitration trays (a plastic solid support) coated with poly-L-lysine (PLL) to provide amine groups on the well surfaces. Single-stranded DNA (ssDNA) was then immobilized on these amine-coated surfaces. Petitioner contended this directly teaches a non-porous support with amine groups and fixed nucleic acid. The limitation requiring the nucleic acid to be in a "hybridizable form" was argued to be inherently disclosed. Although Fish's assay detected antibodies, not nucleic acid hybridization, the non-covalent ionic binding of ssDNA to PLL does not alter its chemical structure, meaning it necessarily remains capable of Watson-Crick base pairing and is therefore in a "hybridizable form."

Ground 2: Anticipation by VPK - Numerous claims, including independent claims 1, 6, 8, 9, 12-15, and 27, are anticipated under 35 U.S.C. §102(b) by VPK.

  • Prior Art Relied Upon: VPK (A. C. Van Prooijen-Knegt, et al. "In Situ Hybridization of DNA Sequences in Human Metaphase Chromosomes...", Experimental Cell Research, Oct. 1982).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that VPK, published in 1982, anticipates the claims. VPK teaches using non-porous glass microscope slides treated with 3-amino-propyltriethoxysilane, which provides amine groups on the glass surface. Human chromosomes (containing DNA) were fixed to these slides. The chromosomal DNA was then denatured into single strands and explicitly used for in situ hybridization with ribosomal RNA probes. Petitioner argued this directly discloses a non-porous glass support with amine groups, with ssDNA fixed thereon in an explicitly demonstrated hybridizable form.
    • Key Aspects: This ground is contingent on Petitioner's argument that the ’197 patent is not entitled to its asserted 1983 priority date, which would make the 1982 VPK publication available as §102(b) prior art.

Ground 3: Obviousness over VPK, Noyes, and Ramachandran - Claims 16, 38, 64, 78, 101, 195, 218, 222, and 230 are obvious under 35 U.S.C. §103 over VPK in view of Noyes and further in view of Ramachandran.

  • Prior Art Relied Upon: VPK (1982 article), Noyes (a 1975 article on nucleic acid hybridization using covalent binding), and Ramachandran (a 1976 article on enzyme immobilization chemistry).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground builds on VPK's disclosure of immobilizing nucleic acids on amine-treated glass slides. It adds Noyes, which teaches covalent immobilization of DNA/RNA on supports via arylamine groups, and Ramachandran, which teaches a method to convert alkylamines (like those in VPK) on glass surfaces to the arylamines needed for Noyes's chemistry. The combination allegedly renders obvious claims requiring covalent immobilization (claims 38, 78, 218) and immobilization of RNA (claims 64, 101, 195).
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine the references to achieve the benefits of covalent binding (a stronger, more stable linkage) as taught by Noyes on the convenient, non-porous glass slide format taught by VPK. Ramachandran provides the known chemical bridge to make the two systems compatible.
    • Expectation of Success: A POSITA would have an expectation of success because the combination involves applying established chemical conversion (Ramachandran) and binding techniques (Noyes) to a well-understood substrate (VPK's glass slides) for a predictable result.

  • Additional Grounds: Petitioner asserted additional challenges, including obviousness of certain claims over Fish alone (Ground 2), obviousness over Fish in view of Gilham to teach covalent binding (Ground 3), and obviousness over VPK in view of Metzgar to teach using slides with wells or depressions (Ground 6).

4. Key Claim Construction Positions

  • "Non-Porous Solid Support": Petitioner proposed this term be given its ordinary and customary meaning, which it argued includes conventional laboratory equipment like microtiter wells and glass slides. This construction is crucial to the petition, as it allows prior art disclosing such items (e.g., Fish's microtiter wells and VPK's glass slides) to be applied directly to the claims.
  • "Hybridizable form": Petitioner argued this term should be construed as "capable of binding through Watson-Crick base pairing," not that the nucleic acid is actually hybridized. This construction is central to the inherency argument against Fish, allowing Petitioner to assert that ssDNA immobilized for one purpose (antibody binding) is still "in hybridizable form" if the immobilization method does not destroy its inherent capability to bind to a complementary strand.

5. Key Technical Contentions (Beyond Claim Construction)

  • Priority Date Challenge: A central contention was that the challenged claims are not entitled to the benefit of their earliest asserted priority date of January 27, 1983. Petitioner argued the 1983 parent application fails to provide adequate written description for the claim limitation "non-porous solid support," as the term itself is absent and the disclosure of only a few specific non-porous examples (e.g., glass plates, cuvettes) is insufficient to demonstrate possession of the full, broad genus. This argument, if successful, pushes the critical date to May 9, 1985, thereby making references published between those dates, like VPK (1982), valid prior art under §102.

6. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1, 6, 8, 9, 12-16, 27, 31-34, 38, 41, 61-64, 68-70, 72-74, 78, 79, 100, 101, 191-195, 212, 213, 218, 219, 222, 225-227, 230, 233, and 236 of the ’197 patent as unpatentable.