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IPR2019-01425

Laboratory Corp Of America Holdings v. Quest Diagnostics Investments LLC

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Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods for Detecting Vitamin D Metabolites by Mass Spectrometry
  • Brief Description: The ’427 patent discloses methods for determining the amount of a vitamin D metabolite in a sample using tandem mass spectrometry. The core method involves generating a protonated and dehydrated precursor ion of the metabolite, generating fragment ions from that precursor, and detecting the ions to quantify the metabolite.

3. Grounds for Unpatentability

Ground 1: Obviousness over Voyksner - Claims 1-5 are obvious over Voyksner.

  • Prior Art Relied Upon: Voyksner (a 1999 scientific article titled "Improvements in LC/Electrospray Ion Trap Mass Spectrometry Performance Using an Off-Axis Nebulizer").
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Voyksner, by itself, teaches every element of claims 1-5. Voyksner describes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the amount of the vitamin D metabolite dihydroxyvitamin D3 in plasma samples. It explicitly discloses the key steps of claim 1: (a) generating a protonated and dehydrated precursor ion ([M + H – H2O]+) of dihydroxyvitamin D3 with a mass-to-charge ratio (m/z) of 399; (b) generating fragment ions from this precursor through collision-induced decomposition (monitoring transitions like 399→381, 399→135, and 399→213); and (c) detecting these ions and relating them to the amount of the metabolite in the sample. For dependent claims 2-5, Voyksner teaches a purification step (claim 2) via liquid-liquid extraction, which is followed by chromatography (claim 3), specifically liquid chromatography (claim 4) and high-performance liquid chromatography (HPLC) (claim 5).
    • Motivation to Combine (for §103 grounds): As a single-reference ground, the motivation was inherent in Voyksner's complete disclosure of a method for achieving the same result as the claimed invention.
    • Expectation of Success (for §103 grounds): A person of ordinary skill in the art (POSITA) would have an expectation of success because Voyksner successfully implemented the very method claimed.

Ground 2: Obviousness over Voyksner and Kissmeyer - Claims 6 and 7 are obvious over Voyksner in view of Kissmeyer.

  • Prior Art Relied Upon: Voyksner (as described in Ground 1) and Kissmeyer (a 2001 scientific article on the analysis of dihydroxyvitamin D3 in biological fluids by LC-MS/MS).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground addresses claim 6, which adds protein precipitation to the purification step, and claim 7, which specifies the purification does not use high turbulence liquid chromatography (HTLC). Petitioner asserted that Voyksner provides the foundational LC-MS/MS method. Kissmeyer explicitly teaches using protein precipitation with acetonitrile as a purification method prior to LC-MS/MS analysis of vitamin D metabolites. Furthermore, Petitioner argued that the purification methods detailed in both Voyksner (liquid-liquid extraction, standard HPLC) and Kissmeyer (protein precipitation, standard HPLC) are characteristic of laminar flow HPLC, not HTLC, thus implicitly disclosing the negative limitation of claim 7.
    • Motivation to Combine (for §103 grounds): A POSITA would combine these references to simplify Voyksner's method. Protein precipitation, as taught by Kissmeyer, was a well-known and often simpler alternative to the liquid-liquid extraction taught by Voyksner. Substituting one standard purification technique for another to improve efficiency was a routine optimization.
    • Expectation of Success (for §103 grounds): Success would be expected because both references apply standard, interchangeable sample preparation techniques to the same class of analytes for the same purpose (LC-MS/MS analysis).

Ground 3: Obviousness over Voyksner and Kamao - Claim 8 is obvious over Voyksner in view of Kamao.

  • Prior Art Relied Upon: Voyksner (as described in Ground 1) and Kamao (a 2004 scientific article on the C-3 epimerization of vitamin D3 metabolites).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground challenges claim 8, which specifies that the purification step comprises chiral chromatography. Voyksner provides the base LC-MS/MS method. Kamao explicitly discloses using chiral chromatography (specifically, a Sumichiral OA-2000 column) to separate epimers of vitamin D metabolites (e.g., 3-epi-25(OH)D3 from 25(OH)D3) prior to detection.
    • Motivation to Combine (for §103 grounds): A POSITA would have been aware that vitamin D metabolites have various epimers and would have been motivated to separate them to improve analytical accuracy. A POSITA would logically apply the known chiral chromatography separation technique taught by Kamao to the established LC-MS/MS detection method of Voyksner.
    • Expectation of Success (for §103 grounds): A POSITA would have a reasonable expectation of success because chiral chromatography was a known technique fully compatible with and directly interfaceable to an LC-MS/MS system for analyzing vitamin D metabolites.

  • Additional Grounds: Petitioner asserted additional obviousness challenges, including that claim 9 (no gas chromatography) is obvious over Voyksner, Watson, and Vogeser, arguing these references teach away from using GC-MS in favor of LC-MS for vitamin D analysis. Petitioner also argued claims 10 and 11 (specifying 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2) are obvious over Voyksner, Watson, and Rainbow, as it would have been obvious to apply Voyksner's method to other structurally similar and more abundant vitamin D metabolites.

4. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-11 of the ’427 patent as unpatentable under 35 U.S.C. §103.