Laboratory Corp Of America Holdings v. Quest Diagnostics Investments LLC

1. Case Identification

• Case #: IPR2019-00738
• Patent #: 8,409,862
• Filed: February 25, 2019
• Petitioner(s): Laboratory Corporation of America Holdings
• Patent Owner(s): Quest Diagnostics Investments LLC
• Challenged Claims: 1, 2, 4-14

2. Patent Overview

• Title: Determination of Testosterone by Mass Spectrometry
• Brief Description: The ’862 patent discloses methods for determining the amount of testosterone in a sample from a female human. The method involves purifying testosterone from the sample, ionizing it, and detecting the ions using a mass spectrometer, specifically claiming the ability to detect concentrations below 10 ng/dL without derivatizing the testosterone prior to analysis.

3. Grounds for Unpatentability

Ground 1: Anticipation over Clarke - Claims 1, 2, 5-7, and 10-14 are anticipated by Clarke under 35 U.S.C. §102(b).

• Prior Art Relied Upon: Clarke (a 2001 conference proceeding titled "Determination of Suppressed Testosterone Levels in Human Serum by LC-MS/MS").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Clarke, a 2001 conference proceeding, expressly or inherently disclosed every limitation of the challenged claims. Clarke described a validated method for the "quantitation of suppressed levels of testosterone in human serum," including the use of female human serum as a control. The method involved purifying testosterone via solid phase extraction (SPE) and high-performance liquid chromatography (HPLC), followed by ionization and tandem mass spectrometry (MS-MS) detection. Petitioner asserted that Clarke’s method did not involve derivatization and reported a lower limit of quantification (LLOQ) of 50 pg/mL (equivalent to 5 ng/dL). Because the limit of detection (LOD) is necessarily less than or equal to the LLOQ, Petitioner contended Clarke’s method was inherently capable of detecting testosterone at concentrations of less than 10 ng/dL, meeting the limitation of claim 1. Clarke also disclosed the specific mass-to-charge ratios for the precursor and product ions recited in the dependent claims.

Ground 2: Obviousness over Clarke - Claims 8 and 9 are obvious over Clarke under 35 U.S.C. §103.

• Prior Art Relied Upon: Clarke (a 2001 conference proceeding).
• Core Argument for this Ground:
  • Prior Art Mapping: Claims 8 and 9 depend on claim 1 and add limitations requiring the method to be capable of detecting testosterone at concentrations of less than 5 ng/dL and less than 1 ng/dL, respectively. Clarke disclosed an LLOQ of 5 ng/dL.
  • Motivation to Combine: This ground relied on a single reference, with motivation arising from the ordinary desire of scientists to optimize known assays. Petitioner argued that a person of ordinary skill in the art (POSITA), knowing of the clinical need to measure very low testosterone levels (e.g., in children or certain female populations), would have been motivated to improve the sensitivity of the method disclosed in Clarke.
  • Expectation of Success: Petitioner asserted a POSITA would have had a reasonable expectation of success in achieving these lower detection limits. Clarke’s reported precision (15.8% CV) at its lowest tested concentration (5 ng/dL) was well within the accepted tolerance (20%), indicating that the method was not at its performance limit. A POSITA could have achieved greater sensitivity through routine and predictable optimizations, such as increasing the sample volume, adjusting instrument parameters, or using a different extraction method, all of which were well-known techniques.

Ground 3: Obviousness over Draisci and Clarke - Claims 1, 2, and 4-14 are obvious over Draisci in view of Clarke under 35 U.S.C. §103.

• Prior Art Relied Upon: Draisci (a 2000 journal article on quantitation of anabolic hormones) and Clarke (a 2001 conference proceeding).

• Core Argument for this Ground:

  • Prior Art Mapping: Draisci disclosed a sensitive LC-MS/MS method for quantifying testosterone in bovine serum and urine. The method included both liquid-liquid and solid-phase extraction, did not require derivatization, and achieved an LLOQ of 10 ng/dL. While Draisci used bovine samples, Clarke provided the explicit teaching of applying a similar LC-MS/MS method to detect suppressed testosterone levels in human female samples.
  • Motivation to Combine: Petitioner argued a POSITA would combine these references because they both described modernizing well-known testosterone assays by replacing gas chromatography with more efficient HPLC. A POSITA seeking to apply an advanced LC-MS/MS method like Draisci's for use in humans would have naturally looked to analogous art like Clarke. The interchangeability of testosterone assays across mammalian species was well-understood, as testosterone is the same chemical entity.
  • Expectation of Success: A POSITA would have reasonably expected success in applying the combined teachings to human samples, as Clarke had already demonstrated the viability of the general LC-MS/MS approach for this purpose. The high precision and accuracy reported in Draisci suggested the method was robust and could be adapted for human samples to achieve a detection limit below 10 ng/dL through routine optimization.

• Additional Grounds: Petitioner asserted that claim 4, which recites liquid extraction, is obvious over Clarke in view of Fitzgerald (a 1996 journal article). Fitzgerald was cited for its explicit teaching of using liquid-liquid extraction in a testosterone assay.

4. Key Claim Construction Positions

• Petitioner argued that the claim term "capable of detecting" should be construed to refer to the limit of detection (LOD), not the limit of quantitation (LOQ).
• Petitioner supported this by noting the ’862 patent itself distinguishes between the two terms, defining the LOD as the point where an analyte is detectable above background and the LOQ as the point where measurements become quantitatively meaningful (e.g., CV < 20%). This distinction was critical to Petitioner's arguments, as the LOD is a less stringent and typically lower concentration than the LOQ, making it easier to meet with prior art that only reports an LLOQ.

5. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1, 2, and 4-14 of Patent 8,409,862 as unpatentable.