Ariosa Diagnostics v. Isis Innovation Ltd

1. Case Identification

• Case #: IPR2012-00022
• Patent #: 6,258,540
• Filed: September 17, 2012
• Petitioner(s): Ariosa Diagnostics
• Patent Owner(s): Sequenom, Inc. (as real party in interest)
• Challenged Claims: 1-2, 4-5, 8, 19-22, and 24-25

2. Patent Overview

• Title: Non-invasive Prenatal Diagnosis
• Brief Description: The ’540 patent discloses methods for detecting paternally inherited nucleic acid of fetal origin from a maternal serum or plasma sample. The method involves amplifying the paternally inherited nucleic acid from the sample and then detecting its presence for prenatal diagnosis.

3. Grounds for Unpatentability

Ground 1: Anticipation over Intervening Publication - Claims 1-2, 4-5, 19-22, and 24-25 are anticipated by Lo 1997.

• Prior Art Relied Upon: Lo et al., "Presence of fetal DNA in maternal plasma and serum," (Lancet; 350:485-87 (1997)) ("Lo 1997").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the ’540 patent is not entitled to its March 1998 British priority date. The priority application allegedly failed to provide an enabling disclosure for the full scope of the claims, particularly for quantitative detection of aneuploidies like Down syndrome, which were not possible until years later. Because the priority claim fails, the inventor's own publication, Lo 1997, qualifies as intervening prior art under 35 U.S.C. §102. Lo 1997 explicitly describes preparing maternal plasma and serum, using PCR to amplify Y-chromosome sequences (a paternally inherited nucleic acid), and detecting the amplified product to show the presence of fetal DNA, thus disclosing every element of the challenged claims.
  • Key Aspects: The core of this ground rested on invalidating the patent’s priority claim, which transforms the inventor's own foundational paper into anticipating prior art.

Ground 2: Anticipation over Kazakov - Claims 1-2, 4-5, 8, 19-22, and 24-25 are anticipated by Kazakov 1995.

• Prior Art Relied Upon: Kazakov et al., "Extracellular DNA in the Blood of Pregnant Women," (Cytology (Tsitologia), vol. 37, No. 3, 1995) ("Kazakov").
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that under the Broadest Reasonable Interpretation—specifically, the broad construction of "detect" and "amplify" advanced by the Patent Owner in co-pending litigation—Kazakov anticipated all challenged claims. Kazakov described extracting and amplifying extracellular DNA from the serum of pregnant women using PCR with primers for inter-Alu sequences. Petitioner’s expert declarations contended these primers would inherently amplify paternally inherited sequences, including those on the Y chromosome and other non-Y chromosomes. Because the Patent Owner’s own interpretation did not require distinguishing or enriching for fetal DNA, Kazakov's process of amplifying total extracellular DNA from pregnant women (which factually contains fetal DNA) and detecting the amplification product met all claim limitations.

Ground 3: Obviousness over Simpson, Schallhammer, and Kazakov - Claims 1-2, 4, 8, 21, 22, 24, and 25 are obvious over Simpson in view of Schallhammer and Kazakov.

• Prior Art Relied Upon: Simpson et al. (Prenat. Diagn. 1994), Schallhammer et al. (Early Pregnancy 1997), and Kazakov (Cytology, 1995).

• Core Argument for this Ground:

  • Prior Art Mapping: Simpson taught that fetal cells, containing fetal DNA, exist in maternal blood circulation. Schallhammer taught that maternal immune cells (natural killer cells) in peripheral blood would recognize circulating fetal cells as "non-self" and destroy them. Petitioner argued this destruction would be expected to release cell-free fetal DNA into the maternal plasma/serum. Kazakov provided a known method for isolating and amplifying total extracellular DNA from the serum of pregnant women using PCR.
  • Motivation to Combine: A POSITA would have been motivated to apply the known DNA detection techniques of Kazakov to maternal serum. The rationale was simple: knowing from Simpson that fetal cells were present in maternal blood, and expecting from Schallhammer that the maternal immune system would destroy these cells and release their DNA, it would have been obvious to look for this cell-free fetal DNA using established PCR methods for diagnostic purposes.
  • Expectation of Success: A POSITA would have had a high expectation of success because each step was based on well-established principles: the presence of fetal cells in maternal blood was known, cell destruction by the immune system was a fundamental concept, and PCR was a routine tool for detecting small quantities of DNA in biological fluids.

• Additional Grounds: Petitioner asserted additional obviousness challenges, including a combination of Gocke (Patent 6,156,504), Robbins (a pathology textbook), and Simpson, arguing it would have been obvious to apply known cancer diagnostic methods for detecting cell-free DNA to pregnant women with choriocarcinoma (a cancer of placental origin), which would inherently detect fetal DNA.

4. Key Claim Construction Positions

• Petitioner argued that the IPR should adopt the Broadest Reasonable Interpretation, which aligned with the broad construction the Patent Owner advocated for in district court litigation.
• "Detect": This term was argued to mean merely discovering the existence or presence of a nucleic acid, without requiring identification of its origin. Under this view, a process meets the limitation if it detects nucleic acids that include paternally inherited fetal DNA, even if it cannot distinguish them from maternal DNA.
• "Amplify": This term was argued to mean simply increasing the amount of a nucleic acid, with no requirement for enriching its relative concentration. This interpretation was critical to the argument that Kazakov's amplification of total extracellular DNA met the claim limitation.

5. Key Technical Contentions (Beyond Claim Construction)

• Failure of Priority Claim via Lack of Enablement: Petitioner's central technical contention was that the ’540 patent’s British priority application did not enable the full scope of the claims. The petition argued that the priority document only described "yes/no" detection of sequences known to be absent in the mother (e.g., Y-chromosome for sexing). However, the patent claims broadly cover quantitative methods needed to detect aneuploidies (e.g., trisomy 21), which involve measuring subtle differences in gene dosage. Petitioner, citing the lead inventor's own later publications, argued that such quantitative analysis was not technologically possible until nearly a decade after the priority date, rendering the priority claim invalid under 35 U.S.C. §112.

6. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-2, 4-5, 8, 19-22, and 24-25 of the ’540 patent as unpatentable.