Progenity Inc v. Natera Inc

1. Case Identification

• Case #: IPR2021-00267
• Patent #: 10,240,202
• Filed: December 3, 2020
• Petitioner(s): Progenity, Inc.
• Patent Owner(s): Natera, Inc.
• Challenged Claims: 1-13, 15-20

2. Patent Overview

• Title: Method for Detecting Fetal Aneuploidy
• Brief Description: The ’202 patent relates to methods for detecting fetal aneuploidy (an abnormal number of chromosomes) from a mixed sample of cell-free DNA (cfDNA) from both the fetus and mother. The method involves measuring the amount of genetic material at multiple loci on a chromosome of interest irrespective of the specific alleles present.

3. Grounds for Unpatentability

Ground 1: Obviousness over Shimkets in View of Bianchi - Claims 1-2, 7-8, 11-13, and 16-20 are obvious over Shimkets in view of Bianchi.

• Prior Art Relied Upon: Shimkets (WO 2005/039389) and Bianchi (a 2004 review article in Placenta).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Shimkets taught a method for detecting aneuploidy by using high-throughput sequencing to measure the amount of genetic material at one million or more loci. This measurement was performed "irrespective of the identity of the alleles" because Shimkets's sequence mapping allowed for a tolerance (e.g., 95% identity), thereby focusing on quantity rather than precise allele identity. While Shimkets mentioned using its method on complex samples like blood and for prenatal screening via amniocentesis or CVS, it did not explicitly teach applying it to a maternal blood sample containing fetal cfDNA. Bianchi, a review article on non-invasive prenatal testing (NIPT), allegedly supplied this missing element by teaching that maternal blood was a known, valuable, and attractive source of fetal cfDNA for aneuploidy detection.
  • Motivation to Combine: A POSITA would combine Shimkets and Bianchi to apply Shimkets’s powerful sequence-based karyotyping method to the safer, more convenient, and well-recognized sample source described by Bianchi (maternal blood cfDNA). Both references are directed to detecting fetal aneuploidy, and combining them represented the application of a known analytical technique to a known and advantageous sample type to achieve the expected benefits of NIPT.
  • Expectation of Success: A POSITA would have an expectation of success because Shimkets's method was designed for complex samples and could amplify small amounts of DNA. Bianchi taught that fetal cfDNA was surprisingly stable and accessible in maternal plasma, making it a suitable input for the Shimkets methodology.

Ground 2: Obviousness over Huang in View of Bianchi - Claims 1-9, 11-13, and 15-20 are obvious over Huang in view of Bianchi.

• Prior Art Relied Upon: Huang (Application # 2005/0064476) and Bianchi (a 2004 review article in Placenta).

• Core Argument for this Ground:

  • Prior Art Mapping: Petitioner asserted that Huang taught a method for detecting aneuploidy by measuring DNA copy number changes using microarrays. Huang’s method measured the gross amount of genetic material for a chromosomal region by analyzing overall hybridization patterns from hundreds of thousands of probes, rather than relying on the identity of specific alleles. Similar to Shimkets, Huang taught its method was useful for prenatal diagnosis but focused on samples like crude whole blood without specifying the use of maternal cfDNA. Bianchi again supplied the teaching that maternal blood containing fetal cfDNA was a known and valuable source for prenatal aneuploidy diagnosis.
  • Motivation to Combine: A POSITA would combine Huang and Bianchi because Bianchi explicitly suggested that then-available microarray technology could be used to achieve a "non-invasive fetal genome scan" from maternal blood. Therefore, a POSITA would have been directly motivated to apply the specific microarray-based aneuploidy detection method of Huang to the ideal maternal blood sample source taught by Bianchi.
  • Expectation of Success: Huang disclosed that its methods worked on mixed samples and included robust amplification techniques suitable for detecting as few as 1-10 copies of genomic DNA. A POSITA would therefore reasonably expect that Huang's microarray method could successfully detect aneuploidy from the mixed fetal and maternal cfDNA sample described in Bianchi.

• Additional Grounds: Petitioner asserted that claim 10 is obvious over Huang and Bianchi in view of Illumina (a 2004 product workflow document). This ground argued a POSITA would have been motivated to employ the commercially available Illumina GoldenGate assay, a specific type of multiplex ligation PCR amplification, to implement the microarray-based aneuploidy detection method taught by Huang.

4. Key Claim Construction Positions

• "the amount of genetic material...is determined irrespective of the identity of the alleles at that locus": Petitioner argued this phrase means the method determines the quantity of genetic material without relying on the identity of the alleles. It does not require that allele information be excluded or ignored. This construction is central to the obviousness arguments, as Petitioner contended that both Shimkets's sequencing method (which tolerates mismatches) and Huang's microarray method (which measures gross hybridization signal) meet this limitation by focusing on quantity over specific allele identity.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) would be inappropriate because the asserted prior art references (Shimkets, Huang, Bianchi, Illumina) are new and were never substantively considered during prosecution of the ’202 patent or its parent applications. The arguments presented are materially different from those overcome by the applicant during prosecution.
• Petitioner also argued against discretionary denial under Fintiv, stating that the parallel district court litigation was in its earliest stages, with no trial date set and minimal investment in the proceedings beyond venue disputes. Petitioner contended that the merits of the petition are strong and that instituting the IPR would promote efficiency and patent quality.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-13 and 15-20 of the ’202 patent as unpatentable.