PTAB

IPR2025-00029

QIAGEN Sciences LLC v. Tecan Group AG

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Nucleic Acid Sequence Enrichment for Next-Generation Sequencing
  • Brief Description: The ’108 patent discloses methods for targeted enrichment of specific nucleic acid sequences from a complex sample. The process is intended to prepare a high-efficiency nucleic acid library for use in next-generation sequencing (NGS).

3. Grounds for Unpatentability

Ground I: Obviousness over Shapero and Delseny - Claims 1-2, 5-7, 9-12, and 14-19

  • Prior Art Relied Upon: Shapero (a 2004 journal article describing the MARA enrichment method) and Delseny (a 2010 journal article reviewing NGS technologies).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Shapero taught the core method of claim 1, a process called Multiplexed Anchored Runoff Amplification (MARA). This method involves ligating a first adaptor (A2) to fragmented DNA, annealing a locus-specific oligonucleotide with a non-complementary 5’ tail containing a second adaptor sequence (A1), extending the oligonucleotide with a polymerase to copy the first adaptor, and then amplifying the resulting product using universal primers for both adaptors. Petitioner asserted that Delseny supplied the final limitation of sequencing the enriched products on a massively parallel sequencing platform, describing NGS technologies like Illumina as a high-resolution replacement for the older microarray genotyping methods used in Shapero.
    • Motivation to Combine: A POSITA would combine Shapero's enrichment method with Delseny's NGS platforms to leverage the known benefits of NGS, such as higher throughput, lower cost, and base-pair level resolution. Delseny explicitly positioned NGS as a superior substitute for the array-based genotyping used in Shapero. Crucially, Petitioner argued that Shapero’s experimental data, which showed high on-target specificity (~95% average sample call rate), would have directly refuted the skepticism about enrichment efficiency that the Patent Owner relied upon during prosecution (via the Brooks declaration) to secure the patent. This data demonstrated the method was robust enough for NGS applications.
    • Expectation of Success: The high on-target enrichment and specificity demonstrated experimentally in Shapero provided a strong reason for a POSITA to expect success when applying the MARA method to the more advanced NGS platforms described by Delseny.

Ground II: Obviousness over Shapero and Delseny in view of Jones - Claims 3-4

  • Prior Art Relied Upon: Shapero, Delseny, and Jones (Application # 2005/0142577).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground addresses dependent claims 3 and 4, which specify the nucleic acid sequence of interest comprises cDNA or RNA. While Shapero focused on genomic DNA, Jones—which discloses the same MARA method and shares inventors with Shapero—explicitly taught that the starting nucleic acid could be "DNA or RNA." Petitioner contended that for an RNA starting material, a POSITA would have known to first perform reverse transcription to create more stable cDNA before proceeding with the MARA protocol.
    • Motivation to Combine: A POSITA would combine Jones' teaching of using RNA as a starting material with the primary Shapero/Delseny combination because Jones and Shapero teach the same underlying enrichment technology. Applying the established and effective MARA method to a different but common type of nucleic acid (RNA) was argued to be an obvious and predictable modification.

Ground III: Obviousness over Shapero and Delseny in view of Hamady - Claim 8

  • Prior Art Relied Upon: Shapero, Delseny, and Hamady (a 2009 journal article on microbial community profiling).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground addresses dependent claim 8, which requires that one or both adaptor sequences comprise a barcode sequence. Hamady taught that in high-throughput sequencing, it is desirable to pool many samples in a single run by tagging sequences from each sample with a unique barcode. These barcodes could be added either by ligation or by incorporating them into PCR primers.
    • Motivation to Combine: A POSITA would be motivated to incorporate Hamady's barcoding techniques into the Shapero/Delseny combination to increase the efficiency and throughput of the NGS process, a primary goal of the technology. Petitioner argued that incorporating a barcode into either the ligated adaptor (A2) or the tailed primer (A1) of Shapero's MARA method was a well-known and straightforward design choice to enable multiplexed sample analysis, a common practice in the field of NGS.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under §325(d) is inappropriate because the petition relies on prior art, particularly Shapero, that was not before the Examiner. Petitioner asserted that Shapero is not cumulative to Jones (which was of record) because Shapero contains critical experimental data showing high on-target specificity. This data directly rebuts the declaration evidence (the Brooks declaration) that the Examiner relied on to allow the claims, indicating the Office materially erred.
  • Petitioner also argued that discretionary denial under §314(a) based on Fintiv is not warranted. The trial date in the parallel district court litigation (July 27, 2026) is scheduled to occur after the projected deadline for a Final Written Decision in the IPR (April 2026). Further, the district court case is in its early stages with minimal investment in invalidity issues.

5. Relief Requested

  • Petitioner requests the institution of an inter partes review and the cancellation of claims 1-12 and 14-19 of the ’108 patent as unpatentable.