QIAGEN Sciences LLC v. Tecan Group AG

1. Case Identification

• Case #: IPR2025-00028
• Patent #: 10,036,012
• Filed: October 10, 2024
• Petitioner(s): QIAGEN Sciences, LLC
• Patent Owner(s): Tecan Genomics, Inc.
• Challenged Claims: 1-15 and 17-22

2. Patent Overview

• Title: Targeted Nucleic Acid Sequence Enrichment
• Brief Description: The ’012 patent discloses methods for enriching target nucleic acid sequences from a sample for use in high-efficiency library generation for next-generation sequencing (NGS). The method involves using partial duplex adaptors and sequence-specific oligonucleotides to selectively amplify regions of interest.

3. Grounds for Unpatentability

Ground I: Claims 1-2, 5-6, 11-15, 17-20, and 22 are obvious over Shapero and Delseny

• Prior Art Relied Upon: Shapero (a 2004 journal article on Multiplexed Anchored Runoff Amplification, "MARA") and Delseny (a 2010 journal article reviewing next-generation sequencing technologies).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Shapero taught all key steps of independent claim 1. Specifically, Shapero’s MARA method disclosed obtaining a nucleic acid fragment ligated to a partial duplex adaptor (first adaptor sequence), annealing a locus-specific oligonucleotide with a non-complementary tail (second adaptor sequence), extending the oligonucleotide with a polymerase to create an extension product, and amplifying that product using universal primers corresponding to the two adaptor sequences. Delseny disclosed applying the amplified products of enrichment methods like Shapero’s to massively parallel sequencing platforms, such as Illumina’s, which require products to have a 3’ end complementary to a sequence on the flow cell surface for bridge amplification and sequencing.
  • Motivation to Combine: A POSITA would combine Shapero’s enrichment method with Delseny’s NGS platforms because NGS was a well-known, higher-resolution, and higher-throughput replacement for the array-based genotyping used in Shapero. Delseny explicitly taught that NGS could substitute for microarrays. The experimental data in Shapero, showing high on-target specificity (~95% call rate and >99% SNP targeting), would have provided a strong motivation to adapt this successful enrichment method for the more advanced NGS platforms described by Delseny.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success because adapting enrichment products for NGS by adding platform-specific sequences (e.g., Illumina’s p5/p7) to the universal primers was a routine and predictable modification at the time. The high on-target efficiency demonstrated in Shapero confirmed the method’s robustness, making its application to NGS a predictable improvement.
  • Key Aspects: Petitioner emphasized that Shapero, which was not before the Examiner, contained critical experimental data showing high target enrichment. This data directly refuted the secondary consideration arguments of skepticism and unexpected results (made in the Brooks declaration) that the Patent Owner successfully used to overcome an obviousness rejection during prosecution based on a similar reference (Jones) that lacked such data.

Ground II: Claims 7-10 are obvious over Shapero and Delseny and further in view of Hamady

• Prior Art Relied Upon: Shapero, Delseny, and Hamady (a 2009 review article on microbial community profiling using high-throughput sequencing).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground built upon the combination in Ground I. Hamady was introduced to teach the use of unique barcodes to tag samples for multiplexed sequencing, a technique for analyzing many samples in a single NGS run. Dependent claims 7-10 require the use of barcodes of specific lengths (e.g., at least 8 or 12 nucleotides) within the adaptor sequences to uniquely identify fragments. Hamady explicitly disclosed using barcoded primers and detailed error-correcting codes, such as 8-base Hamming codes and 12-base Golay codes, for this purpose.
  • Motivation to Combine: A POSITA would be motivated to add Hamady’s barcoding to the Shapero/Delseny method to leverage the high-throughput capabilities of NGS. As NGS generates vast numbers of sequences, it was common practice and highly desirable to pool multiple barcoded samples into a single run to improve efficiency and reduce costs, as taught by Hamady.
  • Expectation of Success: Incorporating a short, known barcode sequence into the adaptor tails of the primers used in the Shapero method was a simple and predictable modification with a high expectation of success.

Ground III: Claims 3-4 and 21 are obvious over Shapero and Delseny and further in view of Jones

• Prior Art Relied Upon: Shapero, Delseny, and Jones (Application # 2005/0142577).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground also built upon the combination in Ground I. Jones, which disclosed the same MARA enrichment method as Shapero, was introduced for its explicit teaching that the starting nucleic acid could be RNA. Dependent claims 3, 4, and 21 relate to using RNA as the starting material, which requires performing reverse transcription to generate cDNA. Jones disclosed that its method could be used with DNA or RNA and taught generating oligonucleotides for use as "primers for reverse transcription."
  • Motivation to Combine: A POSITA would be motivated to incorporate the teachings of Jones because Jones and Shapero disclosed the same core MARA method and shared co-inventors. Given Jones’s explicit disclosure of applying the method to RNA, it would have been obvious to apply the combined Shapero/Delseny method to RNA samples by first performing the standard and necessary step of reverse transcription.
  • Expectation of Success: Converting RNA to cDNA via reverse transcription before performing PCR-based amplification was a routine and well-understood technique, ensuring a high expectation of success.

4. Arguments Regarding Discretionary Denial

• §325(d) - Same Art or Arguments: Petitioner argued that denial under §325(d) was improper because the core prior art (Shapero, Delseny, Hamady) was never before the Examiner. While Jones was previously considered, Petitioner argued Shapero was not cumulative because it contained dispositive experimental data absent from Jones. This data directly rebutted the Brooks declaration, on which the Examiner exclusively relied for allowance. Petitioner contended the Examiner materially erred by allowing the claims based on a factually unsupported and legally flawed declaration.
• §314(a) - Fintiv Factors: Petitioner argued that the Fintiv factors strongly favored institution. The district court trial date (July 2026) was scheduled for well after the projected Final Written Decision (April 2026). The parallel litigation was in its early stages, with minimal investment in discovery related to invalidity. Further, Petitioner stipulated it would not pursue the same invalidity grounds in district court if an IPR was instituted, mitigating concerns of duplicative efforts.

5. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-15 and 17-22 of the ’012 patent as unpatentable.