QIAGEN Sciences LLC v. Tecan Group AG

1. Case Identification

• Case #: IPR2025-00027
• Patent #: 11,725,241
• Filed: October 10, 2024
• Petitioner(s): QIAGEN Sciences, LLC
• Patent Owner(s): Tecan Genomics, Inc.
• Challenged Claims: 1-16

2. Patent Overview

• Title: Methods for Detecting Duplicate Nucleic Acid Sequencing Reads
• Brief Description: The ’241 patent discloses methods for identifying polymerase chain reaction (PCR) duplicates in high-throughput sequencing. The method involves appending an adaptor containing a unique "identifier site"—a random sequence of nucleotides—to each nucleic acid molecule before amplification, allowing for subsequent identification and removal of sequencing reads that have identical target sequences and identical identifier sequences.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-3, 5-7, 9-10, and 13-16 by McCloskey

• Prior Art Relied Upon: McCloskey (Application # 2007/0020640).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that McCloskey teaches every limitation of the challenged claims by disclosing a method for detecting duplicate sequencing reads using "barcodes" to distinguish redundant sequences from valid ones. McCloskey’s "random barcode" is equivalent to the ’241 patent's "identifier site." McCloskey taught incorporating these barcodes into adaptors, such as a hairpin linker or an oligonucleotide primer, which are then appended to target DNA fragments before PCR amplification. After amplification and sequencing, McCloskey explicitly taught that sequence reads having identical barcodes and target sequences are identified as redundant duplicates. Petitioner contended that McCloskey's detailed examples, which show the generation and analysis of barcoded amplicons from both genomic DNA and cDNA, meet the specific limitations of the independent and dependent claims.

Ground 2: Anticipation of Claims 1-3, 5-11, and 13-16 by Porreca

• Prior Art Relied Upon: Porreca (Application # 2012/0165202).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Porreca anticipates the claims by teaching the use of "differentiator tag sequences" to uniquely tag individual nucleic acid molecules. These tags are used to determine whether multiple identical reads originate from a single starting molecule (i.e., a PCR duplicate) or from independent molecules. Porreca’s tags, attached via adaptors prior to amplification, function identically to the claimed "identifier site." Porreca further taught that any "target:differentiator tag combination observed more than once" should be "collapsed into a single read." Petitioner argued this directly teaches the core claimed steps of identifying reads with identical identifier and target sequences and removing them as duplicates, as illustrated in Porreca’s Figure 5. Porreca also disclosed applying this method to various nucleic acids, including cDNA and genomic DNA, and using adaptors containing barcodes (for sample indexing) and primer binding sites.

Ground 3: Obviousness of Claims 4 and 8 over Porreca in view of Illumina 2008

• Prior Art Relied Upon: Porreca (Application # 2012/0165202) and Illumina 2008 (a 2008 product datasheet).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that to the extent Porreca does not explicitly disclose every limitation of dependent claims 4 and 8, the additions would have been obvious in view of Illumina 2008. Claim 4 requires sequencing the identifier site separately from the target sequence. Illumina 2008 taught a standard multiplexed sequencing process that included a separate "index read." Claim 8 requires a "universal target sequencing primer binding site." Illumina 2008 disclosed and depicted the use of such universal sites (e.g., "Rd1 SP" and "Rd2 SP") on its adaptors as a fundamental part of its widely adopted sequencing workflow.
  • Motivation to Combine: A POSITA would combine Porreca with the teachings of the well-known Illumina platform because Porreca explicitly directs users to perform sequencing according to manufacturer directions, such as Illumina's. A POSITA would be motivated to adopt Illumina's separate index read method to maximize the length of the target sequence read, thereby increasing data quality and efficiency. Incorporating Illumina's universal primer sites would be a necessary and obvious step to implement Porreca's method on the predominant sequencing platform of the time.
  • Expectation of Success: A POSITA would have had a high expectation of success, as the combination involved applying a routine, standardized sequencing protocol (from Illumina 2008) to a known method of duplicate detection (from Porreca).
• Additional Grounds: Petitioner asserted additional challenges, including anticipation of claims 1-3, 5-12, and 14-15 by Schmitt; obviousness of claims 4 and 8 over Schmitt in view of Illumina 2008; and obviousness of claim 12 over Porreca in view of Li 2009.

4. Key Claim Construction Positions

• Petitioner argued for construing "adaptor" as "any oligonucleotide that is attached to the target sequence." This construction was based on the patent's specification and the prosecution history of a parent patent, where the examiner concluded that since any oligonucleotide could perform the described function, any oligonucleotide should anticipate the term. This broad construction is central to Petitioner's anticipation arguments, as the prior art's hairpin linkers and oligonucleotide primers fall within this definition.

5. Arguments Regarding Discretionary Denial

• Petitioner argued against denial under 35 U.S.C. §325(d), asserting that the primary prior art references relied upon in the petition (McCloskey, Porreca, Schmitt, and Li 2009) were never presented to or considered by the examiner during prosecution of the ’241 patent. Petitioner contended this constitutes a material difference from the original examination, weighing strongly against discretionary denial.
• Petitioner also argued against discretionary denial under Fintiv, noting that the parallel district court trial date (July 27, 2026) is scheduled to occur well after the PTAB's projected Final Written Decision deadline (approximately April 2026). The litigation was also described as being in its early stages, with minimal investment in discovery related to invalidity, thus favoring institution.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-16 of Patent 11,725,241 as unpatentable.