US 10876108

US Patent 10876108, titled "Compositions and methods for targeted nucleic acid sequence enrichment and high efficiency library generation," was issued on December 29, 2020, from an application filed on June 25, 2018 (Application No. US16/017,340). The current assignee is Tecan Genomics Inc., with the original assignee being Nugen Technologies Inc. The inventors are Doug Amorese, Chris Armour, and Nurith Kurn.

Abstract:
The patent describes methods, compositions, and kits for enriching specific target nucleic acid sequences from a sample and for creating high-efficiency nucleic acid libraries for Next Generation Sequencing (NGS). The disclosed technology is particularly useful for generating and capturing amplification-ready, target-specific, and strand-specific regions of interest from nucleic acid samples containing complex DNA.

Independent Claims Overview:

• Independent Claim 1 (Method for Enriching Target Nucleic Acid Sequences):
  This claim describes a method for enriching specific nucleic acid sequences. It involves first breaking down nucleic acids into fragments. Then, a "first adaptor" is added to one end of each fragment. Next, specialized "oligonucleotides" are attached, each having a part that matches a target sequence within the fragments and another part (a "second adaptor sequence") at its opposite end. These oligonucleotides are then extended using a polymerase, creating products that have the first adaptor at one end and the second adaptor at the other. Finally, these products are amplified using primers specific to both adaptors, thereby increasing the quantity of the desired target sequences.

• Independent Claim 13 (Method for Enriching Target Nucleic Acid Sequences using Partial Duplex Adaptors):
  This claim outlines another method for enriching target sequences, utilizing a "first adaptor" that is a partial duplex (meaning its two strands are of different lengths). This first adaptor has a blocking group on one strand to prevent extension and a specific restriction/cleavage site on the other. After appending this first adaptor and denaturing the nucleic acids into single strands, specific oligonucleotides are annealed to the target sequences and extended by a polymerase. This process creates double-stranded regions that include the restriction/cleavage site. This site is then cut by a nucleic acid modifying enzyme, and a "second adaptor" is ligated into the newly created cleavage site. The resulting complexes are then denatured again into single strands and amplified using primers specific to the second adaptor and the original short strand of the first adaptor, enriching for the target sequences.

• Independent Claim 25 (Method for Generating a Library of Nucleic Acid Sequences):
  This claim details a method for creating a library of nucleic acid sequences. It starts by fragmenting nucleic acids. A "first adaptor" is then added to each fragment. The fragments are denatured to become single-stranded, forming a library. Oligonucleotides are then annealed to these single-stranded fragments; these oligonucleotides have a portion that matches sequences within the fragments and a "second adaptor sequence" at their other end. A polymerase extends these oligonucleotides, yielding products with the first adaptor at one end and the second adaptor at the other. These products are then amplified using primers specific to both the first and second adaptors to generate the final library.

• Independent Claim 35 (Method for Enriching Target Nucleic Acid Sequences from an Existing Library):
  This claim describes a method to enrich specific target sequences from an existing library of nucleic acid inserts that already have a first and second adaptor on their ends. The inserts are denatured into single strands. One or more oligonucleotides are annealed, each containing a 3′ portion complementary to a target sequence of interest within the inserts and a 5′ portion comprising a "third adaptor sequence." These oligonucleotides are then extended by a polymerase, generating extension products with either the first or second adaptor at one end and the third adaptor sequence at the other. These products are subsequently amplified using primers complementary to the appropriate original adaptor (first or second) and the third adaptor, thus enriching the target nucleic acid fragments.

Litigation Status:
US Patent 10876108 is currently active and is involved in litigation.

• There are two US cases filed in Delaware District Court: 1:23-cv-01114 and 1:23-cv-01115.
• There are also two PTAB (Patent Trial and Appeal Board) cases: IPR2025-00016 (Final Written Decision) and IPR2025-00029 (Pending - Instituted).
• The first worldwide family litigation has also been filed.

Known litigation involving US patent 10876108:

1. District Court Case

   • Plaintiff(s): Tecan Genomics Inc
   • Defendant(s): QIAGEN Sciences LLC
   • Jurisdiction: Delaware District Court
   • Case number: 1:23-cv-01114
   • Filing date: October 06, 2023
   • Current status: Case filed in District Court.

2. PTAB Case

   • Case number: IPR2025-00016
   • Plaintiff(s)/Petitioner(s): Not explicitly identified in the provided search results.
   • Defendant(s)/Patent Owner(s): Not explicitly identified in the provided search results.
   • Jurisdiction: Patent Trial and Appeal Board (PTAB)
   • Filing date: Not explicitly identified in the provided search results.
   • Current status: Final Written Decision.

3. PTAB Case

   • Case number: IPR2025-00029
   • Plaintiff(s)/Petitioner(s): Not explicitly identified in the provided search results.
   • Defendant(s)/Patent Owner(s): Not explicitly identified in the provided search results.
   • Jurisdiction: Patent Trial and Appeal Board (PTAB)
   • Filing date: Not explicitly identified in the provided search results.
   • Current status: Pending - Instituted.

4. District Court Case

   • Plaintiff(s): Tecan Genomics Inc
   • Defendant(s): QIAGEN Sciences LLC
   • Jurisdiction: Delaware District Court
   • Case number: 1:23-cv-01115
   • Filing date: October 06, 2023
   • Current status: Case filed in District Court.

Proceedings overview

Two Inter Partes Review (IPR) proceedings have been filed against US Patent 10876108, both of which have reached a Final Written Decision status. The specific claim-level outcomes of these decisions are not publicly available with high confidence through the provided search functionality. Therefore, it is not possible to definitively state whether claims were invalidated or sustained, or to precisely determine the bottom-line defensive posture for a defendant without direct access to the Final Written Decisions.

IPR2025-00029 — QIAGEN Sciences, LLC v. Tecan Group AG

• Type: Inter Partes Review
• Filed: 2024-10-10
• Status: Final Written Decision — The Patent Trial and Appeal Board (PTAB) has issued a final decision in this proceeding.
• Judge panel: Not publicly available with high confidence.
• Petition grounds: Not publicly available with high confidence.
• Institution decision: The institution decision details, including the date and reasoning, are not publicly available with high confidence.
• Final Written Decision (if issued): A Final Written Decision was issued on or before 2026-05-13. The specific verdict at a claim-level granularity (which claims were canceled, sustained, or held patentable, and the panel's reasoning) is not publicly available with high confidence.
• Settlement / termination: Not publicly available with high confidence.
• Appeal: Information regarding any appeal to the Federal Circuit, including docket number, issues, and disposition, is not publicly available with high confidence.
• Defensive value: Without access to the Final Written Decision, the specific impact on a defendant facing assertion of this patent is unclear.

IPR2025-00016 — Integrated DNA Technologies, Inc. et al. v. Tecan Group AG

• Type: Inter Partes Review
• Filed: 2024-10-04
• Status: Final Written Decision — The Patent Trial and Appeal Board (PTAB) has issued a final decision in this proceeding.
• Judge panel: Not publicly available with high confidence.
• Petition grounds: Not publicly available with high confidence.
• Institution decision: The institution decision details, including the date and reasoning, are not publicly available with high confidence.
• Final Written Decision (if issued): A Final Written Decision was issued on or before 2026-04-06. The specific verdict at a claim-level granularity (which claims were canceled, sustained, or held patentable, and the panel's reasoning) is not publicly available with high confidence.
• Settlement / termination: Not publicly available with high confidence.
• Appeal: Information regarding any appeal to the Federal Circuit, including docket number, issues, and disposition, is not publicly available with high confidence.
• Defensive value: Without access to the Final Written Decision, the specific impact on a defendant facing assertion of this patent is unclear.

Strategic summary

Both IPR proceedings (IPR2025-00029 and IPR2025-00016) against US Patent 10876108 have reached the "Final Written Decision" stage, with last modified dates in April and May 2026. However, the specific details of these decisions, including which claims were challenged, the grounds for challenge, the institution decisions, and the claim-level outcomes of the Final Written Decisions, are not publicly available through the conducted searches. Therefore, it is not possible to definitively state which claims of US10876108 are now CANCELED, SUSTAINED, or UNTESTED based on these proceedings.

The estoppel landscape and the availability of prior-art grounds cannot be determined without knowing the specific claims challenged and the grounds considered in the Final Written Decisions. There is no information to suggest a pattern of filings by the same petitioner or aggressive PTAB appeals by the patent owner, nor the involvement of a defensive aggregator like Unified Patents in these specific IPRs as petitioners.

Recommended next steps

Since the specific outcomes of the Final Written Decisions for IPR2025-00029 and IPR2025-00016 on US10876108 are not readily available through public searches, the recommended next steps for a defendant would be:

• Obtain the Final Written Decisions (FWDs): Directly access the official case files for IPR2025-00029 and IPR2025-00016 through the USPTO's Patent Trial and Appeal Case Tracking System (P-TACTS) or by contacting the PTAB. These documents will contain the authoritative claim-level outcomes and reasoning.
• Analyze Claim Status: Once the FWDs are obtained, thoroughly analyze them to determine which claims, if any, were found unpatentable and which were sustained. This will inform any ongoing or prospective infringement theories.
• Assess Estoppel: Based on the FWDs, determine the estoppel effect under 35 U.S.C. § 315(e)(2) for the petitioners and their privies, which would bar them from raising any ground that was raised or reasonably could have been raised in these IPRs.

Inventors

• Doug Amorese
• Chris Armour
• Nurith Kurn
  • Employer at the time of filing: NuGEN Technologies Inc. (implied by the original assignee)

Original assignee

NuGEN Technologies Inc.
NuGEN Technologies Inc. was an operating company that shipped products embodying the claims, specifically in the field of next-generation sequencing (NGS) library preparation, such as the NuGEN Ovation Ultralow Library System mentioned in the patent.
Their primary line of business was developing and commercializing genomics solutions.
Current status: Acquired by Tecan Group Ltd. in 2019 and now operates as Tecan Genomics Inc., which is the current assignee of the patent.

Assignment timeline

As a large language model, I do not have direct, real-time access to the USPTO Patent Assignment Search database (https://assignmentcenter.uspto.gov/) to retrieve specific reel/frame numbers and correspondent details. The following timeline is reconstructed from the "Legal status" and "Application filed by / Assigned to" sections on Google Patents for US10876108, which provides a high-level overview of ownership changes but lacks the detailed information required for a complete patent assignment record analysis, particularly correspondent information.

• 2018-11-30 (executed) / recorded 2018-11-30 (approximate, "Assigned to" date from Google Patents) — Reel N/A

  • Conveyance: Assignment of Assignors Interest
  • Assignor: ARMOUR, Chris, AMORESE, Doug, KURN, NURITH (Inventors)
  • Assignee: NUGEN TECHNOLOGIES, INC.
  • Correspondent: Not available from Google Patents
  • Context: Transfer of inventor rights to the initial corporate assignee.

• 2023-08-28 (executed) / recorded 2023-08-28 (approximate, "Assigned to" date from Google Patents) — Reel N/A

  • Conveyance: Change of Name (SEE DOCUMENT FOR DETAILS)
  • Assignor: NUGEN TECHNOLOGIES, INC.
  • Assignee: TECAN GENOMICS, INC.
  • Correspondent: Not available from Google Patents
  • Context: Corporate name change following the acquisition of Nugen Technologies Inc. by Tecan Group Ltd. in 2019.

Timeline diagram

timeline
    title Ownership of US 10876108
    2018 : Application filed by Nugen
    2018-11-30: Inventors assign to Nugen
    2020-12-29: Patent Issued
    2023-08-28: Nugen becomes Tecan Genomics
    2023-09-29: First infringement suit filed
    2025: PTAB cases filed

NPE / troll-pattern signals

1. Shell-entity transfer — Not present. The transfers indicate the patent moving from the inventors to NuGEN Technologies Inc., an operating company, and subsequently to Tecan Genomics Inc. via a corporate name change after an acquisition. Both NuGEN Technologies Inc. and Tecan Genomics Inc. are operating companies that produce products related to the patented technology.
2. Known asserter in the chain — Not present. Neither NuGEN Technologies Inc. nor Tecan Genomics Inc. are publicly identified as known patent assertion entities (NPEs) or patent trolls.
3. Repeat correspondent across the chain — Unclear. This information cannot be determined from the available Google Patents data, as specific correspondent names and firms for the recorded assignments are not provided.
4. Cascading transfers — Not present. The assignment from inventors to NuGEN and the subsequent name change to Tecan Genomics occurred several years apart and do not represent rapid, consecutive assignments through chained LLCs.
5. Pre-litigation transfer — Unclear. The "CHANGE OF NAME" assignment to TECAN GENOMICS, INC. was recorded on 2023-08-28, approximately one month before the first infringement suits were filed on September 29, 2023. While this transfer predates litigation, it is explicitly noted as a "CHANGE OF NAME" and reflects a corporate restructuring following an acquisition (Tecan acquired NuGEN in 2019), rather than a strategic transfer to a new entity for the purpose of assertion. Thus, it does not strongly indicate an NPE pattern in this specific context, but rather an operating company asserting its own IP.
6. Bankruptcy fire-sale — Not present. There is no indication that NuGEN Technologies Inc. or Tecan Genomics Inc. filed for bankruptcy. The transfer to Tecan Genomics Inc. was a result of an acquisition.
7. Privateering — Not present. There is no public information to suggest that Tecan Genomics Inc. is asserting this patent on behalf of another operating company.
8. Defensive aggregator (anti-NPE) — Not present. The current assignee, Tecan Genomics Inc., is an operating company and not a defensive aggregator like RPX or AST.

Verdict

Operating-company assertion. The patent originated with NuGEN Technologies Inc., an operating company that produced products related to the claims. The subsequent assignment recorded on 2023-08-28 to Tecan Genomics Inc. was explicitly a "CHANGE OF NAME", reflecting NuGEN's prior acquisition by Tecan Group. Tecan Genomics Inc. is an operating company, and the associated litigation (e.g., Delaware District Court cases filed September 29, 2023) appears to be an assertion by an operating company of its own intellectual property.

Verification of assignment records can be performed at the USPTO Patent Assignment Search portal: https://assignmentcenter.uspto.gov/

As a technical patent analyst, I attempted to retrieve the specific list of prior art citations for US Patent 10876108 from the USPTO database using search queries directed at Google Patents, as the initial provided patent text for US10876108 did not contain a dedicated "Prior art citations" section.

Unfortunately, the available google_search tool, in this interactive format, returned general information about patent searching and the USPTO, rather than a structured list of the actual specific patent numbers cited by US10876108. Therefore, I cannot provide the full citations, publication/filing dates, brief descriptions, and specific claim anticipations for each cited patent as requested.

To fully fulfill this request, direct access to the "Prior art citations" section of US10876108 on a patent database like Google Patents or USPTO Patent Public Search is required to extract the definitive list of cited patents.

However, based on the claims and description of US Patent 10876108, I can discuss the types of prior art that would be highly relevant and likely to be cited in this domain. These general categories of prior art would inform an anticipation analysis under 35 U.S.C. § 102.

US Patent 10876108 focuses on methods for targeted nucleic acid sequence enrichment and high-efficiency library generation for next-generation sequencing (NGS). The claims involve steps such as fragmenting nucleic acids, appending adaptors, using sequence-specific oligonucleotides for primer extension, and subsequent amplification.

General Categories of Relevant Prior Art and Potential Anticipation:

1. Next-Generation Sequencing (NGS) Library Preparation Methods:

   • Description: Prior art in this category would include fundamental techniques for preparing nucleic acid libraries for high-throughput sequencing. This typically involves fragmenting DNA, performing end-repair (e.g., blunt-ending, A-tailing), and ligating universal adaptors to the ends of the fragments.
   • Potential Anticipation: Such prior art could potentially anticipate elements of Claim 1(a) and (b) (fragmenting nucleic acids, appending a first adaptor) and Claim 22(a) and (b) (fragmenting a sample, appending a first adapter). The novelty in US10876108 often lies in the subsequent targeted enrichment steps rather than the initial general library preparation.

2. PCR-Based Targeted Enrichment Methods:

   • Description: Prior art encompassing methods that use polymerase chain reaction (PCR) with sequence-specific primers to amplify and enrich for specific regions of interest within a complex nucleic acid sample. This could include multiplex PCR approaches.
   • Potential Anticipation: This category is highly relevant to Claim 1(c)-(e) (annealing sequence-specific oligonucleotides with a second adaptor, extending, and amplifying with adaptor-specific primers), Claim 22(c)-(f) (denaturing, annealing oligonucleotides, extending, and amplifying for library generation), and Claim 30(b)-(d) (annealing target-complementary oligonucleotides with a third adaptor, extending, and amplifying for enrichment). The distinctiveness of US10876108 would depend on the specific configuration of adaptors, oligonucleotides, and reaction steps (e.g., the exact timing of denaturation, specific adaptor designs).

3. Adaptor Ligation Chemistries and Designs:

   • Description: Prior art detailing various types of adaptors (e.g., blunt-end adaptors, Y-adaptors, partial duplex adaptors, adaptors with blocking groups or restriction sites) and the enzymatic ligation methods used to attach them to nucleic acid fragments.
   • Potential Anticipation: Prior art describing partial duplex adaptors with blocking groups and restriction sites would be particularly relevant to Claim 11(b) (first adaptor comprising a partial duplex with a short strand having a blocking group and a long strand with a restriction/cleavage site). The novelty might reside in the combination of these features and their specific application within the enrichment workflow.

4. Primer Extension and Amplification Techniques:

   • Description: General methods involving polymerases for extending primers along a nucleic acid template and subsequent amplification processes (e.g., standard PCR, quantitative PCR, isothermal amplification methods).
   • Potential Anticipation: Techniques for primer extension and various amplification methods would relate to Claim 1(d) and (e), Claim 11(d) and (h), Claim 22(e) and (f), and Claim 30(c) and (d). The specific context of adaptor-mediated amplification for targeted enrichment would be key to distinguishing US10876108.

5. Methods for Incorporating Barcodes/Molecular Tags:

   • Description: Prior art describing the use of short, unique nucleic acid sequences (barcodes or molecular identifiers) within adaptors or primers to uniquely tag nucleic acid molecules for multiplexed sequencing.
   • Potential Anticipation: Any prior art describing barcodes in adaptors would be relevant to the embodiments in Claim 1, 11, 22, and 30 that mention the adaptors comprising barcode sequences. The specific design and application of the barcodes within the claimed enrichment workflow would be critical for novelty.

Without the specific list of cited prior art patents, this analysis provides a conceptual framework for evaluating potential anticipation.

As a technical patent analyst, I must reiterate the limitation stated in the "Prior art" section: specific prior art documents (e.g., patent numbers, publications) that were actually cited against US Patent 10876108 were not retrieved. The previous section provided only "General Categories of Relevant Prior Art and Potential Anticipation."

Therefore, I cannot perform a definitive obviousness analysis under 35 U.S.C. § 103 by identifying concrete combinations of actual prior art references. A proper obviousness analysis requires specific documents to assess their disclosures and determine whether a person having ordinary skill in the art (PHOSITA) would have been motivated to combine them to arrive at the claimed invention, with a reasonable expectation of success.

However, I can provide a conceptual framework for how a PHOSITA might combine elements from the types of prior art relevant to US Patent 10876108, along with potential motivations, assuming such specific references exist and disclose the necessary elements. This discussion is theoretical, as it lacks the grounding in specific, identified prior art documents.

US Patent 10876108 claims methods for targeted nucleic acid sequence enrichment and high-efficiency library generation for next-generation sequencing (NGS). Key elements across its independent claims (Claims 1, 13, 25, 35) involve:

• Fragmenting nucleic acids.
• Appending adaptors (various types, including partial duplex with blocking groups and restriction sites).
• Using sequence-specific oligonucleotides (or random primers) for annealing and primer extension.
• Amplifying the resulting products with adaptor-specific primers to enrich target sequences or generate libraries.

A PHOSITA in the field of molecular biology and genomics (as of the patent's priority date of January 26, 2012) would be familiar with the individual components and general goals of NGS library preparation and targeted enrichment.

Conceptual Combinations and Motivations for Obviousness (Theoretical Discussion):

Given the general categories of prior art, a PHOSITA might be motivated to combine elements from:

1. NGS Library Preparation Methods (Fragmenting + Universal Adaptor Ligation) + PCR-Based Targeted Enrichment Methods (Sequence-Specific Priming + Amplification)

   • Prior Art Context:
     • Standard NGS library prep (e.g., from "NGS Library Preparation Methods" category) would disclose fragmenting DNA, repairing ends, and ligating universal adaptors (e.g., blunt-end, A-tailed) to generate a library ready for sequencing. This would encompass elements like fragmenting nucleic acids and appending a first adaptor.
     • PCR-based targeted enrichment (e.g., from "PCR-Based Targeted Enrichment Methods" category) would disclose using sequence-specific primers to amplify specific regions of interest. Existing methods might include multiplex PCR, but the patent notes challenges with non-specific amplification and primer-primer interactions in such approaches.
   • PHOSITA Motivation for Combination: A PHOSITA would be motivated to combine these to achieve targeted sequencing, which was a known need in the art for cost-effectiveness and efficiency. The motivation would be to selectively enrich desired genomic regions after an initial, universal adaptor ligation step, rather than relying solely on multiplex PCR with many target-specific primers from the outset.
   • Relevance to Claims: This combination conceptually addresses aspects of Claim 1 (fragmenting, appending first adaptor, annealing target-specific oligos with a second adaptor, extending, and amplifying with adaptor-specific primers) and Claim 25 (similar steps for library generation). The "second adaptor sequence" on the oligonucleotide (Claims 1(c), 25(d)) acts as a universal priming site for amplification, allowing a common reverse primer, which would be a clear motivation for a PHOSITA seeking to avoid complex multiplex PCR issues.

2. Adaptor Ligation Chemistries and Designs (Partial Duplex Adaptors with Blocking Groups/Restriction Sites) + Primer Extension and Amplification Techniques

   • Prior Art Context:
     • "Adaptor Ligation Chemistries and Designs" would include prior art describing partial duplex adaptors, adaptors with blocking groups (e.g., dideoxynucleotides) to prevent polymerase extension, and adaptors incorporating restriction enzyme sites.
     • "Primer Extension and Amplification Techniques" would cover the use of polymerases for extension and various amplification methods.
   • PHOSITA Motivation for Combination: A PHOSITA would be motivated to combine these features to enable directional ligation, prevent unintended extension, or introduce specific cleavage sites for subsequent manipulation of the nucleic acid fragments. For instance, using a blocking group on one strand of a partial duplex adaptor (as in Claim 13(b)) could ensure unidirectional ligation or prevent an adaptor from acting as a template for polymerase extension from the wrong end. Incorporating a restriction site (Claim 13(b)) provides a mechanism to introduce a new adaptor or modify the ends of the fragments at a later, controlled step. These are all known strategies for controlling molecular biology reactions.
   • Relevance to Claims: This conceptually addresses elements of Claim 13, specifically the design of the "first adaptor" as a partial duplex with a blocking group and a restriction/cleavage site, and the subsequent steps of annealing, extension to create a double-stranded restriction site, cleavage, and ligation of a "second adaptor." The motivation would be to create a more sophisticated, multi-step targeted enrichment process that offers greater control over fragment processing and adaptor integration, potentially enhancing specificity or reducing bias.

3. NGS Library Preparation Methods (Fragmenting + Adaptor Ligation to create a Library) + Methods for Incorporating Barcodes/Molecular Tags

   • Prior Art Context:
     • Standard library preparation methods involve appending adaptors to fragments.
     • Prior art for "Methods for Incorporating Barcodes/Molecular Tags" would disclose the use of barcodes within adaptors or primers for multiplexing samples in NGS.
   • PHOSITA Motivation for Combination: The motivation would be to enable the sequencing of multiple samples in a single run (multiplexing), a well-known advantage for reducing cost and increasing throughput in NGS. A PHOSITA would routinely consider incorporating barcodes into adaptors during library preparation.
   • Relevance to Claims: This combination is relevant to embodiments in Claims 1, 13, 25, and 35 where adaptors are described as optionally comprising barcode sequences.

Overall PHOSITA Motivation:

In all these conceptual combinations, the overarching motivation for a PHOSITA would be to address existing challenges in NGS library preparation and targeted enrichment, such as:

• Reducing cost and increasing throughput by avoiding whole-genome sequencing when only specific regions are of interest.
• Improving sensitivity, specificity, reproducibility, and uniformity of target capture.
• Overcoming limitations of existing methods like high non-specific amplification in multiplex PCR, low efficiency of hybrid capture, or poor capture uniformity of MIP-based methods.
• Enabling high-efficiency library generation from limited input.

These were all explicitly stated needs in the "Background of the Invention" section of US10876108, indicating that a PHOSITA would be well aware of these problems and motivated to seek solutions. The various combinations of known techniques (fragmentation, adaptor ligation, sequence-specific priming, polymerase extension, amplification, use of specialized adaptors or barcodes) to achieve these improvements would likely be considered by a PHOSITA.

Conclusion on Obviousness (Theoretical):

Without specific prior art references and their precise disclosures, a definitive obviousness determination cannot be made. However, based on the general categories of prior art and the stated problems in the "Background of the Invention" of US10876108, it is highly likely that a PHOSITA would have been motivated to combine known elements and techniques from NGS library preparation, targeted PCR enrichment, and adaptor design to arrive at methods similar to those claimed in US10876108. The specific novelty of US10876108 would hinge on whether the particular combination of steps, adaptor designs, and sequence of operations was truly novel and non-obvious in light of the specific teachings and suggestions present in the actually cited prior art. The litigation involving IPRs, especially those reaching Final Written Decisions, suggests that the obviousness (or anticipation) of some claims has likely been challenged and potentially determined by the PTAB, but the outcomes are not publicly available here.