Tecan Genomics Inc v. Invitae Corp

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Tecan Genomics, Inc. (Delaware)
  • Defendant: Invitae Corporation (Delaware), ArcherDX, LLC (Delaware), and Integrated DNA Technologies, Inc. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• Case Identification: 1:23-cv-01114, D. Del., 10/06/2023
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because all three defendants are incorporated or organized under the laws of Delaware and are therefore residents of the district.
• Core Dispute: Plaintiff alleges that Defendants’ Next Generation Sequencing (NGS) library preparation kits and related services, which utilize a technology called "Anchored Multiplex PCR," infringe five patents related to methods for enriching targeted nucleic acid sequences and identifying duplicate sequencing reads.
• Technical Context: The lawsuit concerns foundational technologies in the field of Next Generation Sequencing, a market-critical domain for genomic research, clinical diagnostics, and personalized medicine, particularly in oncology.
• Key Procedural History: The complaint alleges a long and complex history of Defendants' awareness of the patented technology, dating to at least 2014. This history involves a series of corporate acquisitions involving the Defendants and their predecessors. Plaintiff further alleges that Defendants cited Plaintiff's patent families during the prosecution of their own patents. Plaintiff sent notice letters regarding the alleged infringement to Defendants on September 29, 2023, shortly before filing the complaint.

Case Timeline

Date	Event
2012-01-26	Priority Date for ’012 and ’108 Patents
2013-11-13	Priority Date for ’399, ’357, and ’241 Patents
2017-01-17	U.S. Patent No. 9,546,399 Issues
2018-07-31	U.S. Patent No. 10,036,012 Issues
2020-01-01	Invitae acquires ArcherDX, Inc. (approximate date)
2020-12-29	U.S. Patent No. 10,876,108 Issues
2021-08-24	U.S. Patent No. 11,098,357 Issues
2022-12-01	IDT and Invitae enter into a limited asset purchase agreement (approximate date)
2023-08-15	U.S. Patent No. 11,725,241 Issues
2023-10-06	Complaint Filing Date

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 10,036,012 - Compositions and Methods for Targeted Nucleic Acid Sequence Enrichment and High Efficiency Library Generation (issued 07/31/2018)

The Invention Explained

• Problem Addressed: The patent's background section describes prior art methods for enriching specific nucleic acid sequences—such as PCR-based methods, hybrid capture, and molecular inversion probes—as being insufficient due to high cost, inefficiency, the need for specialized equipment, or low uniformity of results (Compl. ¶¶30-32; ’012 Patent, col. 1:48-2:24).
• The Patented Solution: The invention provides a method for targeted enrichment that begins by ligating a "partial duplex adaptor" to a nucleic acid fragment. A specific oligonucleotide is then introduced, which has a 3' portion designed to bind to the target sequence of interest and a 5' tail portion that is non-complementary and contains a second adaptor sequence. A polymerase extends this oligonucleotide, creating a new DNA strand that incorporates both the first and second adaptor sequences at its ends. This product can then be amplified and prepared for sequencing (Compl. ¶35; ’012 Patent, Abstract, col. 6:25-27). The complaint emphasizes that a novel aspect of this method is the use of a single adaptor for selective targeting and enrichment (Compl. ¶37).
• Technical Importance: The patented method is described as creating a "simple, low cost, high-throughput system for target enrichment and library preparation" that avoids the need for specialized instrumentation previously required (Compl. ¶34; ’012 Patent, col. 6:25-27).

Key Claims at a Glance

• The complaint asserts independent claim 1 (Compl. ¶97).
• The essential elements of Claim 1 include:
  • obtaining a nucleic acid fragment ligated to a partial duplex adaptor, where the adaptor's first strand is longer than its second strand;
  • annealing one or more oligonucleotides to the sequence of interest, where the oligonucleotides have a 3' complementary portion and a 5' non-complementary tail with a second adaptor sequence;
  • extending the annealed oligonucleotides with a polymerase to create extension products having the first adaptor sequence at one end and the second adaptor sequence at the other end;
  • amplifying the extension products using primers for the first and second adaptor sequences;
  • annealing a strand of the amplified products to a surface; and
  • sequencing the enriched nucleic acid on a massively parallel sequencing platform (Compl. ¶35).

U.S. Patent No. 10,876,108 - Compositions and Methods for Targeted Nucleic Acid Sequence Enrichment and High Efficiency Library Generation (issued 12/29/2020)

The Invention Explained

• Problem Addressed: The technical problems are identical to those described for the ’012 Patent, focusing on the cost, inefficiency, and complexity of prior art target enrichment methods (Compl. ¶¶30-33; ’108 Patent, col. 1:47-2:25).
• The Patented Solution: This patent claims a method that starts with a nucleic acid fragment that already "comprises a first adaptor sequence." An oligonucleotide with a target-complementary 3' portion and a 5' non-complementary tail (containing a second adaptor sequence) is annealed to the target sequence within this fragment. A polymerase then extends the oligonucleotide, creating a product with two different adaptor sequences, which is subsequently amplified and sequenced (Compl. ¶38; ’108 Patent, Abstract).
• Technical Importance: Like the ’012 Patent, this invention is presented as a novel method to fulfill the need for "improved methods for selective target enrichment that allow for low-cost, high-throughput capture of genomic regions of interest" (Compl. ¶33; ’108 Patent, col. 2:26-31).

Key Claims at a Glance

• The complaint asserts independent claim 1 (Compl. ¶117).
• The essential elements of Claim 1 include:
  • annealing one or more oligonucleotides in solution to a nucleic acid sequence of interest within a nucleic acid fragment, where the fragment already comprises a first adaptor sequence and the oligonucleotide has a 3' complementary portion and a 5' tail with a second adaptor sequence;
  • extending the annealed oligonucleotides with a polymerase to generate extension products with the first and second adaptor sequences at their ends;
  • amplifying the extension products using primers for both adaptor sequences to enrich the sequence of interest;
  • sequencing the amplified products on a massively parallel sequencing platform (Compl. ¶38).

U.S. Patent No. 9,546,399 - "Compositions and Methods for Identification of a Duplicate Sequencing Read" (issued 01/17/2017)

• Technology Synopsis: This patent addresses the technical challenge of distinguishing authentic, unique nucleic acid molecules from artificial copies (PCR duplicates) created during library amplification (Compl. ¶45). The patented solution involves ligating an adaptor to nucleic acid fragments, where the adaptor comprises an "identifier site" (a unique molecular identifier or barcode) of 1-8 nucleotides. After amplification and sequencing, reads that share both the same identifier site and the same nucleic acid sequence are identified as true duplicates (Compl. ¶¶49-50).
• Asserted Claims: Independent claim 1 (Compl. ¶141).
• Accused Features: The complaint alleges that Defendants' AMP technology and associated products utilize adaptors containing "Molecular Barcodes" to serve as unique identifiers, and that Defendants' analysis software uses these barcodes for read deduplication (Compl. ¶¶145, 157). A diagram in the complaint illustrates the alleged structure of the accused adaptor, showing a "Molecular Barcode (MBC)" region (Compl. p. 69).

U.S. Patent No. 11,098,357 - "Compositions and Methods for Identification of a Duplicate Sequencing Read" (issued 08/24/2021)

• Technology Synopsis: This patent is directed to similar technology as the ’399 Patent. It claims a method for detecting duplicate sequencing reads by ligating an adaptor to nucleic acid fragments. The adaptor comprises a "unique identifier" of 1 to 8 nucleotides, an indexing site, and a primer binding site. Sequence reads with identical identifiers and target sequences are then identified as duplicates (Compl. ¶53).
• Asserted Claims: Independent claim 1 (Compl. ¶164).
• Accused Features: The complaint accuses Defendants' products of using adaptors that contain a unique identifier (Molecular Barcode), an indexing site, and a primer binding site to detect and identify duplicate reads after sequencing (Compl. ¶¶168, 171, 178).

U.S. Patent No. 11,725,241 - "Compositions and Methods for Identification of a Duplicate Sequencing Read" (issued 08/15/2023)

• Technology Synopsis: This patent also addresses the detection of duplicate reads. The claimed method involves obtaining amplicons that each comprise an amplified fragment with an appended adaptor. Each adaptor contains an "identifier site" with a plurality of nucleotides that are unique to the amplified fragment. After sequencing, reads with identical identifier and target sequences are identified as duplicates (Compl. ¶56).
• Asserted Claims: Independent claim 1 (Compl. ¶185).
• Accused Features: The complaint alleges that Defendants' process obtains amplicons by appending adaptors that include a unique identifier site (Molecular Barcode) and that these are subsequently sequenced and identified as duplicates based on the identifier and target sequence (Compl. ¶¶189, 192, 198).

III. The Accused Instrumentality

• Product Identification: The accused instrumentalities include NGS library preparation kits and services marketed as ArcherDX VariantPlex AMP Panels, ArcherDX FusionPlex AMP Panels, and ArcherDX LiquidPlex AMP Panels, as well as the Invitae Personalized Cancer Monitoring™ – Baseline Test and Monitoring Test (Compl. ¶¶60-61).
• Functionality and Market Context: The Accused Products are kits and services used to prepare libraries of targeted nucleic acid sequences for NGS (Compl. ¶99). They operate using a method Defendants refer to as "Anchored Multiplex PCR" (AMP) technology (Compl. ¶60). According to the complaint, this process involves ligating partial duplex adaptors to DNA or RNA fragments, followed by annealing gene-specific primers that also contain a non-complementary tail. A polymerase extends these primers to create a product that can be amplified and sequenced (Compl. ¶¶100, 102, 105). The complaint also alleges the technology uses "Molecular Barcodes" within the adaptors to distinguish between unique fragments and PCR duplicates during data analysis (Compl. ¶¶145, 157). The complaint positions these products as direct competitors to Plaintiff's own offerings (Compl. ¶7).

IV. Analysis of Infringement Allegations

’012 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
a) obtaining a nucleic acid fragment ligated to a partial duplex adaptor...wherein the first strand is longer than the second strand	The accused protocol requires ligating a "first adaptor" to the nucleic acid fragment of interest. The complaint provides a diagram showing this ligation step and states the adaptors are partial duplex adaptors where one strand is longer than the other.	¶100-101	col. 11:25-30
b) annealing one or more oligonucleotides in solution to the nucleic acid sequence of interest...wherein the one or more oligonucleotides comprise a 3' portion with at least 10 bases designed to be complementary...and a 5' tail portion comprising a second adaptor sequence that is non-complementary	The accused protocol anneals oligonucleotides (referred to as "GSP2") to the target sequence. These oligonucleotides are alleged to have a 3' portion complementary to the target and a 5' tail that is non-complementary and comprises a second adaptor sequence.	¶102-104	col. 11:31-39
c) extending the one or more oligonucleotides annealed...with a polymerase, thereby generating one or more oligonucleotide extension products comprising sequence complementary to the first adaptor sequence at a first end...and the second adaptor sequence at a second end	A polymerase in the reaction mixture extends the annealed oligonucleotide. A diagram is provided showing this extension, which results in a product containing sequence from the first adaptor at one end and the second adaptor at the other end.	¶105-106	col. 11:40-47
d) amplifying the one or more oligonucleotide extension products using a first primer that anneals to a complement of the first adaptor sequence and a second primer that anneals at its 3' end to a complement of the second adaptor sequence to enrich for the nucleic acid sequence of interest	The Accused Products are amplified using a first primer complementary to the first adaptor sequence and a second primer that anneals to the complement of the second adaptor sequence. This enriches the population of target fragments.	¶107	col. 11:48-55
e) annealing a strand of the products of the amplifying to the sequence on the surface using the 3' end with sequence complementary to the sequence on the surface	The amplified products are loaded onto a sequencing platform (e.g., MiSeq), where they anneal to a flow cell surface covered with complementary nucleotide fragments. A diagram from Illumina's materials is provided to illustrate this cluster generation step.	¶108-109	col. 11:56-59
f) sequencing the enriched nucleic acid sequence of interest on a massively parallel sequencing platform.	The Accused Products' protocols direct the user to sequence the prepared samples on a massively parallel sequencing platform, such as an Illumina MiSeq or Ion Torrent system.	¶110	col. 11:60-62

’108 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
a) annealing one or more oligonucleotides in solution in a reaction mixture to the nucleic acid sequence of interest in a nucleic acid fragment, wherein the...fragment...comprises a first adaptor sequence, wherein the one or more oligonucleotides comprise a 3' portion with at least 10 bases...complementary...and a 5' tail portion comprising a second adaptor sequence that is non-complementary	The accused method involves ligating a first adaptor to a target nucleic acid fragment. Subsequently, oligonucleotides (alleged to be "GSP2") are annealed to the sequence of interest within this adapted fragment. These oligonucleotides allegedly contain a complementary 3' portion and a non-complementary 5' tail with a second adaptor sequence.	¶120-124	col. 12:44-53
b) extending the one or more oligonucleotides annealed...with a polymerase...thereby generating one or more oligonucleotide extension products comprising sequence complementary to the first adaptor sequence at a first end...and the second adaptor sequence at a second end	The accused process uses a polymerase to extend the annealed oligonucleotides, creating a product that incorporates sequences from both the first and second adaptors at its respective ends. A diagram illustrates this extension.	¶126-129	col. 12:54-61
c) amplifying the one or more oligonucleotide extension products...using a first primer that anneals to the complement of the first adaptor sequence and a second primer that anneals at its 3' end to a complement of the second adaptor sequence, thereby enriching the nucleic acid sequence of interest	The extension products are amplified using primers corresponding to the first and second adaptor sequences, resulting in an enriched population of the target fragments.	¶130-132	col. 12:62-67
d) sequencing the amplified products comprising the enriched nucleic acid sequence of interest on a massively parallel sequencing platform.	The accused protocols direct users to sequence the amplified and enriched products on a massively parallel sequencing platform.	¶133-134	col. 13:1-3

Identified Points of Contention

• Scope Questions: A central question for the ’108 Patent may be the interpretation of "a nucleic acid fragment...comprises a first adaptor sequence" in the context of the annealing step. The complaint alleges this is met by a preceding ligation step (Compl. ¶121), but a potential dispute may arise over whether the claim requires the fragment to be sourced from a pre-existing library of adapted fragments or if it can be created contemporaneously in the same reaction mixture.
• Technical Questions: For both patents, the infringement analysis will turn on whether the accused "Anchored Multiplex PCR" technology performs a sequence of steps that is technically equivalent to the claimed methods. This raises the question of whether there are any operational differences between the accused process and the claimed steps related to the specific structures of the adaptors, the nature of the polymerase extension, or the amplification process that would create a basis for a non-infringement argument.

V. Key Claim Terms for Construction

For the ’012 Patent

• The Term: "partial duplex adaptor"
• Context and Importance: This term defines the initial molecular tool used in Claim 1. The claim requires this adaptor to have a "first strand" that is "longer than the second strand." The infringement analysis depends on whether the adaptors used in the Accused Products meet this structural definition. Practitioners may focus on this term because the precise configuration of the strands (e.g., Y-shape, specific overhangs, presence of blocking groups) could be a critical point of dispute.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The claim language itself is relatively broad, requiring only that one strand be longer than the other, which could encompass various adaptor designs. The specification mentions that the adaptor comprises "a partial duplex with a short strand and a long strand" (’012 Patent, col. 17:20-22), supporting a general structural definition.
  • Evidence for a Narrower Interpretation: The specification's Figure 2 depicts a specific "P1/P1rc" structure. A defendant may argue that this figure, along with its description, defines the scope of a "partial duplex adaptor" more narrowly than the plain words of the claim suggest.

For the ’108 Patent

• The Term: "a nucleic acid fragment...comprising a first adaptor sequence"
• Context and Importance: This phrase appears in the preamble of the "annealing" step of Claim 1, establishing a condition that must exist when the key oligonucleotide binds. The complaint alleges this is met by ligating an adaptor to the fragment (Compl. ¶121). The term's construction is critical because it could impose a temporal or structural requirement on the accused process. Practitioners may focus on this term to argue about the timing and separateness of the ligation and annealing steps.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The plain meaning of "comprising" suggests the first adaptor sequence must simply be part of the fragment's structure at the time of annealing, without specifying when or how it was added. The patent's summary describes "appending a first adaptor" as a step preceding annealing, which may support the plaintiff's view that these can be sequential steps in one overall method (’108 Patent, col. 1:40-42).
  • Evidence for a Narrower Interpretation: A defendant might argue that the claim language requires starting with a population of pre-adapted fragments (e.g., from an existing library) rather than creating them in the same continuous process. The context of the entire claim could be argued to imply that the "reaction mixture" of step (a) is one in which the fragments are already adapted, not one in which they become adapted.

VI. Other Allegations

• Indirect Infringement: The complaint alleges both induced and contributory infringement for all asserted patents. Inducement allegations are based on Defendants providing the Accused Products with instructions, product manuals, technical materials, and marketing that allegedly direct and encourage end-users to perform the patented methods (Compl. ¶¶113, 137). Contributory infringement is alleged on the basis that the Accused Products are a material part of the patented inventions, are not staple articles of commerce suitable for substantial noninfringing uses, and are known by Defendants to be especially made for infringing use (Compl. ¶¶114, 138).
• Willful Infringement: The complaint alleges willful infringement based on both pre- and post-suit knowledge. Pre-suit knowledge is alleged to stem from at least 2014, based on Defendants' and their predecessors' attendance at industry conferences where the technology was presented, alleged plans to sue Plaintiff's predecessor, competitive monitoring of Plaintiff's patent portfolio, and Defendants' own patent applications citing the asserted patent families (Compl. ¶¶7, 75-92). Post-suit knowledge is based on notice letters sent in September and October 2023, after which infringement allegedly continued (Compl. ¶93).

VII. Analyst’s Conclusion: Key Questions for the Case

• A core issue will be one of process mapping and claim construction: Can Plaintiff demonstrate that the specific biochemical steps of Defendants' "Anchored Multiplex PCR" technology meet, element-by-element, the limitations of the asserted method claims? This will likely involve disputes over the construction of key terms like "partial duplex adaptor" ('012 Patent) and the precise sequence of events required by the claims ('108 Patent).
• A key evidentiary question will be one of knowledge and intent: The complaint provides a detailed narrative alleging Defendants' long-standing awareness of the patented technologies. A central question for willfulness will be what evidence supports these allegations and whether it rises to the level of showing Defendants knew of or were willfully blind to an objectively high likelihood of infringement.
• A final dispositive issue may be one of technical differentiation in duplicate identification: For the '399, '357, and '241 patents, the case will likely turn on whether the "Molecular Barcodes" used in the Accused Products function in a manner that is technically and legally congruent with the claimed "identifier site," and whether the accused deduplication software performs the claimed "identifying" step as construed by the court.