DCT
1:17-cv-01623
Guardant Health Inc v. Personal Genome Diagnostics Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Guardant Health, Inc. (Delaware)
- Defendant: Personal Genome Diagnostics, Inc. (Delaware)
- Plaintiff’s Counsel: Farnan LLP (with Weil, Gotshal & Manges LLP as Of Counsel)
- Case Identification: 1:17-cv-01623, D. Del., 11/09/2017
- Venue Allegations: Venue is alleged to be proper as Defendant is a Delaware corporation that transacts business and sells the accused product within the district.
- Core Dispute: Plaintiff alleges that Defendant’s liquid biopsy test infringes a patent related to methods for detecting rare genetic mutations and variations in cell-free DNA.
- Technical Context: The lawsuit concerns liquid biopsy technology, which analyzes a patient's cell-free DNA from a blood sample to detect cancer-related genetic markers, offering a non-invasive alternative to tissue biopsies.
- Key Procedural History: The complaint does not mention any prior litigation, licensing history, or post-grant proceedings involving the patent-in-suit.
Case Timeline
| Date | Event |
|---|---|
| 2012-09-04 | ’731 Patent - Earliest Priority Date |
| Late 2016 | Accused Product (PlasmaSelect 64) Commercialization Begins |
| 2017-03-21 | ’731 Patent - Issue Date |
| 2017-11-09 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,598,731 - Systems and Methods to Detect Rare Mutations and Copy Number Variation, issued March 21, 2017
The Invention Explained
- Problem Addressed: The patent’s background section identifies the technical challenge of accurately detecting rare genetic alterations, such as those indicative of cancer, from the small amounts of cell-free DNA (cfDNA) present in bodily fluids like blood (ʼ731 Patent, col. 1:13-44). A key difficulty is distinguishing true, low-frequency mutations from the background "noise" generated by amplification and sequencing errors (ʼ731 Patent, col. 31:47-54).
- The Patented Solution: The invention describes a method to enhance detection sensitivity by attaching molecular barcodes to the original cfDNA fragments before amplification. This tagging strategy allows the resulting sequence reads to be computationally grouped into "families," where each family originates from a single parent molecule. By comparing the multiple reads within a family, a "consensus sequence" can be determined, which effectively filters out random errors introduced during the process and provides a more accurate representation of the original DNA molecule (ʼ731 Patent, col. 5:37-55; Fig. 9).
- Technical Importance: This error-correction approach using molecular families was a critical step in improving the reliability of liquid biopsy assays, making it more feasible to detect cancer-associated mutations that are present at very low frequencies in a patient's bloodstream (ʼ731 Patent, col. 1:35-44).
Key Claims at a Glance
- The complaint asserts infringement of independent claim 1 and dependent claims 2, 5, 6-9, 11-12, 14, and 16-17 (Compl. ¶22).
- Independent Claim 1 recites a multi-step method, the essential elements of which include:
- Providing at least 10 ng of cell-free DNA.
- Attaching tags with barcodes (from 5 to 1000 distinct sequences) to generate "non-uniquely tagged parent polynucleotides."
- Amplifying the tagged polynucleotides.
- Sequencing the amplified products to produce reads containing both a barcode and a DNA sequence.
- Grouping the sequence reads into "families" based on both the barcode and at least one other feature (sequence start, end, or length).
- Comparing reads within each family to determine a "consensus sequence."
- Providing a reference human genome containing known tumor marker loci.
- Identifying consensus sequences that map to a reported tumor marker locus.
- Calculating the number of consensus sequences containing a specific single nucleotide variant to quantify that variant in the original sample.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Defendant’s "PlasmaSELECT 64" liquid biopsy test, which is alleged to utilize a method referred to as "TEC-Seq" (Compl. ¶¶14, 16).
Functionality and Market Context
- The complaint alleges that PlasmaSELECT 64 is a liquid biopsy test that "identifies clinically actionable and functionally important sequence mutations and structural alterations across multiple cancer types without the need for invasive biopsies" (Compl. ¶14). The underlying TEC-Seq method is alleged to involve extracting cfDNA from blood, converting it into a genomic library using "a pool containing a small number of dual-index barcode adapters," and then performing redundant sequencing and "sequence reconciliation" to identify "bona fide alterations" (Compl. p. 4, Fig. 1 caption).
IV. Analysis of Infringement Allegations
’971 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| (a) providing at least 10 ng of cell-free DNA obtained from a bodily sample of the subject; | The PlasmaSelect 64 test obtains "more than 10 ng of cell free DNA" from a patient's blood draw. | ¶18 | col. 5:18-20 |
| (b) attaching tags comprising barcodes ... to generate non-uniquely tagged parent polynucleotides... | "Tags comprising barcodes are then attached to both ends of the DNA fragments that are present in the sample of cell free DNA." | ¶18 | col. 5:21-27 |
| (c) amplifying the non-uniquely tagged parent polynucleotides... | The tagged DNA sample is subjected to "PCR amplification." | ¶18 | col. 5:28-30 |
| (d) sequencing the amplified non-uniquely tagged progeny polynucleotides to produce a plurality of sequence reads from each parent polynucleotide... | The amplified DNA is sequenced, "resulting in sequence reads that consist of a barcode sequence and a sequence present in the cell free DNA." | ¶18 | col. 5:31-36 |
| (e) grouping the plurality of sequence reads ... into families based on i) the barcode sequence and ii) at least one of: sequence information at a beginning..., at an end..., and length... | Sequence reads are "grouped into families based on the barcode and additional sequence information, allowing one to collect sequence information that arises from the same DNA molecule." | ¶18 | col. 5:37-48 |
| (f) comparing the sequence reads grouped within each family to each other to determine consensus sequences for each family... | "The sequence reads in each family are then compared to one another to arrive at a ‘consensus sequence’ that represents a more accurate determination of the sequence of the molecule in question." | ¶18 | col. 5:49-55 |
| (h) identifying consensus sequences that map to a given locus of said one or more loci of reported tumor markers; and | "Next, the consensus sequences are mapped to a reference genome to identify sequence that map to regions of the genome associated with cancer tumor markers..." | ¶18 | col. 5:61-64 |
| (i) calculating a number of consensus sequences that map to the given locus that include the single nucleotide variant thereby quantifying... | "...Finally, the number of tumor markers present in the original sample are quantified..." | ¶18 | col. 5:65-68 |
Identified Points of Contention
- Scope Questions: Claim 1 requires the generation of "non-uniquely tagged parent polynucleotides." The complaint includes a figure describing the accused TEC-Seq method as using a "small number of dual-index barcode adapters" (Compl. p. 4). A central question may be whether this process results in "non-uniquely tagged" polynucleotides as that term is understood in the patent, or if the combination of barcodes with other data (such as start/end positions) effectively creates a unique identifier for each fragment, potentially placing it outside the claim's literal scope.
- Technical Questions: Claim 1(e) requires a specific two-part test for "grouping" reads into families: it must be based on (i) the barcode and (ii) at least one of start/end sequence information or length. The complaint alleges grouping is based on "the barcode and additional sequence information" and presents a schematic that describes identifying molecules with the "same start and end position and exogenous barcodes" (Compl. ¶18; p. 4, Fig. 1 caption). A key factual dispute will likely be whether the accused "sequence reconciliation" process performs the specific grouping logic recited in the claim, or if it operates in a technically distinct manner.
V. Key Claim Terms for Construction
"non-uniquely tagged parent polynucleotides"
- Context and Importance: This term from claim 1(b) is central to defining the claimed method. The patent specification discusses both unique and non-unique tagging approaches. Therefore, the construction of this term will be critical in determining whether the accused TEC-Seq method, which uses a "small number" of barcode adapters, falls within the scope of the claim.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification suggests that tagging is non-unique when the number of available barcodes is smaller than the number of DNA molecules, necessarily leading to barcode reuse across different molecules ('731 Patent, col. 3:15-17). Plaintiff may argue that any system designed with fewer barcodes than molecules meets this definition.
- Evidence for a Narrower Interpretation: The patent also discloses that a non-unique barcode, when combined with other information like start and stop positions, can create a unique identifier for a specific DNA fragment ('731 Patent, col. 37:43-52). Defendant may argue that their method, by design, uses this combination to uniquely identify fragments and therefore does not generate "non-uniquely tagged" molecules in the sense required by the claim.
"grouping the plurality of sequence reads ... into families"
- Context and Importance: This functional step in claim 1(e) is a core part of the invention's error-correction mechanism. The infringement analysis depends entirely on whether Defendant's "sequence reconciliation" process (Compl. p. 4) performs this specific grouping function.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim requires grouping based on the barcode and "at least one of" several other features (start/end info, length). Plaintiff may argue that any grouping algorithm that uses the barcode plus any of these other listed data points falls within the claim scope.
- Evidence for a Narrower Interpretation: Defendant may argue that its "sequence reconciliation" algorithm is a holistic process that does not perform the discrete two-part "grouping" step as claimed. Practitioners may focus on whether the evidence shows Defendant's system first groups by barcode and then subdivides by another feature, as the claim structure suggests, or if it uses a different, integrated logic.
VI. Other Allegations
- Indirect Infringement: The complaint alleges only direct infringement under 35 U.S.C. § 271(a), based on Defendant’s own performance of the accused PlasmaSelect 64 test (Compl. ¶22). No facts are alleged that would support a claim for induced or contributory infringement.
- Willful Infringement: The complaint does not contain an explicit allegation of willful infringement or plead any facts suggesting Defendant had pre-suit knowledge of the ’731 patent. The prayer for relief requests a determination that the case is "exceptional" for the purpose of attorneys' fees under 35 U.S.C. § 285 (Compl. p. 8).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of technical equivalence: does the accused "sequence reconciliation" process in the TEC-Seq method perform the specific, two-part logical "grouping" function required by claim 1—using a barcode plus at least one other enumerated feature—or is there a fundamental mismatch in the operational logic used to identify and correct for sequencing errors?
- The case will also likely turn on a question of definitional scope: can the term "non-uniquely tagged," which the patent contrasts with methods that uniquely tag every molecule, be construed to read on an accused method that uses a limited set of barcodes but allegedly combines them with start/end position data to achieve unique fragment identification?