DCT
1:25-cv-01013
Guardant Health Inc v. Tempus Ai Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Guardant Health, Inc. (Delaware)
- Defendant: Tempus AI, Inc. (Delaware)
- Plaintiff’s Counsel: Potter Anderson & Corroon LLP
- Case Identification: 1:25-cv-01013, D. Del., 08/12/2025
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is a Delaware corporation.
- Core Dispute: Plaintiff alleges that Defendant’s liquid biopsy cancer diagnostic tests infringe three patents related to methods for preparing and analyzing cell-free DNA to detect residual disease and genetic variants.
- Technical Context: The lawsuit concerns liquid biopsy technology, a method of detecting cancer markers in bodily fluids like blood, which serves as a non-invasive alternative to traditional surgical tissue biopsies.
- Key Procedural History: This action follows a prior patent infringement suit filed by Guardant against Tempus on June 11, 2024, which remains pending. The patents-in-suit in the current case were all issued after the filing of the first suit. The complaint alleges that Tempus was aware of Guardant's patent portfolio prior to this suit, citing Tempus’s S-1 filings and the earlier litigation. The complaint also references the prosecution history of the '961 Patent, noting that the USPTO found certain claimed innovations to be novel and non-obvious over the prior art.
Case Timeline
| Date | Event |
|---|---|
| 2013-12-28 | U.S. Patent No. 12,319,961 Priority Date |
| 2015-01-01 | Tempus was founded |
| 2016-04-14 | U.S. Patent No. 12,116,640 Priority Date |
| 2016-12-22 | U.S. Patent No. 12,312,634 Priority Date |
| 2018-09-14 | Tempus xF liquid biopsy test announced |
| 2023-11-03 | Tempus xM Monitor launched |
| 2024-01-18 | Tempus xM MRD launched for research use |
| 2024-05-31 | Clinical launch of Tempus MRD portfolio including xM MRD |
| 2024-06-11 | First Infringement Suit filed by Guardant against Tempus |
| 2024-10-15 | U.S. Patent No. 12,116,640 Issued |
| 2025-05-27 | U.S. Patent No. 12,312,634 Issued |
| 2025-06-02 | Tempus xM TRM assay launched |
| 2025-06-03 | U.S. Patent No. 12,319,961 Issued |
| 2025-08-12 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 12,116,640 - “Methods for Early Detection of Cancer” (Issued Oct. 15, 2024)
The Invention Explained
- Problem Addressed: The patent addresses the difficulty of detecting minimal residual disease (MRD) after cancer treatment using non-invasive liquid biopsies, as cancer-indicative genetic variants may be present at "exceedingly low frequencies" (e.g., 0.001%) in cell-free DNA (cfDNA) (Compl. ¶46; ’640 Patent, col. 15:2-5). Prior methods allegedly required invasive screening procedures like colonoscopies (Compl. ¶47).
- The Patented Solution: The invention is a method for detecting residual disease by analyzing a cfDNA sample obtained from a subject after cancer treatment. The method involves using "sequence capture" to enrich for a specific "sequencing panel" of genomic regions. This panel is defined by its large size (at least 150kb) and its composition, which includes both regions known to have genetic variants in cancer and regions that are "differentially methylated" (’640 Patent, col. 14:51-15:15; Compl. ¶49). By sequencing this enriched panel, the method allows for the simultaneous detection of both methylation patterns and genetic variants to identify residual disease with high sensitivity (’640 Patent, Abstract).
- Technical Importance: The technology aims to improve on prior art by combining the analysis of both genetic and epigenetic (methylation) markers within a single, high-sensitivity framework for detecting low-frequency variants associated with residual disease (Compl. ¶52).
Key Claims at a Glance
- The complaint asserts at least independent Claim 1 (Compl. ¶49, ¶65).
- The essential elements of Claim 1 include:
- Enriching cfDNA molecules from a post-treatment sample using sequence capture for a sequencing panel of genes or genomic regions.
- The sequencing panel must be at least 150kb, comprise regions with differentially methylated CpG islands, and comprise regions known to be associated with cancer.
- Sequencing the enriched cfDNA to generate sequencing data.
- Determining methylation profiles and detecting one or more genetic variants from the sequencing data to determine the presence or absence of residual disease.
- The complaint reserves the right to assert dependent claims 2-30 (Compl. ¶50).
U.S. Patent No. 12,312,634 - “Methods and Systems for Analyzing Nucleic Acid Molecules” (Issued May 27, 2025)
The Invention Explained
- Problem Addressed: The patent’s background describes a key deficiency in prior art methods: analyzing small cfDNA samples for both methylation and genetic aberrations was "disadvantageous" because it required splitting the sample into two smaller portions, which reduced the amount of DNA available for each type of analysis (’634 Patent, col. 33:55-59; Compl. ¶72).
- The Patented Solution: The invention provides a method to address this efficiency problem. A cfDNA sample is split into a first and a second aliquot. The first aliquot is assayed to obtain sequence data for genetic variants (e.g., SNVs, indels) "irrespective of methylation state." The second aliquot is separately assayed to obtain sequence data comprising information on the methylation state. The data from both analyses are then combined to monitor for residual disease or recurrence (’634 Patent, Abstract; Compl. ¶74).
- Technical Importance: This innovation provides a structured, efficient laboratory technique for obtaining both genetic and epigenetic information from a single, limited cfDNA sample, a process that was previously inefficient (Compl. ¶72, ¶77).
Key Claims at a Glance
- The complaint asserts at least independent Claim 1 (Compl. ¶74, ¶83).
- The essential elements of Claim 1 include:
- Providing a sample comprising at least 10 ng of cfDNA.
- Splitting the sample into first and second aliquots.
- Assaying the first aliquot to obtain sequence data "irrespective of methylation state" for SNVs, indels, and/or gene fusions.
- Assaying the second aliquot to obtain sequence data "comprising information on the methylation state" of the cfDNA.
- Analyzing the sequence data from both aliquots to monitor for residual disease.
- The complaint reserves the right to assert dependent claims 2-20 (Compl. ¶75).
U.S. Patent No. 12,319,961 - “Methods and Systems for Detecting Genetic Variants” (Issued June 3, 2025)
Technology Synopsis
The patent addresses the problem that sample preparation and sequencing processes can introduce errors that "dramatically and adversely affect the sensitivity" of cfDNA analysis, particularly in estimating the true number of DNA molecules in a sample (Compl. ¶89). The patented solution is a method for monitoring a patient's disease status by attaching a surplus of adapters to double-stranded DNA molecules with high efficiency and then sequencing the tagged molecules. The method specifically involves determining amounts of "paired reads" (where both complementary strands are sequenced) and "unpaired reads" (where only one strand is sequenced) to monitor for differences over time (Compl. ¶91, ¶93).
Asserted Claims
At least independent Claim 1 (Compl. ¶93, ¶108).
Accused Features
The complaint alleges that all of the "Accused xM Tests" (which include the Tempus xM Monitor, MRD, and TRM tests) practice the steps of the asserted claims (Compl. ¶106, ¶108).
III. The Accused Instrumentality
Product Identification
- The accused products are the "Accused xM Tests," which include the Tempus xM Monitor, Tempus xM MRD, and Tempus xM TRM tests (Compl. ¶15). These tests are alleged to incorporate Tempus's xF and xF+ liquid biopsy assays (Compl. ¶15).
Functionality and Market Context
- The complaint alleges the Accused xM MRD Test functions by splitting a patient sample into two portions (Compl. ¶42). One portion is analyzed for genetic variants associated with cancer using the Tempus xF or xF+ tests, while the second portion is analyzed for methylation (Compl. ¶42). A sample is designated as positive for minimal residual disease only when the methylation analysis indicates disease and at least one genetic variant is also found (Compl. ¶42).
- The Accused xM Tests generally are alleged to involve obtaining cfDNA from subjects, ligating adapters that include unique molecular identifiers (UMIs) to the cfDNA fragments, and then amplifying and sequencing the ligated DNA to determine single nucleotide variants (SNVs) and copy number variants (CNVs) (Compl. ¶40, ¶41).
- Plaintiff alleges that Tempus competes directly with Guardant in the markets for monitoring cancer patients after treatment and detecting residual disease (Compl. ¶2), and that Tempus has achieved market success with the accused tests (Compl. ¶19).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’640 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| (a) enriching cell-free deoxyribonucleic acid (cfDNA) molecules or amplicons thereof from a sample of the subject using sequence capture for a sequencing panel of genes or genomic regions... | Tempus's xM MRD Test analyzes a patient sample for genetic variants and methylation to detect minimal residual disease. | ¶42, ¶63 | col. 14:1-12 |
| wherein the sequencing panel: (i) is at least 150kb, | The complaint does not provide sufficient detail for analysis of this element. | col. 15:1 | |
| (ii) comprises a plurality of genes or genomic regions having CpG islands which are differentially methylated regions, | Tempus analyzes a second portion of a patient sample specifically for methylation. | ¶42 | col. 15:2-4 |
| (iii) comprises a plurality of genes or genomic regions known to be associated with one or more cancers... | Tempus analyzes a first portion of a patient sample for genetic variants associated with cancer. | ¶42 | col. 15:5-7 |
| (b) sequencing a plurality of enriched cfDNA from the sequencing panel to generate sequencing data; and | After preparing the cfDNA, Tempus sequences it to generate sequence reads for analysis. | ¶41 | col. 15:16-18 |
| (c) determining methylation profiles... and detecting a presence or absence of one or more genetic variants... to detect the presence or absence of residual disease... | Tempus designates a sample as positive for minimal residual disease when the methylation analysis indicates disease and at least one genetic variant is found. | ¶42 | col. 15:19-24 |
- Identified Points of Contention:
- Scope Questions: A primary question for claim construction may be the definition of "sequencing panel." Claim 1 recites enriching for a sequencing panel that comprises both methylation and genetic regions. The complaint alleges Tempus infringes by splitting a sample and performing two separate analyses. This raises the question of whether a two-aliquot, two-analysis process can be said to use a single "sequencing panel" as recited in the claim.
- Technical Questions: The complaint does not provide evidence that the panel of genes and genomic regions targeted by Tempus is "at least 150kb" in size, a specific quantitative limitation of Claim 1.
’634 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| (a) providing a sample comprising at least 10 ng of cell-free DNA (cfDNA); | The complaint does not provide sufficient detail for analysis of this element. | col. 19:15-17 | |
| (b) splitting the sample into first and second aliquots; | The Accused Tempus xM MRD Test "splits the sample into two portions." | ¶42 | col. 19:18 |
| (c) assaying cfDNA of the first aliquot to obtain sequence data... irrespective of methylation state... for SNVs, indels and/or gene fusions and assaying cfDNA of the second aliquot to obtain sequence data comprising information on the methylation state... | Tempus analyzes the first portion for genetic variants and the second portion for methylation. | ¶42 | col. 20:1-12 |
| (d) analyzing the sequence data from the first and second aliquots to monitor residual disease or recurrence of disease. | Tempus combines the results, designating a sample as positive for residual disease when the methylation portion indicates disease and at least one genetic variant is also determined. | ¶42 | col. 20:13-16 |
- Identified Points of Contention:
- Technical Questions: The infringement theory appears to map closely to the claim language. The primary points of contention may be evidentiary, focusing on whether Tempus's process meets the quantitative limitation of starting with "at least 10 ng of cell-free DNA" and whether it consistently performs the separate analyses on two aliquots as alleged.
V. Key Claim Terms for Construction
’640 Patent
- The Term: "sequencing panel"
- Context and Importance: The viability of the infringement allegation for the ’640 Patent may depend on this term's construction. Practitioners may focus on this term because the claim recites enriching for a single "sequencing panel" that has multiple properties (size, methylation regions, genetic regions), while the accused process allegedly involves two separate analyses on two sample portions.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification states that "sequencing panels may be constructed to 'allow for interrogating methylation status and genetic variants'" (’640 Patent, col. 14:51-15:15). This functional language could support an interpretation where the "panel" refers to the total set of targeted regions, regardless of whether they are enriched and analyzed in one or two steps.
- Evidence for a Narrower Interpretation: The claim’s structure, which lists the properties of the "sequencing panel" in sub-parts (i), (ii), and (iii), suggests a single, integrated entity. The detailed description explains that panels can be designed to provide "improved detection of, for instance, colorectal cancer" (’640 Patent, col. 25:9-26:55), which could imply a unitary design for a specific purpose rather than a collection of separate analyses.
’634 Patent
- The Term: "assaying cfDNA of the first aliquot... irrespective of methylation state"
- Context and Importance: This term is critical for distinguishing the analysis of the first aliquot (for genetic variants) from the second (for methylation). Practitioners may focus on this term because the defendant could argue that any standard sequencing method is inherently affected by methylation status (e.g., due to PCR bias against heavily methylated regions), and thus is not truly "irrespective" of it.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent explains that prior to the invention, samples were not analyzed for both types of markers because it "required splitting the sample into two aliquots which... was disadvantageous" (’634 Patent, col. 33:55-59). The term "irrespective of methylation state" is likely used to mean a standard genomic sequencing process that does not include steps, such as bisulfite conversion, intentionally designed to reveal methylation status.
- Evidence for a Narrower Interpretation: The plain meaning suggests a process completely uninfluenced by methylation. If the patent specification contains any language acknowledging that standard library preparation or sequencing can be biased by methylation levels, a defendant might use that to argue that its process does not meet this limitation.
VI. Other Allegations
The complaint does not contain specific counts for indirect or willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of definitional scope: For the ’640 Patent, can the term "sequencing panel," recited as a single entity with combined properties, be construed to cover a process where a sample is split and subjected to two different analyses for those properties on separate aliquots?
- A key evidentiary question will be one of procedural fact: For the ’634 Patent, which appears to describe the accused process with high fidelity, does the Tempus xM MRD test, in practice, consistently perform the claimed steps of splitting a sample and conducting distinct genetic and methylation assays as alleged on "information and belief" in the complaint?
- A central technical question will concern quantitative thresholds: For the ’961 Patent, does the accused process meet the specific numerical requirements of Claim 1, such as using "more than a 10x excess of adapters" and achieving "at least 20%" ligation efficiency, which are crucial limitations allegedly found novel by the USPTO?