Clinical Genomics Pty Ltd v. Grail Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Clinical Genomics Pty Ltd (Australia), Clinical Genomics Technologies Pty Ltd (Australia), and Clinical Genomics, Inc. (Delaware)
  • Defendant: GRAIL, Inc. (Delaware)
  • Plaintiff’s Counsel: Richards, Layton & Finger, P.A.
• Case Identification: 1:26-cv-01147, D. Del., 09/11/2026
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant GRAIL, Inc. is a Delaware corporation and has allegedly committed acts of infringement in the district, including the offer for sale and sale of the accused product.
• Core Dispute: Plaintiff alleges that Defendant’s Galleri multi-cancer early detection test infringes two patents related to methods for detecting cancer by analyzing DNA methylation patterns.
• Technical Context: The technology concerns the field of liquid biopsy, specifically using blood plasma to detect cancer signals by analyzing epigenetic modifications (methylation) on fragments of cell-free DNA (cfDNA).
• Key Procedural History: The complaint notes that Plaintiff previously developed and launched its own commercial blood test for colorectal cancer, Colvera®, in 2016, which was based on similar methylation detection technology. No prior litigation between the parties, Inter Partes Reviews, or licensing agreements are mentioned.

Case Timeline

Date	Event
2012-05-18	’449 Patent Priority Date
2014-06-05	’468 Patent Priority Date
2016-12-20	Plaintiff launches Colvera® test
2020-03-17	’468 Patent Issued
2021-03-09	’449 Patent Issued
2021-06-04	Defendant launches Galleri® test
2026-09-11	Complaint Filed

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

U.S. Patent No. 10,590,468 - Method for Methylation Analysis

The Invention Explained

• Problem Addressed: The patent’s background explains that prior art methods for detecting DNA methylation, such as MethyLight PCR, were significantly less sensitive when a gene region of interest was only "partially methylated" (Compl. ¶¶47-48; ’468 Patent, col. 6:25-40). These methods often required all targeted CpG sites (locations prone to methylation) to be methylated for a detection probe to bind, which could lead to false-negative results if some sites were unmethylated, thereby reducing diagnostic accuracy ('468 Patent, col. 6:30-40).
• The Patented Solution: The invention claims to solve this problem by providing a method that uses "one or more probes capable of collectively hybridising to at least two differing methylation patterns" within the target DNA region ('468 Patent, abstract; ’468 Patent, col. 7:5-14). This can be achieved with a pool of different probes or a single "promiscuous" probe that can bind to multiple patterns of methylation ('468 Patent, col. 9:59-10:2). This design allows the method to detect both fully and partially methylated DNA, increasing the sensitivity of cancer detection from cfDNA samples ('468 Patent, col. 9:30-41).
• Technical Importance: This approach allows for a more nuanced and sensitive detection of cancer signals from blood by accounting for the biological reality that tumor-derived DNA can exhibit varied and incomplete methylation patterns (Compl. ¶48; ’468 Patent, col. 6:45-52).

Key Claims at a Glance

• The complaint asserts one or more claims, including independent claim 1 (Compl. ¶84).
• The essential elements of independent claim 1 are:
  • A method for detecting cytosine methylation of a nucleic acid target.
  • Contacting a nucleic acid sample with an agent that modifies unmethylated cytosine residues (e.g., bisulfite).
  • In a single reaction, measuring partial methylation by contacting the DNA with:
    • A primer set to amplify partially methylated forms of a target region.
    • One or more probes that can "collectively hybridise to at least two differing methylation patterns" at that region.
  • Amplifying the sample, where primer extension causes detection of the hybridized probe.
  • Qualitatively or quantitatively analyzing the detection output.

U.S. Patent No. 10,941,449 - Method of Screening for Colorectal Cancer

The Invention Explained

• Problem Addressed: The patent addresses the challenge that staging large intestine neoplasms traditionally required invasive procedures like tissue biopsies for histological analysis ('449 Patent, col. 3:24-29). These methods are subjective, slow, and not suitable for routine or repeated monitoring of disease progression ('449 Patent, col. 5:48-55).
• The Patented Solution: The patent describes a non-invasive method for classifying a large intestine neoplasm by measuring the methylation level of specific gene markers (e.g., BCAT1, IKZF1) in a blood-derived sample ('449 Patent, abstract; '449 Patent, claim 1). The invention is based on the discovery that while methylation levels in tissue are relatively stable across cancer stages, the level of methylation found in circulating cell-free DNA in blood plasma progressively increases as the cancer becomes more advanced ('449 Patent, col. 5:5-13). This correlation allows for a probabilistic classification of the neoplasm into categories such as premalignant, early-stage, or late-stage cancer ('449 Patent, col. 6:9-14).
• Technical Importance: This technology provided a blood-based method to help classify colorectal cancer stage, potentially enabling more personalized treatment strategies and non-invasive monitoring of disease progression without repeated biopsies ('449 Patent, col. 6:15-22).

Key Claims at a Glance

• The complaint asserts one or more claims, including independent claim 1 (Compl. ¶92).
• The essential elements of independent claim 1 are:
  • A method of measuring a methylation level in a sample from an individual suspected of having a large intestine neoplasm.
  • Selecting an individual from a patient population staged as adenoma or Stage I-IV cancer.
  • Obtaining a blood-derived sample containing cfDNA.
  • Extracting and bisulfite converting the cfDNA.
  • Detecting the methylation level of a DNA region comprising specific gene markers (including BCAT1, IKZF1, IRF4, GRASP, and/or CAHM).
  • Using that measurement to determine a probability of the individual having a premalignant, early-stage, or late-stage neoplasm.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendant GRAIL, Inc.’s Galleri test (Compl. ¶6).

Functionality and Market Context

• The Galleri test is a blood-based multi-cancer early detection (MCED) test that analyzes circulating cell-free DNA (cfDNA) isolated from a patient's blood plasma sample (Compl. ¶¶69; Compl. ¶72). The test subjects the cfDNA to bisulfite sequencing, targeting a panel of what the complaint describes as "more than 100,000 informative methylation regions" (Compl. ¶72). The resulting data is processed by machine-learning classifiers to detect a cancer signal and predict its tissue of origin (Compl. ¶72).
• The test is marketed as being capable of detecting signals for over 50 types of cancer, including colorectal cancer (Compl. ¶71). The complaint alleges the test has generated substantial revenue, citing public financial disclosures of $108.6 million in 2024 U.S. revenue (Compl. ¶8).

IV. Analysis of Infringement Allegations

The complaint includes a diagram illustrating the technical advantage of detecting partial methylation over "all-or-nothing techniques" that require all methylation sites to be active for detection (Compl. p. 15, figure). This visual directly supports the infringement theory for the ’468 Patent, which is centered on the claimed capability to detect varied methylation patterns.

10,590,468 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
(i) contacting a nucleic acid sample with an agent which modifies unmethylated cytosine residues;	The Galleri test subjects cfDNA extracted from a blood plasma sample to bisulfite conversion, a process that modifies unmethylated cytosine residues.	¶73	col. 15:6-15
(ii) measuring... in a single reaction... by contacting the DNA with... a primer set... and... one or more probes...	The Galleri test is performed on a single blood sample and detects methylation status using amplification with methylation-specific primers and probes.	¶69; ¶73	col. 7:6-14
wherein said one or more probes are capable of collectively hybridising to at least two differing methylation patterns at said region...	The complaint alleges that the Galleri test must be capable of detecting partial methylation to be effective, which is the key innovation of the patent for overcoming the limitations of prior art that could only detect fully methylated DNA.	¶48; ¶83	col. 7:50-8:3
(iii) amplifying the sample... wherein the extension of said primers... effects the detection of said hybridised probe...	The Galleri test uses amplification with methylation-specific primers and probes, where primer extension enables probe-based detection.	¶73	col. 16:5-24
(iv) qualitatively or quantitatively analysing the detection output...	The Galleri test uses machine-learning classifiers to process sequencing data and detect a cancer signal.	¶72	col. 7:15-16

• Identified Points of Contention:
  • Scope Questions: A central issue may be whether the term "probes ... capable of collectively hybridising to at least two differing methylation patterns" can be construed to read on the Galleri test's alleged process, which uses "bisulfite sequencing" and "machine-learning classifiers" (Compl. ¶72). The court may need to determine if a computational analysis of sequencing data is equivalent to the physical hybridization of oligonucleotide probes as described in the patent.
  • Technical Questions: The complaint alleges that the Galleri test detects partial methylation, but its support is based on the stated necessity for such a function to achieve its purpose (Compl. ¶¶48-49). A key technical question will be what evidence demonstrates that Grail's accused test actually performs this specific function, as opposed to simply aggregating signals from fully methylated or fully unmethylated DNA regions across its large panel.

10,941,449 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
selecting an individual from a patient population known or suspected to have a large intestine neoplasm staged as adenoma, stage I, stage II, stage III, or stage IV;	The Galleri test is marketed for use in adults at elevated risk for cancer and is used to screen for colorectal cancer, which includes the claimed patient population.	¶74	col. 10:55-11:5
obtaining... a blood-derived sample... comprising circulating cell-free DNA;	The Galleri test obtains a blood-derived sample from an individual, which comprises cfDNA.	¶73	col. 19:10-15
extracting circulating cell-free DNA...; bisulfite converting the cfDNA;	The Galleri test isolates, extracts, and subjects the cfDNA to bisulfite conversion.	¶73	col. 19:20-25
detecting a level of methylation of a DNA region... wherein the DNA region comprises... [a specified gene marker, e.g., BCAT1, IKZF1]...	The Galleri test detects methylation levels in cfDNA by analyzing over 100,000 methylation regions. Plaintiff alleges this infringes on the patented method of using specific markers like BCAT1 and IKZF1.	¶72; ¶92	col. 7:1-15
determining a probability whether said individual has a premalignant neoplasm, an early stage malignant neoplasm or a late stage malignant neoplasm...	The Galleri test is alleged to practice the claimed method, which uses methylation levels to determine the probability of a neoplasm's stage.	¶92	col. 6:9-14

• Identified Points of Contention:
  • Technical Questions: A critical factual question is whether the Galleri test actually analyzes the specific gene markers recited in claim 1 (e.g., BCAT1, IKZF1, CAHM). The complaint alleges infringement but does not specify which of the "100,000 informative methylation regions" (Compl. ¶72) are targeted by the accused test.
  • Scope Questions: The infringement analysis may turn on whether the Galleri test's stated function—to "detect a cancer signal" and "predict the cancer signal origin" (Compl. ¶72)—meets the claim limitation of "determining a probability" of having a "premalignant", "early stage", or "late stage" neoplasm. The court will have to resolve whether a cancer detection and localization tool performs the same function as the claimed cancer staging and classification method.

V. Key Claim Terms for Construction

For the ’468 Patent

• The Term: "probes... capable of collectively hybridising to at least two differing methylation patterns"
• Context and Importance: This term is the central inventive concept of the ’468 Patent. The infringement case hinges on whether GRAIL's sequencing- and machine-learning-based test can be considered to practice a method using such "probes." Practitioners may focus on this term because it represents the primary technical distinction over the prior art, and its interpretation will likely determine whether GRAIL's modern sequencing-based diagnostic platform falls within the scope of a patent drafted around PCR-based probe technologies.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification describes the probes as potentially a "heterogenous pool of probes" or a single "promiscuous" probe designed to "efficiently detect both the amplified fully and partially methylated DNA or RNA molecules" ('468 Patent, col. 9:59-10:2). Plaintiff may argue this language supports a broad functional definition covering any technical means of assessing multiple methylation states simultaneously to achieve a sensitive result.
  • Evidence for a Narrower Interpretation: The patent's detailed description and examples are heavily focused on physical oligonucleotide probes used in amplification reactions, such as "hydrolysis probes" (TaqMan) ('468 Patent, col. 21:44-50; '468 Patent, claim 14). Defendant may argue that the claims, read in light of the specification, are limited to these specific physical embodiments and do not cover a purely computational analysis of sequencing data.

For the ’449 Patent

• The Term: "determining a probability whether said individual has a premalignant neoplasm, an early stage malignant neoplasm or a late stage malignant neoplasm"
• Context and Importance: This term defines the ultimate output of the claimed method. Infringement depends on whether the Galleri test performs this specific classification function. Practitioners may focus on this term because there appears to be a functional mismatch between the accused product, marketed for cancer detection and origin prediction, and the patent, which claims a method for cancer staging.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The claim language is functional, and Plaintiff may argue that any output providing information that allows a clinician to assess the likelihood of a cancer's stage meets this limitation. The patent describes using the methylation levels to "inform the development of the therapeutic treatment," a broad purpose ('449 Patent, col. 6:11-15).
  • Evidence for a Narrower Interpretation: The patent abstract and summary of the invention are explicitly directed to "classifying a large intestine neoplasm" and assessing the "probability that a given neoplasm is premalignant, early stage malignant, or late stage malignant" ('449 Patent, abstract; '449 Patent, col. 6:9-12). Defendant may argue that this requires a specific output of a probabilistic classification into the recited stages, which is a different function from merely detecting the presence of a cancer signal.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Grail induces infringement of both asserted patents by providing the Galleri test, instructions, and marketing materials to healthcare providers, patients, and laboratory personnel with the knowledge and intent that the patented methods be practiced (Compl. ¶85; Compl. ¶93). It also alleges contributory infringement for selling the components of the Galleri test (Compl. ¶86; Compl. ¶94).
• Willful Infringement: Willfulness is alleged based on pre-suit knowledge, which the complaint asserts on "information and belief" that Grail has monitored the scientific literature and patent landscape in the field since before the Galleri test was launched (Compl. ¶77; Compl. ¶78). The complaint also alleges ongoing willful infringement following service of the complaint (Compl. ¶80; Compl. ¶95).

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

The resolution of this case may depend on the court’s answers to several central questions:

• A core issue will be one of definitional scope: Can the term "probes ... capable of collectively hybridising to at least two differing methylation patterns" from the ’468 Patent, which is described in the context of PCR-based assays, be construed to cover the accused test’s use of high-throughput sequencing and machine-learning algorithms?
• A key question will be one of functional equivalence: Does the accused Galleri test, which is marketed for cancer detection and origin prediction, perform the method of cancer staging claimed in the ’449 Patent, which requires "determining a probability" of a neoplasm being premalignant, early-stage, or late-stage?
• A critical evidentiary gap will need to be addressed concerning technical overlap: Does the Galleri test, which analyzes a large panel of methylation regions, actually measure the methylation levels of the specific gene markers (e.g., BCAT1, IKZF1) required by the claims of the ’449 Patent? The complaint does not currently provide direct evidence on this point.