DCT
6:20-cv-00969
Ravgen Inc v. Laboratory Corp Of America Holdings
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Ravgen Inc (Delaware)
- Defendant: Laboratory Corp (Delaware)
- Plaintiff’s Counsel: Desmarais LLP; Dacus Firm
- Case Identification: 6:20-cv-00969, W.D. Tex., 10/16/2020
- Venue Allegations: Plaintiff alleges venue is proper in the Western District of Texas because Defendant LabCorp maintains a permanent and continuous presence, including multiple diagnostic testing facilities and laboratories, and has committed acts of infringement within the district.
- Core Dispute: Plaintiff alleges that Defendant’s non-invasive prenatal and cancer diagnostic tests infringe patents related to methods for preparing and analyzing cell-free DNA from blood samples.
- Technical Context: The technology at issue involves non-invasive prenatal testing (NIPT) and liquid biopsies, which analyze fragments of cell-free DNA (cfDNA) from blood to detect genetic abnormalities and mutations, offering a safer alternative to invasive procedures.
- Key Procedural History: The complaint details extensive pre-suit communications regarding the patents-in-suit between Plaintiff and Defendant, as well as between Plaintiff and Sequenom, Inc., a company Defendant later acquired. It is also alleged that Sequenom cited the ’277 Patent as prior art during the prosecution of its own patents, which may be relevant to the question of knowledge for willful infringement.
Case Timeline
| Date | Event |
|---|---|
| 2002-05-08 | Priority Date for ’277 and ’720 Patents |
| 2008-02-19 | U.S. Patent No. 7332277 Issues |
| 2010-06-01 | U.S. Patent No. 7727720 Issues |
| 2011-10-17 | Accused MaterniT21 PLUS test launched by Sequenom |
| 2014-08-19 | Accused informaSeq test launched by LabCorp |
| 2015-07-13 | Accused MaterniT Genome test launched by Sequenom |
| 2016-07-27 | LabCorp completes acquisition of Sequenom |
| 2020-09-24 | LabCorp begins offering Accused Resolution ctDx Lung Assay test |
| 2020-10-16 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,727,720 - “Methods For Detection Of Genetic Disorders”
- Patent Identification: US7727720B2, “Methods For Detection Of Genetic Disorders,” issued June 1, 2010 (the “’720 Patent”) (Compl. ¶30).
The Invention Explained
- Problem Addressed: The patent’s background section describes the primary challenge in analyzing cell-free fetal DNA from a pregnant mother’s blood: the vast majority of cell-free DNA is maternal, which dilutes the fetal DNA signal. This contamination often results from the lysis (bursting) of maternal blood cells during sample collection and processing, making it difficult to accurately genotype the fetus (Compl. ¶19; ’720 Patent, col. 33:31-36).
- The Patented Solution: The invention claims a method to counteract this problem by adding a specific type of agent to the blood sample at the time of collection. This agent—defined as a "membrane stabilizer, cross-linker, or cell lysis inhibitor"—prevents maternal cells from breaking down, thereby reducing the release of contaminating maternal DNA. This process increases the relative percentage of fetal DNA in the cell-free portion of the sample, which enhances the accuracy of subsequent genetic analysis (Compl. ¶20, ¶34; ’720 Patent, col. 33:37-46).
- Technical Importance: This sample preservation technique provided a critical improvement in the signal-to-noise ratio for cell-free DNA tests, which was a key step toward making non-invasive prenatal testing a commercially viable and reliable diagnostic tool (Compl. ¶22, ¶37).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶130).
- The essential elements of Claim 1 are:
- A method for detecting a free nucleic acid, comprising:
- (a) isolating free nucleic acid from a non-cellular fraction of a sample, wherein the sample comprises an agent that impedes cell lysis and is selected from the group of a membrane stabilizer, cross-linker, and cell lysis inhibitor; and
- (b) detecting the presence or absence of the free nucleic acid.
U.S. Patent No. 7,332,277 - “Methods For Detection Of Genetic Disorders”
- Patent Identification: US7332277B2, “Methods For Detection Of Genetic Disorders,” issued February 19, 2008 (the “’277 Patent”) (Compl. ¶28).
The Invention Explained
- Problem Addressed: The ’277 Patent addresses the same technical problem as the ’720 Patent: the difficulty of detecting fetal genetic abnormalities due to the low percentage of fetal DNA in maternal blood plasma, which is exacerbated by the lysis of maternal cells (Compl. ¶19; ’277 Patent, col. 32:24-28). It also notes that prior art methods were often complex and costly, requiring amplification of entire gene sequences (Compl. ¶39; ’277 Patent, col. 66:14-20).
- The Patented Solution: The ’277 Patent claims methods for preparing a sample for analysis. As in the ’720 Patent, the core inventive step involves using a sample that contains an agent to inhibit cell lysis. By stabilizing the maternal cells in the blood sample, the method increases the relative proportion of fetal nucleic acid available for isolation and subsequent analysis (Compl. ¶32, ¶35; ’277 Patent, col. 32:29-39).
- Technical Importance: The method provided a foundational sample preparation technique that enabled more sensitive and efficient analysis of cell-free DNA, paving the way for improved non-invasive genetic diagnostics (Compl. ¶37).
Key Claims at a Glance
- The complaint asserts at least independent claim 81 (Compl. ¶112).
- The essential elements of Claim 81 are:
- A method for preparing a sample for analysis comprising isolating free fetal nucleic acid from the sample,
- wherein said sample comprises an agent that inhibits lysis of cells, if cells are present,
- and wherein said agent is selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor.
III. The Accused Instrumentality
Product Identification
The complaint identifies four accused services: the MaterniT21 PLUS test, the MaterniT Genome test, the informaSeq test, and the Resolution ctDx Lung Assay test (collectively, the "Accused Tests") (Compl. ¶4).
Functionality and Market Context
- The Accused Tests are diagnostic services that analyze cell-free DNA (cfDNA) from a patient's blood sample. The MaterniT and informaSeq tests are non-invasive prenatal tests (NIPTs) used to screen for fetal chromosomal abnormalities by analyzing cfDNA from maternal blood (Compl. ¶¶45, 49, 66). The Resolution ctDx Lung Assay is a "liquid biopsy" test that analyzes circulating tumor DNA (ctDNA) in plasma samples from cancer patients to identify actionable mutations (Compl. ¶¶78, 80).
- A central allegation is that all Accused Tests require the use of Streck Cell-Free DNA Blood Collection Tubes (BCTs) for sample collection. The complaint alleges these tubes contain a "unique preservative" with "specialized chemistry" that functions to inhibit cell lysis, thereby preserving the integrity of the cfDNA in the sample (Compl. ¶¶46-47, 67-68, 81-82). The complaint includes an image of a specimen collection kit for the MaterniT tests which specifies the requirement of a "1 x 10 mL Streck tube" (Compl. p. 19).
IV. Analysis of Infringement Allegations
’720 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| (a) isolating free nucleic acid from a non-cellular fraction of a sample... | The Accused Tests involve extracting cell-free DNA from the non-cellular plasma fraction of a maternal or patient blood sample. The complaint includes a diagram showing the isolation of cell-free fetal and maternal DNA from a mother’s blood sample (Compl. p. 20). | ¶¶130.a, 131.a, 133.a | col. 27:1-17 |
| ...wherein said sample comprises an agent that impedes cell lysis, if cells are present, and wherein said agent is selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor... | The Accused Tests require that blood samples be collected in Streck BCT tubes, which allegedly contain a preservative agent that "limits the release of genomic DNA" by "limiting cell lysis." | ¶¶130.b, 131.b, 133.b | col. 10:10-15 |
| (b) detecting the presence or absence of the free nucleic acid. | After isolation, the tests analyze the cell-free DNA to detect genetic information, such as chromosomal abnormalities or specific tumor mutations. A sample lab report shows the detection of Trisomy 21 from a blood sample (Compl. p. 21). | ¶¶130.c, 131.c, 133.c | col. 5:58-60 |
’277 Patent Infringement Allegations
| Claim Element (from Independent Claim 81) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for preparing a sample for analysis comprising isolating free fetal nucleic acid from a the sample... | The Accused Tests' protocols require extracting cell-free fetal DNA from a maternal blood sample as part of the preparation for genetic analysis. | ¶¶112.a, 113.a, 114.a | col. 15:38-45 |
| ...wherein said sample comprises an agent that inhibits lysis of cells, if cells are present, and wherein said agent is selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor. | The Accused Tests' protocols require blood collection in Streck BCT tubes, which contain an agent that allegedly inhibits cell lysis to preserve the sample. An image of the specified collection kit is provided in the complaint (Compl. p. 19). | ¶¶112.b, 113.b, 114.b | col. 10:13-18 |
Identified Points of Contention
- Scope Questions: A primary point of contention may be whether the preservative used in the accused Streck BCT tubes qualifies as an "agent that inhibits lysis of cells... selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor" as required by the claims. The defense may argue that the specific chemical and its mechanism of action do not fall within this claimed Markush group.
- Technical Questions: The complaint relies on marketing materials describing the function of the Streck tube preservative. The actual chemical composition and its precise biochemical mechanism for "limiting cell lysis" will likely be a central factual dispute requiring expert testimony.
- Divided Infringement: The complaint alleges that LabCorp performs the infringing methods itself or directs and controls its subsidiaries (Sequenom, Integrated Genetics) and third-party partners (Resolution Bioscience) to perform them (Compl. ¶¶57, 73, 85, 116, 134, 138). This raises the legal question of divided infringement, where the analysis will focus on whether LabCorp exercises sufficient control over these other entities for all steps of the claimed methods to be attributable to a single actor.
V. Key Claim Terms for Construction
The Term
"agent that inhibits [or impedes] cell lysis... selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor"
Context and Importance
This term is the central inventive concept of both asserted patents. Its construction will be dispositive, as the infringement case depends on whether the preservative in the accused Streck BCT tubes falls within its scope.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The specifications provide a broad, functional description, stating that "any agent that prevents the lysis of cells or increases the structural integrity of the cells can be used" (’720 Patent, col. 92:16-19). The patents also provide extensive lists of exemplary chemical compounds that can serve as cross-linkers or membrane stabilizers, suggesting the categories are not intended to be narrowly limited (’720 Patent, Table XXIII, col. 216-218).
- Evidence for a Narrower Interpretation: The claims recite a specific Markush group of three categories ("membrane stabilizer, cross-linker, and cell lysis inhibitor"). A defendant may argue that the term should be strictly limited to agents that function via one of these three specific mechanisms, not merely any agent that has the functional result of preventing lysis. Further, the patent's working examples heavily feature formaldehyde as the agent, which could be used to argue for a narrower construction centered on similar aldehydes or cross-linkers (’720 Patent, col. 92:14-16).
VI. Other Allegations
Indirect Infringement
The complaint alleges that LabCorp induces infringement by providing the Accused Tests, which include test kits and protocols that instruct its subsidiaries and third-party labs to perform the patented methods (Compl. ¶¶120-121, 140-143). It further alleges contributory infringement, asserting that the Accused Tests (which include the specially adapted Streck tubes) are a material component of the invention and not a staple article of commerce (Compl. ¶¶122, 144).
Willful Infringement
The complaint alleges that LabCorp had pre-suit knowledge of the patents-in-suit as early as December 2010 (Compl. ¶¶88, 123, 145). The basis for this allegation includes direct communications between LabCorp and Ravgen regarding the patents, LabCorp's acquisition of companies (Genzyme Genetics, Sequenom) that had also communicated with Ravgen about the patents, and Sequenom's citation to the ’277 Patent as prior art in its own patent filings (Compl. ¶¶88-105).
VII. Analyst’s Conclusion: Key Questions for the Case
Definitional Scope
A core issue will be one of claim construction and technical evidence: does the chemical preservative in the accused Streck BCT tubes function as a "membrane stabilizer, cross-linker, or cell lysis inhibitor" as defined by the patents? The case will likely require a detailed technical inquiry into the preservative's mechanism of action and a legal ruling on the breadth of the claimed Markush group.
Attribution of Acts
Because the accused methods involve multiple steps (sample collection, processing, analysis) performed by LabCorp, its subsidiaries, and potentially third-party laboratories, a key legal question will be one of divided infringement. The court will need to determine if LabCorp's direction and control over these entities is sufficient to attribute all claimed steps to LabCorp as a single infringing actor.
Willfulness and Intent
The complaint presents detailed allegations of pre-suit knowledge, including licensing discussions and citations in patent prosecution. A central question for trial will be whether LabCorp's alleged infringement, if found, was willful. This will turn on evidence of LabCorp's state of mind and the objective reasonableness of its positions, with significant implications for potential enhanced damages.