DCT
1:20-cv-00692
Ravgen Inc v. Natera Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Ravgen, Inc. (Delaware)
- Defendant: Natera, Inc. and NSTX, Inc. (Delaware)
- Plaintiff’s Counsel: The Dacus Firm, P.C.; Desmarais LLP
- Case Identification: 6:20-cv-451, W.D. Tex., 06/01/2020
- Venue Allegations: Plaintiff alleges venue is proper in the Western District of Texas because Defendants maintain a permanent and continuous presence, including CLIA-compliant diagnostic testing facilities, laboratories, and offices in Austin, Texas, where they conduct business related to the accused products.
- Core Dispute: Plaintiff alleges that Defendant’s non-invasive genetic testing services (Panorama, Vistara, Signatera, and Prospera) infringe patents related to methods for preparing and analyzing samples of cell-free DNA by preserving them with an agent that inhibits cell lysis.
- Technical Context: The technology concerns non-invasive diagnostic testing, which analyzes small fragments of cell-free DNA (e.g., from a fetus, tumor, or transplanted organ) circulating in a patient's bloodstream, a field with significant application in prenatal care, oncology, and transplant medicine.
- Key Procedural History: The complaint alleges that in 2014 and 2015, Defendant Natera communicated with Plaintiff Ravgen regarding its patent portfolio, which included the patents-in-suit, and expressed interest in a potential license or acquisition. Plaintiff also sent a letter to Defendant on May 15, 2020, identifying the patents-in-suit and the accused Panorama test before filing the complaint.
Case Timeline
| Date | Event |
|---|---|
| 2002-05-08 | Priority Date for ’277 and ’720 Patents |
| 2008-02-19 | ’277 Patent Issued |
| 2010-06-01 | ’720 Patent Issued |
| 2013-03-01 | Panorama Test Launched |
| 2017-05-01 | Vistara Test Launched |
| 2017-08-21 | Signatera Test Launched |
| 2020-01-01 | Prospera Test Commercial Launch Initiated |
| 2020-06-01 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,332,277 - “Methods For Detection Of Genetic Disorders” (issued Feb. 19, 2008)
The Invention Explained
- Problem Addressed: The patent’s background section describes the difficulty of using cell-free fetal DNA from a pregnant woman's blood for genetic testing because it is present in very low concentrations relative to the mother's own DNA ('277 Patent, col. 32:24-30). The vast majority of DNA in a maternal plasma sample is maternal, which can obscure the fetal DNA signal needed for accurate analysis (Compl. ¶41).
- The Patented Solution: The invention introduces a method to increase the relative percentage of fetal DNA in a sample by adding a chemical agent that inhibits or impedes the breakdown (lysis) of cells present in the blood sample after it is drawn ('277 Patent, col. 32:31-39). Because the vast majority of cells in the sample are maternal, preventing their lysis significantly reduces the release of contaminating maternal DNA, thereby improving the signal-to-noise ratio and making the fetal DNA easier to detect and analyze (Compl. ¶41).
- Technical Importance: This sample preparation technique provided a method to overcome a key obstacle in non-invasive prenatal testing, enabling more reliable and accurate genetic analysis from a simple maternal blood draw (Compl. ¶29).
Key Claims at a Glance
- The complaint asserts "one or more claims" and identifies independent claim 81 as exemplary (Compl. ¶74-75).
- 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.
- The complaint’s allegation of infringement of "one or more claims" suggests it is not limited to claim 81 (Compl. ¶74).
U.S. Patent No. 7,727,720 - “Methods For Detection Of Genetic Disorders” (issued June 1, 2010)
The Invention Explained
- Problem Addressed: Similar to its parent patent, the ’720 Patent addresses the challenge that the low percentage of fetal DNA in maternal plasma makes genotyping the fetus difficult ('720 Patent, col. 33:31-36).
- The Patented Solution: The patent claims a method for detecting any free nucleic acid (not limited to fetal DNA) in a sample. The method involves two primary steps: first, isolating the free nucleic acid from a sample that has been treated with an agent that impedes cell lysis (such as a membrane stabilizer, cross-linker, or cell lysis inhibitor), and second, detecting the presence or absence of that isolated nucleic acid ('720 Patent, col. 536:15-25). Adding the agent is described as a way to "significantly and unexpectedly increase the proportion of free nucleic acid obtained from the non-cellular fraction of a sample" (Compl. ¶43).
- Technical Importance: This patent claims a broader method for improving the yield of any target cell-free nucleic acid from a mixed sample, with applications extending beyond prenatal testing to other areas of genetic diagnostics (Compl. ¶30).
Key Claims at a Glance
- The complaint asserts "one or more claims" and identifies independent claim 1 as exemplary (Compl. ¶87-88).
- 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, or cell lysis inhibitor; and
- (b) detecting the presence or absence of the free nucleic acid.
- The complaint’s allegation of infringement of "one or more claims" suggests it is not limited to claim 1 (Compl. ¶87).
III. The Accused Instrumentality
Product Identification
The accused instrumentalities are four commercial genetic testing services offered by Natera: Panorama, Vistara, Signatera, and Prospera (Compl. ¶5).
Functionality and Market Context
- The accused services are non-invasive tests that analyze cell-free DNA from a patient's blood sample to detect genetic information. Panorama and Vistara are prenatal tests for fetal chromosomal abnormalities and single-gene disorders (Compl. ¶46, ¶51). Signatera is an oncology test for detecting circulating tumor DNA (ctDNA) (Compl. ¶57). Prospera is a post-transplant test for detecting donor-derived cell-free DNA (dd-cfDNA) to assess organ rejection risk (Compl. ¶62).
- A central feature of the accused services is the sample collection protocol. The complaint alleges that all four tests require the use of Streck Cell-Free DNA Blood Collection Tubes (BCTs), which contain a proprietary preservative agent (Compl. ¶48, ¶53, ¶59, ¶64). According to product literature cited in the complaint, this preservative works by "limiting cell lysis" to stabilize the blood cells and preserve the integrity of the cell-free DNA during transport and storage (Compl. ¶49). The complaint provides an image of the Panorama sample collection instructions specifying the use of "2 cell free DNA Streck Tubes" (Compl. p. 18, Ex. 37). After collection, Natera allegedly isolates the target cell-free DNA from the plasma (the non-cellular fraction of the blood) and performs genetic sequencing and analysis (Compl. ¶50). A diagram in the complaint illustrates this process of isolating DNA from plasma for the Panorama test (Compl. p. 19, Ex. 35).
IV. Analysis of Infringement Allegations
’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 Panorama and Vistara tests isolate cell-free fetal DNA from a maternal blood sample. | ¶75a, ¶76a | col. 26:27-33 |
| ...wherein said sample comprises an agent that inhibits lysis of cells, if cells are present... | The tests require the collection of blood in Streck Cell-Free DNA BCTs, which contain a preservative that is alleged to limit and inhibit cell lysis. | ¶75b, ¶76b, ¶49 | col. 10:11-14 |
| ...and wherein said agent is selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor. | The preservative in the Streck tubes is alleged to be a cell lysis inhibitor, falling within the claimed Markush group. | ¶75b, ¶76b, ¶49 | col. 10:15-18 |
’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 (Panorama, Vistara, Signatera, and Prospera) all isolate cell-free DNA from the plasma fraction of a collected blood sample. | ¶88a, ¶89a, ¶90a, ¶91a | col. 10:23-25 |
| ...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... | All accused tests require blood collection in Streck tubes containing a preservative that allegedly limits cell lysis, thus functioning as a cell lysis inhibitor within the claimed group. | ¶88b, ¶89b, ¶90b, ¶91b | col. 10:29-34 |
| ...and (b) detecting the presence or absence of the free nucleic acid. | After isolation, the tests perform sequencing and analysis on the cell-free DNA to identify genetic markers, which necessarily involves detecting the presence of that DNA. | ¶88c, ¶89c, ¶90c, ¶91c | col. 9:43-46 |
Identified Points of Contention
- Technical Questions: A central technical question is whether the preservative agent in the third-party Streck tubes, which is not identified by chemical name in the complaint, in fact operates as a "membrane stabilizer, cross-linker, or cell lysis inhibitor" as those terms are understood in the patent. The complaint relies on Streck's marketing claims that the agent "limits cell lysis," but the actual chemical mechanism will likely be a focus of discovery and expert testimony (Compl. ¶49).
- Scope Questions: Claim 81 of the ’277 Patent is limited to methods involving "fetal nucleic acid." The complaint appropriately limits its allegations for this patent to the Panorama and Vistara tests (Compl. ¶74). In contrast, claim 1 of the ’720 Patent covers "a free nucleic acid," a broader term. The complaint alleges that all four tests, including the oncology (Signatera) and transplant (Prospera) tests, infringe the ’720 Patent (Compl. ¶87). The applicability of the patent's teachings, which are heavily focused on the context of prenatal diagnostics, to these other fields may be a point of dispute.
V. Key Claim Terms for Construction
- The Term: "agent that inhibits lysis of cells" / "agent that impedes cell lysis"
- Context and Importance: This term is the core of the asserted claims in both patents. The infringement case hinges on whether the preservative in the Streck tubes used by Natera falls within the scope of this definition. Practitioners may focus on whether this term should be defined purely by its function (i.e., anything that limits cell breakdown) or by the specific chemical structures and examples disclosed in the patent.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification suggests a broad, functional definition, stating that "any agent that prevents the lysis of cells or increases the structural integrity of the cells can be used" (’277 Patent, col. 91:50-53; ’720 Patent, col. 92:14-17). This language may support an interpretation that covers any chemical that achieves the stated result.
- Evidence for a Narrower Interpretation: The specification provides specific examples of suitable agents, such as formaldehyde, glutaraldehyde, and derivatives thereof, and extensive lists of cross-linking agents ('277 Patent, col. 15:28-29; Table XXIII). A defendant may argue that the term should be construed more narrowly to be limited to aldehydes, cross-linkers, or other agents chemically similar to those explicitly disclosed, rather than any substance that has a stabilizing effect on cells.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendants induce infringement of both patents by providing the Vistara test to third-party laboratories with instructions, manuals, and promotional materials that allegedly direct the labs to perform the patented methods (Compl. ¶78, ¶93). It further alleges contributory infringement, stating that the Vistara tests are a material part of the invention, are not staple articles of commerce, and are sold with the knowledge they will be used to infringe (Compl. ¶80, ¶95).
- Willful Infringement: The complaint alleges willful infringement based on pre-suit knowledge of the patents-in-suit. It cites communications from 2014 and 2015 in which Natera's executives allegedly discussed Ravgen's patent portfolio and expressed interest in a license or acquisition (Compl. ¶68-69, ¶82, ¶97). The complaint further alleges that Natera continued its conduct after receiving notice and launched three additional accused products (Vistara, Signatera, Prospera) after gaining knowledge of the patents (Compl. ¶71).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of evidentiary proof: What is the specific chemical nature of the preservative in the Streck tubes used by Natera? Does its mechanism of action meet the patent's definition of a "membrane stabilizer, cross-linker, or cell lysis inhibitor," a determination that will likely require expert analysis of proprietary chemical formulations.
- A second key issue will be one of claim construction: How broadly will the court construe the term "agent that inhibits/impedes cell lysis"? The case may turn on whether this term is given a broad functional meaning based on the specification's language or a narrower meaning tied to the chemical classes and examples explicitly disclosed.
- A final critical question concerns willfulness: The complaint alleges direct communications between the parties regarding the asserted patent portfolio years before the suit was filed. The court will have to examine the content of these communications to determine if Natera acted with the requisite knowledge and intent to support a finding of willful infringement, which could expose it to enhanced damages.