DCT
6:20-cv-00451
Ravgen Inc v. Natera Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Ravgen, Inc. (Delaware)
- Defendant: Natera, Inc. (Delaware) and NSTX, Inc. (Delaware)
- Plaintiff’s Counsel: The Dacus Firm, P.C.; Desmarais LLP
- Case Identification: 6:20-cv-00451, W.D. Tex., 06/01/2020
- Venue Allegations: Venue is based on Defendants allegedly maintaining a permanent and continuous presence in the Western District of Texas, including diagnostic testing facilities, laboratories, and office space in Austin where infringing activities are alleged to occur.
- Core Dispute: Plaintiff alleges that Defendant’s cell-free DNA genetic testing services infringe patents related to methods for preparing and analyzing biological samples by using an agent that inhibits the breakdown of cells.
- Technical Context: The technology relates to non-invasive genetic diagnostics, such as prenatal testing (NIPT), which analyzes small fragments of cell-free DNA (cfDNA) circulating in blood to detect genetic abnormalities without requiring invasive procedures.
- Key Procedural History: The complaint alleges that Defendants were aware of the patents-in-suit since at least June 2015 as a result of communications with Plaintiff’s founder regarding a potential license or acquisition of Plaintiff's patent portfolio. It further alleges that Plaintiff's counsel sent a letter in May 2020 identifying the patents and the accused products, to which Defendants did not respond. These allegations form the basis for the claim of willful infringement.
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 | Accused Panorama Test Launched |
| 2014-01-01 | Approximate date of initial communications between parties |
| 2015-06-25 | Date of letter referencing licensing/acquisition discussions |
| 2017-05-01 | Approximate month of Accused Vistara Test Launch |
| 2017-08-21 | Accused Signatera Test Launched |
| 2020-01-01 | Approximate date of Accused Prospera Test Launch |
| 2020-05-15 | Plaintiff's counsel sends notice letter to Defendants |
| 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 addresses the difficulty of detecting fetal DNA in a maternal blood sample because the small amount of fetal DNA is overwhelmed by the much larger amount of maternal DNA ('277 Patent, col. 32:24-31). The patent identifies that this problem is worsened when maternal blood cells break down (lyse) after the sample is drawn, releasing more maternal DNA and further diluting the fetal DNA signal (Compl. ¶28).
- The Patented Solution: The invention introduces a method for preparing a blood sample that involves adding an agent to the sample at the time of collection to prevent or impede cell lysis ('277 Patent, col. 32:31-39). By stabilizing the maternal cells, the method prevents the release of additional maternal DNA, thereby increasing the relative percentage of cell-free fetal DNA in the sample’s non-cellular fraction (plasma), which makes subsequent analysis more accurate and reliable ('277 Patent, col. 32:31-39; Compl. ¶42).
- Technical Importance: This sample preparation technique was designed to improve the signal-to-noise ratio in cell-free DNA analysis, providing a more robust foundation for non-invasive genetic testing (Compl. ¶29).
Key Claims at a Glance
- The complaint asserts infringement of at least exemplary independent claim 81 (Compl. ¶¶ 75-76).
- Essential elements of Claim 81:
- A method for preparing a sample for analysis comprising isolating free fetal nucleic acid from a 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 alleges infringement of "one or more claims" of the patent (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 the ’277 Patent, this patent addresses the challenge that the low percentage of fetal DNA in maternal plasma makes it difficult to use that DNA for genotyping the fetus ('720 Patent, col. 33:31-38).
- The Patented Solution: The invention claims a multi-step method that begins with the same sample preparation technique as the ’277 Patent: isolating cell-free nucleic acid from a sample that contains an agent to impede cell lysis ('720 Patent, Abstract). The method then explicitly adds the subsequent step of "detecting the presence or absence of the free nucleic acid," thereby claiming the full diagnostic process from sample preparation through analysis (Compl. ¶40).
- Technical Importance: The claimed method provides an end-to-end framework for conducting non-invasive genetic analysis with improved accuracy by focusing on the critical initial step of sample stabilization (Compl. ¶44).
Key Claims at a Glance
- The complaint asserts infringement of at least exemplary independent claim 1 (Compl. ¶¶ 88-91).
- Essential elements of Claim 1:
- A method for detecting a free nucleic acid, comprising:
- (a) isolating free nucleic acid from a non-cellular fraction of a sample, 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; and
- (b) detecting the presence or absence of the free nucleic acid.
- The complaint alleges infringement of "one or more claims" of the patent (Compl. ¶87).
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are four commercial genetic testing services offered by Defendants: Panorama, Vistara, Signatera, and Prospera (Compl. ¶5).
Functionality and Market Context
- The complaint alleges that all four tests analyze cell-free DNA (cfDNA) obtained from blood samples (Compl. ¶¶ 47, 52, 58, 63). The Panorama and Vistara tests are used for non-invasive prenatal screening; the Signatera test is used to monitor circulating tumor DNA for cancer recurrence; and the Prospera test is used to monitor donor-derived DNA to assess organ transplant rejection (Compl. ¶¶ 5, 46, 51, 57, 62).
- A central allegation is that all accused tests require the use of Streck Cell-Free DNA Blood Collection Tubes (BCTs) for sample collection (Compl. ¶¶ 48, 53, 59, 64). The complaint cites Defendants' instructions and materials stating these tubes contain a "unique preservative" that "limits the release of genomic DNA" by "limiting cell lysis" to ensure sample integrity (Compl. ¶49). The "Panorama Sample Collection Instructions" provided in the complaint explicitly direct the collection of blood into two "cell free DNA Streck Tubes" (Compl. p. 18).
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 Panorama test isolates fetal cell-free DNA from a maternal blood sample for analysis. A diagram in the complaint illustrates the separation of plasma containing maternal and fetal DNA from the maternal blood sample. | ¶¶ 47, 50, 75a; p. 19 | col. 26:22-42 |
| wherein said sample comprises an agent that inhibits lysis of cells, if cells are present, | The Panorama test requires samples to be collected in Streck Cell-Free DNA BCTs, which are alleged to contain a preservative that "limits cell lysis" to stabilize the sample. | ¶¶ 48, 49, 75b | col. 9:11-18 |
| and wherein said agent is selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor. | The complaint alleges that the preservative in the Streck tubes functions as a cell lysis inhibitor, which is a member of the claimed group of agents. | ¶¶ 49, 75b | col. 9:18-24 |
’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, wherein said sample comprises an agent that impedes cell lysis... | The Panorama test isolates cell-free DNA from the plasma (a non-cellular fraction) of a maternal blood sample collected in Streck tubes, which allegedly contain an agent that impedes cell lysis. | ¶¶ 47, 48, 49, 88a, 88b | col. 10:28-40 |
| (b) detecting the presence or absence of the free nucleic acid. | After isolation, the Panorama test analyzes the SNPs in the cell-free DNA to "determine the risk of certain chromosome abnormalities in the fetus," which necessarily includes detecting the presence of that DNA. | ¶¶ 50, 88c | col. 9:35-41 |
- Identified Points of Contention:
- Scope Questions: A central dispute may concern whether the proprietary preservative in the third-party Streck tubes falls within the scope of the term "agent" as defined by the patent's Markush group ("membrane stabilizer, cross-linker, and cell lysis inhibitor"). The analysis could depend on whether the term is limited to the specific chemical examples disclosed in the specification, such as formaldehyde, or is construed more broadly to cover any chemical with the claimed function.
- Technical Questions: The complaint relies on marketing materials to allege that the Streck tube preservative "limit[s] cell lysis." A key technical question will be what evidence confirms that the preservative in the accused tubes actually functions by inhibiting or impeding cell lysis, as required by the claims, versus another potential mechanism for preserving cfDNA.
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 central inventive concept of the patents-in-suit. The infringement case hinges on whether the preservative in the Streck tubes used by Defendants meets this definition. Practitioners may focus on this term because the accused agent is a proprietary third-party chemical, and its precise mechanism of action will be critical.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification suggests a broad, functional definition, stating, "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. 92:13-16). This language may support an interpretation that covers any substance achieving the stated result, regardless of its specific chemical class.
- Evidence for a Narrower Interpretation: The patents repeatedly use formaldehyde as a primary working example of the agent ('277 Patent, col. 91:48-50; '720 Patent, col. 92:12-13). The specification also provides extensive lists of exemplary cross-linkers ('277 Patent, Table XXIII). This focus on specific chemical embodiments could be used to argue for a narrower construction limited to the types of agents explicitly disclosed.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement of infringement for the Vistara test, asserting that Defendants instruct and direct third-party laboratories to perform the patented methods (Compl. ¶¶ 76, 78). The allegations are based on Defendants supplying the Vistara tests, which require use of the Streck tubes, along with promotional materials and instructions that allegedly cause the third-party labs to perform the infringing steps (Compl. ¶¶ 78, 79).
- Willful Infringement: The complaint alleges that Defendants have had knowledge of the patents-in-suit since at least June 2015, based on direct communications with the inventor regarding a potential license or acquisition of the patent portfolio (Compl. ¶¶ 67-69, 82, 97). The complaint further alleges that Defendants launched three of the four accused products after gaining this knowledge and failed to respond to a May 2020 notice letter from Plaintiff's counsel, suggesting deliberate infringement (Compl. ¶¶ 70, 71).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of definitional scope and evidentiary proof: Can the proprietary preservative in the commercially supplied Streck tubes be proven to function as an "agent that inhibits lysis of cells" within the meaning of the claims? The case may turn on evidence from discovery regarding the chemical's mechanism of action and whether that mechanism aligns with the technical teachings of the patents.
- A second key question will be one of scienter and intent: Do the alleged 2015 communications between the parties constitute pre-suit knowledge of infringement sufficient to support the claim for willfulness? The resolution will depend on the specific content of those communications and whether they establish that Defendants proceeded to infringe despite an objectively high likelihood that their actions constituted infringement of a valid patent.
- Finally, the case raises an implicit question regarding patent validity: While not yet at issue, a central defense may challenge whether the claimed invention—adding a known class of chemical preservatives to a blood sample to improve the yield of a known analyte (cfDNA)—was a non-obvious step to one of ordinary skill in the art at the time of the invention.