DCT
1:20-cv-01734
Ravgen, Inc. v. Biora Therapeutics, Inc.
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Ravgen, Inc. (Delaware)
- Defendant: Progenity, Inc. (Delaware)
- Plaintiff’s Counsel: Farnan LLP; Desmarais LLP
- Case Identification: 1:20-cv-01734, D. Del., 12/21/2020
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Progenity is a Delaware corporation and conducts business in the state, at least by offering its services through its website.
- Core Dispute: Plaintiff alleges that Defendant’s non-invasive prenatal testing services infringe patents related to methods for preparing and analyzing cell-free DNA from maternal blood samples to detect fetal genetic disorders.
- Technical Context: The technology at issue is non-invasive prenatal testing (NIPT), a widely used method for screening for fetal genetic abnormalities by analyzing small fragments of fetal DNA circulating in a pregnant person's blood.
- Key Procedural History: The complaint alleges that Progenity was aware of the patents-in-suit through direct business communications with Ravgen’s founder in 2015 and 2016. It also notes that just prior to the complaint's filing, Progenity initiated inter partes review (IPR) proceedings at the Patent Trial and Appeal Board involving related technology, in which Progenity cited the application that led to one of the patents-in-suit as prior art.
Case Timeline
| Date | Event |
|---|---|
| 2002-05-08 | Priority Date for ’277 and ’720 Patents |
| 2008-02-19 | U.S. Patent No. 7,332,277 Issues |
| 2010-06-01 | U.S. Patent No. 7,727,720 Issues |
| 2015-01-01 | Accused Innatal® Prenatal Screen Launched (approximate) |
| 2015-09-23 | Communications Allegedly Begin Between Parties |
| 2019-04-02 | Accused Resura® Prenatal Test Launched |
| 2020-12-21 | 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 explains that detecting fetal DNA in a maternal blood sample is challenging because the vast majority of cell-free DNA is maternal. This problem is exacerbated when maternal cells break down (lyse) during sample collection, shipping, or processing, which further dilutes the small fraction of fetal DNA and makes accurate genetic analysis difficult (Compl. ¶30; ’277 Patent, col. 32:24-39).
- The Patented Solution: The invention addresses this by preparing a blood sample with an agent that inhibits or prevents the lysis of maternal cells. By stabilizing the maternal cells, the method increases the relative percentage of cell-free fetal DNA in the sample, thereby improving the reliability of subsequent genetic analysis (Compl. ¶¶16, 31; ’277 Patent, col. 91:44-51).
- Technical Importance: This sample preparation technique represented a significant step in making non-invasive prenatal testing more accurate and viable by improving the quality of the raw biological sample before analysis began (Compl. ¶¶18, 33).
Key Claims at a Glance
- The complaint asserts infringement of at least independent Claim 81 (Compl. ¶¶66, 71).
- The essential elements of Claim 81 are:
- A method for preparing a sample for analysis comprising isolating free fetal nucleic acid from the sample.
- The sample must comprise an agent that inhibits lysis of cells, if cells are present.
- The agent must be selected from the group consisting of: membrane stabilizer, cross-linker, and cell lysis inhibitor.
- The complaint states that Progenity infringes "one or more claims" of the patent, suggesting it may assert other claims later in the litigation (Compl. ¶65).
U.S. Patent No. 7,727,720, Methods For Detection Of Genetic Disorders (Issued June 1, 2010)
The Invention Explained
- Problem Addressed: Like its related patent, the ’720 Patent addresses the problem of low fetal DNA concentration in maternal plasma, which makes it "difficult" to use that DNA for genotyping the fetus (Compl. ¶30; ’720 Patent, col. 33:31-36).
- The Patented Solution: The invention claims a two-step method for detecting free nucleic acid. First, the nucleic acid is isolated from the non-cellular part (e.g., plasma) of a sample that contains an agent to impede cell lysis. Second, the presence or absence of the isolated nucleic acid is detected (Compl. ¶29; ’720 Patent, col. 535:15-27). This links the innovative sample preparation step with the subsequent analytical step.
- Technical Importance: The claimed method provides a complete process, from sample stabilization to detection, creating a foundational workflow for performing non-invasive genetic tests (Compl. ¶33).
Key Claims at a Glance
- The complaint asserts infringement of at least independent Claim 1 (Compl. ¶¶83, 88).
- The essential elements of Claim 1 are:
- A method for detecting a free nucleic acid comprising two steps:
- (a) isolating the nucleic acid from a non-cellular fraction of a sample, where the sample contains an agent that impedes cell lysis (selected from membrane stabilizers, cross-linkers, or cell lysis inhibitors).
- (b) detecting the presence or absence of the isolated free nucleic acid.
- The complaint alleges infringement of "one or more claims," preserving the right to assert others (Compl. ¶82).
III. The Accused Instrumentality
Product Identification
Progenity’s Innatal® Prenatal Screen and Resura® Prenatal Test services (Compl. ¶¶1, 4-5).
Functionality and Market Context
- The accused instrumentalities are non-invasive prenatal testing (NIPT) services that analyze cell-free DNA (cfDNA) from a maternal blood sample to screen for fetal genetic conditions (Compl. ¶¶39, 46). The Innatal test screens for common chromosomal aneuploidies, while the Resura test screens for both chromosomal and single-gene (monogenic) disorders (Compl. ¶¶4, 5).
- A key technical aspect alleged in the complaint is that the performance of these tests requires that patient blood samples be collected in Streck Cell-Free DNA Blood Collection Tubes (BCTs) (Compl. ¶¶40, 47). The complaint cites Progenity’s own documentation, including a requisition form and specimen guide, specifying the use of these tubes (Compl. ¶¶40, 47). A visual from Progenity's website for the Resura test explicitly states that "six 10mL Streck DNA tubes" are required for prenatal testing (Compl. ¶49, Ex. 30).
- The complaint alleges these Streck BCTs contain a "unique preservative" and "specialized chemistry" that functions to inhibit cell lysis, thereby preserving the integrity of the cfDNA in the sample (Compl. ¶42).
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... | Progenity's process involves receiving a maternal blood sample and isolating cell-free fetal DNA from it for subsequent genetic analysis. A diagram on Progenity's website illustrates this workflow, showing a blood sample being sent to and processed by the Progenity laboratory (Compl. ¶43, Ex. 8). | ¶¶43, 66a | col. 15:20-32 |
| ...wherein said sample comprises an agent that inhibits lysis of cells, if cells are present... | Progenity’s testing protocol requires that blood samples be collected in Streck Cell-Free DNA BCTs. These tubes are alleged to contain a chemical agent that "limits the release of genomic DNA" by "limiting cell lysis." | ¶¶42, 66b | col. 9:15-18 |
| ...and wherein said agent is selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor. | The preservative in the required Streck tubes is alleged to function as a cell lysis inhibitor, thereby satisfying this limitation. | ¶¶42, 66b | col. 9:18-20 |
'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... | Progenity centrifuges the collected maternal blood to separate the plasma (the non-cellular fraction) and then extracts the cell-free DNA from that plasma. | ¶83a | col. 11:13-21 |
| ...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 blood sample is collected in a Streck BCT, which is alleged to contain a preservative that impedes cell lysis and thus falls within the claimed group of agents. | ¶83b | col. 10:44-51 |
| ...(b) detecting the presence or absence of the free nucleic acid. | After isolating the cfDNA, Progenity uses massively parallel sequencing (MPS) to analyze the DNA fragments and thereby detect the presence of fetal genetic abnormalities. | ¶83c | col. 9:58-61 |
- Identified Points of Contention:
- Scope Questions: The central dispute may turn on whether the proprietary preservative in the third-party Streck tubes is properly classified as a "membrane stabilizer, cross-linker, and cell lysis inhibitor" as required by the claims. The defense could argue that the agent, while having a stabilizing effect, does not meet the specific structural or functional definition of any of the three listed categories.
- Technical Questions: A key factual question will be the precise chemical composition and mechanism of action of the agent in the Streck tubes. The complaint relies on Streck’s product descriptions of the agent's function (i.e., that it "limits cell lysis") (Compl. ¶42), but proving that it is a member of the specific Markush group in the claims may require further evidence obtained through discovery.
V. Key Claim Terms for Construction
- The Term: "agent ... selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor"
- Context and Importance: This term is the core of the asserted claims in both patents. The infringement theory depends entirely on the preservative in the Streck tubes meeting this definition. Practitioners may focus on this term because the infringement allegation relies on a third-party product (the Streck tube) that is not described in detail in the complaint, making the scope of this definition critical.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification includes broad functional language, stating that "any agent that prevents the lysis of cells or increases the structural integrity of the cells can be used" ('277 Patent, col. 91:48-51). Plaintiff may argue this supports a construction where the three listed categories are exemplary of any agent that performs the function of preventing lysis.
- Evidence for a Narrower Interpretation: The claim language itself uses the transitional phrase "consisting of," which typically creates a closed-ended Markush group. Defendant may argue that this language strictly limits the claim scope to only agents that can be definitively categorized as a membrane stabilizer, a cross-linker, or a cell lysis inhibitor, regardless of any broader language in the specification. The patent provides specific examples, such as formaldehyde (a cross-linker), which may be used to define the scope of these categories ('277 Patent, col. 91:46-48).
VI. Other Allegations
- Indirect Infringement: The complaint alleges Progenity induces infringement by requiring clinicians and third-party labs to collect patient samples in the specified Streck tubes as part of its testing service, and by providing instructions and materials that direct this infringing use (Compl. ¶¶68-69, 85-86). It further alleges contributory infringement, asserting the tests have no substantial non-infringing use and are a material part of the invention (Compl. ¶¶70, 87).
- Willful Infringement: Willfulness is alleged based on Progenity’s purported knowledge of the patents. This knowledge is allegedly evidenced by direct communications in 2015-2016 between Progenity and Ravgen's founder regarding Ravgen's technology, as well as by Progenity’s use of the application leading to the ’277 Patent as prior art in separate IPR proceedings it initiated (Compl. ¶¶53-61, 77, 94).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of definitional scope and evidence: Can the proprietary preservative in the commercially available Streck tubes be proven to fall within the specific, three-member Markush group of "membrane stabilizer, cross-linker, and cell lysis inhibitor" recited in the claims? The case will likely depend on evidence concerning the chemical nature of the Streck tube preservative, which may not be publicly available.
- A second key question will be one of claim construction: Will the court interpret the claim term "consisting of" strictly, limiting the scope to the three enumerated agent types, or will it be influenced by broader functional language in the specification? This legal determination will set the boundaries for the factual infringement analysis.