DCT
1:20-cv-01730
Ravgen Inc v. Myriad Genetics Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Ravgen, Inc. (Delaware)
- Defendant: Myriad Genetics, Inc. (Delaware) and Myriad Women's Health, Inc. (Delaware)
- Plaintiff’s Counsel: Farnan LLP
- Case Identification: 1:20-cv-01730, D. Del., 12/21/2020
- Venue Allegations: Venue is asserted in Delaware on the basis that both Defendants are Delaware entities and therefore reside in the district for purposes of patent venue. The complaint also alleges that Defendants conduct business and have committed acts of infringement in the district.
- Core Dispute: Plaintiff alleges that Defendant’s noninvasive prenatal genetic screening tests infringe patents related to methods for preparing and analyzing cell-free DNA from a blood sample to detect genetic disorders.
- Technical Context: The lawsuit concerns non-invasive prenatal testing (NIPT), a widely used clinical method for screening for fetal chromosomal abnormalities by analyzing small fragments of cell-free fetal DNA (cffDNA) circulating in a pregnant person's blood.
- Key Procedural History: The complaint alleges that U.S. Patent No. 7,332,277 was cited during the patent prosecution of Defendants' own U.S. Patent Application Publication No. 2010/0022406, which may be relevant to allegations of pre-suit knowledge.
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 |
| 2014-09-01 | Approximate Launch of Accused "Informed Pregnancy Screen" by Counsyl |
| 2018-07-31 | Myriad acquires Counsyl |
| 2019-02-11 | Myriad begins offering the "Prequel Prenatal Screen" |
| 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 describes the challenge of using cell-free fetal DNA from maternal plasma for genetic testing, noting that the low relative percentage of fetal DNA makes genotyping difficult (Compl. ¶15; ’277 Patent, col. 32:24-30). Existing prenatal diagnostic methods were either invasive and risky (e.g., amniocentesis) or non-invasive but lacked high sensitivity and specificity. (Compl. ¶13).
- The Patented Solution: The invention provides methods to improve the reliability of non-invasive genetic testing. One key method involves preparing a maternal blood sample by adding an agent that inhibits or prevents the lysis (breakdown) of maternal blood cells. (’277 Patent, col. 32:31-39). By preventing maternal cells from releasing their DNA into the sample, this technique increases the relative percentage of the target cell-free fetal DNA, effectively boosting the signal-to-noise ratio for subsequent analysis. (Compl. ¶¶ 16, 30).
- Technical Importance: This sample preparation method provided a crucial step toward making non-invasive prenatal testing from maternal blood a viable and reliable clinical tool. (Compl. ¶18).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 81. (Compl. ¶55).
- Claim 81 includes the following essential elements:
- 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 reserves the right to assert other claims of the ’277 Patent. (Compl. ¶54).
U.S. Patent No. 7,727,720: "Methods For Detection Of Genetic Disorders" (Issued June 1, 2010)
The Invention Explained
- Problem Addressed: The patent addresses the same fundamental problem as the ’277 Patent: the vast majority of cell-free DNA in a maternal plasma sample is maternal, which makes it difficult to detect and analyze the small fraction of fetal DNA present. (Compl. ¶30; ’720 Patent, col. 33:31-37).
- The Patented Solution: The patent claims a method for detecting free nucleic acid that comprises two primary steps. First, isolating the nucleic acid from the non-cellular fraction (e.g., plasma) of a sample that contains an agent to impede cell lysis. Second, detecting the presence or absence of that nucleic acid. (’720 Patent, col. 33:38-46). By including the stabilizing agent, the method ensures that the relative percentage of fetal DNA is increased, which facilitates the subsequent detection step. (Compl. ¶¶ 29, 31).
- Technical Importance: The claimed method provides a complete workflow, from sample preparation to detection, for analyzing cell-free DNA in a way that overcomes the signal dilution problem caused by maternal cell lysis. (Compl. ¶19).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1. (Compl. ¶67).
- Claim 1 includes the following essential elements:
- A method for detecting a free nucleic acid, wherein said method comprises:
- (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 reserves the right to assert other claims of the ’720 Patent. (Compl. ¶66).
III. The Accused Instrumentality
Product Identification
The accused instrumentalities are Defendants' noninvasive prenatal tests, marketed as the "Informed Pregnancy Screen," "Prelude Prenatal Screen," and "Prequel Prenatal Screen," collectively referred to as the "Myriad Prenatal Screens." (Compl. ¶¶ 5, 41).
Functionality and Market Context
- The Myriad Prenatal Screens are described as tests that analyze cell-free DNA (cfDNA) from a maternal blood sample to screen for an increased risk of common fetal chromosomal abnormalities, such as Down syndrome. (Compl. ¶42).
- The process begins with collecting a maternal blood sample in a "Streck Cell-Free DNA Blood Collection Tube" ("BCT"), which the complaint alleges contains an agent that inhibits cell lysis. (Compl. ¶¶ 43-44).
- The collected sample is sent to Defendants' laboratory, where cfDNA is isolated from the plasma and analyzed using a "whole genome sequencing" ("WGS") approach to detect aneuploidies. (Compl. ¶¶ 45, 55.a). A poster attributed to Myriad employees, included in the complaint, describes the Myriad Prequel screen as a NIPS test that utilizes a WGS approach. (Compl. ¶45, Ex. 32).
IV. Analysis of Infringement Allegations
U.S. Patent No. 7,332,277 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 method involves isolating cell-free fetal DNA from a maternal blood sample by extracting cfDNA from maternal plasma. | ¶55.a | col. 15:23-32 |
| ...wherein said sample comprises an agent that inhibits lysis of cells, if cells are present... | The maternal blood sample is collected in a Streck Cell-Free DNA BCT, which contains a preservative chemistry alleged to limit cell lysis and the release of genomic DNA. | ¶55.b | col. 10:11-19 |
| ...and wherein said agent is selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor. | The preservative in the Streck tube is alleged to function as a cell lysis inhibitor, membrane stabilizer, or cross-linker, thereby satisfying the claim's Markush group. | ¶¶44, 55.b | col. 10:11-19 |
U.S. Patent No. 7,727,720 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 method involves extracting cfDNA from maternal plasma, which is the non-cellular fraction of the blood sample. | ¶67.a | col. 11:3-16 |
| ...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 and contained within a Streck tube, which is alleged to include a preservative that impedes cell lysis and falls within the claimed group of agents. | ¶67.b | col. 33:38-46 |
| ...and (b) detecting the presence or absence of the free nucleic acid. | Defendants analyze the extracted cfDNA via whole genome sequencing to report results, such as whether a chromosomal aneuploidy is detected, suspected, or not detected. | ¶67.c | col. 21:1-8 |
Identified Points of Contention
- Scope Questions: A central question may be whether the specific chemical preservative in the commercial "Streck Cell-Free DNA BCT" falls within the definitional scope of the claim term "agent that inhibits [or impedes] cell lysis... selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor." The complaint relies on third-party product literature to make this connection, which may be a point of dispute. (Compl. ¶¶ 44, 55.b).
- Technical Questions: The analysis may raise the question of whether the function of the Streck tube preservative is technically equivalent to the function described in the patents. The complaint alleges the Streck tube's chemistry "limits cell lysis," but the degree and mechanism of this limitation compared to the patent's teachings (which include examples using formaldehyde) could be scrutinized. (Compl. ¶¶ 31, 44).
V. Key Claim Terms for Construction
- The Term: "agent that inhibits [or impedes] cell lysis"
- Context and Importance: This term is the central inventive concept recited in the asserted claims of both patents. The infringement case rests on whether the preservative contained in the Streck tubes used for the Myriad Prenatal Screens meets this definition. Practitioners may focus on this term because the complaint's allegation is based on the function of a third-party commercial product, the Streck tube.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specifications provide a broad and varied list of potential agents. The patents state that "any agent that prevents the lysis of cells or increases the structural integrity of the cells can be used." (’277 Patent, col. 91:49-51; ’720 Patent, col. 92:14-17). They also provide extensive lists of exemplary cross-linkers and agents that stabilize cell membranes. (’277 Patent, Tables XXIII, XXIV).
- Evidence for a Narrower Interpretation: The patents' working examples repeatedly use formaldehyde as the agent for inhibiting cell lysis. (’277 Patent, Example 4, col. 89:15-22; ’720 Patent, Example 15, col. 210:22-30). A party could argue that the term should be construed more narrowly to cover only agents that function in a manner similar to formaldehyde, such as by cross-linking cellular proteins.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b). It asserts that Defendants knowingly and intentionally induce infringement by supplying the Myriad Prenatal Screens and providing instructions, manuals, and other materials that direct customers and partners (such as third-party laboratories or healthcare providers) to perform the patented methods. (Compl. ¶¶ 57-58, 69-70).
- Willful Infringement: Willfulness is alleged based on both pre- and post-suit knowledge. The complaint alleges that Defendants knew of the patents and their infringement since at least the launch date of the accused products. (Compl. ¶¶ 60-61, 72-73). This allegation is supported by the assertion that Defendants are sophisticated participants in the field and, more specifically, that the ’277 Patent was cited during the prosecution of one of Defendants' own patent applications. (Compl. ¶¶ 46-49).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of chemical and functional scope: does the specific preservative chemistry within the commercially available Streck tubes, as used in the accused tests, perform the function of inhibiting or impeding cell lysis in a manner that falls within the scope of the terms as defined in the asserted patents?
- A second key question will be one of knowledge and intent: what evidence will be presented to establish that Defendants had pre-suit knowledge of the patents-in-suit and formed a specific intent to encourage infringement, particularly as it relates to the claim for willful infringement? The allegation that the ’277 Patent was cited in Defendants' own patent prosecution file may be a significant factual point in this inquiry.