DCT
6:20-cv-00452
Ravgen Inc v. PerkinElmer Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Ravgen, Inc. (Delaware)
- Defendant: PerkinElmer, Inc. (Massachusetts); PerkinElmer Genetics, Inc. (Pennsylvania); and Bioo Scientific Corporation (Texas)
- Plaintiff’s Counsel: Desmarais LLP
- Case Identification: Ravgen, Inc. v. PerkinElmer, Inc., et al., 6:20-cv-00452, 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 in the district, including established places of business in Austin, Texas. Defendant Bioo Scientific Corporation is alleged to be a Texas corporation with its principal place of business within the district.
- Core Dispute: Plaintiff alleges that Defendant’s non-invasive prenatal testing (NIPT) assays and related cell-free DNA (cfDNA) preparation kits infringe patents directed to methods for preserving and isolating cell-free nucleic acids from biological samples.
- Technical Context: The technology relates to non-invasive prenatal testing, a field that analyzes trace amounts of cell-free fetal DNA circulating in a pregnant mother's blood to screen for genetic abnormalities without the risks of invasive procedures.
- Key Procedural History: The complaint alleges that Plaintiff provided Defendants with notice of the patents-in-suit and their alleged infringement via a letter dated May 15, 2020. During the prosecution of one of the patents-in-suit, the applicant argued to the U.S. Patent and Trademark Office that the addition of a cell lysis inhibitor to a sample provided "significant and unexpectedly" improved results.
Case Timeline
| Date | Event |
|---|---|
| 2002-05-08 | Earliest Priority Date ('277 & '720 Patents) |
| 2008-02-19 | U.S. Patent No. 7,332,277 Issues |
| 2010-06-01 | U.S. Patent No. 7,727,720 Issues |
| 2015-02-01 | Bioo Scientific launches NextPrep-Mag/NEXTflex kits (approximate) |
| 2016-01-01 | PerkinElmer begins commercializing chemagic cfDNA 5k Kits (approximate) |
| 2018-01-01 | PerkinElmer launches Vanadis® NIPT Assay (approximate) |
| 2020-05-15 | Ravgen 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 February 19, 2008
The Invention Explained
- Problem Addressed: The patent addresses the difficulty of detecting fetal DNA in a maternal blood sample (Compl. ¶54). This difficulty arises because fetal DNA is present in very low concentrations relative to maternal DNA, and this problem is exacerbated when maternal blood cells break down (lyse) after the sample is drawn, releasing more maternal DNA that contaminates the sample ('277 Patent, col. 32:24-39).
- The Patented Solution: The invention proposes adding an agent to the blood sample at the time of collection that inhibits or prevents cell lysis ('277 Patent, col. 91:48-52). By stabilizing the maternal cells and preventing them from releasing their DNA, the method increases the relative percentage of the naturally occurring cell-free fetal DNA in the sample's plasma fraction, making it easier to detect and analyze for genetic abnormalities (Compl. ¶55; '277 Patent, col. 32:31-39).
- Technical Importance: This method provided a way to improve the signal-to-noise ratio in non-invasive genetic testing, enhancing the accuracy and reliability of tests that rely on detecting minute quantities of target DNA (Compl. ¶42).
Key Claims at a Glance
- The complaint asserts at least independent claim 81 (Compl. ¶88).
- The essential elements of Claim 81 are:
- 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 notes that Defendants have infringed "one or more claims" of the patent (Compl. ¶87).
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 vast majority of DNA in a maternal plasma sample is maternal, which "makes using the DNA for genotyping the fetus difficult" ('720 Patent, col. 33:31-37).
- The Patented Solution: The patented method involves a two-step process: first, isolating free nucleic acid from the non-cellular part of a sample that contains an agent to impede cell lysis, and second, detecting that isolated nucleic acid ('720 Patent, col. 9:56-65). The addition of a cell lysis inhibitor, membrane stabilizer, or cross-linker prevents the release of contaminating DNA from maternal cells, thereby increasing the relative proportion of fetal DNA available for detection ('720 Patent, col. 33:38-46).
- Technical Importance: This invention provides a complete method, from sample preparation to detection, for improving the accuracy of non-invasive genetic tests by preserving the integrity of the initial sample (Compl. ¶57).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶101).
- 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 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 notes that Defendants have infringed "one or more claims" of the patent (Compl. ¶100).
III. The Accused Instrumentality
Product Identification
The complaint identifies two categories of accused instrumentalities: (1) the Vanadis® NIPT Assay and associated system; and (2) various "cfDNA Kits," including the chemagic™ cfDNA 5k Kits, NextPrep-Mag™ cfDNA Automated Isolation Kits, and NEXTflex® Cell-Free DNA-Seq Kits (Compl. ¶4).
Functionality and Market Context
- The Vanadis® NIPT Assay is described as a commercial, non-invasive prenatal test used to screen for fetal chromosomal abnormalities by extracting and analyzing cfDNA from maternal blood (Compl. ¶60). The complaint alleges that this assay uses maternal blood samples collected in Streck Cell-Free DNA BCT® tubes, which are said to contain a "unique preservative" that "limits the release of genomic DNA" by "limiting cell lysis" (Compl. ¶62, ¶63). A diagram in the complaint shows the first step of the Vanadis process is "cfDNA is extracted from maternal plasma" (Compl. ¶60, Ex. 34 at 1).
- The cfDNA Kits are identified as products designed to extract cell-free DNA from a sample, which can then be used for applications like NIPT (Compl. ¶70, ¶76). The complaint alleges these kits are used to process blood samples that have been collected in the same Streck Cell-Free DNA BCT® tubes, which contain an agent that inhibits cell lysis (Compl. ¶77, ¶78). A workflow diagram provided in the complaint shows a "chemagic™ 360 instrument for automated cfDNA extraction from 5mL plasma" as a key part of the process for these kits (Compl. ¶75, Ex. 55).
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 Vanadis® NIPT Assay and the cfDNA Kits are used to extract cell-free fetal DNA from maternal blood samples. | ¶88a, ¶89a | col. 473:78-80 |
| wherein said sample comprises an agent that inhibits lysis of cells, if cells are present, | The accused methods allegedly use maternal blood samples collected in Streck Cell-Free DNA BCT® tubes, which are alleged to contain a preservative chemistry that "limit[s] cell lysis." | ¶88b, ¶89b | col. 473:4-6 |
| 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, by inhibiting cell lysis, functions as one of the claimed agent types. | ¶88b, ¶89b | col. 473:5-7 |
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 Vanadis Extract® platform performs plasma separation and cfDNA extraction; the cfDNA Kits are used to extract cfDNA from plasma samples. | ¶101a, ¶102a | col. 535:15-17 |
| 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 methods allegedly use maternal blood samples collected in Streck Cell-Free DNA BCT® tubes, which contain a preservative that is alleged to impede cell lysis. | ¶101b, ¶102b | col. 535:17-21 |
| and (b) detecting the presence or absence of the free nucleic acid. | The Vanadis system analyzes the extracted cfDNA using fluorescent probes; the cfDNA kits prepare libraries from the extracted cfDNA for sequencing, which is a form of detection. | ¶101c, ¶102c | col. 535:15 |
Identified Points of Contention
- Scope Questions: A central question may be whether the "unique preservative" in the third-party Streck tubes falls within the scope of the claimed Markush group of "membrane stabilizer, cross-linker, and cell lysis inhibitor." The complaint relies on Streck’s marketing language that its product "limits cell lysis" to connect the accused methods to the patents, but the chemical identity and mechanism of the agent are not specified.
- Technical Questions: The infringement analysis may depend on factual discovery into the chemical composition of the preservative in the Streck tubes. The patents provide formaldehyde as a working example of a cross-linker, and a key technical question will be whether the agent in the Streck tubes operates via a similar or different mechanism of cell stabilization.
V. Key Claim Terms for Construction
- The Term: "agent that inhibits [or impedes] lysis of cells"
- Context and Importance: This term is the central inventive concept recited in the asserted claims. The Plaintiff's infringement theory appears to depend entirely on the preservative within the third-party Streck blood collection tubes meeting this definition. Practitioners may focus on this term because its construction will determine whether the use of those tubes brings the accused methods within the scope of the claims.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specifications provide a broad, functional description, stating "any agent that prevents the lysis of cells or increases the structural integrity of the cells can be used" ('277 Patent, col. 91:50-52; ’720 Patent, col. 92:17-19). This language may support an interpretation covering any chemical that achieves the result of limiting cell breakdown, regardless of its specific mechanism.
- Evidence for a Narrower Interpretation: The specifications repeatedly use formaldehyde as a primary example of an effective agent ('277 Patent, col. 91:48-49; ’720 Patent, col. 92:15-16). A defendant may argue that the term should be construed as limited to agents that function as covalent cross-linkers like formaldehyde, potentially excluding other types of preservatives that might stabilize cells through different means.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement of infringement on the basis that Defendants sell and supply the accused assays and kits with the knowledge and intent that their customers will use them in an infringing manner (Compl. ¶91, ¶104). This is allegedly supported by Defendants' dissemination of promotional materials, instructions, and product manuals that instruct users to perform the patented methods (Compl. ¶91, ¶104). The complaint also pleads contributory infringement, alleging the products are a material part of the invention, are not staple articles of commerce, and are especially adapted for infringement (Compl. ¶93, ¶106).
- Willful Infringement: The complaint alleges willful infringement based on Defendants' continued infringing conduct after receiving actual notice of the patents-in-suit and their alleged infringement via a letter from Ravgen dated May 15, 2020 (Compl. ¶95, ¶108).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of technical and definitional scope: does the unspecified chemical preservative in the third-party Streck blood collection tubes, which are used as part of the accused methods, function in a manner that falls within the patent's claimed definition of an "agent that inhibits lysis of cells," as construed by the court? Resolution will likely depend on expert evidence regarding the agent's precise chemical mechanism.
- A second key question will be one of infringement liability: assuming the use of Streck tubes is found to be infringing, the analysis will focus on whether Defendants' actions—selling and providing instructions for assays and kits intended for use with these specific third-party tubes—are sufficient to establish liability for induced or contributory infringement.