DCT
4:21-cv-00034
Biospyder Tech Inc v. HTG Molecular Diagnostics Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: BioSpyder Technologies, Inc. (Delaware)
- Defendant: HTG Molecular Diagnostics, Inc. (Delaware)
- Plaintiff’s Counsel: Wilson Sonsini Goodrich & Rosati
- Case Identification: 4:21-cv-00034, N.D. Cal., 08/12/2020
- Venue Allegations: Plaintiff BioSpyder alleges venue is proper because Defendant HTG maintains a facility in the Northern District of California, where it conducts business, develops products, and is building an NGS-based cancer diagnostic assay.
- Core Dispute: Plaintiff seeks a declaratory judgment that its TempO-Seq gene expression profiling products and services do not infringe Defendant’s patent related to quantitative nuclease protection assays.
- Technical Context: The lawsuit concerns molecular diagnostic assays for gene expression profiling, a technology used to measure the activity of thousands of genes at once to create a global picture of cellular function.
- Key Procedural History: The complaint was filed in response to a series of letters from HTG, beginning on June 29, 2020, which accused BioSpyder’s TempO-Seq technology of infringing at least Claim 1 of HTG’s patent and demanded that BioSpyder cease and desist. The correspondence, which included a claim chart provided by HTG, establishes the "actual controversy" required for a declaratory judgment action.
Case Timeline
| Date | Event |
|---|---|
| 2011-05-04 | ’564 Patent - Earliest Priority Date |
| 2014-06-03 | ’564 Patent - Issue Date |
| 2020-06-29 | HTG sends first letter to BioSpyder alleging infringement |
| 2020-07-14 | BioSpyder responds to HTG, requesting more information |
| 2020-07-17 | HTG sends second letter with claim chart alleging infringement |
| 2020-07-31 | BioSpyder responds to HTG, disputing claim interpretation |
| 2020-08-04 | HTG sends third letter again alleging infringement |
| 2020-08-12 | Complaint for Declaratory Judgment filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,741,564 - "Quantitative Nuclease Protection Assay (qNPA) and Sequencing (qNPS) Improvements"
- Patent Identification: U.S. Patent No. 8,741,564, "Quantitative Nuclease Protection Assay (qNPA) and Sequencing (qNPS) Improvements," issued June 3, 2014.
The Invention Explained
- Problem Addressed: The patent describes a need for improved methods to detect and sequence nucleic acid molecules, particularly methods that permit the simultaneous analysis of multiple samples or sequences in a way that is simpler and performs better than prior art techniques (’564 Patent, col. 1:36-42).
- The Patented Solution: The invention uses a specialized "nuclease protection probe" that includes flanking sequences at its ends (an NPPF) (’564 Patent, col. 1:52-58). This NPPF hybridizes to a target nucleic acid molecule (e.g., an mRNA molecule indicating gene expression). Crucially, separate molecules called "complementary to the flanking sequence" (CFS) are also added, which hybridize to the NPPF's own flanking sequences (’564 Patent, col. 2:41-48). This creates a fully double-stranded complex that protects the entire NPPF, including its universal flanking ends, from being destroyed by a nuclease that digests single-stranded nucleic acids (’564 Patent, col. 2:55-65). The surviving, intact NPPFs, which are proportional to the amount of target nucleic acid, can then be amplified using universal primers that bind to the flanking sequences and subsequently detected or sequenced (’564 Patent, Abstract; Fig. 2).
- Technical Importance: This method allows for highly multiplexed and quantitative analysis of nucleic acids from difficult-to-process samples, such as formalin-fixed, paraffin-embedded (FFPE) tissues, which are common in clinical settings (’564 Patent, col. 7:13-16).
Key Claims at a Glance
- The complaint asserts non-infringement of Claim 1 of the ’564 patent (Compl. ¶11).
- The essential elements of independent Claim 1, a method claim, include:
- contacting a sample with at least one nuclease protection probe comprising a flanking sequence (NPPF) which is complementary to a target nucleic acid molecule;
- contacting the sample with a nucleic acid molecule comprising a sequence complementary to the flanking sequence (CFS) under conditions for it to bind to the NPPF's flanking sequence;
- contacting the sample with a nuclease specific for single-stranded nucleic acid molecules to remove unbound molecules;
- amplifying the surviving NPPFs to generate NPPF amplicons; and
- sequencing at least a portion of the NPPF amplicons.
- The complaint does not explicitly reserve the right to assert non-infringement of other claims but focuses its narrative entirely on Claim 1.
III. The Accused Instrumentality
Product Identification
- BioSpyder’s TempO-Seq™ molecular profiling techniques, products, and services (Compl. ¶6).
Functionality and Market Context
- The TempO-Seq technology is described as a "novel" gene expression profiling assay that can monitor the expression of hundreds of thousands of genes with high throughput and minimal background signal (Compl. ¶6). The assay is designed for use with next-generation sequencing (NGS) instruments (Compl. ¶7).
- The central technical feature relevant to the dispute, as alleged by BioSpyder, is that "TempO-Seq does not include any nucleic acid molecules that have a sequence complementary to a flanking sequence ('CFS')" (Compl. ¶8, ¶16). This forms the basis of BioSpyder's non-infringement position.
IV. Analysis of Infringement Allegations
The complaint seeks a declaratory judgment of non-infringement, and its infringement analysis is based on allegations made by Defendant HTG in pre-suit correspondence, including a claim chart (Compl. ¶¶13-15).
’564 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a method of determining a sequence of at least one target nucleic acid molecule in a sample, comprising: contacting the sample with at least one nuclease protection probe comprising a flanking sequence (NPPF) ... | The complaint does not provide sufficient detail for analysis of this element. | col. 7:17-23 | |
| contacting the sample with a nucleic acid molecule comprising a sequence complementary to the flanking sequence (CFS) under conditions sufficient for the flanking sequence to specifically bind to the CFS ... | HTG alleges that "The TempO-Seq system and method includes contacting the sample with a nucleic acid molecule comprising a sequence complementary to the flanking sequence (CFS)..." | ¶15 | col. 8:26-40 |
| contacting the sample with a nuclease specific for single-stranded nucleic acid molecules under conditions sufficient to remove unbound nucleic acid molecules... | The complaint does not provide sufficient detail for analysis of this element. | col. 8:50-59 | |
| amplifying NPPFs in the digested sample with the amplification primer, thereby generating NPPF amplicons | The complaint does not provide sufficient detail for analysis of this element. | col. 9:6-12 | |
| sequencing at least a portion of the NPPF amplicons... | The complaint does not provide sufficient detail for analysis of this element. | col. 9:48-51 |
No probative visual evidence provided in complaint.
Identified Points of Contention
- Technical Question: The primary point of contention is a factual dispute over how the TempO-Seq technology operates. Does the accused method, in fact, involve contacting the sample with a "nucleic acid molecule comprising a sequence complementary to the flanking sequence (CFS)"? BioSpyder's complaint is predicated on the assertion that it does not (Compl. ¶16).
- Scope Questions: The dispute raises a critical claim construction question regarding the definition of a "CFS." Does this term require a distinct, separate oligonucleotide molecule to be added to the reaction for the purpose of protecting the NPPF's flanking sequence, as depicted in the patent's specification (e.g., Figure 2, element 204), or might HTG be advancing a broader interpretation that reads on a component or step of the TempO-Seq process that BioSpyder does not consider to be a "CFS"?
V. Key Claim Terms for Construction
- The Term: "a nucleic acid molecule comprising a sequence complementary to the flanking sequence (CFS)" (from Claim 1).
- Context and Importance: This term is the linchpin of the dispute. BioSpyder’s entire argument for non-infringement rests on its assertion that the TempO-Seq technology does not use a "CFS" (Compl. ¶8, ¶16). The definition of this term will therefore be determinative of infringement. Practitioners may focus on this term because its construction appears to be the central disagreement outlined in the pre-suit correspondence (Compl. ¶¶14-17).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent states that a CFS is a molecule having a sequence "complementary to all or a portion of a flanking sequence" (’564 Patent, col. 2:42-44, emphasis added). This language could potentially support an argument that something less than a fully complementary, separate molecule could meet the definition.
- Evidence for a Narrower Interpretation: The patent's summary and detailed description repeatedly describe the CFS as one or more molecules that are added to the sample to "protect[] its corresponding flanking sequence from digestion" (’564 Patent, col. 8:38-40). Figure 2, which illustrates the claimed method, explicitly depicts the CFS (element 204) as a separate molecule that hybridizes to the flanking sequence of the NPPF (element 202) prior to nuclease digestion. This consistent depiction of the CFS as a distinct, protective component added to the reaction may support a narrower construction.
VI. Other Allegations
- Indirect Infringement: HTG's pre-suit correspondence accused BioSpyder of both direct infringement and inducing infringement by others (’564 Patent, Compl. ¶13). The complaint does not provide further factual details on the basis for the inducement allegation.
- Willful Infringement: As a declaratory judgment complaint, this action does not allege willfulness. However, the complaint documents a series of letters from HTG to BioSpyder beginning on June 29, 2020, which provided BioSpyder with actual notice of the patent and HTG's infringement allegations (Compl. ¶¶11, 13, 18). This correspondence would be relevant to any future claim of willful infringement that HTG might bring against BioSpyder.
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this declaratory judgment action will likely depend on the answers to two central questions:
- A core issue will be one of claim construction: What is the proper legal scope of the term "a nucleic acid molecule comprising a sequence complementary to the flanking sequence (CFS)"? Must this be a distinct molecule added for the express purpose of protecting the probe's flanking sequence, as the patent's figures and embodiments suggest, or can the term encompass a different structure or process step within an assay?
- A key evidentiary question will be one of technical operation: Assuming a definition for "CFS" is established, does BioSpyder’s TempO-Seq method in fact practice this claim step? The case will turn on the evidence presented regarding the precise molecular biology and protocol of the accused technology.