DCT
1:21-cv-00653
10X Genomics Inc v. Brucker Spatial Biology Inc
I. Executive Summary and Procedural Information
- Case Name: 10X Genomics, Inc. v. NanoString Technologies, Inc.
- Parties & Counsel:
- Plaintiff: 10X Genomics, Inc. (Delaware) and Prognosys Biosciences, Inc. (Delaware)
- Defendant: NanoString Technologies, Inc. (Delaware)
- Plaintiff’s Counsel: Richards, Layton & Finger, P.A.; Tensegrity Law Group LLP
- Case Identification: 1:21-cv-00653, D. Del., 05/04/2022
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant NanoString is a Delaware corporation and therefore resides in the district.
- Core Dispute: Plaintiffs allege that Defendant’s GeoMx Digital Spatial Profiler system, reagents, and services infringe seven patents related to methods and systems for spatially encoded biological assays.
- Technical Context: The technology at issue is spatial genomics, a field that enables the analysis of biological molecules like RNA and proteins while preserving their spatial context within a tissue sample, which is of significant value in complex biological research such as oncology and neuroscience.
- Key Procedural History: This Second Amended Complaint follows a series of notices provided to the Defendant. Plaintiffs allege that Defendant had knowledge of the first four asserted patents no later than May 5, 2021, via a detailed letter, and had knowledge of the subsequently issued patents on or around their respective issue dates, which may be relevant to the allegations of willful infringement.
Case Timeline
| Date | Event |
|---|---|
| 2010-04-05 | Earliest Priority Date for all Asserted Patents |
| 2019-03-27 | Accused GeoMx DSP Commercial Launch Announced |
| 2019-11-12 | U.S. Patent No. 10,472,669 Issued |
| 2021-03-30 | U.S. Patent No. 10,961,566 Issued |
| 2021-04-20 | U.S. Patent No. 10,983,113 Issued |
| 2021-05-04 | U.S. Patent No. 10,996,219 Issued |
| 2021-05-05 | NanoString allegedly put on notice of infringement of ’669, ’566, ’113, and ’219 Patents |
| 2021-05-11 | U.S. Patent No. 11,001,878 Issued |
| 2021-05-18 | U.S. Patent No. 11,008,607 Issued |
| 2022-04-05 | U.S. Patent No. 11,293,917 Issued |
| 2022-04-08 | NanoString allegedly put on notice of infringement of ’917 Patent |
| 2022-05-04 | Second Amended Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,472,669 - "Spatially encoded biological assays"
The Invention Explained
- Problem Addressed: The patent’s background describes a need for methods that can simultaneously measure the expression of many genes or the activity of multiple proteins at numerous distinct spatial locations within a biological sample, noting that prior methods lacked the necessary combination of high resolution, multiplexing capability, and scalability (’669 Patent, col. 1:46-62).
- The Patented Solution: The invention provides a method for creating high-resolution spatial maps of biological activity. The process involves delivering probes (e.g., antibodies conjugated to oligonucleotides) to a tissue sample, allowing them to bind to targets (e.g., proteins), imaging the sample to identify a location of interest, determining the sequence of the oligonucleotide tags from the bound probes, and then using that sequence information to associate the presence or abundance of the target back to its specific location in the sample (’669 Patent, col. 2:9-17; FIG. 1).
- Technical Importance: This approach combines the spatial resolution of in-situ analysis with the high-throughput data generation of nucleic acid sequencing, enabling highly multiplexed biological analysis within a preserved tissue context (’669 Patent, Abstract).
Key Claims at a Glance
- The complaint asserts independent claim 1 and a number of its dependent claims (Compl. ¶39).
- Claim 1 of the ’669 Patent contains the following essential elements:
- A method of delivering a plurality of probes to a tissue sample, where at least one probe comprises a protein (e.g., an antibody) that specifically binds a target biological molecule and is conjugated to an oligonucleotide.
- Imaging the tissue sample to identify a location of interest.
- Sequencing all or a portion of the oligonucleotide from the probe that is specifically bound to the target molecule in the location of interest.
- Using the determined sequence to associate the presence or abundance of the target biological molecule with the location of interest in the tissue sample.
- The complaint reserves the right to assert additional claims, including dependent claims 2, 3, 5, 10, 16, 17, 19, 22, 25, and 27 (Compl. ¶39).
U.S. Patent No. 10,961,566 - "Spatially encoded biological assays"
The Invention Explained
- Problem Addressed: Similar to the ’669 Patent, this patent addresses the technical challenge of obtaining high-resolution spatial maps of many different biological molecules simultaneously within a tissue sample, which conventional methods could not achieve efficiently (’566 Patent, col. 1:51-64).
- The Patented Solution: The patent describes a method where probes (e.g., antibodies) are conjugated to oligonucleotides via a cleavable linker and delivered to a tissue sample. After the probes bind to their targets, the oligonucleotide is released from the probe specifically within a region of interest. The sequence of this released oligonucleotide is then determined and used to map the presence or abundance of the target molecule back to that specific region of the tissue (’566 Patent, col. 2:25-42; FIG. 1).
- Technical Importance: This solution provides a mechanism for selectively analyzing molecules only from a user-defined region of a tissue sample, enabling precise spatial profiling with a high degree of multiplexing (’566 Patent, Abstract).
Key Claims at a Glance
- The complaint asserts independent claim 1 and a number of its dependent claims (Compl. ¶48).
- Claim 1 of the ’566 Patent contains the following essential elements:
- A method of delivering a plurality of probes to a tissue sample, where at least one probe comprises a protein conjugated to an oligonucleotide via a cleavable linker.
- Allowing the probe to bind to a target biological molecule.
- Releasing the oligonucleotide from the probe in a region of interest of the tissue sample.
- Determining a sequence of the released oligonucleotide.
- Associating the presence or abundance of the target biological molecule with the region of interest based on the determined sequence.
- The complaint reserves the right to assert additional claims, including dependent claims 4, 6, 17, 20, 27, 29, and 30 (Compl. ¶48).
U.S. Patent No. 10,983,113 - "Spatially encoded biological assays"
- Technology Synopsis: This patent covers methods for spatially resolved biological analysis. The invention addresses the need for high-resolution spatial maps by delivering probes to a tissue sample, allowing them to interact with biological targets, and then determining the sequence of oligonucleotide tags associated with the probes to map the targets back to their locations (’113 Patent, Abstract; col. 1:51-64).
- Asserted Claims: Independent claim 1 (Compl. ¶57).
- Accused Features: The NanoString GeoMx DSP system, GeoMx Protein Assays, and related services used for spatial profiling of proteins in conjunction with nCounter or NGS platforms (Compl. ¶56).
U.S. Patent No. 10,996,219 - "Spatially encoded biological assays"
- Technology Synopsis: This patent relates to methods for determining the spatial distribution of biological molecules in a sample. The described solution involves delivering probes conjugated to oligonucleotides to a tissue sample, releasing the oligonucleotides in a specific region, and sequencing the released oligonucleotides to associate the target molecules with that region (’219 Patent, Abstract; col. 1:51-64).
- Asserted Claims: Independent claim 1 (Compl. ¶66).
- Accused Features: The NanoString GeoMx DSP system, GeoMx Protein or RNA Assays, and related workflows and services used with nCounter or NGS platforms (Compl. ¶65).
U.S. Patent No. 11,001,878 - "Spatially encoded biological assays"
- Technology Synopsis: This patent also describes methods for spatially encoded biological assays. The invention addresses the need for highly multiplexed spatial analysis by delivering oligonucleotide-conjugated probes to a biological sample, allowing them to bind to targets, and then determining the sequence of the oligonucleotides to map the biological targets to their locations in the sample (’878 Patent, Abstract; col. 1:51-64).
- Asserted Claims: Dependent claims 2, 13, and 25 are asserted, which depend from at least one unstated independent claim (Compl. ¶75).
- Accused Features: The NanoString GeoMx DSP system, GeoMx Protein or RNA Assays, and related workflows and services for use with an nCounter platform (Compl. ¶74).
U.S. Patent No. 11,008,607 - "Spatially encoded biological assays"
- Technology Synopsis: This patent discloses methods for spatially resolving biological molecules in a sample. The technology involves delivering probes conjugated to cleavable oligonucleotide tags, releasing those tags from a specific region of interest, and sequencing the tags to identify the location and abundance of the target molecules (’607 Patent, Abstract; col. 1:51-64).
- Asserted Claims: Independent claim 1 (Compl. ¶84).
- Accused Features: The NanoString GeoMx DSP system, GeoMx RNA Assays, and related workflows and services for use with an NGS platform (Compl. ¶83).
U.S. Patent No. 11,293,917 - "Systems for analyzing target biological molecules via sample imaging and delivery of probes to substrate wells"
- Technology Synopsis: This patent describes a system, rather than just a method, for spatial biological analysis. The system comprises an imager to obtain an image of a tissue sample, a processing circuit to identify a region of interest, and a reagent delivery system to remove a portion of the sample from that region for analysis (’917 Patent, Abstract; col. 2:9-24). This allows for the physical isolation of material from a precise location for subsequent analysis.
- Asserted Claims: Independent claim 1 (Compl. ¶93).
- Accused Features: The NanoString GeoMx Digital Spatial Profiler System, including instruments, components, and consumables (Compl. ¶92).
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are Defendant’s GeoMx® Digital Spatial Profiler ("GeoMx DSP") systems, including associated instruments, consumables such as GeoMx Protein and RNA Assays, and related services, including the Technology Access Program (TAP) (Compl. ¶¶ 15, 17, 18, 19).
Functionality and Market Context
- The complaint alleges the GeoMx DSP system provides spatial profiling for protein or RNA from tissue samples (Compl. ¶16). For protein analysis, the system allegedly uses antibodies coupled to photocleavable oligonucleotide tags. After the antibodies bind to proteins in a tissue section, a user selects a discrete region of interest, and UV exposure releases the oligonucleotide tags from that specific region. The released tags are then collected and analyzed by either an nCounter® system or a next-generation sequencing (NGS) platform, and the counts are mapped back to the tissue location to create a "spatially resolved digital profile of protein abundance" (Compl. ¶17). A similar process is alleged for RNA analysis, using in situ hybridization (ISH) probes conjugated to unique DNA indexing-oligonucleotides via a UV-photocleavable linker (Compl. ¶18).
- The complaint positions the accused products as being marketed for a range of research applications, including oncology, immunology, and neuroscience (Compl. ¶16).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
’669 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a method of...delivering a plurality of probes to a tissue sample, wherein at least one probe...comprises a protein that specifically binds a target biological molecule of the tissue sample, wherein the protein is conjugated to an oligonucleotide having a sequence | Defendant's GeoMx Protein Assays allegedly rely on antibodies (proteins) coupled to photocleavable oligonucleotide tags, which are delivered to slide-mounted tissue sections. | ¶17 | col. 15:40-54 |
| imaging the tissue sample to identify a location of interest of the tissue sample | The GeoMx DSP system allegedly allows researchers to image tissue sections and select discrete regions of the tissue for analysis. | ¶¶16, 17, 18 | col. 8:43-49 |
| sequencing all or a portion of the sequence(s) of the oligonucleotide(s)...from the at least one probe specifically bound to the target biological molecule(s) in the location of interest of the tissue sample | After release from the selected region, the oligonucleotide tags are allegedly sequenced using NGS platforms. | ¶17 | col. 6:50-55 |
| and using the determined sequence(s) to associate presence or abundance of the target biological molecule(s) with the location of interest of the tissue sample. | The counts from the sequenced tags are allegedly mapped back to the tissue location to yield a spatially resolved profile of protein abundance. | ¶17 | col. 2:33-37 |
’566 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a method of...delivering a plurality of probes to a tissue sample...wherein at least one probe of the plurality of probes comprises a protein conjugated to an oligonucleotide via a cleavable linker | Defendant's GeoMx Protein and RNA Assays allegedly use antibodies or ISH probes conjugated to oligonucleotide tags via a UV-photocleavable linker. | ¶¶17, 18 | col. 15:40-54 |
| allowing the probe to bind to a target biological molecule of the tissue sample | The system involves hybridization of antibodies or ISH probes to slide-mounted tissue sections to bind to protein or RNA targets. | ¶¶17, 18 | col. 9:35-44 |
| releasing the oligonucleotide from the probe in a region of interest of the tissue sample | After a user selects a region of interest (ROI), the oligonucleotide tags are allegedly released from discrete regions of the tissue via UV exposure. | ¶¶17, 18 | col. 10:3-7 |
| determining a sequence of the released oligonucleotide | The released oligonucleotide tags are allegedly collected and sequenced using NGS platforms. | ¶17 | col. 6:50-55 |
| associating the presence or abundance of the target biological molecule with the region of interest based on the determined sequence. | The counts from the sequenced tags are allegedly mapped back to the tissue location to create a spatially resolved profile of the target molecule's abundance. | ¶17 | col. 2:33-37 |
Identified Points of Contention
- Scope Questions: The asserted claims require a step of "sequencing" the oligonucleotide tags. The complaint alleges that the accused workflow uses either NGS platforms for sequencing or nCounter systems for "counting" (Compl. ¶17). This raises the question of whether the functionality of the nCounter system, which the complaint describes as counting fluorescent barcodes (Compl. ¶18), meets the legal definition of "sequencing" as recited in the claims.
- Technical Questions: A central technical question may be whether the accused system's alleged process—delivering probes with pre-attached, photocleavable oligonucleotide tags and releasing them from a specific region—practices all the limitations of the asserted method claims, which describe systems for spatially encoding biological assays.
V. Key Claim Terms for Construction
- The Term: "sequencing"
- Context and Importance: The construction of this term is critical because the complaint alleges that the accused GeoMx workflow can use either NGS platforms ("sequenced") or nCounter platforms ("counted") (Compl. ¶17). Whether the nCounter workflow infringes the asserted claims may depend entirely on whether the act of "counting" fluorescent barcodes falls within the scope of "sequencing."
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specifications define "Sequencing" as the "determination of information relating to the nucleotide base sequence of a nucleic acid," which "may include the identification or determination of partial as well as full sequence information" (’669 Patent, col. 6:50-55). This language may support an interpretation that encompasses identifying a tag without determining its complete linear base order.
- Evidence for a Narrower Interpretation: The specifications provide numerous examples of "high throughput digital sequencing" methods, including pyrosequencing, sequencing by ligation, and sequencing by synthesis, all of which determine the linear order of nucleotide bases (’669 Patent, col. 7:1-15). This may support an interpretation limited to such traditional sequencing methods, thereby excluding the barcode counting of the nCounter system.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for all asserted patents. The inducement allegations are based on Defendant’s alleged marketing, user manuals, and instructions that encourage and guide customers to use the GeoMx DSP system in an infringing manner (Compl. ¶¶ 40, 49, 58, 67, 76, 85, 94). The contributory infringement allegations are based on the assertion that components of the GeoMx DSP system are material to the inventions and are not staple articles of commerce with substantial non-infringing uses (Compl. ¶¶ 41, 50, 59, 68, 77, 86, 96).
- Willful Infringement: Willfulness is alleged for all asserted patents based on Defendant’s alleged pre-suit knowledge. The complaint specifies that NanoString was notified of its infringement of the ’669, ’566, ’113, and ’219 patents via a letter on or around May 5, 2021, and was contemporaneously on notice of the later-issuing patents as a consequence of this letter and ongoing litigation (Compl. ¶36).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of claim construction: does the term "sequencing," as used in the patents-in-suit, encompass the digital "counting" of oligonucleotide tags performed by the accused nCounter workflow, or is its meaning limited to methods that determine the linear order of nucleotide bases, which would be relevant only to the accused NGS workflow?
- A key evidentiary question will be one of infringement and damages: assuming infringement is found, what is the proper scope of damages, particularly in light of the allegations of willful infringement based on a series of specific notice dates for each asserted patent?
- A foundational issue for the ’917 patent will be one of system vs. method: does the accused GeoMx DSP instrument, as sold and assembled by customers, meet all the limitations of the asserted system claims, which may present a different infringement analysis than for the asserted method claims practiced by end-users?