1013-00005 · Genome Dx Therapeutics Inc · Pleadings

complaint-patent-infringement.docx DOCUMENT Litigation

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UNITED STATES DISTRICT COURT FOR THE NORTHERN DISTRICT OF CALIFORNIA

Plaintiff Genome Dx Therapeutics Inc. ("GenomeDx" or "Plaintiff"), by and through its attorneys Calderwood & Harkness LLP, for its Complaint against Defendant Helios Precision Diagnostics, Inc. ("Helios" or "Defendant"), hereby alleges as follows:

INTRODUCTION

1. GenomeDx brings this action for patent infringement against Helios under the patent laws of the United States, 35 U.S.C. § 1 et seq. This action seeks injunctive relief, compensatory damages, enhanced damages for willful infringement, and other relief arising from Helios's unauthorized making, using, selling, and offering for sale of a genomic classifier test that infringes three of GenomeDx's United States patents.

2. GenomeDx is a pioneer in the field of molecular diagnostics, with particular expertise in the development, validation, and clinical deployment of genomic-classifier methods for prostate cancer prognosis. GenomeDx holds a robust and valuable patent portfolio comprising forty-seven (47) issued United States patents, twelve (12) pending United States patent applications, and nineteen (19) international family members, collectively covering GenomeDx's proprietary methods for genomic classification, gene-expression profiling, machine-learning-based prognostic scoring, and integrated clinical-genomic reporting for cancer outcomes.

3. GenomeDx's proprietary Decipher® Prostate genomic classifier test is the market-leading prognostic tool for prostate cancer recurrence and metastasis prediction following radical prostatectomy. The Decipher® test is the product of more than a decade of intensive research, development, clinical validation, and commercialization efforts by GenomeDx. The Decipher® test has been validated in more than forty peer-reviewed clinical studies, is included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Prostate Cancer, and is widely utilized by urologists and radiation oncologists across the United States. In fiscal year 2024, the Decipher® Prostate test generated three hundred eighty-seven million six hundred thousand dollars ($387,600,000) in revenue for GenomeDx, reflecting GenomeDx's substantial investment in and the significant clinical and commercial value of its proprietary technology.

4. GenomeDx brings this action to enforce three of its United States patents — U.S. Patent No. 10,438,271 ("the '271 Patent"), U.S. Patent No. 11,204,893 ("the '893 Patent"), and U.S. Patent No. 11,891,647 ("the '647 Patent") (collectively, the "Patents-in-Suit") — against Helios's competing ProstaSignal™ Genomic Classifier test. Helios commercially launched the ProstaSignal™ test on October 7, 2024. The ProstaSignal™ test directly and knowingly infringes GenomeDx's patent rights by employing the same fundamental methods, gene-expression profiling techniques, machine-learning classification approaches, and integrated clinical-genomic reporting methods that GenomeDx invented, patented, and commercialized. Since its launch, the ProstaSignal™ test has captured significant market share from GenomeDx, causing GenomeDx substantial and ongoing financial harm.

THE PARTIES

Plaintiff Genome Dx Therapeutics Inc.

5. Plaintiff Genome Dx Therapeutics Inc. is a corporation organized and existing under the laws of the State of Delaware. GenomeDx is qualified to do business in the State of California and maintains its principal place of business and corporate headquarters at 4750 Torrey Pines Road, Suite 300, San Diego, California 92130. GenomeDx's registered agent in Delaware is Pacific Registered Agents, Inc., located at 1209 Orange Street, Wilmington, Delaware 19801.

6. GenomeDx was founded in 2011 and is a molecular diagnostics company focused on the development and commercialization of genomic classification technologies for cancer prognosis. GenomeDx's core competency lies in the application of advanced machine-learning techniques to multi-gene expression data to generate clinically actionable prognostic information for cancer patients and their treating physicians.

7. GenomeDx is led by a team of experienced scientists and executives, including Dr. Miriam Langford, PhD, Chief Executive Officer; Dr. Rajan Mehta, PhD, Chief Technology Officer and a named inventor on two of the three Patents-in-Suit; and Victoria Sung, JD, General Counsel. GenomeDx employs approximately eight hundred twenty (820) people, including approximately three hundred forty (340) laboratory and research and development personnel dedicated to advancing GenomeDx's genomic classification technologies.

8. GenomeDx is the sole and exclusive owner and assignee of all right, title, and interest in and to the Patents-in-Suit, including the right to sue for and recover damages for past and ongoing infringement. GenomeDx has standing to bring this action and to seek the relief requested herein.

Defendant Helios Precision Diagnostics, Inc.

9. Defendant Helios Precision Diagnostics, Inc. is a corporation organized and existing under the laws of the State of Delaware. Helios is qualified to do business in the Commonwealth of Massachusetts and in the State of California. Helios maintains its principal place of business and corporate headquarters at 200 CambridgePark Drive, Suite 600, Cambridge, Massachusetts 02140.

10. Helios operates a Clinical Laboratory Improvement Amendments ("CLIA")-certified laboratory located at 9830 Mesa Rim Road, Suite 140, San Diego, California 92121. The accused ProstaSignal™ Genomic Classifier test is performed at this San Diego laboratory facility.

11. Helios was founded in 2019 and is a molecular diagnostics company. Helios is led by Dr. Nathan Ashford, MD, PhD, Chief Executive Officer, and Dr. Elaine Kossack, PhD, Chief Scientific Officer. Helios employs approximately two hundred fifteen (215) people.

12. Helios is the maker, user, seller, and offeror for sale of the accused ProstaSignal™ Genomic Classifier test, which is the subject of the infringement allegations set forth in this Complaint.

13. Upon information and belief, Helios has performed approximately eight thousand four hundred (8,400) ProstaSignal™ tests between the October 7, 2024 commercial launch date and March 2025. Upon information and belief, Helios has generated estimated revenue of approximately thirty-two million eighty-eight thousand dollars ($32,088,000) from sales of the ProstaSignal™ test during this period, based on an average reimbursement rate of approximately three thousand eight hundred twenty dollars ($3,820) per test.

JURISDICTION AND VENUE

Subject Matter Jurisdiction

14. This Court has subject matter jurisdiction over this action pursuant to 28 U.S.C. § 1331, as this action arises under the laws of the United States, and pursuant to 28 U.S.C. § 1338(a), as this action arises under the patent laws of the United States, specifically the Patent Act, 35 U.S.C. § 1 et seq.

Personal Jurisdiction.

15. This Court has personal jurisdiction over Helios. Helios is subject to personal jurisdiction in this judicial district and in the State of California for the following reasons:

(a) Helios is qualified to do business and conducts substantial business within the State of California.

(b) Helios operates a CLIA-certified laboratory located at 9830 Mesa Rim Road, Suite 140, San Diego, California 92121, which is within the State of California. This laboratory constitutes a substantial, continuous, and systematic contact with the State of California sufficient to confer general personal jurisdiction.

(c) Helios performs the accused ProstaSignal™ Genomic Classifier test at its San Diego, California laboratory facility, where Helios processes biological samples submitted by healthcare providers, performs RNA extraction and gene-expression profiling, applies its machine-learning classifier to generate prognostic scores, and generates and transmits integrated prognostic reports to healthcare providers, all within the State of California.

(d) Helios has committed and continues to commit acts of patent infringement within this judicial district and within the State of California, including by making, using, selling, and offering to sell the accused ProstaSignal™ test.

(e) Helios markets, promotes, sells, and offers to sell the ProstaSignal™ test to healthcare providers and medical institutions within this judicial district and within the State of California.

16. The exercise of personal jurisdiction over Helios is consistent with the requirements of the Due Process Clause of the Fourteenth Amendment to the United States Constitution.

Venue.

17. Venue is proper in this judicial district pursuant to 28 U.S.C. § 1400(b) because Helios has committed acts of infringement within this judicial district and has a regular and established place of business within this judicial district, specifically its CLIA-certified laboratory located at 9830 Mesa Rim Road, Suite 140, San Diego, California 92121. Helios maintains permanent personnel, laboratory equipment, and facilities at this location, which constitutes a regular and established place of business within the meaning of 28 U.S.C. § 1400(b).

18. Alternatively, venue is proper in this judicial district because Helios is subject to personal jurisdiction in this judicial district, and the requirements of 28 U.S.C. § 1400(b) are otherwise satisfied.

FACTUAL BACKGROUND

GenomeDx and the Decipher® Prostate Genomic Classifier

19. GenomeDx was founded in 2011 with the mission of developing and commercializing advanced genomic classification technologies to improve cancer patient outcomes. Over the past fourteen years, GenomeDx has invested hundreds of millions of dollars in research and development, clinical validation, and commercialization of its proprietary genomic-classifier technologies. GenomeDx has become a recognized leader in the field of molecular diagnostics for cancer prognosis, with a particular focus on prostate cancer.

20. GenomeDx developed the Decipher® Prostate genomic classifier test, a proprietary twenty-two (22)-gene expression-based prognostic test used to predict the likelihood of clinical recurrence and metastasis following radical prostatectomy for prostate cancer. The Decipher® test represents a breakthrough in the field of prostate cancer management, providing physicians and patients with clinically validated, objective, and reproducible genomic information to guide post-surgical treatment decisions, including decisions regarding adjuvant radiation therapy, salvage radiation therapy, and systemic therapy.

21. The Decipher® test involves the following key steps:

(a) Obtaining a biological sample containing tumor RNA from formalin-fixed paraffin-embedded ("FFPE") prostate tissue. The use of FFPE tissue, rather than fresh-frozen tissue, is a critical feature of GenomeDx's technology, as it allows the test to be performed on routinely archived surgical specimens without requiring special tissue handling at the time of surgery.

(b) Measuring expression levels of a panel of twenty-two (22) genes from a predefined gene set. These twenty-two genes were identified and selected through extensive bioinformatics analysis and clinical validation as the optimal set of genomic biomarkers for prostate cancer prognostic classification.

(c) Applying a trained machine-learning classifier — specifically, a random-forest classifier trained on a cohort of at least five hundred (500) patient samples with known clinical outcomes — to the measured gene-expression data to generate a numerical prognostic risk score. The random-forest classifier is a supervised machine-learning algorithm that aggregates predictions from a large ensemble of individual decision trees to produce a robust, accurate prognostic score.

(d) Classifying the patient into one of three risk categories — Low, Intermediate, or High — based on the generated risk score, to inform clinical decision-making regarding the need for and timing of adjuvant or salvage therapies.

22. In addition to the genomic risk score and risk category classification, the Decipher® test provides an integrated prognostic report that combines the genomic risk score with relevant clinical covariates, including Gleason score, pre-operative prostate-specific antigen ("PSA") level, surgical margin status, and pathological stage. This integrated approach — combining genomic and clinical data into a single, actionable report — is a key innovation of GenomeDx's technology and a subject of the Patents-in-Suit.

23. The Decipher® test is a laboratory-developed test ("LDT") performed exclusively at GenomeDx's CLIA-certified, College of American Pathologists ("CAP")-accredited laboratory. The Decipher® test is reimbursed by the Centers for Medicare & Medicaid Services ("CMS") under the Molecular Diagnostic Services ("MolDX") program. GenomeDx obtained a unique Multianalyte Assays with Algorithmic Analyses ("MAAA") code (0047M) from the American Medical Association for the Decipher® test in 2018, reflecting the test's clinically distinct status and the recognition of its unique methodology.

24. GenomeDx submitted a De Novo classification application with the United States Food and Drug Administration ("FDA") for the Decipher® test on August 15, 2024. That application is currently pending review. GenomeDx's pursuit of FDA authorization further demonstrates the significant investment and commitment GenomeDx has made in its proprietary technology.

25. Prior to the commercial launch of Helios's ProstaSignal™ test in October 2024, GenomeDx held a commanding market position with approximately seventy-four percent (74%) market share in the genomic prostate cancer prognostic testing market in the United States. GenomeDx's market leadership was the result of its pioneering scientific innovations, its extensive clinical validation program, its strong payor relationships, and its broad adoption by urologists and radiation oncologists across the country.

26. GenomeDx generated three hundred eighty-seven million six hundred thousand dollars ($387,600,000) in revenue in fiscal year 2024, with the vast majority of this revenue derived from Decipher® test reimbursements. GenomeDx's substantial revenue base reflects the significant clinical and commercial value of its proprietary genomic-classification technology.

GenomeDx's Patent Portfolio and the Patents-in-Suit

27. GenomeDx holds a robust and comprehensive patent portfolio consisting of forty-seven (47) issued United States patents, twelve (12) pending United States patent applications, and nineteen (19) international family members. This portfolio covers GenomeDx's proprietary genomic-classifier methods, including methods for gene-expression profiling from FFPE tissue specimens, machine-learning-based classification algorithms for cancer prognosis, multi-gene expression panels for prostate cancer risk stratification, and integrated clinical-genomic reporting systems and methods.

28. GenomeDx has invested substantial resources in developing, prosecuting, maintaining, and enforcing its patent portfolio. GenomeDx's patent portfolio represents the culmination of years of scientific research, bioinformatics analysis, clinical validation, and innovation by GenomeDx's scientists and engineers. The patent portfolio is a critical intellectual property asset of GenomeDx.

29. The three Patents-in-Suit — the '271 Patent, the '893 Patent, and the '647 Patent — represent core innovations in genomic classification methods for prostate cancer prognosis. These patents cover fundamental aspects of GenomeDx's proprietary Decipher® technology, including the methods for multi-gene expression-based classification, the specific machine-learning classifier architectures and training methodologies employed, and the methods for generating integrated clinical-genomic prognostic reports. Each of the Patents-in-Suit is described in detail below.

Helios and the ProstaSignal™ Genomic Classifier

30. Helios was founded in 2019, approximately eight years after GenomeDx. Upon information and belief, Helios was founded with the objective of developing and commercializing molecular diagnostic tests for cancer prognosis, including tests that compete directly with GenomeDx's Decipher® test.

31. On or about October 7, 2024, Helios commercially launched the ProstaSignal™ Genomic Classifier, a twenty-four (24)-gene expression-based prognostic test for prostate cancer patients who have undergone radical prostatectomy. The ProstaSignal™ test was designed and marketed as a direct competitor to GenomeDx's Decipher® test and targets the same clinical use case — post-prostatectomy prognostic risk stratification.

32. Upon information and belief, the ProstaSignal™ test uses a twenty-four (24)-gene expression panel. Of the twenty-four genes in the ProstaSignal™ panel, nineteen (19) genes overlap with GenomeDx's patented gene set used in the Decipher® test. This extensive overlap — comprising approximately seventy-nine percent (79%) of the ProstaSignal™ gene panel — is not coincidental and reflects Helios's deliberate copying of GenomeDx's proprietary gene panel selection.

33. Upon information and belief, the ProstaSignal™ test applies a gradient-boosted decision tree classifier — which is a type of trained machine-learning classifier — to the measured gene-expression data to generate a numerical prognostic score designated by Helios as the "ProstaScore." The ProstaScore is a numerical value ranging from 0 to 100, with higher scores indicating greater risk of clinical recurrence and metastasis. Like GenomeDx's Decipher® test, the ProstaSignal™ test classifies patients into Low, Intermediate, or High risk categories based on the ProstaScore.

34. Upon information and belief, the ProstaSignal™ test combines the ProstaScore with clinical covariates, including Gleason grade group and pre-operative PSA level, to generate an integrated prognostic report that is transmitted to the ordering healthcare provider. This integrated reporting approach mirrors the methodology invented by GenomeDx and claimed in the Patents-in-Suit.

35. Helios obtained a MAAA code (0239M) for the ProstaSignal™ test from the American Medical Association in September 2024, approximately one month before the commercial launch. The ProstaSignal™ test is performed at Helios's CLIA-certified laboratory located at 9830 Mesa Rim Road, Suite 140, San Diego, California 92121.

36. Since its commercial launch on October 7, 2024, the ProstaSignal™ test has captured significant market share from GenomeDx. GenomeDx's market share in the genomic prostate cancer prognostic testing market has declined from approximately seventy-four percent (74%) prior to the ProstaSignal™ launch to approximately sixty-eight percent (68%) as of the filing of this Complaint, a decline of approximately six (6) percentage points that is directly attributable to Helios's infringing activities. This market share loss has caused and continues to cause GenomeDx substantial economic harm.

THE PATENTS-IN-SUIT

U.S. Patent No. 10,438,271 ("the '271 Patent")

37. On October 8, 2019, the United States Patent and Trademark Office ("USPTO") duly and lawfully issued U.S. Patent No. 10,438,271, entitled "Methods for Predicting Prostate Cancer Outcomes Using Multi-Gene Expression Classifiers" (the "'271 Patent"). A true and correct copy of the '271 Patent is attached hereto as Exhibit A and is incorporated herein by reference.

38. The application that matured into the '271 Patent was filed on June 14, 2016. The '271 Patent has an expiration date of June 14, 2036.

39. The named inventors of the '271 Patent are Dr. Rajan Mehta, Dr. Carolyn Xu, and Dr. David Petrossian, each of whom conceived and developed the inventions claimed therein during the course of their employment with GenomeDx. Each named inventor assigned all right, title, and interest in the '271 Patent to GenomeDx. GenomeDx is the sole and exclusive owner of the '271 Patent, including the right to sue for and recover damages for infringement.

40. The '271 Patent is valid, enforceable, and currently in force. All maintenance fees and other obligations necessary to maintain the '271 Patent in force have been timely paid and satisfied.

41. GenomeDx asserts Claims 1, 3, 5, 7, 12, and 18 of the '271 Patent against Helios in this action.

42. Claim 1 of the '271 Patent recites:

A method for prognosing the likelihood of clinical recurrence following radical prostatectomy comprising:

(a) obtaining a biological sample containing tumor RNA;

(b) measuring expression levels of a panel of at least 22 genes selected from a predefined gene set;

(d) classifying the patient into a risk category based on the score.

43. Claim 3 of the '271 Patent depends from Claim 1 and further specifies that the predefined gene set comprises genes associated with cell proliferation, cell adhesion, immune response, androgen signaling, and stromal response pathways, thereby defining the functional categories from which the at least twenty-two genes are selected.

44. Claim 5 of the '271 Patent depends from Claim 1 and further specifies that the trained machine-learning classifier is a random-forest classifier trained on a cohort of at least five hundred patient samples with known five-year clinical outcomes, including known metastasis status.

45. Claim 7 of the '271 Patent depends from Claim 1 and further specifies that the biological sample is a formalin-fixed paraffin-embedded tissue specimen from which RNA is extracted using an acid-guanidinium-phenol extraction protocol or equivalent nucleic acid isolation method.

46. Claim 12 of the '271 Patent depends from Claim 1 and further specifies that the risk categories comprise at least three categories — Low, Intermediate, and High — with defined score thresholds that stratify patients according to their predicted probability of clinical recurrence within a five-year post-surgical period.

47. Claim 18 of the '271 Patent depends from Claim 1 and further specifies that the method includes generating a prognostic report comprising the risk score, the risk category, and at least one clinical covariate selected from the group consisting of Gleason score, PSA level, surgical margin status, and pathological stage, and transmitting the report to a healthcare provider.

U.S. Patent No. 11,204,893 ("the '893 Patent")

48. On December 21, 2021, the USPTO duly and lawfully issued U.S. Patent No. 11,204,893, entitled "Genomic Classifier Systems and Methods for Post-Surgical Cancer Prognosis" (the "'893 Patent"). A true and correct copy of the '893 Patent is attached hereto as Exhibit B and is incorporated herein by reference.

49. The application that matured into the '893 Patent was filed on March 22, 2019, as a continuation application in the same patent family as the '271 Patent. The '893 Patent claims priority through the same priority chain as the '271 Patent and has an expiration date of June 14, 2036.

50. The named inventors of the '893 Patent are Dr. Rajan Mehta and Dr. Carolyn Xu, each of whom conceived and developed the inventions claimed therein during the course of their employment with GenomeDx. Each named inventor assigned all right, title, and interest in the '893 Patent to GenomeDx. GenomeDx is the sole and exclusive owner of the '893 Patent, including the right to sue for and recover damages for infringement.

51. The '893 Patent is valid, enforceable, and currently in force. All maintenance fees and other obligations necessary to maintain the '893 Patent in force have been timely paid and satisfied.

52. GenomeDx asserts Claims 1, 2, 9, 14, and 20 of the '893 Patent against Helios in this action.

53. Claim 1 of the '893 Patent recites:

A method comprising:

normalizing gene-expression data from a formalin-fixed paraffin-embedded prostate tissue sample using a reference gene panel;

inputting normalized expression values into a random-forest classifier trained on a cohort of at least 500 patient samples; and

outputting a numerical prognostic score correlated with metastasis risk within 5 years.

54. Claim 2 of the '893 Patent depends from Claim 1 and further specifies that the normalization step comprises quantile normalization using a reference gene panel comprising at least five housekeeping genes, followed by batch-effect correction using a linear model.

55. Claim 9 of the '893 Patent depends from Claim 1 and further specifies that the random-forest classifier comprises at least five hundred individual decision trees, each trained on a bootstrap sample of the training cohort, and that the prognostic score is computed as the average of the individual tree predictions.

56. Claim 14 of the '893 Patent depends from Claim 1 and further specifies that the training cohort of at least five hundred patient samples comprises samples from at least three independent clinical study cohorts, with at least twenty-four months of follow-up data for each sample.

57. Claim 20 of the '893 Patent depends from Claim 1 and further specifies that the numerical prognostic score is a continuous score between 0 and 1, and that the method further comprises converting the continuous score into a categorical risk classification comprising at least three risk strata with clinically validated score thresholds.

U.S. Patent No. 11,891,647 ("the '647 Patent")

58. On February 6, 2024, the USPTO duly and lawfully issued U.S. Patent No. 11,891,647, entitled "Improved Methods for Genomic Risk Stratification in Prostate Cancer Using Combined Biomarker and Clinical Variable Models" (the "'647 Patent"). A true and correct copy of the '647 Patent is attached hereto as Exhibit C and is incorporated herein by reference.

59. The application that matured into the '647 Patent was filed on September 9, 2021. The '647 Patent has an expiration date of September 9, 2041.

60. The named inventors of the '647 Patent are Dr. Rajan Mehta, Dr. Kevin Ostrowski, and Dr. Priya Shah, each of whom conceived and developed the inventions claimed therein during the course of their employment with GenomeDx. Each named inventor assigned all right, title, and interest in the '647 Patent to GenomeDx. GenomeDx is the sole and exclusive owner of the '647 Patent, including the right to sue for and recover damages for infringement.

61. The '647 Patent is valid, enforceable, and currently in force. All maintenance fees and other obligations necessary to maintain the '647 Patent in force have been timely paid and satisfied.

62. GenomeDx asserts Claims 1, 4, 6, 11, and 15 of the '647 Patent against Helios in this action.

63. Claim 1 of the '647 Patent recites:

A method for generating an integrated prognostic report comprising:

(a) performing RNA extraction and expression profiling on a prostate tumor specimen;

(b) computing a genomic risk score using a classifier comprising at least 20 gene features;

(c) combining the genomic risk score with at least two clinical covariates selected from Gleason score, PSA level, surgical margin status, and pathological stage; and

(d) generating a composite risk metric and transmitting it to a healthcare provider.

64. Claim 4 of the '647 Patent depends from Claim 1 and further specifies that the RNA extraction step comprises extracting total RNA from a formalin-fixed paraffin-embedded tissue specimen using a column-based extraction method and assessing RNA quality using a DV200 metric or equivalent fragmentation index prior to expression profiling.

65. Claim 6 of the '647 Patent depends from Claim 1 and further specifies that the classifier is an ensemble-based machine-learning classifier selected from the group consisting of random forest, gradient-boosted decision trees, and adaptive boosting classifiers, trained on a cohort comprising at least three hundred patient samples with known clinical outcomes.

66. Claim 11 of the '647 Patent depends from Claim 1 and further specifies that the at least two clinical covariates comprise Gleason score and PSA level, and that the combining step comprises applying a multivariate logistic regression model or a Cox proportional hazards model to the genomic risk score and the clinical covariates to generate the composite risk metric.

67. Claim 15 of the '647 Patent depends from Claim 1 and further specifies that the integrated prognostic report comprises a graphical representation of the composite risk metric, a numerical risk score, a categorical risk classification, and a summary of the clinical covariates used in the computation, and that the report is formatted for electronic transmission to a healthcare provider's electronic health record system.

COUNT I: INFRINGEMENT OF U.S. PATENT NO. 10,438,271

68. GenomeDx incorporates by reference and re-alleges each and every allegation set forth in paragraphs 1 through 67 above as though fully set forth herein.

Direct Infringement (35 U.S.C. § 271(a))

69. Helios has directly infringed and continues to directly infringe one or more of Claims 1, 3, 5, 7, 12, and 18 of the '271 Patent, literally and/or under the doctrine of equivalents, by making, using, selling, and/or offering to sell the ProstaSignal™ Genomic Classifier test within the United States, including within this judicial district, without authorization, license, or consent from GenomeDx.

70. Specifically, Helios's ProstaSignal™ test performs each and every limitation of at least Claim 1 of the '271 Patent, as well as the additional limitations of dependent Claims 3, 5, 7, 12, and 18, including:

(a) Obtaining a biological sample containing tumor RNA. Helios obtains biological samples containing tumor RNA from prostate tissue specimens submitted by healthcare providers to Helios's CLIA-certified laboratory in San Diego, California. The biological samples are prostate tissue specimens obtained from patients who have undergone radical prostatectomy, and they contain tumor RNA suitable for gene-expression profiling.

(b) Measuring expression levels of a panel of at least 22 genes selected from a predefined gene set. The ProstaSignal™ test measures expression levels of a panel of twenty-four (24) genes. Nineteen (19) of the twenty-four genes in the ProstaSignal™ panel overlap with GenomeDx's patented predefined gene set used in the Decipher® test. The twenty-four-gene panel used by ProstaSignal™ satisfies the "at least 22 genes" limitation recited in the claims. Moreover, the genes in the ProstaSignal™ panel are selected from functional categories — including cell proliferation, cell adhesion, immune response, androgen signaling, and stromal response pathways — that correspond to those specified in the predefined gene set of the '271 Patent.

(c) Applying a trained machine-learning classifier to generate a risk score. The ProstaSignal™ test applies a gradient-boosted decision tree classifier to the measured gene-expression data to generate the "ProstaScore," a numerical risk score ranging from 0 to 100. A gradient-boosted decision tree classifier is a trained machine-learning classifier within the meaning of the '271 Patent claims. The gradient-boosted decision tree classifier used by ProstaSignal™ is an ensemble-based supervised learning algorithm that, like the random-forest classifier specifically described in the '271 Patent specification, combines predictions from multiple decision trees to generate an accurate prognostic score.

(d) Classifying the patient into a risk category based on the score. The ProstaSignal™ test classifies patients into Low, Intermediate, or High risk categories based on the ProstaScore, thereby satisfying this claim limitation. The three risk categories used by ProstaSignal™ correspond directly to the risk categories recited in the claims of the '271 Patent.

71. Helios's infringement of the '271 Patent has been and continues to be willful. Upon information and belief, Helios had actual knowledge of the '271 Patent prior to the commercial launch of the ProstaSignal™ test on October 7, 2024. The '271 Patent issued on October 8, 2019, more than five years before Helios's launch of the ProstaSignal™ test. The '271 Patent is publicly available and readily accessible through the USPTO patent database and other patent search databases. Upon information and belief, Helios and its officers, including Dr. Nathan Ashford, Dr. Elaine Kossack, and their technical and legal advisors, were aware of GenomeDx's patent portfolio, including the '271 Patent, and launched the ProstaSignal™ test despite knowing that it infringes GenomeDx's patent rights. Helios's decision to launch the ProstaSignal™ test with a gene panel substantially overlapping GenomeDx's patented gene set, using the same fundamental classification methodology, and targeting the identical clinical use case, reflects a deliberate and willful decision to infringe GenomeDx's patents.

72. GenomeDx has been and continues to be damaged as a result of Helios's infringement of the '271 Patent. GenomeDx is entitled to recover damages adequate to compensate for such infringement, but in no event less than a reasonable royalty, pursuant to 35 U.S.C. § 284.

Indirect Infringement — Inducement (35 U.S.C. § 271(b))

73. Helios has induced and continues to induce infringement of the '271 Patent in violation of 35 U.S.C. § 271(b) by actively and knowingly encouraging, instructing, and aiding healthcare providers, medical institutions, laboratories, and other third parties to order and use the ProstaSignal™ test in a manner that directly infringes the asserted claims of the '271 Patent.

74. Upon information and belief, Helios provides detailed instructions, marketing materials, sales presentations, technical literature, published clinical data, test ordering protocols, specimen collection and submission guidelines, and technical support to healthcare providers and other third parties, all of which guide and direct them to order and use the ProstaSignal™ test in a manner that practices each and every step of the methods claimed in the '271 Patent. By providing these materials and support, Helios specifically intends that healthcare providers and other third parties will use the ProstaSignal™ test in an infringing manner, and Helios knows that such use constitutes infringement of the '271 Patent.

75. Helios has had knowledge of the '271 Patent at least since the filing and service of this Complaint. Upon information and belief, as set forth above, Helios had knowledge of the '271 Patent prior to the filing of this Complaint. Despite such knowledge, Helios has continued and continues to actively induce infringement of the '271 Patent.

Indirect Infringement — Contributory Infringement (35 U.S.C. § 271(c))

76. Helios has committed and continues to commit contributory infringement of the '271 Patent in violation of 35 U.S.C. § 271(c). Helios offers to sell and sells components, reagents, kits, software, and services that form a material part of the inventions claimed in the '271 Patent and that are especially made or especially adapted for use in practicing the infringing methods. These components, reagents, kits, software, and services — including the specific gene-expression profiling reagents, the trained gradient-boosted decision tree classifier software, and the test reporting system — are not staple articles or commodities of commerce suitable for substantial noninfringing use. Helios knows that these components are especially made or especially adapted for use in infringing the '271 Patent, and Helios knows that the use of these components in the ProstaSignal™ test constitutes infringement of the '271 Patent.

COUNT II: INFRINGEMENT OF U.S. PATENT NO. 11,204,893

77. GenomeDx incorporates by reference and re-alleges each and every allegation set forth in paragraphs 1 through 76 above as though fully set forth herein.

Direct Infringement (35 U.S.C. § 271(a))

78. Helios has directly infringed and continues to directly infringe one or more of Claims 1, 2, 9, 14, and 20 of the '893 Patent, literally and/or under the doctrine of equivalents, by making, using, selling, and/or offering to sell the ProstaSignal™ Genomic Classifier test within the United States, including within this judicial district, without authorization, license, or consent from GenomeDx.

79. Specifically, Helios's ProstaSignal™ test performs each and every limitation of at least Claim 1 of the '893 Patent, as well as the additional limitations of dependent Claims 2, 9, 14, and 20, including:

(a) Normalizing gene-expression data from a formalin-fixed paraffin-embedded prostate tissue sample using a reference gene panel. Upon information and belief, the ProstaSignal™ test processes gene-expression data obtained from FFPE prostate tissue samples and normalizes the raw expression data using a reference gene panel comprising housekeeping genes to control for variability in RNA quality, quantity, and batch effects. This normalization step is performed at Helios's San Diego laboratory as part of the standard ProstaSignal™ testing workflow.

(b) Inputting normalized expression values into a random-forest classifier trained on a cohort of at least 500 patient samples. The ProstaSignal™ test inputs normalized gene-expression values into a trained machine-learning classifier to generate a prognostic score. The '893 Patent specifically recites a "random-forest classifier trained on a cohort of at least 500 patient samples." Upon information and belief, the ProstaSignal™ test uses a gradient-boosted decision tree classifier, which is an ensemble-based machine-learning classifier that, like a random-forest classifier, aggregates predictions from multiple decision trees. Upon information and belief, Helios's classifier was trained on a cohort of patient samples comparable in size to the claimed cohort.

(c) Outputting a numerical prognostic score correlated with metastasis risk within 5 years. The ProstaSignal™ test outputs the "ProstaScore," a numerical prognostic score ranging from 0 to 100 that is correlated with the risk of metastasis within five years following radical prostatectomy.

80. To the extent that Helios's ProstaSignal™ test does not literally use a "random-forest classifier" as recited in Claim 1 of the '893 Patent, Helios infringes the '893 Patent under the doctrine of equivalents. The gradient-boosted decision tree classifier used by ProstaSignal™ performs substantially the same function as the claimed random-forest classifier — namely, ensemble-based classification of multi-gene expression data to generate a prognostic score — in substantially the same way — namely, by aggregating predictions from multiple individual decision trees, each of which evaluates a subset of gene-expression features to make a classification prediction — to achieve substantially the same result — namely, a numerical prognostic score correlated with metastasis risk within five years that is used to stratify patients into risk categories. The differences between a gradient-boosted decision tree classifier and a random-forest classifier are insubstantial in the context of the claimed invention. Both are ensemble-based, tree-based, supervised machine-learning algorithms that operate on the same type of input data (normalized gene-expression values), employ the same fundamental building blocks (decision trees), and produce the same type of output (a numerical prognostic score). A person of ordinary skill in the art would recognize that a gradient-boosted decision tree classifier is an interchangeable equivalent of a random-forest classifier for the purpose of the claimed invention.

81. Helios's infringement of the '893 Patent has been and continues to be willful. Upon information and belief, Helios had actual knowledge of the '893 Patent prior to the commercial launch of the ProstaSignal™ test. The '893 Patent issued on December 21, 2021, approximately three years before Helios's launch of the ProstaSignal™ test. Upon information and belief, Helios was aware of GenomeDx's patent portfolio, including the '893 Patent, and launched the ProstaSignal™ test despite knowing that it infringes GenomeDx's patent rights.

82. GenomeDx has been and continues to be damaged as a result of Helios's infringement of the '893 Patent. GenomeDx is entitled to recover damages adequate to compensate for such infringement, but in no event less than a reasonable royalty, pursuant to 35 U.S.C. § 284.

Indirect Infringement — Inducement (35 U.S.C. § 271(b))

83. Helios has induced and continues to induce infringement of the '893 Patent in violation of 35 U.S.C. § 271(b) by actively and knowingly encouraging, instructing, and aiding healthcare providers, medical institutions, laboratories, and other third parties to order and use the ProstaSignal™ test in a manner that directly infringes the asserted claims of the '893 Patent.

84. Upon information and belief, Helios provides detailed instructions, marketing materials, sales presentations, technical literature, test ordering protocols, specimen collection and submission guidelines, and technical support to healthcare providers and other third parties, all of which guide and direct them to order and use the ProstaSignal™ test in a manner that practices each and every step of the methods claimed in the '893 Patent. By providing these materials and support, Helios specifically intends that healthcare providers and other third parties will use the ProstaSignal™ test in an infringing manner, and Helios knows that such use constitutes infringement of the '893 Patent.

85. Helios has had knowledge of the '893 Patent at least since the filing and service of this Complaint. Upon information and belief, as set forth above, Helios had knowledge of the '893 Patent prior to the filing of this Complaint. Despite such knowledge, Helios has continued and continues to actively induce infringement of the '893 Patent.

Indirect Infringement — Contributory Infringement (35 U.S.C. § 271(c))

86. Helios has committed and continues to commit contributory infringement of the '893 Patent in violation of 35 U.S.C. § 271(c). Helios offers to sell and sells components, reagents, kits, software, and services that form a material part of the inventions claimed in the '893 Patent and that are especially made or especially adapted for use in practicing the infringing methods. These components, reagents, kits, software, and services — including the specific normalization algorithms, the trained gradient-boosted decision tree classifier software, and the prognostic score computation modules — are not staple articles or commodities of commerce suitable for substantial noninfringing use. Helios knows that these components are especially made or especially adapted for use in infringing the '893 Patent, and Helios knows that the use of these components in the ProstaSignal™ test constitutes infringement of the '893 Patent.

COUNT III: INFRINGEMENT OF U.S. PATENT NO. 11,891,647

87. GenomeDx incorporates by reference and re-alleges each and every allegation set forth in paragraphs 1 through 86 above as though fully set forth herein.

Direct Infringement (35 U.S.C. § 271(a))

88. Helios has directly infringed and continues to directly infringe one or more of Claims 1, 4, 6, 11, and 15 of the '647 Patent, literally and/or under the doctrine of equivalents, by making, using, selling, and/or offering to sell the ProstaSignal™ Genomic Classifier test within the United States, including within this judicial district, without authorization, license, or consent from GenomeDx.

89. Specifically, Helios's ProstaSignal™ test performs each and every limitation of at least Claim 1 of the '647 Patent, as well as the additional limitations of dependent Claims 4, 6, 11, and 15, including:

(a) Performing RNA extraction and expression profiling on a prostate tumor specimen. The ProstaSignal™ test involves the extraction of RNA from prostate tumor specimens submitted to Helios's CLIA-certified laboratory, followed by gene-expression profiling of the extracted RNA to measure the expression levels of the twenty-four genes in the ProstaSignal™ gene panel. This step is performed at Helios's San Diego laboratory as part of the standard ProstaSignal™ testing workflow.

(b) Computing a genomic risk score using a classifier comprising at least 20 gene features. The ProstaSignal™ test computes the ProstaScore using a gradient-boosted decision tree classifier that employs twenty-four (24) gene features — expression levels of the twenty-four genes in the ProstaSignal™ panel — as inputs to the classification algorithm. The twenty-four gene features used by ProstaSignal™ satisfy the "at least 20 gene features" limitation recited in the claims of the '647 Patent.

(c) Combining the genomic risk score with at least two clinical covariates selected from Gleason score, PSA level, surgical margin status, and pathological stage. Upon information and belief, the ProstaSignal™ test combines the ProstaScore with at least two clinical covariates, specifically Gleason grade group (which corresponds to and is derived from Gleason score) and pre-operative PSA level. Both Gleason score (via Gleason grade group) and PSA level are among the clinical covariates expressly enumerated in the claims of the '647 Patent. The combination of the genomic risk score with these clinical covariates satisfies this claim limitation.

(d) Generating a composite risk metric and transmitting it to a healthcare provider. The ProstaSignal™ test generates an integrated prognostic report containing a composite risk assessment that combines the ProstaScore genomic risk score with the clinical covariate data, and Helios transmits this integrated report to the ordering healthcare provider. The composite risk assessment contained in the ProstaSignal™ report constitutes a "composite risk metric" within the meaning of the '647 Patent claims, and the transmission of the report to the ordering healthcare provider satisfies the transmitting limitation.

90. Helios's infringement of the '647 Patent has been and continues to be willful. Upon information and belief, Helios had actual knowledge of the '647 Patent prior to the commercial launch of the ProstaSignal™ test on October 7, 2024. The '647 Patent issued on February 6, 2024, approximately eight months before Helios's launch of the ProstaSignal™ test. Upon information and belief, Helios was aware of GenomeDx's patent portfolio, including the '647 Patent, and launched the ProstaSignal™ test despite knowing that it infringes GenomeDx's patent rights. Indeed, the '647 Patent issued during the very period in which Helios was finalizing the development and preparing for the commercial launch of the ProstaSignal™ test, and upon information and belief, Helios was monitoring GenomeDx's patent portfolio during this critical pre-launch period.

91. GenomeDx has been and continues to be damaged as a result of Helios's infringement of the '647 Patent. GenomeDx is entitled to recover damages adequate to compensate for such infringement, but in no event less than a reasonable royalty, pursuant to 35 U.S.C. § 284.

Indirect Infringement — Inducement (35 U.S.C. § 271(b))

92. Helios has induced and continues to induce infringement of the '647 Patent in violation of 35 U.S.C. § 271(b) by actively and knowingly encouraging, instructing, and aiding healthcare providers, medical institutions, laboratories, and other third parties to order and use the ProstaSignal™ test in a manner that directly infringes the asserted claims of the '647 Patent.

93. Upon information and belief, Helios provides detailed instructions, marketing materials, sales presentations, technical literature, test ordering protocols, specimen collection and submission guidelines, and technical support to healthcare providers and other third parties, all of which guide and direct them to order and use the ProstaSignal™ test in a manner that practices each and every step of the methods claimed in the '647 Patent. Specifically, Helios provides ordering healthcare providers with instructions to submit clinical covariates — including Gleason grade group and pre-operative PSA level — along with the tissue specimen, so that Helios can generate the integrated prognostic report that combines the ProstaScore with the clinical covariates. By providing these materials, instructions, and support, Helios specifically intends that healthcare providers and other third parties will use the ProstaSignal™ test in an infringing manner, and Helios knows that such use constitutes infringement of the '647 Patent.

94. Helios has had knowledge of the '647 Patent at least since the filing and service of this Complaint. Upon information and belief, as set forth above, Helios had knowledge of the '647 Patent prior to the filing of this Complaint. Despite such knowledge, Helios has continued and continues to actively induce infringement of the '647 Patent.

Indirect Infringement — Contributory Infringement (35 U.S.C. § 271(c))

95. Helios has committed and continues to commit contributory infringement of the '647 Patent in violation of 35 U.S.C. § 271(c). Helios offers to sell and sells components, reagents, kits, software, and services that form a material part of the inventions claimed in the '647 Patent and that are especially made or especially adapted for use in practicing the infringing methods. These components, reagents, kits, software, and services — including the RNA extraction reagents and kits, the gene-expression profiling reagents and platforms, the trained gradient-boosted decision tree classifier software, the clinical covariate integration algorithms, and the composite risk metric computation and report generation software — are not staple articles or commodities of commerce suitable for substantial noninfringing use. Helios knows that these components are especially made or especially adapted for use in infringing the '647 Patent, and Helios knows that the use of these components in the ProstaSignal™ test constitutes infringement of the '647 Patent.

DAMAGES

96. GenomeDx has suffered and will continue to suffer damages as a result of Helios's infringement of the Patents-in-Suit, including but not limited to lost profits and/or a reasonable royalty, in an amount to be proven and determined at trial.

97. GenomeDx is the market leader in genomic prostate cancer prognostic testing. Prior to the commercial launch of the ProstaSignal™ test on October 7, 2024, GenomeDx held approximately seventy-four percent (74%) market share in this market. As a direct result of Helios's infringing activities, GenomeDx's market share has declined to approximately sixty-eight percent (68%), representing a loss of approximately six (6) percentage points of market share. This market share loss translates directly into lost revenue, lost profits, and erosion of GenomeDx's competitive position and goodwill, all of which are attributable to Helios's infringement of the Patents-in-Suit.

98. GenomeDx is entitled to damages adequate to compensate for the infringement, but in no event less than a reasonable royalty for the use made of the inventions by Helios, pursuant to 35 U.S.C. § 284.

99. Upon information and belief, Helios's infringement of the Patents-in-Suit has been willful and deliberate, as set forth in detail above. Helios was aware of GenomeDx's patent rights prior to launching the ProstaSignal™ test and proceeded to launch the infringing product despite that knowledge. GenomeDx is therefore entitled to enhanced damages of up to three times the amount of compensatory damages found or assessed, pursuant to 35 U.S.C. § 284, and as further authorized by Halo Electronics, Inc. v. Pulse Electronics, Inc., 579 U.S. 93 (2016).

100. GenomeDx is entitled to recover pre-judgment interest on the damages award from the date of first infringement to the date of judgment, and post-judgment interest from the date of judgment until the date of payment, at such rates and for such periods as the Court may determine to be just.

PRAYER FOR RELIEF

WHEREFORE, Plaintiff Genome Dx Therapeutics Inc. respectfully requests that this Court enter judgment in its favor and against Defendant Helios Precision Diagnostics, Inc. and grant the following relief:

1. A judgment and declaration that Helios has infringed and continues to infringe U.S. Patent Nos. 10,438,271, 11,204,893, and 11,891,647, both directly and indirectly, literally and/or under the doctrine of equivalents;

2. A permanent injunction prohibiting Helios, its officers, directors, agents, servants, employees, attorneys, successors, assigns, and all persons acting in concert or participation with any of them, from further infringement of U.S. Patent Nos. 10,438,271, 11,204,893, and 11,891,647, including from making, using, selling, offering to sell, or importing into the United States the ProstaSignal™ Genomic Classifier test or any other product, method, or service that infringes the Patents-in-Suit;

3. An award of damages adequate to compensate GenomeDx for Helios's past and ongoing infringement, including lost profits and/or a reasonable royalty, in an amount to be determined at trial, but in no event less than a reasonable royalty pursuant to 35 U.S.C. § 284;

4. A finding that Helios's infringement of the Patents-in-Suit has been willful and deliberate, and an award of enhanced damages of up to three (3) times the amount of compensatory damages, pursuant to 35 U.S.C. § 284;

5. A finding that this is an exceptional case and an award of GenomeDx's reasonable attorneys' fees and costs incurred in this action, pursuant to 35 U.S.C. § 285;

6. An award of pre-judgment interest on all damages from the date of first infringement to the date of judgment, and post-judgment interest from the date of judgment until the date of full payment, at the maximum rate permitted by law;

7. An order requiring Helios to provide a full accounting of all revenues, profits, costs, units sold, and other financial information related to Helios's making, using, selling, offering to sell, and importing of the ProstaSignal™ Genomic Classifier test and any other infringing products;

8. Such other and further relief as this Court deems just and proper.

DEMAND FOR JURY TRIAL

Plaintiff Genome Dx Therapeutics Inc. hereby demands a trial by jury on all issues and claims in this action that are so triable as of right, pursuant to Federal Rule of Civil Procedure 38(b).

Respectfully submitted,

Dated: March 28, 2025

CALDERWOOD & HARKNESS LLP

By: ________

Catherine Bloom (CA Bar No. 247831) Responsible Partner, intellectual Property 555 Mission Street, Suite 3100 San Francisco, CA 94105 Telephone: (415) 773-6200 Facsimile: (415) 773-6201

Email: cbloom@calderwoodharkness.com

Peter Vassiliev (CA Bar No. 312045) Lead Associate, intellectual Property

Wendy Schultz (CA Bar No. 319782) Associate, intellectual Property

Attorneys for Plaintiff Genome Dx Therapeutics Inc.

EXHIBITS

The following exhibits are attached hereto and incorporated herein by reference:

Exhibit A: Certified Copy of U.S. Patent No. 10,438,271, entitled "Methods for Predicting Prostate Cancer Outcomes Using Multi-Gene Expression Classifiers," issued October 8, 2019.

Exhibit B: Certified Copy of U.S. Patent No. 11,204,893, entitled "Genomic Classifier Systems and Methods for Post-Surgical Cancer Prognosis," issued December 21, 2021.

Exhibit C: Certified Copy of U.S. Patent No. 11,891,647, entitled "Improved Methods for Genomic Risk Stratification in Prostate Cancer Using Combined Biomarker and Clinical Variable Models," issued February 6, 2024.

GENOME DX THERAPEUTICS INC., a Delaware corporation,	Case No. 3:25-cv-01847-JWL
Plaintiff,	COMPLAINT FOR PATENT INFRINGEMENT
v.	DEMAND FOR JURY TRIAL

HELIOS PRECISION DIAGNOSTICS, INC., a Delaware corporation,

Defendant.

UNITED STATES DISTRICT COURT FOR THE NORTHERN DISTRICT OF CALIFORNIA
Plaintiff Genome Dx Therapeutics Inc. ("GenomeDx" or "Plaintiff"), by and through its attorneys Calderwood & Harkness LLP, for its Complaint against Defendant Helios Precision Diagnostics, Inc. ("Helios" or "Defendant"), hereby alleges as follows:
INTRODUCTION
1. GenomeDx brings this action for patent infringement against Helios under the patent laws of the United States, 35 U.S.C. § 1 et seq. This action seeks injunctive relief, compensatory damages, enhanced damages for willful infringement, and other relief arising from Helios's unauthorized making, using, selling, and offering for sale of a genomic classifier test that infringes three of GenomeDx's United States patents.
2. GenomeDx is a pioneer in the field of molecular diagnostics, with particular expertise in the development, validation, and clinical deployment of genomic-classifier methods for prostate cancer prognosis. GenomeDx holds a robust and valuable patent portfolio comprising forty-seven (47) issued United States patents, twelve (12) pending United States patent applications, and nineteen (19) international family members, collectively covering GenomeDx's proprietary methods for genomic classification, gene-expression profiling, machine-learning-based prognostic scoring, and integrated clinical-genomic reporting for cancer outcomes.
3. GenomeDx's proprietary Decipher® Prostate genomic classifier test is the market-leading prognostic tool for prostate cancer recurrence and metastasis prediction following radical prostatectomy. The Decipher® test is the product of more than a decade of intensive research, development, clinical validation, and commercialization efforts by GenomeDx. The Decipher® test has been validated in more than forty peer-reviewed clinical studies, is included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Prostate Cancer, and is widely utilized by urologists and radiation oncologists across the United States. In fiscal year 2024, the Decipher® Prostate test generated three hundred eighty-seven million six hundred thousand dollars ($387,600,000) in revenue for GenomeDx, reflecting GenomeDx's substantial investment in and the significant clinical and commercial value of its proprietary technology.
4. GenomeDx brings this action to enforce three of its United States patents — U.S. Patent No. 10,438,271 ("the '271 Patent"), U.S. Patent No. 11,204,893 ("the '893 Patent"), and U.S. Patent No. 11,891,647 ("the '647 Patent") (collectively, the "Patents-in-Suit") — against Helios's competing ProstaSignal™ Genomic Classifier test. Helios commercially launched the ProstaSignal™ test on October 7, 2024. The ProstaSignal™ test directly and knowingly infringes GenomeDx's patent rights by employing the same fundamental methods, gene-expression profiling techniques, machine-learning classification approaches, and integrated clinical-genomic reporting methods that GenomeDx invented, patented, and commercialized. Since its launch, the ProstaSignal™ test has captured significant market share from GenomeDx, causing GenomeDx substantial and ongoing financial harm.
THE PARTIES
Plaintiff Genome Dx Therapeutics Inc.
5. Plaintiff Genome Dx Therapeutics Inc. is a corporation organized and existing under the laws of the State of Delaware. GenomeDx is qualified to do business in the State of California and maintains its principal place of business and corporate headquarters at 4750 Torrey Pines Road, Suite 300, San Diego, California 92130. GenomeDx's registered agent in Delaware is Pacific Registered Agents, Inc., located at 1209 Orange Street, Wilmington, Delaware 19801.
6. GenomeDx was founded in 2011 and is a molecular diagnostics company focused on the development and commercialization of genomic classification technologies for cancer prognosis. GenomeDx's core competency lies in the application of advanced machine-learning techniques to multi-gene expression data to generate clinically actionable prognostic information for cancer patients and their treating physicians.
7. GenomeDx is led by a team of experienced scientists and executives, including Dr. Miriam Langford, PhD, Chief Executive Officer; Dr. Rajan Mehta, PhD, Chief Technology Officer and a named inventor on two of the three Patents-in-Suit; and Victoria Sung, JD, General Counsel. GenomeDx employs approximately eight hundred twenty (820) people, including approximately three hundred forty (340) laboratory and research and development personnel dedicated to advancing GenomeDx's genomic classification technologies.
8. GenomeDx is the sole and exclusive owner and assignee of all right, title, and interest in and to the Patents-in-Suit, including the right to sue for and recover damages for past and ongoing infringement. GenomeDx has standing to bring this action and to seek the relief requested herein.
Defendant Helios Precision Diagnostics, Inc.
9. Defendant Helios Precision Diagnostics, Inc. is a corporation organized and existing under the laws of the State of Delaware. Helios is qualified to do business in the Commonwealth of Massachusetts and in the State of California. Helios maintains its principal place of business and corporate headquarters at 200 CambridgePark Drive, Suite 600, Cambridge, Massachusetts 02140.
10. Helios operates a Clinical Laboratory Improvement Amendments ("CLIA")-certified laboratory located at 9830 Mesa Rim Road, Suite 140, San Diego, California 92121. The accused ProstaSignal™ Genomic Classifier test is performed at this San Diego laboratory facility.
11. Helios was founded in 2019 and is a molecular diagnostics company. Helios is led by Dr. Nathan Ashford, MD, PhD, Chief Executive Officer, and Dr. Elaine Kossack, PhD, Chief Scientific Officer. Helios employs approximately two hundred fifteen (215) people.
12. Helios is the maker, user, seller, and offeror for sale of the accused ProstaSignal™ Genomic Classifier test, which is the subject of the infringement allegations set forth in this Complaint.
13. Upon information and belief, Helios has performed approximately eight thousand four hundred (8,400) ProstaSignal™ tests between the October 7, 2024 commercial launch date and March 2025. Upon information and belief, Helios has generated estimated revenue of approximately thirty-two million eighty-eight thousand dollars ($32,088,000) from sales of the ProstaSignal™ test during this period, based on an average reimbursement rate of approximately three thousand eight hundred twenty dollars ($3,820) per test.
JURISDICTION AND VENUE
Subject Matter Jurisdiction
14. This Court has subject matter jurisdiction over this action pursuant to 28 U.S.C. § 1331, as this action arises under the laws of the United States, and pursuant to 28 U.S.C. § 1338(a), as this action arises under the patent laws of the United States, specifically the Patent Act, 35 U.S.C. § 1 et seq.
Personal Jurisdiction.
15. This Court has personal jurisdiction over Helios. Helios is subject to personal jurisdiction in this judicial district and in the State of California for the following reasons:
(a) Helios is qualified to do business and conducts substantial business within the State of California.
(b) Helios operates a CLIA-certified laboratory located at 9830 Mesa Rim Road, Suite 140, San Diego, California 92121, which is within the State of California. This laboratory constitutes a substantial, continuous, and systematic contact with the State of California sufficient to confer general personal jurisdiction.
(c) Helios performs the accused ProstaSignal™ Genomic Classifier test at its San Diego, California laboratory facility, where Helios processes biological samples submitted by healthcare providers, performs RNA extraction and gene-expression profiling, applies its machine-learning classifier to generate prognostic scores, and generates and transmits integrated prognostic reports to healthcare providers, all within the State of California.
(d) Helios has committed and continues to commit acts of patent infringement within this judicial district and within the State of California, including by making, using, selling, and offering to sell the accused ProstaSignal™ test.
(e) Helios markets, promotes, sells, and offers to sell the ProstaSignal™ test to healthcare providers and medical institutions within this judicial district and within the State of California.
16. The exercise of personal jurisdiction over Helios is consistent with the requirements of the Due Process Clause of the Fourteenth Amendment to the United States Constitution.
Venue.
17. Venue is proper in this judicial district pursuant to 28 U.S.C. § 1400(b) because Helios has committed acts of infringement within this judicial district and has a regular and established place of business within this judicial district, specifically its CLIA-certified laboratory located at 9830 Mesa Rim Road, Suite 140, San Diego, California 92121. Helios maintains permanent personnel, laboratory equipment, and facilities at this location, which constitutes a regular and established place of business within the meaning of 28 U.S.C. § 1400(b).
18. Alternatively, venue is proper in this judicial district because Helios is subject to personal jurisdiction in this judicial district, and the requirements of 28 U.S.C. § 1400(b) are otherwise satisfied.
FACTUAL BACKGROUND
GenomeDx and the Decipher® Prostate Genomic Classifier
19. GenomeDx was founded in 2011 with the mission of developing and commercializing advanced genomic classification technologies to improve cancer patient outcomes. Over the past fourteen years, GenomeDx has invested hundreds of millions of dollars in research and development, clinical validation, and commercialization of its proprietary genomic-classifier technologies. GenomeDx has become a recognized leader in the field of molecular diagnostics for cancer prognosis, with a particular focus on prostate cancer.
20. GenomeDx developed the Decipher® Prostate genomic classifier test, a proprietary twenty-two (22)-gene expression-based prognostic test used to predict the likelihood of clinical recurrence and metastasis following radical prostatectomy for prostate cancer. The Decipher® test represents a breakthrough in the field of prostate cancer management, providing physicians and patients with clinically validated, objective, and reproducible genomic information to guide post-surgical treatment decisions, including decisions regarding adjuvant radiation therapy, salvage radiation therapy, and systemic therapy.
21. The Decipher® test involves the following key steps:
(a) Obtaining a biological sample containing tumor RNA from formalin-fixed paraffin-embedded ("FFPE") prostate tissue. The use of FFPE tissue, rather than fresh-frozen tissue, is a critical feature of GenomeDx's technology, as it allows the test to be performed on routinely archived surgical specimens without requiring special tissue handling at the time of surgery.
(b) Measuring expression levels of a panel of twenty-two (22) genes from a predefined gene set. These twenty-two genes were identified and selected through extensive bioinformatics analysis and clinical validation as the optimal set of genomic biomarkers for prostate cancer prognostic classification.
(c) Applying a trained machine-learning classifier — specifically, a random-forest classifier trained on a cohort of at least five hundred (500) patient samples with known clinical outcomes — to the measured gene-expression data to generate a numerical prognostic risk score. The random-forest classifier is a supervised machine-learning algorithm that aggregates predictions from a large ensemble of individual decision trees to produce a robust, accurate prognostic score.
(d) Classifying the patient into one of three risk categories — Low, Intermediate, or High — based on the generated risk score, to inform clinical decision-making regarding the need for and timing of adjuvant or salvage therapies.
22. In addition to the genomic risk score and risk category classification, the Decipher® test provides an integrated prognostic report that combines the genomic risk score with relevant clinical covariates, including Gleason score, pre-operative prostate-specific antigen ("PSA") level, surgical margin status, and pathological stage. This integrated approach — combining genomic and clinical data into a single, actionable report — is a key innovation of GenomeDx's technology and a subject of the Patents-in-Suit.
23. The Decipher® test is a laboratory-developed test ("LDT") performed exclusively at GenomeDx's CLIA-certified, College of American Pathologists ("CAP")-accredited laboratory. The Decipher® test is reimbursed by the Centers for Medicare & Medicaid Services ("CMS") under the Molecular Diagnostic Services ("MolDX") program. GenomeDx obtained a unique Multianalyte Assays with Algorithmic Analyses ("MAAA") code (0047M) from the American Medical Association for the Decipher® test in 2018, reflecting the test's clinically distinct status and the recognition of its unique methodology.
24. GenomeDx submitted a De Novo classification application with the United States Food and Drug Administration ("FDA") for the Decipher® test on August 15, 2024. That application is currently pending review. GenomeDx's pursuit of FDA authorization further demonstrates the significant investment and commitment GenomeDx has made in its proprietary technology.
25. Prior to the commercial launch of Helios's ProstaSignal™ test in October 2024, GenomeDx held a commanding market position with approximately seventy-four percent (74%) market share in the genomic prostate cancer prognostic testing market in the United States. GenomeDx's market leadership was the result of its pioneering scientific innovations, its extensive clinical validation program, its strong payor relationships, and its broad adoption by urologists and radiation oncologists across the country.
26. GenomeDx generated three hundred eighty-seven million six hundred thousand dollars ($387,600,000) in revenue in fiscal year 2024, with the vast majority of this revenue derived from Decipher® test reimbursements. GenomeDx's substantial revenue base reflects the significant clinical and commercial value of its proprietary genomic-classification technology.
GenomeDx's Patent Portfolio and the Patents-in-Suit
27. GenomeDx holds a robust and comprehensive patent portfolio consisting of forty-seven (47) issued United States patents, twelve (12) pending United States patent applications, and nineteen (19) international family members. This portfolio covers GenomeDx's proprietary genomic-classifier methods, including methods for gene-expression profiling from FFPE tissue specimens, machine-learning-based classification algorithms for cancer prognosis, multi-gene expression panels for prostate cancer risk stratification, and integrated clinical-genomic reporting systems and methods.
28. GenomeDx has invested substantial resources in developing, prosecuting, maintaining, and enforcing its patent portfolio. GenomeDx's patent portfolio represents the culmination of years of scientific research, bioinformatics analysis, clinical validation, and innovation by GenomeDx's scientists and engineers. The patent portfolio is a critical intellectual property asset of GenomeDx.
29. The three Patents-in-Suit — the '271 Patent, the '893 Patent, and the '647 Patent — represent core innovations in genomic classification methods for prostate cancer prognosis. These patents cover fundamental aspects of GenomeDx's proprietary Decipher® technology, including the methods for multi-gene expression-based classification, the specific machine-learning classifier architectures and training methodologies employed, and the methods for generating integrated clinical-genomic prognostic reports. Each of the Patents-in-Suit is described in detail below.
Helios and the ProstaSignal™ Genomic Classifier
30. Helios was founded in 2019, approximately eight years after GenomeDx. Upon information and belief, Helios was founded with the objective of developing and commercializing molecular diagnostic tests for cancer prognosis, including tests that compete directly with GenomeDx's Decipher® test.
31. On or about October 7, 2024, Helios commercially launched the ProstaSignal™ Genomic Classifier, a twenty-four (24)-gene expression-based prognostic test for prostate cancer patients who have undergone radical prostatectomy. The ProstaSignal™ test was designed and marketed as a direct competitor to GenomeDx's Decipher® test and targets the same clinical use case — post-prostatectomy prognostic risk stratification.
32. Upon information and belief, the ProstaSignal™ test uses a twenty-four (24)-gene expression panel. Of the twenty-four genes in the ProstaSignal™ panel, nineteen (19) genes overlap with GenomeDx's patented gene set used in the Decipher® test. This extensive overlap — comprising approximately seventy-nine percent (79%) of the ProstaSignal™ gene panel — is not coincidental and reflects Helios's deliberate copying of GenomeDx's proprietary gene panel selection.
33. Upon information and belief, the ProstaSignal™ test applies a gradient-boosted decision tree classifier — which is a type of trained machine-learning classifier — to the measured gene-expression data to generate a numerical prognostic score designated by Helios as the "ProstaScore." The ProstaScore is a numerical value ranging from 0 to 100, with higher scores indicating greater risk of clinical recurrence and metastasis. Like GenomeDx's Decipher® test, the ProstaSignal™ test classifies patients into Low, Intermediate, or High risk categories based on the ProstaScore.
34. Upon information and belief, the ProstaSignal™ test combines the ProstaScore with clinical covariates, including Gleason grade group and pre-operative PSA level, to generate an integrated prognostic report that is transmitted to the ordering healthcare provider. This integrated reporting approach mirrors the methodology invented by GenomeDx and claimed in the Patents-in-Suit.
35. Helios obtained a MAAA code (0239M) for the ProstaSignal™ test from the American Medical Association in September 2024, approximately one month before the commercial launch. The ProstaSignal™ test is performed at Helios's CLIA-certified laboratory located at 9830 Mesa Rim Road, Suite 140, San Diego, California 92121.
36. Since its commercial launch on October 7, 2024, the ProstaSignal™ test has captured significant market share from GenomeDx. GenomeDx's market share in the genomic prostate cancer prognostic testing market has declined from approximately seventy-four percent (74%) prior to the ProstaSignal™ launch to approximately sixty-eight percent (68%) as of the filing of this Complaint, a decline of approximately six (6) percentage points that is directly attributable to Helios's infringing activities. This market share loss has caused and continues to cause GenomeDx substantial economic harm.
THE PATENTS-IN-SUIT
U.S. Patent No. 10,438,271 ("the '271 Patent")
37. On October 8, 2019, the United States Patent and Trademark Office ("USPTO") duly and lawfully issued U.S. Patent No. 10,438,271, entitled "Methods for Predicting Prostate Cancer Outcomes Using Multi-Gene Expression Classifiers" (the "'271 Patent"). A true and correct copy of the '271 Patent is attached hereto as Exhibit A and is incorporated herein by reference.
38. The application that matured into the '271 Patent was filed on June 14, 2016. The '271 Patent has an expiration date of June 14, 2036.
39. The named inventors of the '271 Patent are Dr. Rajan Mehta, Dr. Carolyn Xu, and Dr. David Petrossian, each of whom conceived and developed the inventions claimed therein during the course of their employment with GenomeDx. Each named inventor assigned all right, title, and interest in the '271 Patent to GenomeDx. GenomeDx is the sole and exclusive owner of the '271 Patent, including the right to sue for and recover damages for infringement.
40. The '271 Patent is valid, enforceable, and currently in force. All maintenance fees and other obligations necessary to maintain the '271 Patent in force have been timely paid and satisfied.
41. GenomeDx asserts Claims 1, 3, 5, 7, 12, and 18 of the '271 Patent against Helios in this action.
42. Claim 1 of the '271 Patent recites:
A method for prognosing the likelihood of clinical recurrence following radical prostatectomy comprising:
(a) obtaining a biological sample containing tumor RNA;
(b) measuring expression levels of a panel of at least 22 genes selected from a predefined gene set;
(c) applying a trained machine-learning classifier to generate a risk score; and
(d) classifying the patient into a risk category based on the score.
43. Claim 3 of the '271 Patent depends from Claim 1 and further specifies that the predefined gene set comprises genes associated with cell proliferation, cell adhesion, immune response, androgen signaling, and stromal response pathways, thereby defining the functional categories from which the at least twenty-two genes are selected.
44. Claim 5 of the '271 Patent depends from Claim 1 and further specifies that the trained machine-learning classifier is a random-forest classifier trained on a cohort of at least five hundred patient samples with known five-year clinical outcomes, including known metastasis status.
45. Claim 7 of the '271 Patent depends from Claim 1 and further specifies that the biological sample is a formalin-fixed paraffin-embedded tissue specimen from which RNA is extracted using an acid-guanidinium-phenol extraction protocol or equivalent nucleic acid isolation method.
46. Claim 12 of the '271 Patent depends from Claim 1 and further specifies that the risk categories comprise at least three categories — Low, Intermediate, and High — with defined score thresholds that stratify patients according to their predicted probability of clinical recurrence within a five-year post-surgical period.
47. Claim 18 of the '271 Patent depends from Claim 1 and further specifies that the method includes generating a prognostic report comprising the risk score, the risk category, and at least one clinical covariate selected from the group consisting of Gleason score, PSA level, surgical margin status, and pathological stage, and transmitting the report to a healthcare provider.
U.S. Patent No. 11,204,893 ("the '893 Patent")
48. On December 21, 2021, the USPTO duly and lawfully issued U.S. Patent No. 11,204,893, entitled "Genomic Classifier Systems and Methods for Post-Surgical Cancer Prognosis" (the "'893 Patent"). A true and correct copy of the '893 Patent is attached hereto as Exhibit B and is incorporated herein by reference.
49. The application that matured into the '893 Patent was filed on March 22, 2019, as a continuation application in the same patent family as the '271 Patent. The '893 Patent claims priority through the same priority chain as the '271 Patent and has an expiration date of June 14, 2036.
50. The named inventors of the '893 Patent are Dr. Rajan Mehta and Dr. Carolyn Xu, each of whom conceived and developed the inventions claimed therein during the course of their employment with GenomeDx. Each named inventor assigned all right, title, and interest in the '893 Patent to GenomeDx. GenomeDx is the sole and exclusive owner of the '893 Patent, including the right to sue for and recover damages for infringement.
51. The '893 Patent is valid, enforceable, and currently in force. All maintenance fees and other obligations necessary to maintain the '893 Patent in force have been timely paid and satisfied.
52. GenomeDx asserts Claims 1, 2, 9, 14, and 20 of the '893 Patent against Helios in this action.
53. Claim 1 of the '893 Patent recites:
A method comprising:
normalizing gene-expression data from a formalin-fixed paraffin-embedded prostate tissue sample using a reference gene panel;
inputting normalized expression values into a random-forest classifier trained on a cohort of at least 500 patient samples; and
outputting a numerical prognostic score correlated with metastasis risk within 5 years.
54. Claim 2 of the '893 Patent depends from Claim 1 and further specifies that the normalization step comprises quantile normalization using a reference gene panel comprising at least five housekeeping genes, followed by batch-effect correction using a linear model.
55. Claim 9 of the '893 Patent depends from Claim 1 and further specifies that the random-forest classifier comprises at least five hundred individual decision trees, each trained on a bootstrap sample of the training cohort, and that the prognostic score is computed as the average of the individual tree predictions.
56. Claim 14 of the '893 Patent depends from Claim 1 and further specifies that the training cohort of at least five hundred patient samples comprises samples from at least three independent clinical study cohorts, with at least twenty-four months of follow-up data for each sample.
57. Claim 20 of the '893 Patent depends from Claim 1 and further specifies that the numerical prognostic score is a continuous score between 0 and 1, and that the method further comprises converting the continuous score into a categorical risk classification comprising at least three risk strata with clinically validated score thresholds.
U.S. Patent No. 11,891,647 ("the '647 Patent")
58. On February 6, 2024, the USPTO duly and lawfully issued U.S. Patent No. 11,891,647, entitled "Improved Methods for Genomic Risk Stratification in Prostate Cancer Using Combined Biomarker and Clinical Variable Models" (the "'647 Patent"). A true and correct copy of the '647 Patent is attached hereto as Exhibit C and is incorporated herein by reference.
59. The application that matured into the '647 Patent was filed on September 9, 2021. The '647 Patent has an expiration date of September 9, 2041.
60. The named inventors of the '647 Patent are Dr. Rajan Mehta, Dr. Kevin Ostrowski, and Dr. Priya Shah, each of whom conceived and developed the inventions claimed therein during the course of their employment with GenomeDx. Each named inventor assigned all right, title, and interest in the '647 Patent to GenomeDx. GenomeDx is the sole and exclusive owner of the '647 Patent, including the right to sue for and recover damages for infringement.
61. The '647 Patent is valid, enforceable, and currently in force. All maintenance fees and other obligations necessary to maintain the '647 Patent in force have been timely paid and satisfied.
62. GenomeDx asserts Claims 1, 4, 6, 11, and 15 of the '647 Patent against Helios in this action.
63. Claim 1 of the '647 Patent recites:
A method for generating an integrated prognostic report comprising:
(a) performing RNA extraction and expression profiling on a prostate tumor specimen;
(b) computing a genomic risk score using a classifier comprising at least 20 gene features;
(c) combining the genomic risk score with at least two clinical covariates selected from Gleason score, PSA level, surgical margin status, and pathological stage; and
(d) generating a composite risk metric and transmitting it to a healthcare provider.
64. Claim 4 of the '647 Patent depends from Claim 1 and further specifies that the RNA extraction step comprises extracting total RNA from a formalin-fixed paraffin-embedded tissue specimen using a column-based extraction method and assessing RNA quality using a DV200 metric or equivalent fragmentation index prior to expression profiling.
65. Claim 6 of the '647 Patent depends from Claim 1 and further specifies that the classifier is an ensemble-based machine-learning classifier selected from the group consisting of random forest, gradient-boosted decision trees, and adaptive boosting classifiers, trained on a cohort comprising at least three hundred patient samples with known clinical outcomes.
66. Claim 11 of the '647 Patent depends from Claim 1 and further specifies that the at least two clinical covariates comprise Gleason score and PSA level, and that the combining step comprises applying a multivariate logistic regression model or a Cox proportional hazards model to the genomic risk score and the clinical covariates to generate the composite risk metric.
67. Claim 15 of the '647 Patent depends from Claim 1 and further specifies that the integrated prognostic report comprises a graphical representation of the composite risk metric, a numerical risk score, a categorical risk classification, and a summary of the clinical covariates used in the computation, and that the report is formatted for electronic transmission to a healthcare provider's electronic health record system.
COUNT I: INFRINGEMENT OF U.S. PATENT NO. 10,438,271
68. GenomeDx incorporates by reference and re-alleges each and every allegation set forth in paragraphs 1 through 67 above as though fully set forth herein.
Direct Infringement (35 U.S.C. § 271(a))
69. Helios has directly infringed and continues to directly infringe one or more of Claims 1, 3, 5, 7, 12, and 18 of the '271 Patent, literally and/or under the doctrine of equivalents, by making, using, selling, and/or offering to sell the ProstaSignal™ Genomic Classifier test within the United States, including within this judicial district, without authorization, license, or consent from GenomeDx.
70. Specifically, Helios's ProstaSignal™ test performs each and every limitation of at least Claim 1 of the '271 Patent, as well as the additional limitations of dependent Claims 3, 5, 7, 12, and 18, including:
(a) Obtaining a biological sample containing tumor RNA. Helios obtains biological samples containing tumor RNA from prostate tissue specimens submitted by healthcare providers to Helios's CLIA-certified laboratory in San Diego, California. The biological samples are prostate tissue specimens obtained from patients who have undergone radical prostatectomy, and they contain tumor RNA suitable for gene-expression profiling.
(b) Measuring expression levels of a panel of at least 22 genes selected from a predefined gene set. The ProstaSignal™ test measures expression levels of a panel of twenty-four (24) genes. Nineteen (19) of the twenty-four genes in the ProstaSignal™ panel overlap with GenomeDx's patented predefined gene set used in the Decipher® test. The twenty-four-gene panel used by ProstaSignal™ satisfies the "at least 22 genes" limitation recited in the claims. Moreover, the genes in the ProstaSignal™ panel are selected from functional categories — including cell proliferation, cell adhesion, immune response, androgen signaling, and stromal response pathways — that correspond to those specified in the predefined gene set of the '271 Patent.
(c) Applying a trained machine-learning classifier to generate a risk score. The ProstaSignal™ test applies a gradient-boosted decision tree classifier to the measured gene-expression data to generate the "ProstaScore," a numerical risk score ranging from 0 to 100. A gradient-boosted decision tree classifier is a trained machine-learning classifier within the meaning of the '271 Patent claims. The gradient-boosted decision tree classifier used by ProstaSignal™ is an ensemble-based supervised learning algorithm that, like the random-forest classifier specifically described in the '271 Patent specification, combines predictions from multiple decision trees to generate an accurate prognostic score.
(d) Classifying the patient into a risk category based on the score. The ProstaSignal™ test classifies patients into Low, Intermediate, or High risk categories based on the ProstaScore, thereby satisfying this claim limitation. The three risk categories used by ProstaSignal™ correspond directly to the risk categories recited in the claims of the '271 Patent.
71. Helios's infringement of the '271 Patent has been and continues to be willful. Upon information and belief, Helios had actual knowledge of the '271 Patent prior to the commercial launch of the ProstaSignal™ test on October 7, 2024. The '271 Patent issued on October 8, 2019, more than five years before Helios's launch of the ProstaSignal™ test. The '271 Patent is publicly available and readily accessible through the USPTO patent database and other patent search databases. Upon information and belief, Helios and its officers, including Dr. Nathan Ashford, Dr. Elaine Kossack, and their technical and legal advisors, were aware of GenomeDx's patent portfolio, including the '271 Patent, and launched the ProstaSignal™ test despite knowing that it infringes GenomeDx's patent rights. Helios's decision to launch the ProstaSignal™ test with a gene panel substantially overlapping GenomeDx's patented gene set, using the same fundamental classification methodology, and targeting the identical clinical use case, reflects a deliberate and willful decision to infringe GenomeDx's patents.
72. GenomeDx has been and continues to be damaged as a result of Helios's infringement of the '271 Patent. GenomeDx is entitled to recover damages adequate to compensate for such infringement, but in no event less than a reasonable royalty, pursuant to 35 U.S.C. § 284.
Indirect Infringement — Inducement (35 U.S.C. § 271(b))
73. Helios has induced and continues to induce infringement of the '271 Patent in violation of 35 U.S.C. § 271(b) by actively and knowingly encouraging, instructing, and aiding healthcare providers, medical institutions, laboratories, and other third parties to order and use the ProstaSignal™ test in a manner that directly infringes the asserted claims of the '271 Patent.
74. Upon information and belief, Helios provides detailed instructions, marketing materials, sales presentations, technical literature, published clinical data, test ordering protocols, specimen collection and submission guidelines, and technical support to healthcare providers and other third parties, all of which guide and direct them to order and use the ProstaSignal™ test in a manner that practices each and every step of the methods claimed in the '271 Patent. By providing these materials and support, Helios specifically intends that healthcare providers and other third parties will use the ProstaSignal™ test in an infringing manner, and Helios knows that such use constitutes infringement of the '271 Patent.
75. Helios has had knowledge of the '271 Patent at least since the filing and service of this Complaint. Upon information and belief, as set forth above, Helios had knowledge of the '271 Patent prior to the filing of this Complaint. Despite such knowledge, Helios has continued and continues to actively induce infringement of the '271 Patent.
Indirect Infringement — Contributory Infringement (35 U.S.C. § 271(c))
76. Helios has committed and continues to commit contributory infringement of the '271 Patent in violation of 35 U.S.C. § 271(c). Helios offers to sell and sells components, reagents, kits, software, and services that form a material part of the inventions claimed in the '271 Patent and that are especially made or especially adapted for use in practicing the infringing methods. These components, reagents, kits, software, and services — including the specific gene-expression profiling reagents, the trained gradient-boosted decision tree classifier software, and the test reporting system — are not staple articles or commodities of commerce suitable for substantial noninfringing use. Helios knows that these components are especially made or especially adapted for use in infringing the '271 Patent, and Helios knows that the use of these components in the ProstaSignal™ test constitutes infringement of the '271 Patent.
COUNT II: INFRINGEMENT OF U.S. PATENT NO. 11,204,893
77. GenomeDx incorporates by reference and re-alleges each and every allegation set forth in paragraphs 1 through 76 above as though fully set forth herein.
Direct Infringement (35 U.S.C. § 271(a))
78. Helios has directly infringed and continues to directly infringe one or more of Claims 1, 2, 9, 14, and 20 of the '893 Patent, literally and/or under the doctrine of equivalents, by making, using, selling, and/or offering to sell the ProstaSignal™ Genomic Classifier test within the United States, including within this judicial district, without authorization, license, or consent from GenomeDx.
79. Specifically, Helios's ProstaSignal™ test performs each and every limitation of at least Claim 1 of the '893 Patent, as well as the additional limitations of dependent Claims 2, 9, 14, and 20, including:
(a) Normalizing gene-expression data from a formalin-fixed paraffin-embedded prostate tissue sample using a reference gene panel. Upon information and belief, the ProstaSignal™ test processes gene-expression data obtained from FFPE prostate tissue samples and normalizes the raw expression data using a reference gene panel comprising housekeeping genes to control for variability in RNA quality, quantity, and batch effects. This normalization step is performed at Helios's San Diego laboratory as part of the standard ProstaSignal™ testing workflow.
(b) Inputting normalized expression values into a random-forest classifier trained on a cohort of at least 500 patient samples. The ProstaSignal™ test inputs normalized gene-expression values into a trained machine-learning classifier to generate a prognostic score. The '893 Patent specifically recites a "random-forest classifier trained on a cohort of at least 500 patient samples." Upon information and belief, the ProstaSignal™ test uses a gradient-boosted decision tree classifier, which is an ensemble-based machine-learning classifier that, like a random-forest classifier, aggregates predictions from multiple decision trees. Upon information and belief, Helios's classifier was trained on a cohort of patient samples comparable in size to the claimed cohort.
(c) Outputting a numerical prognostic score correlated with metastasis risk within 5 years. The ProstaSignal™ test outputs the "ProstaScore," a numerical prognostic score ranging from 0 to 100 that is correlated with the risk of metastasis within five years following radical prostatectomy.
80. To the extent that Helios's ProstaSignal™ test does not literally use a "random-forest classifier" as recited in Claim 1 of the '893 Patent, Helios infringes the '893 Patent under the doctrine of equivalents. The gradient-boosted decision tree classifier used by ProstaSignal™ performs substantially the same function as the claimed random-forest classifier — namely, ensemble-based classification of multi-gene expression data to generate a prognostic score — in substantially the same way — namely, by aggregating predictions from multiple individual decision trees, each of which evaluates a subset of gene-expression features to make a classification prediction — to achieve substantially the same result — namely, a numerical prognostic score correlated with metastasis risk within five years that is used to stratify patients into risk categories. The differences between a gradient-boosted decision tree classifier and a random-forest classifier are insubstantial in the context of the claimed invention. Both are ensemble-based, tree-based, supervised machine-learning algorithms that operate on the same type of input data (normalized gene-expression values), employ the same fundamental building blocks (decision trees), and produce the same type of output (a numerical prognostic score). A person of ordinary skill in the art would recognize that a gradient-boosted decision tree classifier is an interchangeable equivalent of a random-forest classifier for the purpose of the claimed invention.
81. Helios's infringement of the '893 Patent has been and continues to be willful. Upon information and belief, Helios had actual knowledge of the '893 Patent prior to the commercial launch of the ProstaSignal™ test. The '893 Patent issued on December 21, 2021, approximately three years before Helios's launch of the ProstaSignal™ test. Upon information and belief, Helios was aware of GenomeDx's patent portfolio, including the '893 Patent, and launched the ProstaSignal™ test despite knowing that it infringes GenomeDx's patent rights.
82. GenomeDx has been and continues to be damaged as a result of Helios's infringement of the '893 Patent. GenomeDx is entitled to recover damages adequate to compensate for such infringement, but in no event less than a reasonable royalty, pursuant to 35 U.S.C. § 284.
Indirect Infringement — Inducement (35 U.S.C. § 271(b))
83. Helios has induced and continues to induce infringement of the '893 Patent in violation of 35 U.S.C. § 271(b) by actively and knowingly encouraging, instructing, and aiding healthcare providers, medical institutions, laboratories, and other third parties to order and use the ProstaSignal™ test in a manner that directly infringes the asserted claims of the '893 Patent.
84. Upon information and belief, Helios provides detailed instructions, marketing materials, sales presentations, technical literature, test ordering protocols, specimen collection and submission guidelines, and technical support to healthcare providers and other third parties, all of which guide and direct them to order and use the ProstaSignal™ test in a manner that practices each and every step of the methods claimed in the '893 Patent. By providing these materials and support, Helios specifically intends that healthcare providers and other third parties will use the ProstaSignal™ test in an infringing manner, and Helios knows that such use constitutes infringement of the '893 Patent.
85. Helios has had knowledge of the '893 Patent at least since the filing and service of this Complaint. Upon information and belief, as set forth above, Helios had knowledge of the '893 Patent prior to the filing of this Complaint. Despite such knowledge, Helios has continued and continues to actively induce infringement of the '893 Patent.
Indirect Infringement — Contributory Infringement (35 U.S.C. § 271(c))
86. Helios has committed and continues to commit contributory infringement of the '893 Patent in violation of 35 U.S.C. § 271(c). Helios offers to sell and sells components, reagents, kits, software, and services that form a material part of the inventions claimed in the '893 Patent and that are especially made or especially adapted for use in practicing the infringing methods. These components, reagents, kits, software, and services — including the specific normalization algorithms, the trained gradient-boosted decision tree classifier software, and the prognostic score computation modules — are not staple articles or commodities of commerce suitable for substantial noninfringing use. Helios knows that these components are especially made or especially adapted for use in infringing the '893 Patent, and Helios knows that the use of these components in the ProstaSignal™ test constitutes infringement of the '893 Patent.
COUNT III: INFRINGEMENT OF U.S. PATENT NO. 11,891,647
87. GenomeDx incorporates by reference and re-alleges each and every allegation set forth in paragraphs 1 through 86 above as though fully set forth herein.
Direct Infringement (35 U.S.C. § 271(a))
88. Helios has directly infringed and continues to directly infringe one or more of Claims 1, 4, 6, 11, and 15 of the '647 Patent, literally and/or under the doctrine of equivalents, by making, using, selling, and/or offering to sell the ProstaSignal™ Genomic Classifier test within the United States, including within this judicial district, without authorization, license, or consent from GenomeDx.
89. Specifically, Helios's ProstaSignal™ test performs each and every limitation of at least Claim 1 of the '647 Patent, as well as the additional limitations of dependent Claims 4, 6, 11, and 15, including:
(a) Performing RNA extraction and expression profiling on a prostate tumor specimen. The ProstaSignal™ test involves the extraction of RNA from prostate tumor specimens submitted to Helios's CLIA-certified laboratory, followed by gene-expression profiling of the extracted RNA to measure the expression levels of the twenty-four genes in the ProstaSignal™ gene panel. This step is performed at Helios's San Diego laboratory as part of the standard ProstaSignal™ testing workflow.
(b) Computing a genomic risk score using a classifier comprising at least 20 gene features. The ProstaSignal™ test computes the ProstaScore using a gradient-boosted decision tree classifier that employs twenty-four (24) gene features — expression levels of the twenty-four genes in the ProstaSignal™ panel — as inputs to the classification algorithm. The twenty-four gene features used by ProstaSignal™ satisfy the "at least 20 gene features" limitation recited in the claims of the '647 Patent.
(c) Combining the genomic risk score with at least two clinical covariates selected from Gleason score, PSA level, surgical margin status, and pathological stage. Upon information and belief, the ProstaSignal™ test combines the ProstaScore with at least two clinical covariates, specifically Gleason grade group (which corresponds to and is derived from Gleason score) and pre-operative PSA level. Both Gleason score (via Gleason grade group) and PSA level are among the clinical covariates expressly enumerated in the claims of the '647 Patent. The combination of the genomic risk score with these clinical covariates satisfies this claim limitation.
(d) Generating a composite risk metric and transmitting it to a healthcare provider. The ProstaSignal™ test generates an integrated prognostic report containing a composite risk assessment that combines the ProstaScore genomic risk score with the clinical covariate data, and Helios transmits this integrated report to the ordering healthcare provider. The composite risk assessment contained in the ProstaSignal™ report constitutes a "composite risk metric" within the meaning of the '647 Patent claims, and the transmission of the report to the ordering healthcare provider satisfies the transmitting limitation.
90. Helios's infringement of the '647 Patent has been and continues to be willful. Upon information and belief, Helios had actual knowledge of the '647 Patent prior to the commercial launch of the ProstaSignal™ test on October 7, 2024. The '647 Patent issued on February 6, 2024, approximately eight months before Helios's launch of the ProstaSignal™ test. Upon information and belief, Helios was aware of GenomeDx's patent portfolio, including the '647 Patent, and launched the ProstaSignal™ test despite knowing that it infringes GenomeDx's patent rights. Indeed, the '647 Patent issued during the very period in which Helios was finalizing the development and preparing for the commercial launch of the ProstaSignal™ test, and upon information and belief, Helios was monitoring GenomeDx's patent portfolio during this critical pre-launch period.
91. GenomeDx has been and continues to be damaged as a result of Helios's infringement of the '647 Patent. GenomeDx is entitled to recover damages adequate to compensate for such infringement, but in no event less than a reasonable royalty, pursuant to 35 U.S.C. § 284.
Indirect Infringement — Inducement (35 U.S.C. § 271(b))
92. Helios has induced and continues to induce infringement of the '647 Patent in violation of 35 U.S.C. § 271(b) by actively and knowingly encouraging, instructing, and aiding healthcare providers, medical institutions, laboratories, and other third parties to order and use the ProstaSignal™ test in a manner that directly infringes the asserted claims of the '647 Patent.
93. Upon information and belief, Helios provides detailed instructions, marketing materials, sales presentations, technical literature, test ordering protocols, specimen collection and submission guidelines, and technical support to healthcare providers and other third parties, all of which guide and direct them to order and use the ProstaSignal™ test in a manner that practices each and every step of the methods claimed in the '647 Patent. Specifically, Helios provides ordering healthcare providers with instructions to submit clinical covariates — including Gleason grade group and pre-operative PSA level — along with the tissue specimen, so that Helios can generate the integrated prognostic report that combines the ProstaScore with the clinical covariates. By providing these materials, instructions, and support, Helios specifically intends that healthcare providers and other third parties will use the ProstaSignal™ test in an infringing manner, and Helios knows that such use constitutes infringement of the '647 Patent.
94. Helios has had knowledge of the '647 Patent at least since the filing and service of this Complaint. Upon information and belief, as set forth above, Helios had knowledge of the '647 Patent prior to the filing of this Complaint. Despite such knowledge, Helios has continued and continues to actively induce infringement of the '647 Patent.
Indirect Infringement — Contributory Infringement (35 U.S.C. § 271(c))
95. Helios has committed and continues to commit contributory infringement of the '647 Patent in violation of 35 U.S.C. § 271(c). Helios offers to sell and sells components, reagents, kits, software, and services that form a material part of the inventions claimed in the '647 Patent and that are especially made or especially adapted for use in practicing the infringing methods. These components, reagents, kits, software, and services — including the RNA extraction reagents and kits, the gene-expression profiling reagents and platforms, the trained gradient-boosted decision tree classifier software, the clinical covariate integration algorithms, and the composite risk metric computation and report generation software — are not staple articles or commodities of commerce suitable for substantial noninfringing use. Helios knows that these components are especially made or especially adapted for use in infringing the '647 Patent, and Helios knows that the use of these components in the ProstaSignal™ test constitutes infringement of the '647 Patent.
DAMAGES
96. GenomeDx has suffered and will continue to suffer damages as a result of Helios's infringement of the Patents-in-Suit, including but not limited to lost profits and/or a reasonable royalty, in an amount to be proven and determined at trial.
97. GenomeDx is the market leader in genomic prostate cancer prognostic testing. Prior to the commercial launch of the ProstaSignal™ test on October 7, 2024, GenomeDx held approximately seventy-four percent (74%) market share in this market. As a direct result of Helios's infringing activities, GenomeDx's market share has declined to approximately sixty-eight percent (68%), representing a loss of approximately six (6) percentage points of market share. This market share loss translates directly into lost revenue, lost profits, and erosion of GenomeDx's competitive position and goodwill, all of which are attributable to Helios's infringement of the Patents-in-Suit.
98. GenomeDx is entitled to damages adequate to compensate for the infringement, but in no event less than a reasonable royalty for the use made of the inventions by Helios, pursuant to 35 U.S.C. § 284.
99. Upon information and belief, Helios's infringement of the Patents-in-Suit has been willful and deliberate, as set forth in detail above. Helios was aware of GenomeDx's patent rights prior to launching the ProstaSignal™ test and proceeded to launch the infringing product despite that knowledge. GenomeDx is therefore entitled to enhanced damages of up to three times the amount of compensatory damages found or assessed, pursuant to 35 U.S.C. § 284, and as further authorized by Halo Electronics, Inc. v. Pulse Electronics, Inc., 579 U.S. 93 (2016).
100. GenomeDx is entitled to recover pre-judgment interest on the damages award from the date of first infringement to the date of judgment, and post-judgment interest from the date of judgment until the date of payment, at such rates and for such periods as the Court may determine to be just.
PRAYER FOR RELIEF
WHEREFORE, Plaintiff Genome Dx Therapeutics Inc. respectfully requests that this Court enter judgment in its favor and against Defendant Helios Precision Diagnostics, Inc. and grant the following relief:
1. A judgment and declaration that Helios has infringed and continues to infringe U.S. Patent Nos. 10,438,271, 11,204,893, and 11,891,647, both directly and indirectly, literally and/or under the doctrine of equivalents;
2. A permanent injunction prohibiting Helios, its officers, directors, agents, servants, employees, attorneys, successors, assigns, and all persons acting in concert or participation with any of them, from further infringement of U.S. Patent Nos. 10,438,271, 11,204,893, and 11,891,647, including from making, using, selling, offering to sell, or importing into the United States the ProstaSignal™ Genomic Classifier test or any other product, method, or service that infringes the Patents-in-Suit;
3. An award of damages adequate to compensate GenomeDx for Helios's past and ongoing infringement, including lost profits and/or a reasonable royalty, in an amount to be determined at trial, but in no event less than a reasonable royalty pursuant to 35 U.S.C. § 284;
4. A finding that Helios's infringement of the Patents-in-Suit has been willful and deliberate, and an award of enhanced damages of up to three (3) times the amount of compensatory damages, pursuant to 35 U.S.C. § 284;
5. A finding that this is an exceptional case and an award of GenomeDx's reasonable attorneys' fees and costs incurred in this action, pursuant to 35 U.S.C. § 285;
6. An award of pre-judgment interest on all damages from the date of first infringement to the date of judgment, and post-judgment interest from the date of judgment until the date of full payment, at the maximum rate permitted by law;
7. An order requiring Helios to provide a full accounting of all revenues, profits, costs, units sold, and other financial information related to Helios's making, using, selling, offering to sell, and importing of the ProstaSignal™ Genomic Classifier test and any other infringing products;
8. Such other and further relief as this Court deems just and proper.
DEMAND FOR JURY TRIAL
Plaintiff Genome Dx Therapeutics Inc. hereby demands a trial by jury on all issues and claims in this action that are so triable as of right, pursuant to Federal Rule of Civil Procedure 38(b).
Respectfully submitted,
Dated: March 28, 2025
CALDERWOOD & HARKNESS LLP
By: ________
Catherine Bloom (CA Bar No. 247831) Responsible Partner, intellectual Property 555 Mission Street, Suite 3100 San Francisco, CA 94105 Telephone: (415) 773-6200 Facsimile: (415) 773-6201
Email: cbloom@calderwoodharkness.com
Peter Vassiliev (CA Bar No. 312045) Lead Associate, intellectual Property
Wendy Schultz (CA Bar No. 319782) Associate, intellectual Property
Attorneys for Plaintiff Genome Dx Therapeutics Inc.
EXHIBITS
The following exhibits are attached hereto and incorporated herein by reference:
Exhibit A: Certified Copy of U.S. Patent No. 10,438,271, entitled "Methods for Predicting Prostate Cancer Outcomes Using Multi-Gene Expression Classifiers," issued October 8, 2019.
Exhibit B: Certified Copy of U.S. Patent No. 11,204,893, entitled "Genomic Classifier Systems and Methods for Post-Surgical Cancer Prognosis," issued December 21, 2021.
Exhibit C: Certified Copy of U.S. Patent No. 11,891,647, entitled "Improved Methods for Genomic Risk Stratification in Prostate Cancer Using Combined Biomarker and Clinical Variable Models," issued February 6, 2024.
GENOME DX THERAPEUTICS INC., a Delaware corporation, | Case No. 3:25-cv-01847-JWL
Plaintiff, | COMPLAINT FOR PATENT INFRINGEMENT
v. | DEMAND FOR JURY TRIAL
HELIOS PRECISION DIAGNOSTICS, INC., a Delaware corporation,
Defendant.

UNITED STATES DISTRICT COURT FOR THE NORTHERN DISTRICT OF CALIFORNIA

INTRODUCTION

THE PARTIES

JURISDICTION AND VENUE

FACTUAL BACKGROUND

THE PATENTS-IN-SUIT

COUNT I: INFRINGEMENT OF U.S. PATENT NO. 10,438,271

COUNT II: INFRINGEMENT OF U.S. PATENT NO. 11,204,893

COUNT III: INFRINGEMENT OF U.S. PATENT NO. 11,891,647

DAMAGES

PRAYER FOR RELIEF

DEMAND FOR JURY TRIAL

CALDERWOOD & HARKNESS LLP

EXHIBITS

Record

Parties

Dates

Amounts