Contract analysis

I. EXECUTIVE SUMMARY Calderwood & Harkness LLP has been engaged by Genome Dx Therapeutics Inc. ("GenomeDx" or "GDT"), a Delaware corporation headquartered at 4750 Torrey Pines Road, Suite 300, San Diego, California 92130, to evaluate the merits of filing a patent infringement action against Helios Precision Diagnostics, Inc. ("Helios"), a Delaware corporation headquartered at 200 CambridgePark Drive, Suite 600, Cambr

1. Infringement. GenomeDx has strong literal infringement claims against Helios under the '271 and '647 Patents. Each element of the independent claims of these patents is satisfied by the ProstaSignal™ product as currently marketed and sold. The '893 Patent presents a literal infringement question with respect to the "random-forest classifier" limitation in independent Claim 1, as ProstaSignal™ employs a gradient-bo

2. Validity. Validity risks exist under 35 U.S.C. §§ 101, 102, and 103, but each is manageable based on our review of the prosecution histories, the prior art landscape, and current Federal Circuit jurisprudence. The '647 Patent presents the strongest validity position, supported by a 37 C.F.R. § 1.132 declaration establishing unexpected results and by claim language that integrates clinical covariates with genomic d

3. Enforceability. No enforceability concerns have been identified. Our review of the prosecution files reveals no inequitable conduct, patent misuse, or other enforceability defenses available to Helios.

4. Forum. We recommend filing in the U.S. District Court for the Northern District of California, where venue and personal jurisdiction can be established based on Helios's California operations, marketing activities, and sales within the district.

5. Damages. Preliminary damages estimates range from approximately $5.8 million under a reasonable royalty theory to approximately $18.5 million under a lost profits theory for the infringement period to date (October 2024 through March 2025), with ongoing accrual at an estimated rate of $3 million to $5 million per month. Enhanced damages may be available if willful infringement is established. Based on these conclu

II. BACKGROUND A. The Client — Genome Dx Therapeutics Inc. Genome Dx Therapeutics Inc. was founded in 2011 and is organized as a corporation under the laws of the State of Delaware. GenomeDx is qualified to do business in the State of California, where its principal offices are located at 4750 Torrey Pines Road, Suite 300, San Diego, California 92130.

1. Key Management GenomeDx is led by the following members of senior management, each of whom may be relevant to the anticipated litigation as fact witnesses, inventors, or corporate representatives: • Chief Executive Officer: Dr. Miriam Langford, PhD. Dr. Langford holds a doctorate in molecular biology from Stanford University and has served as CEO since 2017. She provides overall strategic direction for the company

2. Ownership Structure GenomeDx's equity ownership is structured as follows: Pinnacle Biosciences Capital, LP is a Delaware limited partnership managed by its general partner, Pinnacle Biosciences Capital GP, LLC. Pinnacle's Managing Partner is Jonathan Hargrove. The fund manages approximately $4.2 billion in assets under management ("AUM") across three investment vehicles. Pinnacle's principal office is located at 6

3. Business Overview and Products GenomeDx's primary product is the Decipher® Prostate genomic classifier test, a 22-gene expression-based prognostic test designed for patients who have undergone radical prostatectomy for prostate cancer. The Decipher® test measures the expression levels of 22 specific genes in tumor tissue obtained from formalin-fixed paraffin-embedded ("FFPE") surgical specimens, applies a trained

4. Financial Profile For the fiscal year ending December 31, 2024, GenomeDx reported the following key financial metrics: GenomeDx's auditor is Whitfield & Garner LLP, located in San Diego, California. GenomeDx's primary lending relationship is with Meridian Commercial Bank, N.A., which provides a $75 million revolving credit facility. GenomeDx's registered agent in Delaware is Pacific Registered Agents, Inc., locate

5. Market Position Prior to the commercial launch of the ProstaSignal™ test in October 2024, GenomeDx held approximately 74% of the U.S. market for genomic prostate cancer prognostic testing in the post-radical prostatectomy setting. This market share has declined to approximately 68% following the ProstaSignal™ launch. The decline in market share is directly attributable to the ProstaSignal™ test, which competes for

6. IP Enforcement Insurance GenomeDx carries intellectual property enforcement insurance through Greystone Specialty Insurance Co. under policy number GSI-IP-2024-07812. The policy provides $10 million in coverage for offensive patent litigation costs, subject to a $2.5 million deductible and an 80/20 co-insurance structure above the deductible up to the policy limit. The policy period runs from January 1, 2025, thro

1. Key Management Based on publicly available information, Helios's senior management team includes the following individuals: • Chief Executive Officer: Dr. Nathan Ashford, MD, PhD. Dr. Ashford holds a medical degree and a doctorate in oncology and bioinformatics from Johns Hopkins University. He co-founded Helios in 2019 and has led the company's strategy to develop and commercialize genomic diagnostic products for

2. Ownership Structure Helios's equity ownership is structured as follows: Corinth Ventures Fund III, LP, Helios's majority investor, is a venture capital fund managed by Priya Chandrasekaran with approximately $2.1 billion in AUM. Corinth's principal office is located at 399 Boylston Street, Suite 1100, Boston, Massachusetts 02116. Corinth's investment in Helios and its board representation may be relevant to discov

3. Financial Overview For the fiscal year ending December 31, 2024, Helios reported revenue of $71.2 million. This figure includes revenue from the ProstaSignal™ test (launched in the fourth quarter of 2024) as well as revenue from other diagnostic products and services in Helios's portfolio.

4. Anticipated Outside Counsel Based on our investigation, Helios is likely to retain Ridgecrest Durneval LLP as outside litigation counsel. Ridgecrest Durneval is a prominent intellectual property litigation firm with a strong track record in pharmaceutical and life sciences patent disputes. The anticipated lead partner is Marcus Pellegrini, who has more than 25 years of experience in patent litigation, including ex

1. Regulatory and Reimbursement Status Helios obtained MAAA code 0239M for the ProstaSignal™ test from the AMA CPT Editorial Panel in September 2024, enabling billing and reimbursement through Medicare and commercial payers. Like the Decipher® test, ProstaSignal™ is classified and marketed as a laboratory-developed test under the CLIA framework. Both the ProstaSignal™ and Decipher® tests are reimbursed by Medicare un

2. Laboratory Operations ProstaSignal™ is performed exclusively at Helios's CLIA-certified laboratory located at 9830 Mesa Rim Road, Suite 140, San Diego, California 92121. Tissue specimens are sent to this laboratory by ordering physicians and hospitals nationwide. The fact that all ProstaSignal™ testing occurs at a single, centralized laboratory is relevant to both the direct infringement analysis (Helios itself pe

3. Technical Description Based on our review of publicly available materials, including Helios's marketing brochures, clinical white papers, the MAAA code filing documentation, and published abstracts, the ProstaSignal™ test operates as follows: • Sample Input: ProstaSignal™ operates on formalin-fixed paraffin-embedded ("FFPE") prostate tumor tissue obtained from radical prostatectomy specimens. The test requires sub

4. Test Volume and Revenue Based on our investigation, including analysis of public filings, investor presentations, MolDX billing data obtained through public records requests, and industry estimates, we estimate that Helios performed approximately 8,400 ProstaSignal™ tests between October 2024 and March 2025, at an average reimbursement rate of approximately $3,820 per test. This yields estimated ProstaSignal™ reve

5. Gene Panel Overlap A critical factual element of the infringement analysis is the degree of overlap between the gene panels used in the Decipher® and ProstaSignal™ tests. The Decipher® test measures 22 genes. The ProstaSignal™ test measures 24 genes. Our analysis, set forth in detail in the gene panel comparison table attached as Appendix C, reveals that 19 of ProstaSignal™'s 24 genes are identical to genes in the

III. PATENTS-IN-SUIT This section describes the three patents recommended for assertion against Helios, including their prosecution histories, priority chains, key claims, and relevant claim construction issues. Full texts of the patents and prosecution history summaries are attached as Appendices A and B, respectively. A. U.S. Patent No. 10,438,271 (the "'271 Patent") Title: "Methods for Predicting Prostate Cancer O

1. Claims Recommended for Assertion We recommend asserting Claims 1, 3, 5, 7, 12, and 18 of the '271 Patent against Helios. These claims were selected based on their alignment with the ProstaSignal™ product, the breadth of their claim language, and their defensibility against anticipated invalidity challenges.

2. Key Independent Claim (Claim 1) Claim 1 of the '271 Patent recites: A method for prognosing the likelihood of clinical recurrence following radical prostatectomy in a patient diagnosed with prostate cancer, the method comprising: (a) obtaining a biological sample containing tumor RNA from the patient; (b) measuring expression levels of a panel of at least 22 genes selected from a predefined gene set; (c) applying

3. Prosecution History The '271 Patent was prosecuted through three office actions. During the first office action, the Examiner issued a rejection under 35 U.S.C. § 101, characterizing the claims as directed to an abstract idea (a mathematical correlation between gene expression and cancer outcomes). The applicant responded by amending the claims to recite specific technical steps — including RNA extraction from FFP

4. Named Inventor Status Dr. Rajan Mehta remains employed by GenomeDx as CTO and is fully available as a witness. Dr. Carolyn Xu departed GenomeDx in 2023 and is currently employed by Cascadia Genomics, Inc., a Washington corporation. Dr. Xu's departure was amicable according to client representatives, but she is no longer under any contractual obligation to cooperate with GenomeDx in litigation matters beyond the ge

1. Claims Recommended for Assertion We recommend asserting Claims 1, 2, 9, 14, and 20 of the '893 Patent. While literal infringement of the "random-forest classifier" limitation is problematic, the inclusion of this patent in the assertion portfolio provides additional coverage and supports a doctrine-of-equivalents theory.

2. Key Independent Claim (Claim 1) Claim 1 of the '893 Patent recites: A method for determining a prognosis for a prostate cancer patient following radical prostatectomy, the method comprising: (a) normalizing gene-expression data obtained from a formalin-fixed paraffin-embedded prostate tissue sample using a reference gene panel comprising at least three reference genes; (b) inputting the normalized expression value

3. Prosecution History The '893 Patent was prosecuted through two office actions. The Examiner rejected Claims 1–22 under 35 U.S.C. § 102(a)(1) based on Nakamura et al., U.S. Patent No. 9,617,340 ("Nakamura"), issued April 4, 2017. Nakamura discloses gene expression profiling methods for cancer prognosis but does not disclose a random-forest classifier trained on a cohort of at least 500 patient samples. The applican

4. Named Inventor Status Dr. Rajan Mehta and Dr. Carolyn Xu are the named inventors, with the same status and availability considerations discussed above. C. U.S. Patent No. 11,891,647 (the "'647 Patent") Title: "Improved Methods for Genomic Risk Stratification in Prostate Cancer Using Combined Biomarker and Clinical Variable Models" The '647 Patent is the most recently issued patent in the portfolio and has the late

1. Claims Recommended for Assertion We recommend asserting Claims 1, 4, 6, 11, and 15 of the '647 Patent. These claims are the strongest in GenomeDx's portfolio for assertion against ProstaSignal™ due to their breadth (use of the generic term "classifier" rather than "random-forest classifier") and their recitation of the combined genomic-clinical covariate methodology that ProstaSignal™ employs.

2. Key Independent Claim (Claim 1) Claim 1 of the '647 Patent recites: A method for generating an integrated prognostic report for a prostate cancer patient, the method comprising: (a) performing RNA extraction and expression profiling on a prostate tumor specimen obtained from the patient following radical prostatectomy; (b) computing a genomic risk score using a classifier comprising at least 20 gene features, wher

3. Prosecution History The '647 Patent was prosecuted through three office actions. The Examiner initially rejected the claims under 35 U.S.C. § 103, combining Nakamura with Gagnon (WO 2018/065413). The applicant responded with a combination of claim amendments and a declaration under 37 C.F.R. § 1.132 submitted by Dr. Rajan Mehta. Dr. Mehta's declaration presented clinical validation data demonstrating that the comb

4. Named Inventor Status Dr. Rajan Mehta and Dr. Kevin Ostrowski are both currently employed by GenomeDx and are fully available as witnesses. Dr. Priya Shah is a named inventor on the '647 Patent. Dr. Shah is a former Senior Research Scientist at GenomeDx who contributed to the development of the combined biomarker-clinical variable model. Client representatives indicate that Dr. Shah remains in the San Diego area a

IV. INFRINGEMENT ANALYSIS This section presents our element-by-element analysis of Helios's infringement of each patent-in-suit, addressing both literal infringement and, where applicable, infringement under the doctrine of equivalents. Our analysis is based on publicly available information regarding the ProstaSignal™ test, including marketing materials, clinical white papers, the MAAA code filing, published abstrac

1. Claim 1 Element-by-Element Analysis We have analyzed each element of independent Claim 1 of the '271 Patent against the ProstaSignal™ product. Our analysis is as follows: Element (a): "obtaining a biological sample containing tumor RNA from the patient" ProstaSignal™ operates on tissue samples obtained from radical prostatectomy specimens. Ordering physicians submit FFPE tissue blocks or unstained slides to Helios

2. Dependent Claims 3, 5, 7, 12, and 18 The dependent claims recommended for assertion add the following additional limitations: • Claim 3 requires that the biological sample is an FFPE sample. ProstaSignal™ processes FFPE tissue. Satisfied. • Claim 5 requires that the gene panel includes specific named genes from a defined subset. Preliminary analysis, based on the gene panel comparison in Appendix C, indicates that

3. Assessment. The literal infringement case for the '271 Patent is strong. All elements of independent Claim 1 are met by ProstaSignal™, including the critical gene panel limitation (22 of 24 ProstaSignal™ genes fall within the predefined gene set). The use of the broad term "trained machine-learning classifier" in the '271 Patent — rather than the more specific "random-forest classifier" of the '893 Patent — elimin

1. Claim 1 Element-by-Element Analysis Element (a): "normalizing gene-expression data obtained from a formalin-fixed paraffin-embedded prostate tissue sample using a reference gene panel comprising at least three reference genes" ProstaSignal™ processes FFPE prostate tissue samples and employs a normalization step using reference genes. Helios's published methodology references the use of a reference gene panel for n

2. Doctrine of Equivalents — '893 Patent Because literal infringement of the "random-forest classifier" limitation is not established, GenomeDx should assert infringement under the doctrine of equivalents ("DOE") for the '893 Patent claims. Under the DOE, a product or process infringes a patent claim if it performs substantially the same function, in substantially the same way, to achieve substantially the same resul

3. Dependent Claims 2, 9, 14, and 20 Each of the dependent claims recommended for assertion incorporates the independent claim limitations, including the "random-forest classifier" limitation. The DOE analysis described above extends to each dependent claim. The additional limitations in these claims (relating to specific output formats, training cohort characteristics, and gene panel subsets) are likely satisfied by

1. Claim 1 Element-by-Element Analysis Element (a): "performing RNA extraction and expression profiling on a prostate tumor specimen obtained from the patient following radical prostatectomy" ProstaSignal™ performs RNA extraction from prostate tumor specimens obtained from patients following radical prostatectomy and profiles the expression of 24 genes. Helios's marketing materials and laboratory requisition forms co

2. Dependent Claims 4, 6, 11, and 15 The dependent claims recommended for assertion add the following additional limitations: • Claim 4 requires that the gene features include at least 15 genes from a specified list. The gene panel comparison in Appendix C indicates that ProstaSignal™'s panel includes the requisite number of listed genes. Confirmation through discovery is recommended. • Claim 6 requires the integrate

3. Assessment. The literal infringement case for the '647 Patent is strong — the strongest of the three patents-in-suit. Every element of independent Claim 1 is clearly met by ProstaSignal™. The '647 Patent's use of the generic term "classifier" (rather than "random-forest classifier") eliminates the literal infringement gap that complicates the '893 Patent. The claim's recitation of the combined biomarker-clinic