BioTech IP Review

Assignee: GRAIL, Inc., Menlo Park, CA, USA
Patent Number: 12,509,726 B2
Filed: February 20, 2025 (Application No. 19/058,911)
Issued: December 30, 2025
Inventors: Anton Valouev (Palo Alto, CA) & Arash Jamshidi (Redwood City, CA)
Patent Classification: Sequencing & Library Preparation (C12Q 1/6874)

What This Patent Covers

This patent protects novel laboratory methods for constructing dual‑indexed DNA libraries specifically optimized for bisulfite conversion sequencing — a key technique used to profile DNA methylation signatures, which are fundamental biomarkers in cancer detection.

Core technical coverage includes:

• Methods to prepare cell‑free DNA (cfDNA) libraries where unmethylated cytosines are chemically converted (typically to uracils) to reveal methylation status.
• A dual‑indexing process that tags these bisulfite‑treated DNA fragments with unique molecular identifiers (UMIs) and sample identifiers, improving identification accuracy and reducing sequencing errors.
• Use of these libraries in next‑generation sequencing (NGS) workflows to accurately determine methylation profiles from biological samples such as blood plasma — directly relevant to non‑invasive cancer detection.
• Claims also cover kits and reagents that facilitate these preparation steps, enabling high‑fidelity quantification of methylation patterns.

Why This Patent Is Important

• Foundational to Galleri and MCED tests: DNA methylation profiling — especially from circulating tumor DNA — is central to GRAIL’s commercial test portfolio (e.g., Galleri multi‑cancer early detection test).
• Enhances analytical accuracy: Dual‑indexed library preparation with UMIs meaningfully reduces sequencing artifacts and improves confidence in detecting subtle epigenetic signatures — crucial for early cancer signal detection.
• Commercial leverage & IP moat: Robust IP around library prep and sequencing library quality strengthens GRAIL’s competitive position in the crowded liquid biopsy market, supporting future product iterations and potentially licensing.
• Long‑term impact: Bisulfite sequencing and methylation profiling remain core to many oncology diagnostics, so this patent underpins technology likely to support revenue growth and clinical adoption through the late 2020s.