Denovo Biopharma (San Diego, USA) received US Patent No. 12,612,261 from the US Patent and Trademark Office (USPTO) for its DGM4 genetic biomarker, designated ANK3, which is used to identify patient subpopulations likely to respond to liafensine (DB104), the company’s triple reuptake inhibitor currently in Phase III development for treatment-resistant depression (TRD). The patent, titled “Compositions and methods for assessing the efficacy of inhibitors of neurotransmitter transporters,” extends IP protection on the ANK3 genetic biomarker patent through 2043, providing a longer exclusivity runway than a conventional composition-of-matter claim would confer given that the molecule itself is already in late-stage development. The issuance is scientifically notable because it codifies a pharmacogenomic selection method that prospectively stratifies TRD patients based on a single nucleotide polymorphism (SNP) within the ANK3 gene, a locus encoding a scaffolding protein with documented roles in neuronal membrane organization and psychiatric disease susceptibility.
Liafensine was originally licensed from Albany Molecular Research (now Curia) and was previously developed by Bristol-Myers Squibb, which conducted 14 clinical trials establishing the molecule’s safety profile but failed to demonstrate efficacy in unselected TRD populations. Denovo’s hypothesis was that the absence of a biomarker-driven enrollment strategy masked a treatment signal confined to a genetically defined subgroup. The ANK3 gene encodes Ankyrin-3, a scaffolding protein expressed predominantly in the nervous system that modulates the localization and function of ion channels and other membrane-associated proteins. Variants in ANK3 have been associated with bipolar disorder and major depressive disorder in prior genetic studies, making it a biologically plausible locus for pharmacogenomic stratification in a CNS indication.
DGM4 is a specific SNP within ANK3 that Denovo identified using archived samples from patients previously treated with liafensine, processed through the company’s AI-assisted whole-genome scanning platform, referred to internally as the Denovo Genomic Marker (DGM) platform. Unlike companion diagnostics built around previously characterized biomarkers, DGM4 was discovered de novo from clinical data, which the company states distinguishes it from most approved companion diagnostic frameworks. The resulting ANK3 genetic biomarker patent covers the use of this SNP as a selection tool for liafensine therapy, rather than the molecule itself.
Liafensine operates as a triple reuptake inhibitor, blocking the reuptake transporters for serotonin, norepinephrine, and dopamine simultaneously. This mechanism differentiates it from selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors that form the backbone of first- and second-line antidepressant therapy. In Denovo’s Phase IIb ENLIGHTEN trial, liafensine demonstrated efficacy specifically in ANK3-positive patients with TRD, with results published in JAMA Psychiatry. The asset has received Fast Track Designation from the US FDA and has advanced into Phase III development. Specific Phase III clinical results remain undisclosed at this time.
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