Biomarker-Guided Antidepressants — PatSnap Eureka
Biomarker-Guided Antidepressant Pipeline: Precision Psychiatry & Triple Reuptake Inhibitor Approaches
Major depressive disorder represents a critical unmet need, with a substantial proportion of patients failing first-line SSRI/SNRI therapies. Discover how pharmacogenomic biomarkers, triple reuptake inhibitors, and kappa-opioid antagonism are reshaping the antidepressant pipeline.
Precision Psychiatry Biomarker Modalities
Distribution of biomarker types across the antidepressant patent landscape in this dataset.
From Trial-and-Error to Biology-Driven Prescribing
Retrieved results converge on major depressive disorder (MDD), treatment-resistant depression (TRD), and related psychiatric conditions — including bipolar disorder, suicidality, PTSD, and schizophrenia — as the primary disease contexts driving precision psychiatry innovation. The National Institute of Mental Health recognises treatment-resistant depression as a major public health challenge, underscoring the urgency of biomarker-guided approaches.
The molecular target landscape is heterogeneous, spanning multiple neurotransmitter systems. Monoamine systems remain central: retrieved patents identify serotonin (5-HT) reuptake transporters, norepinephrine transporters, and dopamine transporters as co-inhibition targets for triple reuptake inhibitors. Beyond monoamines, the kappa-opioid receptor (KOR), NMDA/glutamate pathways, vasopressin/CRH stress axis, and circadian clock gene markers all feature prominently across patent filings.
Blood gene expression biomarkers for suicidality and mood subtypes — including SAT1, FOXN3, GBP1, PIK3R5, APOL2, MARCKS, and GCOM1 — are featured prominently across Indiana University and US Department of Veterans Affairs filings. Metabolomic biomarkers (acylcarnitine C3, acylcarnitine C5, α-aminoadipate) are documented as diagnostic and treatment-monitoring tools. The PatSnap analytics platform enables deep landscape analysis across all these target classes simultaneously.
This convergence of pharmacology and molecular diagnostics is reshaping how drug developers, IP teams, and clinical researchers approach antidepressant development. Explore the full patent landscape with PatSnap Eureka to map freedom-to-operate, identify assignee strategies, and track emerging biomarker IP.
Seven Precision Psychiatry Approaches in the Antidepressant Pipeline
From triple reuptake inhibitors with companion diagnostics to TAAR1 agonism and microbiome-guided dosing — the patent landscape reveals a field moving decisively beyond classical monoamine pharmacology.
Triple Reuptake Inhibitors with Companion Diagnostics
DeNovo Biopharma's liafensine (DB1/DB104) simultaneously inhibits serotonin, norepinephrine, and dopamine transporters, developed to "synergize the individual, though complementary, monoaminergic treatments for depression to maximize antidepressant efficacy and tolerability." The program completed multiple Phase 2 clinical studies in TRD before discontinuation; DeNovo's IP strategy now pivots to pharmacogenomic biomarkers to identify the responsive sub-population. Euthymics' EB-1010 provides a second TRI scaffold, with Phase 2 data indicating no sexual dysfunction — a key differentiation from SSRIs.
Phase 2 completed · Biomarker re-stratification proposedKappa-Opioid Receptor Antagonism (Aticaprant, Janssen)
Janssen Pharmaceuticals' filings on aticaprant represent the clearest example of a fully biomarker-gated MDD therapy in this dataset. Patient eligibility requires a positive biomarker signature. The filings specifically address patients with inadequate SSRI/SNRI response, positioning aticaprant as an adjunctive or subsequent-line agent. Filings span WO, CA, and US jurisdictions (2023–2025), signaling global commercial intent. New entrants to KOR antidepressant development should conduct freedom-to-operate analysis against these biomarker-linked claim sets.
Clinical stage · Biomarker-gated enrollmentNMDA/Glutamate Receptor Modulators with SNP-Based Patient Selection
AstraZeneca's GABR-A2 filings focus on SNPs (rs3756007, rs11503016, rs17537359, rs1372472) in the GABA-A receptor alpha-2 subunit to predict response to NMDA antagonists including ketamine. University of Michigan filings extend pharmacogenomic decision support to NMDA antagonists, glycine receptor beta (GLRB) modulators, and AMPA receptor modulators, incorporating SNP panels and ketamine-specific topological association domain analysis. Both ketamine-derivative programs and novel NMDA-adjacent programs may benefit from licensing these SNP panels.
Preclinical/translational · Multi-SNP panelsTAAR1/5-HT1A Agonism (Ulotaront) as Augmentation
Sumitomo Pharma America's filings describe ulotaront as a trace amine-associated receptor 1 (TAAR1) and 5-HT1A agonist augmentation agent for inadequate antidepressant responders. Retrieved text describes preclinical antidepressant behavioral activity in rat models that "many conventional antidepressants are unable to treat." Its non-D2, non-classical monoamine mechanism positions it as a mechanistically novel augmentation option for treatment-resistant and refractory MDD subpopulations. A large randomized, double-blind, placebo-controlled clinical trial demonstrating efficacy in schizophrenia is referenced.
Clinical (schizophrenia) · Preclinical (MDD augmentation)Metabolomic Biomarker Diagnostics for Depression and Treatment Monitoring
Multiple patent families (Dunlop/Jia Wei/Krishnan/Rush Medical College) cover a metabolomic biomarker suite for MDD diagnosis and treatment response monitoring, spanning acylcarnitines (C3, C5), alpha-aminoadipate, and other metabolites. These are positioned to evaluate likelihood of SSRI/SNRI response and guide treatment switching. Specific antidepressants cited include escitalopram, citalopram, fluoxetine, sertraline, vortioxetine, and duloxetine. Patents span CA, WO, IL, AU, US, and JP jurisdictions, representing a well-prosecuted academic IP campaign.
Diagnostic/translational · Multi-jurisdiction prosecutionBlood Gene Expression Panels for Suicidality and Mood Subtypes
Indiana University Research and Technology Corporation and the US Department of Veterans Affairs have filed an extensive series of precision psychiatry patents using blood gene expression panels (SAT1, FOXN3, GBP1, PIK3R5, APOL2, MARCKS, GCOM1) to stratify suicidality risk, identify treatment candidates, and repurpose existing compounds. Algorithms combine biomarkers with clinical measures for universal and gender/diagnosis-personalized predictions. The approach is described as a "liquid biopsy" validated across multiple clinical cohorts using stepwise discovery, prioritization, and validation methodology.
Translational · Multi-cohort validatedVisualising the Biomarker-Guided Antidepressant Pipeline
Patent activity signals and therapeutic modality coverage derived from PatSnap Eureka analysis of this dataset.
Antidepressant Pipeline Modalities: Relative Patent Activity
Relative patent filing intensity across novel therapeutic approaches, from established TRI/KOR programs to emerging microbiome and circadian modalities.
Key Assignee IP Activity: Jurisdictions & Filing Intensity
Patent filing breadth and jurisdictional coverage for the top organisations in this precision psychiatry dataset.
Molecular Target Landscape: From Transporters to Clock Genes
The precision psychiatry patent landscape spans a diverse range of molecular targets, each with distinct IP ownership and clinical development implications.
DAT/SERT/NET Transporters
The most extensively patented pharmacological target cluster in this dataset. DeNovo Biopharma's liafensine program represents the most advanced TRI with pharmacogenomic companion diagnostics, having completed Phase 2 studies. Retrieved data confirm that genomic biomarkers are being developed post hoc to rescue clinical programs that showed insufficient efficacy on unselected populations.
Kappa-Opioid Receptor (KOR/OPRK1)
Janssen's aticaprant filings represent a major commercial interest. The "biomarker signature positive" construct positions KOR antagonism squarely within the precision psychiatry framework for MDD with SSRI/SNRI failure. Multi-jurisdictional filings (WO/US/CA, 2023–2025) establish a strong IP position. New entrants should conduct freedom-to-operate analysis against these biomarker-linked claim sets.
GABR-A2 & NMDAR/AMPAR/GLRB Network
AstraZeneca's GABR-A2 SNP panel (rs3756007, rs11503016, rs17537359, rs1372472) is described as predictive of response to NMDA antagonists in MDD. University of Michigan filings describe a pharmacogenomic assay incorporating SNPs, topological association domain analysis (ketamine-specific), and clinical values to stratify patients for NMDA, AMPA, or glycine receptor-based therapies in TRD.
Circadian Clock Per Gene CRE Sequence
The University of Chinese Academy of Sciences describes deletions/insertions and epigenetic modifications at the CRE sequence of the Per1/Per2 promoter as major-effect markers determining antidepressant response, linked to adenosine A1 receptor agonist CCPA's antidepressant-like action. This represents an early but active IP claim in a mechanistically novel antidepressant direction.
Seven Convergence Strategies Reshaping the Antidepressant Pipeline
Among retrieved results, multiple combination strategies and emerging directions are signalled. TRI + Pharmacogenomics: DeNovo Biopharma's filings signal a strategy of using genomic biomarker panels to identify the TRI-responsive subpopulation within the MDD continuum — a paradigm of rescuing failed broad-population trials through retrospective/prospective biomarker stratification. This model is explicitly described as replicable across other negative MDD trials in DAT/NET/SERT-targeting compounds.
KOR Antagonist + Prior SSRI/SNRI Failure as Enrichment Criterion: Janssen's aticaprant patents define the clinical combination (SSRI/SNRI inadequate response → KOR antagonist) and use biomarker signature as an enrollment gate, signaling the convergence of pharmacogenomics with adjunctive depression therapy. The PatSnap life sciences intelligence platform enables teams to track these evolving claim sets across jurisdictions in real time.
NMDA Antagonist + Multi-Receptor SNP Panel: University of Michigan filings extend beyond single-gene pharmacogenomics to multi-SNP panels combined with topological association domain analysis for ketamine-adjacent therapies, representing an emerging computational pharmacogenomics direction. The World Health Organization has identified depression as a leading cause of disability globally, reinforcing the commercial urgency of these approaches.
Gut Microbiome Metabolite Monitoring for Dynamic Antidepressant Dosing: A 2025 Chinese patent from Beijing Huilongguan Hospital describes a system integrating gut microbiota metabolite monitoring (short-chain fatty acids) with antidepressant drug metabolism kinetics for real-time dose adjustment — an emerging computational-biological convergence direction. EEG + Genomic Biomarker Co-Selection: Ortho Neuroscience's NSI-189 filings describe EEG characteristics alongside genetic biomarkers for patient selection, suggesting a multimodal precision approach combining neurophysiology with genomics. Explore the full combination strategy patent landscape via PatSnap Eureka.
Pipeline Stage Summary: Key Agents in Biomarker-Guided Antidepressant Development
Clinical stage and key differentiators for the principal compounds identified in this precision psychiatry patent dataset.
Track Every Antidepressant Patent Filing in Real Time
PatSnap Eureka monitors new filings, assignee activity, and biomarker claim sets across all jurisdictions automatically.
Biomarker-Guided Antidepressants — key questions answered
Triple reuptake inhibitors (TRIs) simultaneously inhibit serotonin, norepinephrine, and dopamine transporters. The compound liafensine (DB1/DB104), developed by DeNovo Biopharma, is described as an inhibitor of all three neurotransmitter transporters, developed to synergize the individual, though complementary, monoaminergic treatments for depression to maximize antidepressant efficacy and tolerability. A related TRI, EB-1010 by Euthymics Bioscience, showed in Phase 2 data that it does not cause sexual dysfunction, a key differentiation from SSRIs.
Multiple biomarker modalities are being developed. These include pharmacogenomic SNP panels (GABR-A2 SNPs rs3756007, rs11503016, rs17537359, rs1372472 for NMDA antagonist response; AVPR1B SNP rs28373064 for V1B antagonist response), blood gene expression panels (SAT1, FOXN3, GBP1, PIK3R5, APOL2, MARCKS, GCOM1 for suicidality and mood subtypes), metabolomic biomarkers (acylcarnitine C3, acylcarnitine C5, alpha-aminoadipate), and circadian clock gene markers (Per gene promoter CRE sequence mutations/epigenetic modifications).
Aticaprant is a kappa-opioid receptor (KOR) antagonist developed by Janssen Pharmaceuticals. Janssen's filings represent the clearest example in this dataset of a fully biomarker-gated MDD therapy. Patient eligibility requires a positive biomarker signature. The filings specifically address patients with inadequate SSRI/SNRI response, positioning aticaprant as an adjunctive or subsequent-line agent. Filings span WO, CA, and US jurisdictions (2023–2025), signaling global commercial intent.
Ulotaront is a trace amine-associated receptor 1 (TAAR1) and 5-HT1A agonist developed by Sumitomo Pharma America. It is described as an augmentation agent for inadequate antidepressant responders. Retrieved text describes preclinical antidepressant behavioral activity in rat models that many conventional antidepressants are unable to treat. The patent identifies patient subpopulations who would benefit from augmentation. Its non-D2, non-classical monoamine mechanism positions it as a mechanistically novel augmentation option.
Liafensine (DB1/DB104) is explicitly described as having completed multiple Phase 2 clinical studies in treatment-resistant depression. The program was discontinued after Phase 2 based on overall population results. DeNovo Biopharma's pharmacogenomic biomarker strategy is positioned as the mechanism to enable a re-stratified Phase 2 or Phase 3 attempt, using genomic biomarker panels to identify the TRI-responsive subpopulation within the MDD continuum.
In this dataset, the key organisations are: DeNovo Biopharma LLC (most concentrated patent family in the TRI/pharmacogenomics intersection, multiple filings across IL, TW, MX, JP jurisdictions); Janssen Pharmaceuticals (aticaprant KOR antagonist, WO/US/CA 2023–2025); Indiana University Research and Technology Corporation and US Department of Veterans Affairs (joint and independent patent families on blood biomarker panels, multiple US, WO, CA filings from 2014 to 2024); Max-Planck-Gesellschaft (AVPR1B/CRHR1 biomarker patents, EP and ES jurisdictions); and The Regents of the University of Michigan (pharmacogenomic decision support for glutamatergic receptor modulators, active JP patents 2022–2025).
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References
- Compositions and methods for assessing the efficacy of inhibitors of neurotransmitter transporters — DeNovo Biopharma LLC, 2022 [Patent, IL]
- Compositions and methods for assessing the efficacy of inhibitors of neurotransmitter transporters — DeNovo Biopharma LLC, 2022 [Patent, IL]
- Compositions and methods for assessing the efficacy of inhibitors of neurotransmitter transporters — DeNovo Biopharma LLC, 2023 [Patent, JP]
- Preparation and use of (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane in the treatment of conditions affected by monoamine neurotransmitters — Euthymics Bioscience, Inc., 2012 [Patent, CA]
- Compositions and methods for the treatment of depression — Janssen Pharmaceuticals, Inc., 2025 [Patent, US]
- Compositions and methods for the treatment of depression — Janssen Pharmaceuticals, Inc., 2023 [Patent, WO]
- gabr-a2 diagnosis — AstraZeneca Aktiebolag, 2015 [Patent, JP]
- Pharmacogenomic decision support for modulators of NMDA, glycine and AMPA receptors — The Regents of the University of Michigan, 2024 [Patent, JP]
- Pharmacogenomic decision support for modulators of NMDA, glycine, and AMPA receptors — The Regents of the University of Michigan, 2022 [Patent, JP]
- Ulotaront for adjunctive treatment of major depressive disorder — Sumitomo Pharma America, Inc., 2025 [Patent, CN]
- Methods and compositions for diagnosing depression — Boadie W. Dunlop, 2020 [Patent, CA]
- Methods and compositions for diagnosing depression — Jia, Wei, 2020 [Patent, WO]
- Methods and compositions for diagnosing depression — Krishnan, Ranga R., 2022 [Patent, US]
- Blood biomarkers for suicidality — Indiana University Research & Technology Corporation, 2016 [Patent, US]
- Precision medicine for treating and preventing suicidality — US Department of Veterans Affairs, 2020 [Patent, US]
- Precision medicine for suicidality: from universality to subtypes and personalization — Niculescu et al., Marion County Coroner's Office, 2017 [Paper]
- Method for predicting a treatment response to a V1B antagonist — Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., 2019 [Patent, EP]
- Major-effect markers influencing depressive or antidepressant behavior and their applications — University of Chinese Academy of Sciences [Patent]
- Biomarkers for monitoring neuropsychiatric disease treatment — Richer Diagnostics [Patent]
- Neuropsychiatric test reports — Genomind, LLC, 2013 [Patent, WO]
- Methods for treating depressed patients with poor cognition — Ortho Neuroscience, 2024 [Patent, JP]
- A method and device for dynamic adjustment of antidepressant dosage based on gut microbiota metabolite monitoring — Beijing Huilongguan Hospital, 2025 [Patent, CN]
- Concomitant medications for the treatment of depression — Nippon Medical School, 2025 [Patent, JP]
- Genetic polymorphism useful for predicting responsiveness to antidepressants — Shinsan Sozo Kenkyu Kiko [Patent]
- World Health Organization — Depression Fact Sheet
- National Institute of Mental Health — Treatment-Resistant Depression
- European Bioinformatics Institute — Pharmacogenomics Resources
All data and statistics on this page are sourced from the references above and from PatSnap's proprietary innovation intelligence platform. This report is derived from a limited set of patent and literature records retrieved across targeted searches and represents a snapshot of innovation signals within this dataset only. It should not be interpreted as a comprehensive view of the full field, clinical pipeline, or regulatory landscape.
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