PARP1-Selective Inhibitors in HRD Tumors — PatSnap Eureka
PARP1-Selective Inhibitors in HRD-Positive Tumors
Isoform selectivity, therapeutic index strategies, and combination approaches for homologous recombination-deficient cancers — synthesized from 60+ patent families and clinical literature by PatSnap Eureka.
PARP Inhibitor Patent Activity
Filings by therapeutic modality across 60+ patent families in this dataset
Synthetic Lethality in HRD-Positive Tumors
Homologous recombination deficiency (HRD) defines a clinically actionable vulnerability in multiple solid tumors, most prominently ovarian, breast, and prostate cancers carrying mutations in BRCA1/2 and related DNA repair genes. The canonical synthetic lethality rationale — that tumor cells lacking functional HR repair become entirely dependent on PARP1-mediated base excision repair for survival — is articulated across multiple patent families and academic literature in this dataset.
Multiple TESARO/Janssen filings define HRD-responsive patient populations as those carrying deficiency in at least one gene from a panel including BRCA1, BRCA2, ATM, ATR, BAP1, BARD1, BLM, BRIP1, MRE11A, NBN, PALB2, RAD51 (and paralogs RAD51B/C/D), RAD52, RAD54L, XRCC2, TP53, and RB1, with emphasis on non-BRCA HRR gene defects as an expanding biomarker population for niraparib. The Janssen mCRPC filings further specify biallelic DNA repair defects in BRCA1/2, ATM, FANCA, PALB2, CHEK2, and BRIP1 as determinants of niraparib benefit in metastatic castration-resistant prostate cancer.
A key isoform selectivity rationale emerges from Nerviano Medical Sciences' patent: dual PARP-1/2 knockout is embryonic lethal in mice while PARP-1 single knockout is not, providing a mechanistic basis for developing PARP1-selective agents with a potentially improved safety profile. The PatSnap analytics platform enables researchers to map these evolving IP landscapes across all assignees in real time.
The University of Texas System patent identifies PARP1 phosphorylation at Tyr907 by c-Met as a resistance mechanism, framing this post-translational modification as a biomarker for stratifying patients who may not respond to PARP1 inhibitors. Regeneron Pharmaceuticals has separately filed on PARP1-selective inhibition specifically for treatment of clonal hematopoiesis of indeterminate potential (CHIP), extending PARP1-targeted therapy into non-solid tumor indications.
From Pan-PARPi to Isoform-Selective Agents
Retrieved results span four distinct therapeutic modality classes, from clinically approved pan-inhibitors through preclinical PARP1-selective chemistry and RNA-based approaches.
Pan-PARP1/2 Small-Molecule Inhibitors
The most densely populated area of retrieved results involves pan-PARPi — agents inhibiting both PARP1 and PARP2 — including olaparib, niraparib, rucaparib, talazoparib, veliparib, fluzoparib, and BGB-290 (pamiparib). These are referenced across at least 15 distinct patent filings, predominantly from TESARO/GSK, Pfizer, Merck KGaA, and Sierra Oncology. The mechanism involves catalytic inhibition of PARP NAD+ binding and/or trapping of the PARP1-DNA complex at damage sites, with trapped PARP-DNA complexes described as more cytotoxic than unrepaired single-strand breaks alone.
15+ patent families · Phase III evidencePARP1-Selective Small-Molecule Inhibitors
Nerviano Medical Sciences discloses substituted 3-phenyl-isoquinolin-1(2H)-one derivatives that selectively inhibit PARP1 over PARP2, framing this selectivity as a strategy to reduce mechanism-based toxicity while retaining antitumor activity in BRCA-deficient settings. AstraZeneca has separately filed on selective PARP1 inhibitor + ATR inhibitor combinations specifically citing a "selective PARP1 inhibitor" as a distinct entity from pan-PARPi. KSQ Therapeutics discloses therapeutic combinations pairing a USP1 inhibitor with a PARP1-selective inhibitor, noting that PARP1 selectivity may reduce monotherapy toxicity while enabling synergistic tumor killing.
6 patent families · Preclinical–early clinicalPARP7 & PARP14 Isoform-Selective Agents
Ribon Therapeutics has filed two separate patent families covering PARP7-selective pyridazinones and PARP14-degrading quinazolinones. PARP7 is highlighted as relevant to immune evasion and cancer cell survival. PARP14 (also known as BAL2) is targeted via quinazolinone-based degraders for cancer and inflammatory indications. Azkarra Therapeutics further discloses pyridazin-3(2H)-one and pyridin-2(1H)-one core compounds active against PARP7, explicitly noting that multi-PARP inhibitors are expected to have broader cell-killing profiles than PARP7-selective agents. All filings are at preclinical stage.
3 patent families · PreclinicalRNAi-Based PARP Inhibition
The University of Sheffield has filed patents across multiple jurisdictions on the use of RNAi agents that inhibit PARP activity for the treatment of HR-deficient cancers, establishing an RNA-based modality for targeting PARP in addition to small molecules. This approach appears to be at early preclinical stage based on available data in this dataset. The Sheffield filings ground the synthetic lethality mechanism in base excision repair pathway inhibition selectively lethal to HR-deficient cells, complementing the small-molecule mechanistic framework.
Early preclinical · University of SheffieldKey Innovation Signals at a Glance
Visualising the patent intelligence signals extracted from 60+ filings in this dataset by PatSnap Eureka.
HRD Gene Panel Expansion for PARPi Eligibility
TESARO/Janssen filings show expansion from BRCA1/2 alone to a 19+ gene panel, broadening the treatable patient population for niraparib across 8+ distinct patent families.
Combination Strategy Landscape: 8 Mechanistic Axes
Retrieved results reveal at least 8 distinct combination mechanistic axes for PARP inhibitors, with DDR pathway combinations (ATR, CHK1, USP1) and immune modulation as the most active innovation areas.
Eight Mechanistic Axes for PARP Inhibitor Combinations
Retrieved results reveal a rich combination strategy landscape spanning DDR pathway inhibition, immune modulation, and novel sensitization mechanisms across at least six distinct mechanistic axes with active IP coverage.
AstraZeneca's 2025 BR and KR filings explicitly pair a "selective PARP1 inhibitor" with an ATR kinase inhibitor across ovarian, breast, gastrointestinal, lung, brain, and prostate cancers — the most direct evidence in this dataset for clinical-stage PARP1-selective + DDR combination development.
KSQ Therapeutics' filings across multiple jurisdictions propose synergistic tumor killing with reduced PARP1-selective inhibitor monotherapy toxicity, citing decreased dose requirements as a therapeutic index benefit.
Sierra Oncology holds active patents in JP and MX demonstrating synergistic growth inhibition across multiple PARPi agents (olaparib, niraparib, talazoparib, rucaparib), with sequential dosing schedules described.
Multiple large pharma filings (TESARO/GSK, Pfizer, Merck KGaA) cover PARPi + anti-PD-1/PD-L1 combinations, with talazoparib + avelumab and niraparib + pembrolizumab among the specific pairs described. Stratification by HRD score and PD-L1 tumor proportion score is referenced in Merck KGaA filings.
Eisbach Bio's 2025 CN filing on ALC1 allosteric inhibitors describes PARP1/2/3 trapping on chromatin as a mechanism to enhance PARPi efficacy, overcome PARPi resistance, and broaden activity to "BRCAness" tumors beyond germline BRCA1/2 deficiency.
Dana-Farber Cancer Institute's 2023 CN filing addresses PARPi-resistant ovarian tumors with M2-polarized tumor-associated macrophages, proposing STING agonists (e.g., MSA-2, ADU-S100) to repolarize macrophages and restore PARPi sensitivity in combination with olaparib + anti-PD-1.
Track all combination IP filings in real time
PatSnap Eureka monitors new filings across all eight combination axes as they publish globally.
Beyond PARP1/2: Emerging Target Landscape
Retrieved results reveal an expanding molecular target landscape including non-PARP1 isoforms, novel sensitization pathways, and resistance biomarkers with direct therapeutic implications.
PARP1 Tyr907 Phosphorylation (Resistance Biomarker)
The University of Texas System patent identifies PARP1 phosphorylation at Tyr907 by c-Met kinase as a resistance mechanism. This post-translational modification is framed as a biomarker for stratifying patients who may not respond to PARP1 inhibitors, with combined c-Met + PARP1 inhibition restoring sensitivity in TNBC models.
DNPH1 — Novel Non-PARP Synthetic Lethality
The Francis Crick Institute holds patents across five jurisdictions (KR, BR, MX, SG, CA) demonstrating that HR-deficient cells are sensitized to PARP inhibition by DNPH1 catalytic inhibition or genetic ablation, or by its substrate hmdU. Combined DNPH1 ablation + hmdU administration can cause synthetic lethality in HR-deficient cells even in the absence of PARPi — a structurally and mechanistically novel sensitization approach.
USP1 — Dose-Sparing Synergistic Partner
KSQ Therapeutics' filings across MX, TW, KR, and CN establish USP1 as a synergistic partner target for PARP1-selective inhibition, with the combination producing synergistic tumor regression at doses that reduce PARPi monotherapy toxicity. The synergy claim and reduced monotherapy toxicity framing could be a regulatory differentiation strategy.
ALC1 (CHD1L) — PARP Trapping Enhancer
Asbach Bio (Eisbach Bio) discloses ALC1 allosteric inhibitors that trap PARP1/2/3 on chromatin, enhancing PARPi killing and enabling a combination strategy that can overcome PARPi resistance and target BRCA-deficient tumors. This approach broadens activity to "BRCAness" tumors beyond germline BRCA1/2 deficiency.
Key Patent Holders & Innovation Hubs
Patent activity substantially dominates over academic literature in this dataset, with one academic paper identified versus more than 60 patent records across a diverse set of commercial and academic assignees.
Additional assignees in this dataset include Ribon Therapeutics (PARP7/14 isoform targeting), Foundation Medicine and Myriad Genetics (HRD classification models as companion diagnostic assets), Nerviano Medical Sciences (PARP1-selective isoquinolinone chemistry), and academic institutions including the University of Sheffield, University of Texas System, and Dana-Farber Cancer Institute. Explore the full PatSnap customer case studies to see how IP teams navigate competitive landscapes like this.
What the Patent Landscape Signals for Drug Developers
PARP1-selective chemistry is an active medicinal chemistry frontier with commercial IP coverage by AstraZeneca, Nerviano Medical Sciences, and KSQ Therapeutics in this dataset. Developers should monitor IP positions around PARP1-selective scaffolds (isoquinolinone, azaquinolinone, pyridazinone-adjacent structures) as differentiated from pan-PARPi nicotinamide/benzimidazole scaffolds, particularly given the therapeutic index rationale of sparing PARP2 to reduce hematological toxicity. The PatSnap life sciences solution enables systematic scaffold-level freedom-to-operate analysis.
The USP1 + PARP1-selective inhibitor combination (KSQ Therapeutics) represents a dose-sparing rationale that may expand the therapeutic window for PARP1-selective agents. The synergy claim and reduced monotherapy toxicity framing could be a regulatory differentiation strategy; early-stage IP coverage across MX, TW, KR, and CN indicates active commercial protection efforts.
Non-BRCA HRR gene defects (ATM, PALB2, RAD51C/D, BRIP1, CDK12) represent the next patient stratification frontier. Retrieved patent data from TESARO/Janssen demonstrates that these populations are already subject to IP protection for niraparib, and the Foundation Medicine and Myriad Genetics HRD classification model patents signal that computational genomic stratification tools are being positioned as companion diagnostic assets. Genomic biomarker strategies are central to next-generation PARPi development.
The DNPH1 pathway (Francis Crick Institute) offers a structurally and mechanistically novel sensitization approach for HR-deficient cancers, including a PARPi-independent synthetic lethality mechanism. The breadth of jurisdictional coverage (5 countries) and the absence of large pharma assignees in these filings represents a potential partnering opportunity or acquisition target for organizations seeking to differentiate from the crowded PARPi space.
PARPi resistance represents a defined unmet need with multiple emerging countermeasures in this dataset — STING agonist-mediated macrophage repolarization (Dana-Farber), ALC1 inhibitor-mediated PARP trapping (Eisbach Bio), c-Met inhibition to reverse PARP1 Tyr907 phosphorylation (UT System). Developers evaluating next-generation HRD oncology programs should assess these resistance reversal strategies as combination or follow-on opportunities. See how PatSnap analytics accelerates competitive intelligence in the DDR space.
Patent Filing Geography & Assignee Distribution
Understanding where PARP inhibitor IP is being filed reveals commercial priorities and freedom-to-operate opportunities across key markets.
Assignee Type: Commercial vs. Academic in Dataset
Patent activity substantially dominates over academic literature in this dataset, with commercial pharma and biotech assignees holding the majority of filings versus academic institutions.
Key Filing Jurisdictions Represented in Dataset
PARP inhibitor patent filings span a broad geographic footprint, with CN, BR, KR, and WO filings most frequently represented, reflecting commercial priorities in major pharmaceutical markets.
PARP1-Selective Inhibitors in HRD Tumors — key questions answered
Dual PARP-1/2 knockout is embryonic lethal in mice while PARP-1 single knockout is not, providing a mechanistic rationale for isoform selectivity. PARP2 inhibition is hypothesized to contribute to hematological toxicity such as anemia and thrombocytopenia, so selective PARP1 agents may improve tolerability while retaining antitumor activity in BRCA-deficient settings.
Multiple TESARO/Janssen filings define HRD-responsive patient populations as those carrying deficiency in at least one gene from a panel including BRCA1, BRCA2, ATM, ATR, BAP1, BARD1, BLM, BRIP1, MRE11A, NBN, PALB2, RAD51 and paralogs RAD51B/C/D, RAD52, RAD54L, XRCC2, TP53, and RB1, with emphasis on non-BRCA HRR gene defects as an expanding biomarker population for niraparib.
AstraZeneca's 2025 filings explicitly pair a selective PARP1 inhibitor with an ATR kinase inhibitor across ovarian, breast, gastrointestinal, lung, brain, and prostate cancers. KSQ Therapeutics proposes USP1 inhibitor plus PARP1-selective inhibitor combinations for synergistic tumor killing with reduced monotherapy toxicity. Additional combinations include CHK1 inhibitor plus PARPi, PARPi plus PD-1/PD-L1 checkpoint inhibitors, ALC1 inhibition plus PARPi, and STING agonist plus PARPi plus anti-PD-1.
The University of Texas System patent identifies PARP1 phosphorylation at Tyr907 by c-Met as a resistance mechanism, framing this post-translational modification as a biomarker for stratifying patients who may not respond to PARP1 inhibitors. Combined c-Met plus PARP1 inhibition restores sensitivity in TNBC models.
The Francis Crick Institute holds patents across five jurisdictions demonstrating that HR-deficient cells are sensitized to PARP inhibition by DNPH1 catalytic inhibition or genetic ablation, or by its substrate hmdU (5-hydroxymethyl-deoxyuridine). Combined DNPH1 ablation plus hmdU administration can cause synthetic lethality in HR-deficient cells even in the absence of PARPi, defining a novel non-PARP pathway to exploit HRD.
A retrieved academic paper from Centre Léon Bérard (2020) summarizes clinical evidence from SOLO-2, NOVA, and ARIEL3 trials demonstrating progression-free survival improvements with olaparib and niraparib as maintenance therapy in platinum-sensitive recurrent ovarian cancer, establishing the clinical framework within which newer agents are being developed.
Still have questions about PARP1-selective inhibitor IP? Let PatSnap Eureka answer them for you.
Ask PatSnap Eureka About PARP1 InhibitorsAccelerate Your HRD Oncology Drug Discovery
Join 18,000+ innovators already using PatSnap Eureka to map PARP inhibitor IP landscapes, identify combination white spaces, and track resistance mechanism patents in real time.
References
- Methods for Treating Cancer — TESARO, INC., 2020, BR [Patent]
- Methods of treating cancer — TESARO, INC., 2019, WO [Patent]
- Methods of treating cancer — TESARO, INC., 2019, CA [Patent]
- Prostate cancer treatments with combinations of abiraterone acetate and niraparib — JANSSEN PHARMACEUTICA N.V., 2022, BR [Patent]
- 3-Phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors — Nerviano Medical Sciences, 2014, CN [Patent]
- Method of treating diseases with PARP inhibitors — BIPAR SCIENCES, INC., 2012, IL [Patent]
- Use of RNAi inhibiting PARP activity for the manufacture of a medicament for the treatment of cancer — The University of Sheffield, 2015, PL [Patent]
- Overcoming resistance to PARP inhibitor in epithelial ovarian cancer, are we ready? — Centre Léon Bérard, 2020 [Paper]
- Prediction of response to PARP inhibitors and combination therapy targeting c-MET and PARP1 — Board of Regents, The University of Texas System, 2017, CN [Patent]
- Methods of treating clonal hematopoiesis of indeterminate potential (CHIP) with LY75, CD164, or PARP1 inhibitors — Regeneron Pharmaceuticals, 2024, CN [Patent]
- Combination therapy for cancer treatment — ASTRAZENECA AB, 2025, BR [Patent]
- Combination therapy for cancer treatment — AstraZeneca AB, 2025, KR [Patent]
- Therapeutic combinations comprising USP1 inhibitors and PARP1-selective inhibitors — KSQ Therapeutics, 2025, CN [Patent]
- Therapeutic combinations comprising USP1 inhibitors and PARP inhibitors — KSQ THERAPEUTICS, INC., 2022, MX [Patent]
- Pyridazinones as PARP7 inhibitors — RIBON THERAPEUTICS, INC., 2022, AR [Patent]
- Targeted degradation of PARP14 proteins for use in therapy — RIBON THERAPEUTICS, INC., 2024, AR [Patent]
- Pyridazin-3(2H)-one and pyridin-2(1H)-one PARP inhibitor compounds — Azkarra Therapeutics, 2025, CN [Patent]
- National Cancer Institute — Homologous Recombination Deficiency (HRD) in Cancer
- National Human Genome Research Institute — BRCA1 and BRCA2 Gene Mutations
- University of Sheffield — PARP RNAi Cancer Research Program
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 and represents a snapshot of innovation signals within this dataset only.
PatSnap Eureka searches patents and research to answer instantly.