PD-L1/VEGF Bispecific Antibody Pipeline — PatSnap Eureka
PD-L1/VEGF Bispecific Antibody Pipeline in Solid Tumors
Pumitamig and the broader class of PD-L1/VEGF bispecific antibodies simultaneously disable tumor immune evasion and block tumor vasculogenesis—addressing both immunological and structural barriers to durable anti-tumor responses in solid tumors. Explore the patent and literature landscape with PatSnap Eureka.
Why PD-L1 and VEGF Are Targeted Together in Solid Tumors
PD-L1 (CD274) is a type-I transmembrane protein expressed on tumor cells, T cells, B cells, dendritic cells, and macrophages. Its interaction with PD-1 (CD279) on activated T cells delivers inhibitory signals that enable tumor immune evasion. Approved PD-1/PD-L1 inhibitors—nivolumab, pembrolizumab, and atezolizumab—achieve response rates of only 14–23% in unselected patient populations, underscoring the need for augmented strategies.
VEGF (vascular endothelial growth factor) is identified across multiple retrieved patents as a key driver of tumor angiogenesis and, critically, as a mediator of immune suppression within the tumor microenvironment. Anti-VEGF therapy can restore anti-PD-1/PD-L1 activity by inhibiting VEGF-associated immunosuppression, promoting T cell infiltration into tumors, and enabling T cell priming against tumor antigens.
The scientific rationale for simultaneous PD-L1 and VEGF blockade is articulated across at least six retrieved patent families as producing superior anti-tumor efficacy compared to monotherapy. This mechanistic convergence is the foundation of the bispecific antibody programs now entering clinical development across multiple solid tumor types.
Six Molecular Architectures Targeting PD-L1 and VEGF
Retrieved patent records reveal a diverse engineering landscape—from canonical bispecific antibodies to recombinant fusion proteins and VEGFR-trap domain designs—all seeking to co-block PD-L1 and VEGF in a single molecule or combination regimen.
PD-L1 × VEGF Bispecific Antibodies
WuXi Biologics describes a bispecific antibody that simultaneously binds human PD-L1 and VEGF with high affinity, blocking both the PD-1/PD-L1 signaling axis and VEGF/VEGFR signaling in a single molecule. This is the architecture associated with pumitamig's competitive class. First PCT application filed January 2020 (PCT/CN2020/073497), with publications through 2023–2025 across WO and JP jurisdictions.
WuXi Biologics · 4+ patent familiesPD-L1/VEGF Recombinant Fusion Proteins
ImmunOnco Biopharmaceuticals (Shanghai) describes fusion proteins linking an anti-PD-L1 antibody or fragment to a VEGF-binding peptide via a linker at the N-terminus of the heavy or light chain. Claimed to achieve comparable ADCC, ADCP, and PD-1/PD-L1 and VEGF/VEGFR blockade as combination use of separate agents, with superior in vivo performance versus combination regimens.
ImmunOnco · CN & JP jurisdictionsAnti-PD-L1 × VEGF Bifunctional Antibody
Huabo Biopharmaceutical Technology (Shanghai) describes bifunctional antibodies combining anti-PD-L1 with anti-VEGF elements via a linker peptide containing antibody constant region sequences, linking the anti-VEGF element to the N-terminus of the anti-PD-L1 heavy chain variable region. AP Biosciences describes a VEGF inhibitory domain (VID) fused to the Fc domain of an anti-PD-L1 antibody, with demonstrated retention of antigen-binding specificity in IFN-γ-stimulated A549 (NSCLC) and NCI-H292 cell lines.
Huabo · AP Biosciences · preclinicalAnti-VEGF/PD-L1 Bispecific with VEGFR-Trap Domain
Unimonoantibody (Beijing) Biotechnology describes a bispecific fusion protein where an anti-PD-L1 full antibody is combined with one Ig-like domain from VEGFR1 and one Ig-like domain from VEGFR2 fused to the C-terminus of the antibody heavy chains. This VEGFR trap-based design is structurally distinct from anti-VEGF antibody fragments and claimed to enable effective tumor cell killing.
Unimonoantibody · JP jurisdiction · 2024Multi-Domain Fusion Proteins (PD-L1 + VEGF + TGF-β)
Zhejiang Dao'er Biotechnology describes a triplicate fusion protein combining an anti-PD-L1 single-domain antibody fragment, a VEGF antagonist fragment, and a TGF-β binding fragment in a single molecule. The rationale is to integrate three independent immunosuppressive barriers—immune checkpoint, angiogenesis, and TGF-β-mediated immune exclusion—in a unified construct.
Zhejiang Dao'er · 2024 · next-genAnti-VEGF + Anti-PD-L1 Combination (Separate Agents)
Genentech describes combination regimens using a VEGF antagonist and a PD-L1 axis binding antagonist as separate agents, with preclinical evidence in mouse ovarian cancer (OV2944-HM-1) and colorectal cancer (Colon 38) models. MedImmune describes clinical dosing regimens for ramucirumab (anti-VEGFR-2) combined with durvalumab (anti-PD-L1) for gastric/GEJ adenocarcinoma, NSCLC, and HCC—with specified dosing regimens indicating active clinical trial context.
Genentech · MedImmune · clinical signalsKey Data Points from the PD-L1/VEGF Patent Record
Quantitative signals extracted from retrieved patent families—assignee activity, indication breadth, and response rate context—visualised from the PatSnap Eureka dataset.
PD-L1/VEGF Patent Families by Assignee
WuXi Biologics leads with at least 4 retrieved patent families; ImmunOnco and Sanyou Biopharmaceuticals each hold 2 families in this space.
Indication Coverage Across PD-L1/VEGF Patent Families
NSCLC and HCC are the most frequently cited indications; broad solid tumor labeling strategies cover 10+ tumor types within the same patent families.
PD-L1/VEGF Bispecific Molecular Architecture Landscape
Five distinct engineering formats have been patented for simultaneous PD-L1 and VEGF blockade, from canonical bispecific antibodies to VEGFR-trap fusions and triple-target constructs.
Who Is Filing in the PD-L1/VEGF Bispecific Space?
Innovation is concentrated among Chinese biotech companies and large multinational pharmaceutical corporations, with activity predominantly patent-driven. Parties entering this space must conduct freedom-to-operate analysis across multiple architectural claims.
WuXi Biologics — Lead Filer
The most prominently represented assignee for PD-L1 × VEGF bispecific antibodies specifically, with at least four patent families retrieved across WO and JP jurisdictions (2021–2025), covering the bispecific antibody structure, antigen-binding portions, manufacturing methods, and therapeutic applications. This is the assignee associated with pumitamig's competitive class.
ImmunOnco & Biotheus — Chinese Biotech Challengers
ImmunOnco Biopharmaceuticals (Shanghai) holds retrieved patent families in both CN and JP jurisdictions (2023–2025) covering recombinant anti-PD-L1/VEGF fusion proteins. Biotheus Inc. holds a retrieved patent (CA jurisdiction, 2022) for anti-VEGF-anti-PD-L1 bispecific antibody, claiming dual immunoactivation and angiogenesis blockade.
From Preclinical to Clinical: What the Patent Record Reveals
Retrieved results yield limited direct clinical evidence for PD-L1/VEGF bispecific antibodies as a unified molecule. The most proximate clinical signal comes from the combination-agent literature. MedImmune's retrieved patent explicitly specifies clinical dosing regimens—anti-VEGFR-2 (ramucirumab) at 8 mg/kg every two weeks combined with anti-PD-L1 (durvalumab) at 750 mg every two weeks for gastric/GEJ or HCC; 10 mg/kg every three weeks with 1125 mg anti-PD-L1 for NSCLC—indicating IND-enabling or active clinical trial context.
Genentech's retrieved patent explicitly addresses patients with "locally advanced or metastatic sarcomatoid RCC" not previously treated, suggesting clinical stage biomarker-selection methodology is in active development. A retrieved patent from Pfizer (TW jurisdiction) describes a PD-1 antagonist + VEGFR inhibitor combination specifically for PD-L1-expressing cancers, indicating clinical-stage translation of the mechanistic rationale underlying PD-L1/VEGF bispecifics.
Retrieved results do not contain pivotal trial outcome data or regulatory submission records for any single PD-L1/VEGF bispecific molecule. For comprehensive clinical pipeline analytics, PatSnap Eureka integrates patent, literature, and trial data in a unified view.
- Anti-VEGFR-2 + anti-PD-L1: clinical dosing regimens specified for gastric/GEJ, HCC, and NSCLC
- Sarcomatoid RCC: biomarker-selection methodology in active clinical development (Genentech)
- PD-L1 monotherapy biomarkers: IFNG, CXCL9, CD274, and LAG3 companion signatures described (MedImmune)
- PD-1 + VEGFR inhibitor combination: clinical-stage translation described by Pfizer for PD-L1-expressing cancers
- No pivotal trial outcome data or regulatory submissions identified for a unified PD-L1/VEGF bispecific molecule
Beyond Dual Targeting: Next-Generation Combination Strategies
Retrieved patent signals reveal the competitive frontier is advancing beyond PD-L1/VEGF dual-targeting toward triple-target constructs, innate immune activation, and conditionally active architectures.
PD-L1 + VEGF + TGF-β Fusion Proteins
Zhejiang Dao'er Biotechnology (2024) describes multi-domain fusion proteins combining anti-PD-L1 sdAb, VEGF antagonist fragment, and TGF-β binding fragment. TGF-β immunosuppression—a documented resistance mechanism to PD-1/PD-L1 therapy—is being incorporated into next-generation multi-functional fusion designs. GlaxoSmithKline describes a related ICOS antibody + anti-PD-L1/TGF-βR fusion protein combination (JP, 2023).
Zhejiang Dao'er · GSK · resistance mechanismPD-L1/CD47 Bispecific Antibodies
WuXi Biologics Ireland (WO, 2024) describes bispecific antibodies targeting PD-L1 and CD47 (the "don't eat me" signal), combining immune checkpoint blockade with innate immune activation via phagocytosis promotion. This represents a mechanistic extension of the WuXi bispecific platform beyond the VEGF axis.
WuXi Biologics · CD47 · innate immunityPD-L1/PD-L2 Dual Blockade
The University of Texas System (JP/CN, 2023–2024) provides preclinical xenograft data demonstrating superiority of dual PD-L1/PD-L2 bispecific antibodies over single-target anti-PD-L1 in MDA-MB-231 (TNBC) and MC38-PDL2 (colorectal) models. PD-L2-positive/PD-L1-positive patients achieve double the objective response rate compared to PD-L1-positive/PD-L2-negative patients (ChiaTai Tianqing clinical data).
University of Texas · 2× ORR in PD-L2+ patientsActivatable Anti-PD-L1 Antibodies
CytomX Therapeutics (JP, 2018, 2023) describes protease-cleavable "masked" anti-PD-L1 antibodies that are activated preferentially in the tumor microenvironment, reducing systemic toxicity. This represents a precision engineering direction complementary to bispecific approaches, addressing the safety profile challenge of systemic checkpoint blockade.
CytomX · tumor microenvironment activationWhat the Patent Record Signals for Developers and Investors
Five strategic implications derived from the retrieved patent dataset, relevant to parties evaluating freedom-to-operate, clinical differentiation, and pipeline durability in the PD-L1/VEGF bispecific space.
| Strategic Signal | Evidence from Retrieved Patent Record | Implication |
|---|---|---|
| Highly competitive IP landscape | At least five independent assignees (WuXi Biologics, ImmunOnco, Biotheus, Sanyou, Huabo) pursuing distinct molecular architectures covering the PD-L1/VEGF bispecific space, with Chinese biotech firms representing the majority of new filings. | Freedom-to-operate analysis required across full bispecific antibodies, fusion proteins with VEGF-binding peptides, and VEGFR-trap domain fusions. |
| Mechanistic rationale is prior art | Multiple independent assignees converge on the same mechanistic argument—VEGF suppresses T cell infiltration and priming, which directly undermines PD-L1 blockade—across at least six retrieved patent families. | Differentiation must come from molecular format, PK/PD properties, or indication-specific biomarker strategies rather than mechanism claims. |
| Broad indication strategies dominate | Retrieved results do not restrict claimed indications to single tumor types; NSCLC, HCC, gastric/GEJ, RCC, TNBC, colorectal, and ovarian cancers are all cited within the same patent families. | Developers are pursuing broad solid tumor labeling strategies, consistent with the observed approach for approved checkpoint inhibitors. |
| Biomarker selection is a differentiator | Genentech, MedImmune, and Regeneron show active IP development around PD-L1 expression-based patient stratification—immunoPET imaging, IFNG/CXCL9/LAG3 signatures, sarcomatoid histology—as companion strategies. | Bispecific programs that co-develop predictive biomarkers will likely have stronger clinical differentiation and regulatory positioning. |
| Triple-target constructs are the next frontier | Patents covering PD-L1 + VEGF + TGF-β and PD-L1 + VEGF + PD-L2 formats signal that the competitive frontier is advancing beyond dual-targeting. | Investors and developers should evaluate pipeline durability against the multi-functional protein engineering trend now visible in the 2023–2024 filing cohort. |
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PD-L1/VEGF Bispecific Antibodies — key questions answered
A PD-L1/VEGF bispecific antibody simultaneously binds human PD-L1 and VEGF with high affinity, blocking both the PD-1/PD-L1 signaling axis and VEGF/VEGFR signaling in a single molecule. The scientific rationale holds that combining immune checkpoint inhibition with anti-angiogenic activity can overcome the limited response rates observed with PD-L1 monotherapy.
Retrieved results from WuXi Biologics describe response rates in unselected patient populations ranging from 14–23% for approved PD-1/PD-L1 inhibitors such as nivolumab, pembrolizumab, and atezolizumab, and 16–48% in PD-L1-expressing tumors, establishing the therapeutic rationale for augmented strategies.
Solid tumor indications foregrounded in retrieved results include non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), gastric/gastroesophageal junction (GEJ) adenocarcinoma, renal cell carcinoma (RCC), triple-negative breast cancer (TNBC), bladder/urothelial cancer, ovarian cancer, colorectal cancer, head and neck cancer, and melanoma.
Innovation in PD-L1/VEGF bispecific antibodies is concentrated among Chinese biotech companies and large multinational pharmaceutical corporations. WuXi Biologics is the most prominently represented assignee with at least four patent families retrieved across WO and JP jurisdictions (2021–2025). Other key assignees include ImmunOnco Biopharmaceuticals, Biotheus Inc., Sanyou Biopharmaceuticals, Huabo Biopharmaceutical Technology, Genentech, MedImmune/AstraZeneca, and F. Hoffmann-La Roche AG.
VEGF is identified as a dual-function target: driving tumor vasculogenesis and suppressing anti-tumor immunity in the tumor microenvironment. Retrieved results from WuXi Biologics and Biotheus explicitly describe how VEGF-mediated immunosuppression reduces the activity of anti-PD-L1 therapy, providing mechanistic rationale for dual targeting. Anti-VEGF therapy can restore anti-PD-1/PD-L1 activity by inhibiting VEGF-associated immunosuppression, promoting T cell infiltration into tumors, and enabling T cell priming against tumor antigens.
Retrieved results signal several next-generation directions: triple-target fusion proteins combining PD-L1 + VEGF + TGF-β (Zhejiang Dao'er Biotechnology), PD-L1/CD47 bispecific antibodies (WuXi Biologics), PD-L1/PD-L2 dual blockade (University of Texas System), PD-L1/4-1BB bispecific combinations (ABL Bio, MSD), activatable conditionally active anti-PD-L1 antibodies (CytomX Therapeutics), and ANG-2/VEGF + PD-L1 triplet signaling blockade (F. Hoffmann-La Roche).
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References
- A bispecific Anti-PD-L1/VEGF antibody and uses thereof — WuXi Biologics (Shanghai) Co. Ltd., 2021, WO [Patent]
- A bispecific Anti-PD-L1/VEGF antibody and uses thereof — WuXi Biologics Ireland Limited, 2023, WO [Patent]
- Bispecific anti-PD-L1/VEGF antibodies and uses thereof — WuXi Biologics Ireland Limited, 2024, JP [Patent]
- Recombinant fusion protein targeting PD-L1 and VEGF, its preparation and use — ImmunOnco Biopharmaceuticals (Shanghai) Inc., 2025, JP [Patent]
- Recombinant fusion protein targeting PD-L1 and VEGF, its preparation and use — ImmunOnco Biopharmaceuticals (Shanghai) Inc., 2023, CN [Patent]
- Anti-VEGF-Anti-PD-L1 bispecific antibody, pharmaceutical composition of same, and uses thereof — Biotheus Inc., 2022, CA [Patent]
- Anti-PD-L1/VEGF bifunctional antibodies and their uses — Huabo Biopharmaceutical Technology (Shanghai) Co., Ltd., 2023, JP [Patent]
- Bifunctional proteins combining checkpoint blockade for targeted therapy — AP Biosciences Inc., 2021, JP [Patent]
- Bispecific fusion proteins — Unimonoantibody (Beijing) Biotechnology Co., Ltd., 2024, JP [Patent]
- Multidomain fusion proteins and their applications — Zhejiang Dao'er Biotechnology Co., Ltd., 2024, JP [Patent]
- Methods and drugs for treating cancer non-responsive to PD-1/PD-L1 signaling inhibitors — Genentech, Inc., 2022, CN [Patent]
- Combination of anti-VEGFR-2 and anti-PD-L1 antibodies for the treatment of cancer — MedImmune Limited, 2022, JP [Patent]
- Diagnostic and therapeutic methods for sarcomatoid kidney cancer — Genentech, Inc., 2025, JP [Patent]
- Combination therapy of an antibody that binds to angiopoietin 2 with an antibody that binds to programmed death ligand 1 — F. Hoffmann-La Roche AG, 2018, JP [Patent]
- Bispecific antibodies against human PD-L1 and PD-L2 and methods of use thereof — Board of Regents, The University of Texas System, 2024, JP [Patent]
- Bispecific antibodies against PD-L1 and CD47, method for preparing the same, and use thereof — WuXi Biologics Ireland Limited, 2024, WO [Patent]
- Anti-PD-L1/Anti-4-1BB bispecific antibodies and uses thereof — ABL Bio Inc., 2021, SG [Patent]
- Radiolabeled anti-PD-L1 antibodies for immunoPET imaging — Regeneron Pharmaceuticals, Inc., 2022, JP [Patent]
- Compositions and methods for characterizing the response of solid tumors to anti-PD-L1 antibody monotherapy — MedImmune, LLC, 2019, JP [Patent]
- Liver Cancer (HCC) — National Cancer Institute
- CD274 (PD-L1) Gene — NCBI Gene Database
- Oncology Guidelines — European Medicines Agency (EMA)
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.
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