IP Library › Granted Patent US 12,528,866
Granted Patent B2
US 12,528,866 · App. 17/737,159 · Granted Jan 20, 2026

Recombinant protein targeting PD-L1 and VEGF and compositions thereof

Inventors: Wenzhi Tian (Shanghai, CN); Song Li (Shanghai, CN)
Assignee: IMMUNEONCO BIOPHARMACEUTICALS (SHANGHAI) INC.
C07K16/2827A61P35/00C07K14/71A61K38/00A61K2039/505C07K2317/31C07K2317/732C07K2319/30
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,528,866
App. No.
17/737,159
Granted
Jan 20, 2026
Kind
B2
Abstract

Disclosed is a recombinant protein containing 1) an anti-PD-L1 antibody heavy chain and an anti-PD-L1 antibody light chain, which two are linked by a disulfide bond to bind PD-L1, and 2) an extracellular Ig-like domain of a vascular epithelial growth factor receptor (VEGFR), linked via a linker to the N-terminus or C-terminus of the heavy chain or the light chain, wherein the recombinant protein is capable of binding PD-L1, VEGF and Fc receptor simultaneously. Also disclosed are a recombinant antibody containing two recombinant proteins of the disclosure, a polynucleotide encoding the recombinant protein, an expression vector containing the polynucleotide, a method for producing the recombinant protein and a method for treating a disease caused by over expression of VEGF and/or PD-L1 using the recombinant protein.

Claims (12)

1 . A recombinant protein, comprising:

an anti-PD-L1 antibody comprising a heavy chain and a light chain;

an extracellular Ig-like domain of a vascular epithelial growth factor receptor (VEGFR), linked via a linker to N-terminus of the light chain;

wherein the heavy chain comprises SEQ ID NO: 2, and the light chain comprises SEQ ID NO: 6;

wherein the extracellular Ig-like domain of the VEGFR is a second extracellular Ig-like domain of VEGFR1 and comprises SEQ ID NO: 8;

wherein the linker comprises SEQ ID NO: 12; and

wherein the recombinant protein is capable of binding PD-L1, VEGF and Fc receptor simultaneously.

2 . The recombinant protein according to claim 1 , wherein the light chain with the extracellular Ig-like domain of VEGFR comprises SEQ ID NO: 18.

3 . A polynucleotide encoding the recombinant protein according to claim 1 .

4 . A vector containing the polynucleotide according to claim 3 .

5 . A host cell containing the vector according to claim 4 .

6 . A pharmaceutical composition, comprising the recombinant protein according to claim 1 , and a pharmaceutically acceptable carrier.

Assignments (2)
CHANGE OF NAME Recorded Jul 6, 2022
From: IMMUNEONCO BIOPHARMACEUTICALS (SHANGHAI) CO., LTD.
To: IMMUNEONCO BIOPHARMACEUTICALS (SHANGHAI) INC.
Reel/Frame 060594/0209 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 5, 2022
From: TIAN, WENZHI; LI, SONG
To: IMMUNEONCO BIOPHARMACEUTICALS (SHANGHAI) CO., LTD.
Reel/Frame 059825/0455 →
Continuity (3)
Continuation 16699732 · Dec 2, 2019
Provisional Application 62774849 · Dec 3, 2018
Related Publication 20220340664A1 · Oct 27, 2022
References Cited (62)
US 8217149B2 · Irving et al. · 2012 [cited by applicant]
US 9920123B2 · Irving et al. · 2018 [cited by applicant]
US 10647773B2 · Sheng et al. · 2020 [cited by applicant]
US 11407832B2 · Tian et al. · 2022 [cited by applicant]
US 11692042B2 · Wilson et al. · 2023 [cited by applicant]
US 11780922B2 · Her et al. · 2023 [cited by applicant]
US 20100331250A1 · Zhou et al. · 2010 [cited by applicant]
US 20150266942A1 · Tian · 2015 [cited by applicant]
US 20170275353A1 · Sheng et al. · 2017 [cited by applicant]
US 20200172623A1 · Tian et al. · 2020 [cited by applicant]
US 20210388090A1 · Ishikura et al. · 2021 [cited by applicant]
US 20220002418A1 · Zhu et al. · 2022 [cited by applicant]
US 20230340158A1 · Miao et al. · 2023 [cited by applicant]
AU 2023279765A1 · 2024 [cited by applicant]
CN 103319610A · 2013 [cited by applicant]
CN 108671229A · 2018 [cited by applicant]
CN 113166258A · 2021 [cited by applicant]
CN 113773401A · 2021 [cited by applicant]
CN 109942712B · 2022 [cited by applicant]
CN 117186238A · 2023 [cited by applicant]
CN 119256018A · 2025 [cited by applicant]
EP 3891182A1 · 2021 [cited by applicant]
EP 3954712A1 · 2022 [cited by applicant]
EP 3758735B1 · 2023 [cited by applicant]
EP 4534564A1 · 2025 [cited by applicant]
JP 2021531099A · 2021 [cited by applicant]
JP 2025518152A · 2025 [cited by applicant]
KR 20250021342A · 2025 [cited by applicant]
WO WO2013123861A1 · 2013 [cited by applicant]
WO WO2015000181A1 · 2015 [cited by applicant]
WO 2015103072A1 · 2015 [cited by applicant]
WO WO2015148416A1 · 2015 [cited by applicant]
WO 2015200805A2 · 2015 [cited by applicant]
WO WO2016169261A1 · 2016 [cited by applicant]
WO WO2017001990A1 · 2017 [cited by applicant]
WO 2017136562A2 · 2017 [cited by applicant]
WO 2017181111A2 · 2017 [cited by applicant]
WO WO2017188570A1 · 2017 [cited by applicant]
WO 2017215590A1 · 2017 [cited by applicant]
WO 2019062642A1 · 2019 [cited by applicant]
WO WO2019075270A1 · 2019 [cited by applicant]
WO WO2019080883A1 · 2019 [cited by applicant]
WO 2019168947A1 · 2019 [cited by applicant]
WO WO2019214551A1 · 2019 [cited by applicant]
WO WO2020114355A1 · 2020 [cited by applicant]
WO WO2020200210A1 · 2020 [cited by applicant]
WO WO2023232022A1 · 2023 [cited by applicant]
Lloyd et al., Protein Engineering, Design & Selection 22, 159-168, 2009. (Year: 2009). [cited by examiner]
EPO, European search report of EP19892300.5, the counterpart application filed with EPO, Jul. 15, 2022. [cited by applicant]
Prasads Adusumilli et al: “New Cancer Immunotherapy Agents in Development: a report from an associated program of the 31Annual Meeting of the Society for Immunotherapy of Cancer, 2016”, Journal for Immunotherapy of Canc… [cited by applicant]
ISA/CN, International search report and written opinion issued Mar. 4, 2020 in counterpart International Application No. PCTICN2019/122446. [cited by applicant]
Cheng et al., “First report of efficacy and safety results from a phase 2 trial evaluating BNT327/PM8002 plus chemotherapy (chemo) as first-line treatment (1L) in unresectable malignant mesothelioma.” Journal of Clinica… [cited by applicant]
Cui et al., “A novel bispecific antibody targeting PD-L1 and VEGF with combined anti-tumor activities.” Frontiers in Immunology 12 (2021): 778978. [cited by applicant]
Du et al., “Safety and efficacy of HB0025, an anti-PD-1/VEGF bispecific antibody fusion protein, in patients with advanced solid tumors: Preliminary results from an FIH trial.” J. Clin. Onco. (2023): 2589-2589. [cited by applicant]
Frentzas et al., “Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors.” Journal for Immunotherapy of Cancer 12 (2024): e008037. [cited by applicant]
Kim et al., “PD-L1-directed PIGF/VEGF blockade synergizes with chemotherapy by targeting CD141+ cancer-associated fibroblasts in pancreatic cancer.” Nature Communications 13 (2022): 6292. [cited by applicant]
Shields et al., “High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and design of IgG1 variants with improved binding to the FcγR.” Journal of Biological Chemistry 276(9) (200… [cited by applicant]
Tzuri et al., “Developing a dual VEGF/PDL1 inhibitor based on high-affinity scFv heterodimers as an anti-cancer therapeutic strategy.” Scientific Reports 13 (2023): 11923. [cited by applicant]
Wang et al., “A phase 1b study of ivonescimab, a programmed cell death protein-1 and vascular endothelial growth factor bispecific antibody, as first- or second-line therapy for advanced or metastatic immunotherapy-naiv… [cited by applicant]
Wu et al., “A phase Ib/IIa trial to evaluate the safety and efficacy of PM8002, a bispecific antibody targeting PD-L1 and VEGF-A, as a monotherapy in patients with advanced NSCLC.” Journal of Clinical Oncology 42(16) (2… [cited by applicant]
Wu et al., “Phase II Study of BNT327/PM8002 in EGFR-mutated NSCLC, (NCT05756972), Presentation 1255MO.” ESMO (2024). [cited by applicant]
Zhou et al., “Phase 3 Study of Ivonescimab (AK112) vs. Pembrolizumab as First-line Treatment for PD-L1-positive Advanced NSCLC: Primary Analysis of HARMONi-2.” World Conference on Lung Cancer [Abstract] (2024). [cited by applicant]