Anti-VEGF antibodies and methods of use
Inventors
Dengl, Stefan • Fenn, Sebastian • Georges, Guy • Moelleken, Joerg • ROS, Francesca • KOENIGSBERGER, Esther
Assignees
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Publication Number
US-11820816-B2
Publication Date
2023-11-21
Expiration Date
Abstract
The present invention relates to anti-VEGF antibodies and methods of their production and their use.
Core Innovation
The invention relates to anti-VEGF antibodies that preferentially inhibit VEGF binding to VEGF-R2 over VEGF-R1. The disclosed antibodies bind vascular endothelial growth factor (VEGF) and are characterized by selectivity for VEGF-R2 blocking relative to VEGF-R1. This receptor selectivity is presented as a route to improved safety while maintaining VEGF-targeting activity.
The antibodies are defined by specific heavy chain variable domain (VH) and light chain variable domain (VL) amino acid sequences selected from defined SEQ ID NO options. Affinity and binding performance are described using surface plasmon resonance (SPR), including reported high affinity characteristics, and receptor-binding inhibition characterization is described using VEGF:VEGF-R2/R1 inhibition ELISA. Additional characterization is reported using IC50 and reporter gene assay (RGA), together with chemical stability/aggregation assessment and structural information.
Structural characterization is also provided, including X-ray crystallography that defines the VEGF epitope residues bound by a VEGF-0089 Fab in complex with VEGF-A121 dimer. The disclosure further includes recombinant nucleic acid and host-cell embodiments for producing the VEGF-binding antibodies, and it provides pharmaceutical and therapeutic uses for VEGF-related diseases.
Claims Coverage
The independent claim is clm-00001. It covers a VEGF-binding antibody defined by a specific set of VH and a single VL sequence pairing option, and it is refined by dependent claims that define additional antibody formats, nucleic acid and host cell embodiments, and pharmaceutical compositions. The main inventive features focus on (i) VEGF binding, (ii) selective VEGF receptor blocking, and (iii) sequence-defined VH/VL specificity using SEQ ID NOs.
VEGF-binding antibody with specified VH and VL sequence options
An antibody that binds to vascular endothelial growth factor (VEGF), comprising a pair of heavy chain variable domain (VH) and light chain variable domain (VL) amino acid sequences selected from the group consisting of: (a) VH of SEQ ID NO: 01 and VL of SEQ ID NO: 02; (b) VH of SEQ ID NO: 09 and VL of SEQ ID NO: 02; (c) VH of SEQ ID NO: 11 and VL of SEQ ID NO: 02; (d) VH of SEQ ID NO: 33 and VL of SEQ ID NO: 02; (e) VH of SEQ ID NO: 42 and VL of SEQ ID NO: 02; and (f) VH of SEQ ID NO: 44 and VL of SEQ ID NO: 02.
Receptor-selective VEGF inhibition over VEGF-R1
The antibody preferentially inhibits VEGF binding to VEGF-R2 over VEGF-R1.
High-affinity VEGF binding by SPR with binding characterization
Binding and affinity are characterized by surface plasmon resonance (SPR), including high-affinity behavior and receptor inhibition characterization (VEGF:VEGF-R2/R1 inhibition ELISA), as reported in the disclosure.
Across the independent claim and the supported disclosure, the coverage is centered on a VEGF-binding antibody defined by particular SEQ ID NO-paired VH/VL sequence selections, together with described preferential VEGF-R2 over VEGF-R1 inhibition and binding/inhibition characterization, and further embodiments directed to Fab formatting, nucleic acid/host-cell expression, and pharmaceutical compositions.
Stated Advantages
Preferential inhibition of VEGF binding to VEGF-R2 over VEGF-R1 is presented as aiming for improved safety.
Documented Applications
Therapeutic use for VEGF-related diseases including cancer.
Therapeutic use for VEGF-related diseases including eye diseases (e.g., AMD).
Pharmaceutical composition and medicament use including formulations that include the VEGF-binding antibody with a pharmaceutically acceptable carrier.
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