High-affinity anti-VEGF antibody
Inventors
MURAKAMI, Yasufumi • MUKOUBATA, Shigeki • AKIYAMA, Hirotada • Konomi, Koji
Assignees
ORDER-MADE MEDICAL RESEARCH Inc • Santen Pharmaceutical Co Ltd
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Publication Number
US-11007259-B2
Publication Date
2021-05-18
Expiration Date
Abstract
An object of the present invention is to provide an antibody having significantly high affinity for VEGF compared to the prior art. The present invention provides a monoclonal antibody against VEGF, which binds to a vascular endothelial growth factor (VEGF) with a dissociation constant of 1×10−11 mol/L or less.
Core Innovation
The invention relates to a monoclonal antibody against vascular endothelial growth factor (VEGF), or an antigen-binding fragment thereof, defined by specific complementarity-determining regions (CDRs) comprising amino acid sequences corresponding to SEQ ID NOs. The antibody binds VEGF and is described as a high-affinity VEGF-binding antibody.
The invention further provides that the antibody binds VEGF with a dissociation constant (KD) of 1×10^-11 mol/L or less and inhibits VEGF binding to VEGF receptors, particularly VEGFR1 and VEGFR2. The antibody and fragments are presented in chimeric, humanized, and caninized (canine IgGB) formats.
Functional effects and binding characterization are also described. The antibody inhibits VEGF-mediated VEGFR signaling and reduces HUVEC proliferation, and in vivo tumor growth suppression is reported in xenograft mouse models using human tumor cells and canine-relevant cancer models.
Claims Coverage
The provided claims coverage centers on three main inventive constructs: a VEGF-binding monoclonal antibody defined by specific CDR amino-acid sequences, a binding-affinity threshold, and functional inhibition of VEGF receptor binding. The material also includes independent therapeutic method and kit embodiments.
CDR-defined VEGF-binding monoclonal antibody
A monoclonal antibody against VEGF, or an antigen-binding fragment thereof, that binds VEGF comprising CDR-H1, CDR-H2, CDR-H3, and CDR-L1, CDR-L2, and CDR-L3 with the specified amino acid sequences defined by SEQ ID NOs.
Sub-1×10^-11 mol/L VEGF-binding dissociation constant
A monoclonal antibody, or antigen-binding fragment, that binds VEGF with a dissociation constant of 1×10^-11 mol/L or less.
Inhibition of VEGF binding to VEGFR1 or VEGFR2
A monoclonal antibody, or antigen-binding fragment, that inhibits binding of VEGF to at least one of VEGFR1 or VEGFR2.
Therapeutic administration for VEGF-mediated cancer or eye disease
A method for treating a VEGF-mediated cancer or a VEGF-mediated eye disease by administering a therapeutically effective amount of an antibody or its antigen-binding fragment to a subject in need.
Kit comprising the VEGF antibody with buffer and optional components
A kit that includes the monoclonal antibody, or its antigen-binding fragment, along with a buffer and optional components such as an enzyme solution, a secondary antibody, a dilution solution, and/or instructions.
The inventive scope is centered on a defined VEGF-binding monoclonal antibody with specified CDR sequences, a high-affinity binding threshold, and inhibition of VEGF binding to VEGFR1 and/or VEGFR2. The provided material also includes therapeutic method coverage and kit coverage.
Stated Advantages
Binds VEGF with a dissociation constant of 1×10^-11 mol/L or less.
Inhibits VEGF binding to at least one of VEGFR1 or VEGFR2.
Provides neutralizing activity for VEGF by inhibiting VEGF-mediated VEGFR signaling and reducing HUVEC proliferation.
Reduces in vivo tumor growth in mouse xenograft models.
Caninized antibody shows cross-reactivity to human VEGF isoforms and binds VEGF exon 1–5 regions.
Documented Applications
VEGF-mediated cancers, including treatment methods for selected cancer types listed in the claims.
VEGF-mediated eye diseases, as stated in the therapeutic method claims.
Xenograft in vivo tumor growth suppression in mouse models using human tumor cells and canine-relevant cancer models.
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