Dual-targeting antibody targeting SCF and galectin-1 and use thereof
Inventors
Assignees
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Publication Number
US-11377489-B2
Publication Date
2022-07-05
Expiration Date
Abstract
The present invention relates to a dual-targeting antibody targeting stem cell factor (SCF) and galectin-1 and a composition for preventing or treating angiogenesis-related diseases comprising the same. The present invention provides a dual-targeting antibody derived from a human monoclonal antibody which may effectively inhibit angiogenesis by simultaneously neutralizing SCF and galectin-1 involved in angiogenesis, and a pharmaceutical composition for preventing or treating angiogenesis-related diseases comprising the antibody. The dual-targeting antibody according to the present invention may effectively prevent or treat angiogenesis-related diseases by simultaneously neutralizing two targets involved in angiogenesis wherein the angiogenesis-related diseases cause hemorrhaging by blood vessels changing due to abnormal angiogenesis and thus increasing the permeability thereof.
Core Innovation
The invention relates to a human monoclonal dual-targeting antibody that specifically binds both stem cell factor (SCF) and galectin-1. The dual-targeting antibody neutralizes SCF and galectin-1 to inhibit angiogenesis and reduce pathological neovascularization and hemorrhaging.
The antibody is defined by specified light-chain and heavy-chain CDR amino acid sequences, where the light-chain variable region comprises light-chain CDR1 (SEQ ID NO: 1), light-chain CDR2 (SEQ ID NO: 2), and light-chain CDR3 (SEQ ID NO: 3). The heavy-chain variable region comprises heavy-chain CDR1 (SEQ ID NO: 4), heavy-chain CDR2 (SEQ ID NO: 5), and heavy-chain CDR3 (SEQ ID NO: 6).
The dual-targeting concept extends to DNA encoding the antibody and related embodiments including encoding sequences linked to the recited CDRs, vectors containing the DNA, and transformed cells carrying the vectors. The document also provides characterization for dual binding to SCF and galectin-1 and for functional effects on downstream signaling and angiogenic behaviors.
Claims Coverage
The independent claims cover two categories: a dual-targeting antibody protein defined by specified light- and heavy-chain CDR sequences, and DNA encoding that dual-targeting antibody defined by nucleotide sequence identifiers corresponding to the same CDRs.
Dual-targeting antibody binding to SCF and galectin-1
A dual-targeting antibody specifically binding to SCF (Stem Cell Factor) and galectin-1, wherein the dual-targeting antibody comprises a light-chain variable region defined by light-chain CDR1 (SEQ ID NO: 1), light-chain CDR2 (SEQ ID NO: 2), and light-chain CDR3 (SEQ ID NO: 3), and a heavy-chain variable region defined by heavy-chain CDR1 (SEQ ID NO: 4), heavy-chain CDR2 (SEQ ID NO: 5), and heavy-chain CDR3 (SEQ ID NO: 6).
DNA encoding dual-targeting antibody binding to SCF and galectin-1
DNA encoding a dual-targeting antibody specifically binding to SCF (Stem Cell Factor) and galectin-1, wherein the DNA comprises DNA encoding a light-chain variable region comprising nucleotide sequences comprising SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12 respectively encoding a light-chain CDR1 comprising SEQ ID NO: 1, a light-chain CDR2 comprising SEQ ID NO: 2, and a light-chain CDR3 comprising SEQ ID NO: 3; and DNA encoding a heavy-chain variable region comprising nucleotide sequences comprising SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15 respectively encoding a heavy-chain CDR1 comprising SEQ ID NO: 4, a heavy-chain CDR2 comprising SEQ ID NO: 5, and a heavy-chain CDR3 comprising SEQ ID NO: 6.
Across the independent claims, the core coverage is a dual-targeting antibody that specifically binds SCF and galectin-1 and is structurally defined by specified CDR amino acid sequences, together with DNA encoding the same dual-targeting antibody by nucleotide sequences corresponding to those CDRs. Dependent claims further refine the variable-region sequence identifiers and can include a human IgG1-derived invariable region, plus vector and transformed-cell embodiments.
Stated Advantages
Inhibits angiogenesis.
Reduces pathological neovascularization.
Reduces hemorrhaging.
Neutralizes SCF and galectin-1.
Demonstrates inhibition of c-Kit/AKT/ERK signaling.
Inhibits galectin-1-induced tube formation and proliferation.
Shows comparative superiority versus a commercial anti-SCF polyclonal antibody.
Potential benefit in VEGF-non-responsive patients.
Potential synergy with VEGF-targeting drugs.
Documented Applications
Therapeutic and pharmaceutical composition use for angiogenesis-related diseases, including ocular vascular diseases such as age-related macular degeneration and diabetic retinopathy.
Optional use for detection and/or simultaneous detection kit embodiments.
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