Antibody specifically binding to an isolated peptide derived from vimentin or a fragment binding to the peptide
Inventors
KIM, Yoon Won • Kim, Young Jin • Hong, Hyo Jeong • Park, Sang Jin • Kim, Min Woo • Park, Sung Man
Assignees
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Publication Number
US-10961300-B2
Publication Date
2021-03-30
Expiration Date
Abstract
The present invention relates to an antibody specifically binding to the peptide of SEQ ID NO: 1, and specifically, to an antibody specifically binding to an isolated peptide of SEQ ID NO: 1 or a fragment binding to the peptide specifically binding to the peptide, a polynucleotide encoding the antibody or the fragment binding to the peptide, a vector containing the polynucleotide, a cell introduced with the vector, a method of producing the antibody or the fragment binding to the peptide using the cell, an antibody or a fragment binding to the peptide produced by the method, an antiviral composition containing the antibody or the fragment binding to the peptide, a composition for preventing or treating inflammatory diseases containing the antibody or the fragment binding to the peptide, and a method of treating infectious viral diseases or inflammatory diseases using the composition.
Core Innovation
The invention provides humanized antibodies that specifically bind to an isolated vimentin-derived peptide of SEQ ID NO: 1, corresponding to vimentin residues 142-294. The peptide includes an epitope-containing region, including vimentin residues 142-211 or 211-294, and the disclosed binding is extended to antibody fragments, including scFv fragments, that specifically bind the same peptide of SEQ ID NO: 1 and target virus-infected cells through VSF receptors exposed on the cell surface.
The humanized antibodies and fragments are defined by heavy chain variable regions and light chain variable regions comprising specified CDR sets. Heavy chain CDR1, CDR2, and CDR3 are defined by SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 14, and SEQ ID NO: 4 or SEQ ID NO: 15, respectively, while light chain CDR1, CDR2, and CDR3 are defined by SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 16/17/18, and SEQ ID NO: 7 or SEQ ID NO: 19, respectively, with variants additionally defined by framework region sequences in the disclosed embodiments.
The binding specificity is further constrained to particular peptide amino-acid positions within SEQ ID NO: 1, including binding to the 9th, 45th, 54th, 76th, 94th, and 129th residues. The document also describes scFv fragments comprising a heavy chain variable region of SEQ ID NO: 131 and a light chain variable region of SEQ ID NO: 133 linked by a linker, and provides the disclosed antibodies and fragments as therapeutic compositions for treating infectious viral diseases and inflammatory diseases, including use in antiviral compositions administered to an individual in need thereof.
Claims Coverage
The independent claims cover two inventive features: a humanized antibody or binding fragment defined by specified heavy- and light-chain CDR sets that specifically bind the peptide of SEQ ID NO: 1, and an scFv fragment defined by specified heavy- and light-chain variable regions linked by a linker that specifically binds the peptide of SEQ ID NO: 1.
Humanized antibody binding to peptide of SEQ ID NO: 1 via defined heavy- and light-chain CDRs
A humanized antibody specifically binding to the peptide of SEQ ID NO: 1 or a fragment specifically binding to the peptide, wherein the humanized antibody or fragment comprises a heavy chain variable region comprising a heavy chain CDR1 of SEQ ID NO: 2; a heavy chain CDR2 of SEQ ID NO: 3 or SEQ ID NO: 14; and a heavy chain CDR3 of SEQ ID NO: 4 or SEQ ID NO: 15; and a light chain variable region comprising a light chain CDR1 of SEQ ID NO: 5; a light chain CDR2 of SEQ ID NO: 6, SEQ ID NO: 16, SEQ ID NO: 17, or SEQ ID NO: 18; and a light chain CDR3 of SEQ ID NO: 7 or SEQ ID NO: 19.
scFv binding to peptide of SEQ ID NO: 1 via defined heavy- and light-chain variable regions linked by a linker
An scFv that specifically binds to the peptide of SEQ ID NO: 1, wherein the scFv consists of a heavy chain variable region of SEQ ID NO: 131 and a light chain variable region of SEQ ID NO: 133, which are linked by a linker.
Overall, the claims focus on binding a vimentin-derived peptide of SEQ ID NO: 1 using defined CDR-defined humanized antibodies and defined-variable-region scFv fragments, with dependent refinements that tighten binding to particular peptide residue positions and constrain additional sequence regions in certain embodiments.
Stated Advantages
Reduced HLA epitope counts relative to commercial antibodies.
Low T-cell proliferation.
Comparable IgG-like physical properties and pharmacokinetics.
High antiviral affinity (Ka/Kd).
Antiviral activity across multiple viruses.
Anti-inflammatory effects by suppressing immune-cell infiltration and proinflammatory cytokine secretion (e.g., IL-6, TNF-α, IFN-γ, CCL2).
Documented Applications
Treating an infectious or inflammatory viral disease by administering an antiviral composition comprising the humanized antibody specifically binding to the peptide of SEQ ID NO: 1 (or a binding fragment) to an individual in need thereof.
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