Anti-human ninjurin-1 (NINJ-1) antibodies and methods for detecting human NINJ-1
Inventors
Shin, Young Kee • LEE, Seahyung • Song, Kyoung • Lee, Ji Hye
Assignees
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Publication Number
US-11286296-B2
Publication Date
2022-03-29
Expiration Date
Abstract
The present invention provides: an antibody which specifically bonds to human NINJ-1; and a fragment thereof. The antibody or the fragment thereof according to the present invention has very high bonding affinity and bonding specificity with respect to a human NINJ-1 or a homogeneous binding site of the protein, and does not exhibit cross-reactivity with NINJ-1 proteins that are derived from other organisms and have high protein similarity. Accordingly, the present invention provides significant advantages with respect to accuracy and sensitivity and the like, not only in diagnosing disease related to NINJ-1 proteins but also in inhibiting pathological conditions involving NINJ-1 proteins. In particular, the antibody provided according to the present invention has a remarkable effect of inhibiting attachment between immunocytes and human cerebral endothelial cells, and thus has an effect of treating multiple sclerosis.
Core Innovation
The disclosed invention relates to anti-human NINJ-1 antibodies and antigen-binding fragments that specifically bind to a residue region between 26th and 37th in a human-derived Ninjurin-1 (NINJ-1) protein sequence defined by SEQ ID NO: 25. The binding residue region is described as a corresponding extracellular epitope in the residue region P26–N37 (SEQ ID NO: 25). The antibodies are characterized by high affinity and specificity for this extracellular epitope while maintaining minimal cross-reactivity, notably to mouse NINJ-1.
The invention further defines antibody variable regions by specifying antibody light chain variable region (VL) complementarity determining regions (CDRs) L1, L2, and L3 with amino acid sequences defined by SEQ ID NOs: 7, 8, and 9, respectively, and antibody heavy chain variable region (VH) CDRs H1, H2, and H3 with amino acid sequences defined by SEQ ID NOs: 10, 11, and 12, respectively. The disclosure includes multiple antibody formats and fragment types, including IgG and antibody fragments such as diabody, Fab, Fab′, F(ab)2, F(ab′)2, Fv, and scFv, all directed to the same human NINJ-1 residue region epitope.
The disclosure links these specific binding antibodies to improved diagnostic detection accuracy/sensitivity for human NINJ-1 and to therapeutic inhibition of immune-cell adhesion to human cerebral endothelial cells. The therapeutic utility is described in relation to multiple sclerosis, and the disclosure additionally supports cancer prevention/treatment by inhibiting metastasis through inhibition of NINJ-1-related processes.
Claims Coverage
The claim set centers on 6 inventive features directed to human NINJ-1 epitope-specific antibodies and related uses. Independent claim coverage includes the defined antibody or antigen-binding fragment, fragment formats, composition, isolated polynucleotide, host cell preparation, and detection of human NINJ-1 by binding-complex detection.
Epitope-specific antibody for human NINJ-1 (residues 26–37)
An antibody or antigen-binding fragment thereof that specifically binds to a residue region between 26th and 37th in a human-derived Ninjurin-1 (NINJ-1) protein sequence defined by SEQ ID NO: 25, with VL CDR L1-L3 defined by SEQ ID NOs: 7-9 and VH CDR H1-H3 defined by SEQ ID NOs: 10-12.
Specific antigen-binding fragment formats
The antibody or antigen-binding fragment is an antigen-binding fragment chosen from diabody, Fab, Fab′, F(ab)2, F(ab′)2, Fv, or scFv.
Antibody composition with the antigen-binding fragment as active ingredient
A composition comprising the antibody or an antigen-binding fragment thereof as an active ingredient.
Isolated polynucleotide encoding the defined antibody
An isolated polynucleotide encoding the antibody or the antigen-binding fragment described in the epitope-specific antibody claim with the specified VL and VH CDR sequences.
Host cell expression and recovery of the defined antibody
A method for preparing an antibody or an antigen-binding fragment that specifically binds to a human NINJ-1 protein (SEQ ID NO: 25) by culturing a host cell to express and produce the antibody, then recovering it from the host cell or the culture medium, where the antibody contains the specified VL and VH CDR regions.
Detection of human NINJ-1 by binding-complex detection
A method for detecting human NINJ-1 by contacting an antibody or an antigen-binding fragment with a biological sample containing human NINJ-1 (SEQ ID NO: 25) and detecting the binding complex formed between the antibody or antigen-binding fragment and the human NINJ-1.
The claims are anchored on antibodies or antigen-binding fragments that specifically bind the human NINJ-1 residue region between positions 26 and 37 (SEQ ID NO: 25) via defined VL and VH CDR sequences. Dependent claim coverage further includes fragment formats, composition, isolated polynucleotide encoding, host-cell expression and recovery, and detection by binding-complex detection.
Stated Advantages
Improved diagnostic detection accuracy/sensitivity for human NINJ-1.
Therapeutic inhibition of immune-cell adhesion to human cerebral endothelial cells.
Minimal cross-reactivity to other species’ NINJ-1, notably mouse.
Support for multiple sclerosis utility.
Support for cancer prevention/treatment via inhibition of metastasis.
Documented Applications
Diagnostic detection of human NINJ-1 in biological samples using antibodies/antigen-binding fragments that form a detectable binding complex.
Therapeutic inhibition of immune-cell adhesion to human cerebral endothelial cells, described for multiple sclerosis.
Cancer prevention/treatment via inhibition of metastasis, including support for NINJ-1-related contexts described in the disclosure.
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