Monoclonal antibody against D-dimer and methods of use therefor
Inventors
Doh, Hyun-Ju • Kim, Doo-Sik • Chung, Kwang-Hoe
Assignees
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Publication Number
US-9897616-B2
Publication Date
2018-02-20
Expiration Date
Abstract
Disclosed are a monoclonal antibody against human D-dimer produced in a mouse and high molecular weight cross-linked fibrin including a corresponding epitope, a cell line secreting the monoclonal antibody, and methods for producing the same. The anti-D-dimer monoclonal antibody of the present invention may be effectively used as a diagnosis agent for screening and detecting in-vivo D-dimer, and high molecular weight cross-linked fibrin and its derivatives containing the D-dimer since the monoclonal antibody specifically reacts with D-dimer, and cross-linked fibrin and its derivatives containing the D-dimer, which do not bind to human fibrinogen or fibrin.
Core Innovation
The invention relates to murine IgG1 kappa monoclonal antibodies B2, C3, B4, and C5 that specifically bind to human D-dimer and cross-linked fibrin containing D-dimer, with no cross-reactivity to fibrinogen. The antibodies are characterized by an epitope comprising an N-terminal beta-chain region corresponding to amino acid residues 134 to 142 (SEQ ID NO: 1) and/or an alpha-chain region corresponding to amino acid residues 124 to 214 (SEQ ID NO: 2).
A described objective is to provide antibodies that recognize D-dimer in biological samples containing partially degraded high-molecular-weight cross-linked fibrin degradation products. The document states that the detection signal is consistent with recognizing high-molecular-weight targets, including in DIC- and thrombosis-related plasma.
The document further describes a rapid detection kit using a monoclonal antibody that binds D-dimer and crosslinked fibrin containing D-dimer, where D-dimer is produced by converting human fibrinogen into fibrin using thrombin and then cutting fibrin using plasmin. The antibodies are used in diagnosis agents such as sandwich ELISA systems employing a marker-conjugated secondary antibody and chromogenic couplers.
Claims Coverage
Independent claim 1 covers a rapid detection kit based on a monoclonal antibody that specifically binds D-dimer and crosslinked fibrin containing D-dimer, together with constraints on the D-dimer generation process and the antibody epitope defined by specific amino acid residue ranges in SEQ ID NO: 1 or SEQ ID NO: 2. The inventive coverage is driven by three main constraints: kit composition, D-dimer formation context, and epitope specificity for the antibody.
Rapid detection kit using an anti-d-dimer monoclonal antibody with constrained crosslinked fibrin binding
A rapid detection kit comprising a monoclonal antibody, wherein the monoclonal antibody specifically binds to D-dimer and crosslinked fibrin containing D-dimer, with the binding directed to an epitope site defined by SEQ ID NO: 1 or SEQ ID NO: 2.
D-dimer produced by thrombin conversion and plasmin cutting of human fibrinogen
D-dimer is produced by converting human fibrinogen into fibrin using an enzyme thrombin, followed by cutting fibrin using an enzyme plasmin.
Epitope defined by beta-chain N-terminal residues 134–142 or alpha-chain residues 124–214
The antibody binds to a site including amino acid residues 134th to 142nd from N-terminal region of a beta-chain, set forth in SEQ ID NO: 1, or the antibody binds with a site including amino acid residues 124th to 214th from N-terminal region of a beta-chain, set forth in SEQ ID NO: 2.
The independent claim protects a rapid detection kit whose key requirement is a monoclonal antibody that specifically binds D-dimer and crosslinked fibrin containing D-dimer, where the D-dimer is generated from human fibrinogen via thrombin conversion to fibrin and plasmin cutting, and where antibody binding is constrained to defined residue ranges corresponding to SEQ ID NO: 1 or SEQ ID NO: 2.
Stated Advantages
Improved reliability for detecting D-dimer in DIC- and thrombosis-related plasma containing partially degraded high-molecular-weight fibrin degradation products.
Reduced over-/underestimation versus commercial kits after plasmin treatment.
Documented Applications
Diagnosis agents using the antibodies in sandwich ELISA systems, including the use of a marker-conjugated secondary antibody and chromogenic couplers.
Detection in DIC- and thrombosis-related plasma, including samples containing partially degraded high-molecular-weight fibrin degradation products after plasmin treatment.
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