Antibodies against fibrin degradation products, reagents and kits for detecting fibrin degradation products

Abstract

The present invention discloses an anti-fibrin degradation product antibody, a reagent and a kit for detecting fibrin degradation products, and relates to the field of antibodies. The anti-fibrin degradation product antibody disclosed in the present invention comprises a heavy chain complementary determining region and a light chain complementary determining region, and the antibody provides an important source of raw materials for the detection of fibrin degradation products and has good affinity or activity.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] The present invention claims priority to Chinese patent application No. 202211222866.8 filed with the Chinese Patent Office on October 8, 2022, and entitled “Anti-fibrin degradation product antibodies or functional fragments thereof, reagents and kits for detecting fibrin degradation products”, the entire contents of which are incorporated by reference into the present disclosure. Technical Field

[0003] The present invention relates to the field of antibody technology, in particular to an anti-fibrin degradation product antibody, and a reagent and a kit for detecting fibrin degradation products. Background Art

[0004] Fibrin degradation products (FDPs) are protein components or polypeptide fragments generated by the hydrolysis of fibrin or fibrinogen under the action of plasmin. Fibrinolytic enzymes are mainly formed locally on the surface of endothelial cells in the blood vessels and act to remove the small amount of fibrin formed on the surface of endothelial cells. Under normal circumstances, FDPs in the blood are maintained at a very low level, usually less than 10μg / mL. When the body's fibrinolytic system is active, it will increase significantly, which is the body's response to endogenous coagulation. High FDPs concentrations are also seen in hyperfibrinolyticemia or exogenous coagulation. Therefore, FDPs detection can be used to detect the function of the fibrinolytic system, and is most commonly used in the diagnosis of disseminated intravascular coagulation, hypercoagulable conditions and thrombotic diseases. In addition, elevated FDPs can also be detected in patients with chronic kidney disease and uremia. Elevated FDPs can also be seen in liver disease, intracavitary hemorrhage, severe burns, tetramine poisoning, protein-losing nephropathy or enteropathy, etc. In addition, FDPs can also be used as a marker for tumor detection and for detecting colorectal cancer.

[0005] Biological immunological detection methods have the advantages of being simple, rapid and inexpensive. Biological immunological detection methods require antibodies specific to FDPs. There is a strong demand in the field for antibodies that can effectively bind to FDPs and detect them.

[0006] In view of this, the present invention is proposed. Summary of the invention

[0007] The object of the present invention is to provide an anti-fibrin degradation product antibody, a reagent and a kit for detecting fibrin degradation products.

[0008] The present invention is achieved in that:

[0009] In a first aspect, an embodiment of the present invention provides an anti-fibrin degradation product antibody, the antibody comprising HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3, the HCDR1 / HCDR2 / HCDR3 combination being the same as the HCDR1 / HCDR2 / HCDR3 combination contained in the heavy chain variable region shown in any one of SEQ ID NO:18 to SEQ ID NO:21, and the LCDR1 / LCDR2 / LCDR3 combination being the same as the LCDR1 / LCDR2 / LCDR3 combination contained in the light chain variable region shown in SEQ ID NO:22 or 23.

[0010] In alternative embodiments, the CDRs are defined by the Kabat, Chothia, AbM, Contact or IMGT systems.

[0011] In a second aspect, an embodiment of the present invention provides an anti-fibrin degradation product antibody, the antibody comprising HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3, the amino acid sequences of the HCDR1, HCDR2, HCDR3 comprising SEQ ID NOs: 1 to 3 in sequence, or as shown in SEQ ID NOs: 1 to 3 in sequence; the amino acid sequences of the LCDR1, LCDR2, LCDR3 comprising SEQ ID NOs: 4 to 6 in sequence, or as shown in SEQ ID NOs: 4 to 6 in sequence.

[0012] In a third aspect, an embodiment of the present invention provides an anti-fibrin degradation product antibody, comprising a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising a sequence structure of HFR1-HCDR1-HFR2-HCDR2-HFR3-HCDR3-HFR4, the light chain variable region comprising a sequence structure of LFR1-LCDR1-LFR2-LCDR2-LFR3-LCDR3-LFR4, and the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are the above-mentioned amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3.

[0013] In a fourth aspect, an embodiment of the present invention provides an anti-fibrin degradation product antibody, the antibody comprising a heavy chain variable region and / or a light chain variable region, the heavy chain variable region comprising the amino acid sequence shown in any one of SEQ ID NOs: 18 to 21; or, consisting of the amino acid sequence shown in any one of SEQ ID NOs: 18 to 21; the light chain variable region comprising the amino acid sequence shown in SEQ ID NOs: 22 or 23; or, consisting of the amino acid sequence shown in SEQ ID NOs: 22 or 23.

[0014] In a fifth aspect, an embodiment of the present invention provides an anti-fibrin degradation product antibody, comprising a heavy chain and a light chain; the heavy chain comprises the amino acid sequence shown in any one of SEQ ID NOs: 26 to 29; or, consists of the amino acid sequence shown in any one of SEQ ID NOs: 26 to 29; the light chain comprises the amino acid sequence shown in SEQ ID NOs: 30 or 31; or, consists of the amino acid sequence shown in SEQ ID NOs: 30 or 31.

[0015] In a sixth aspect, an embodiment of the present invention provides an anti-fibrin degradation product antibody, wherein the antibody binds to the same epitope in the amino acid sequence of the fibrin degradation product as the antibody described in the preceding embodiment; or, the antibody competitively binds to the fibrin degradation product with the antibody described in the preceding embodiment.

[0016] In a seventh aspect, an embodiment of the present invention provides an antibody conjugate, which includes the antibody described in the above embodiment.

[0017] In an eighth aspect, an embodiment of the present invention provides a reagent or a kit, which includes the antibody as described in the preceding embodiments or the antibody conjugate as described in the preceding embodiments.

[0018] In a ninth aspect, an embodiment of the present invention provides a method for detecting fibrin degradation products, comprising: contacting the antibody, antibody conjugate, reagent or kit as described in the above embodiments with the fibrin degradation products in a sample to be tested to form an immune complex.

[0019] In a tenth aspect, an embodiment of the present invention provides an isolated nucleic acid encoding the antibody described in the preceding embodiments.

[0020] In the eleventh aspect, an embodiment of the present invention provides a vector comprising the isolated nucleic acid described in the preceding embodiments.

[0021] In a twelfth aspect, an embodiment of the present invention provides a cell containing the isolated nucleic acid described in the preceding embodiment or the vector described in the preceding embodiment.

[0022] In a thirteenth aspect, an embodiment of the present invention provides a method for preparing the antibody described in the preceding embodiment, comprising: culturing the cells described in the preceding embodiment.

[0023] In a fourteenth aspect, embodiments of the present invention provide use of the antibodies, antibody conjugates, reagents or kits described in the preceding embodiments in detecting fibrin degradation products or preparing products for detecting fibrin degradation products.

[0024] The present invention has the following beneficial effects:

[0025] The anti-fibrin degradation product antibody disclosed in the present invention comprises the heavy chain complementary determining region and the light chain complementary determining region. The antibody provides an important source of raw materials for the detection of fibrin degradation products and has improved affinity or activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0027] Figure 1 The results of reducing SDS-PAGE of Anti-FDPs 5C1 Rmb1 to Anti-FDPs 5C1Rmb7 are shown. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0029] The features and performance of the present invention are further described in detail below in conjunction with the embodiments.

[0030] In a first aspect, an embodiment of the present invention provides an anti-fibrin degradation product antibody, the antibody comprising HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3, the HCDR1 / HCDR2 / HCDR3 combination being the same as the HCDR1 / HCDR2 / HCDR3 combination contained in the heavy chain variable region shown in any one of SEQ ID NO:18 to SEQ ID NO:21, and the LCDR1 / LCDR2 / LCDR3 combination being the same as the LCDR1 / LCDR2 / LCDR3 combination contained in the light chain variable region shown in SEQ ID NO:22 or 23.

[0031] In alternative embodiments, the CDRs are defined by the Kabat, Chothia, AbM, Contact or IMGT systems.

[0032] It should be noted that HCDR1, HCDR2 and HCDR3 are amino acid sequences consistent with HCDR1, HCDR2 and HCDR3 of the same heavy chain variable region defined in the antibody described in the first aspect, and LCDR1, LCDR2 and LCDR3 are amino acid sequences consistent with LCDR1, LCDR2 and LCDR3 of the same light chain variable region defined in the antibody described in the first aspect.

[0033] For example, the HCDR1, HCDR2, and HCDR3 are amino acid sequences consistent with HCDR1, HCDR2, and HCDR3 of the heavy chain variable region shown in SEQ ID NO:18; the LCDR1, LCDR2, and LCDR3 are amino acid sequences consistent with LCDR1, LCDR2, and LCDR3 of the light chain variable region shown in SEQ ID NO:22.

[0034] In the present invention, the term "antibody" is used in the broadest sense, and it can include full-length monoclonal antibodies, bispecific antibodies, multispecific antibodies, chimeric antibodies, or antigen-binding fragments, as long as they exhibit the desired biological activity. Full-length monoclonal antibodies are composed of a heavy chain variable region (VH), a light chain variable region (VL), a heavy chain constant region (CH), and a light chain constant region (CL). In the present invention, the heavy chain variable region, the light chain variable region, the heavy chain constant region, and the light chain constant region are represented by VH, VL, CH, and CL, respectively.

[0035] The above antigen-binding fragments usually have the same binding specificity as the antibody from which they are derived. It is easy for a person skilled in the art to understand based on the contents described in the present invention that the above antigen-binding fragments can be obtained by methods such as enzymatic digestion (including pepsin or papain) and / or by chemical reduction to split disulfide bonds. Based on the structure of the complete antibody disclosed in the present invention, a person skilled in the art can easily obtain the above antigen-binding fragments.

[0036] The above antigen-binding fragments can also be synthesized by recombinant genetic techniques also known to those skilled in the art or by, for example, an automatic peptide synthesizer, such as those sold by Applied BioSystems and the like.

[0037] In the present invention, the term "complementarity determining region", "CDR" or "CDRs" refers to the highly variable regions of the heavy and light chains of immunoglobulins, and refers to the region containing one or more or even all of the major amino acid residues that contribute to the binding of an antibody or antigen-binding fragment to its recognized antigen or epitope.

[0038] In the present invention, the term "heavy chain complementarity determining region", "HCDR" or "HCDRs" refers to one or more or even all of the complementarity determining regions in the heavy chain variable region. The three HCDRs contained in the heavy chain variable region include HCDR1, HCDR2 and HCDR3.

[0039] In the present invention, the term "light chain complementarity determining region", "LCDR" or "LCDRs" refers to one or more or even all complementarity determining regions in the light chain variable region. The three LCDRs contained in the light chain variable region include LCDR1, LCDR2 and LCDR3.

[0040] The definition of CDRs is known in the art, for example, can be defined according to the Kabat, Chothia, AbM, Contact or IMGT systems. There are other definitions of CDRs that may not strictly follow one of the above 25 methods, but still overlap at least a portion of the CDRs defined by Kabat, although they may be shortened or extended based on predictions or experimental results of specific residues or residue groups. In the present invention, CDRs may refer to definitions by any method known in the art, including a combination of known methods.

[0041] As used herein, the "Kabat definition" refers to the definition system described in Kabat et al., U. S. Patent. of Health and Human Services, "Sequence of Proteins of Immunological Interest" (1983). The "Chothia definition" is found in Chothia et al., J Mol Biol 196: 901-917 (1987). Exemplary defined CDRs are listed in Table 1 below, and the definitions in different documents are slightly different. Given the variable region amino acid sequence of an antibody, a person skilled in the art can routinely determine which residues comprise a particular CDR. It should be noted that CDRs defined by other methods not limited to those in Table 1 also fall within the scope of protection of the present disclosure.

[0042] Table 1: CDR Definition 1

[0043] CDR Kabat <![CDATA[AbM 2 ]]> IMGT Chothia HCDR1 <![CDATA[H31~H35 3 ]]> <![CDATA[H26~H35 3 ]]> <![CDATA[H26~H33..5 5 ]]> <![CDATA[H26~H32..34 4 ]]> HCDR2 H50~H65 H50~H58 H51~H57 H52~H56 HCDR3 H95~H102 H95~H102 H93~H102 H95~H102 LCDR1 L24~L34 L24~L34 L27~L32 L24~L34 LCDR2 L50~L56 L50~L56 L50~L51 L50~L56 LCDR3 L89~L97 L89~L97 L89~L97 L89~L97

[0044] 1The numbering of all CDR definitions in Table 1 is based on the Kabat numbering system (see below), with the amino acid numbering on the heavy chain represented by "H+number" and the amino acid numbering on the light chain represented by "L+number". One of ordinary skill in the art can unambiguously map the Kabat numbering system to any variable region sequence without relying on any experimental data other than the sequence itself. As used herein, "Kabat numbering" refers to the numbering system described by Kabat et al., U.S. Patent. of Health and Human Services, "Sequence of Proteins of Immunological Interest" (1983).

[0045] 2 "AbM" as used in Table 1 with a lowercase "b" refers to CDRs defined by Oxford Molecular's "AbM" antibody modeling software.

[0046] 3 If both H35A and H35B are absent, CDR-H1 ends at position 35; if only H35A is present, CDR-H1 ends at position 35A; if both H35A and H35B are present, CDR-H1 ends at position 35B.

[0047] 4 If both H35A and H35B are absent, CDR-H1 ends at position 32; if only H35A is present, CDR-H1 ends at position 33; if both H35A and H35B are present, CDR-H1 ends at position 34.

[0048] 5 If both H35A and H35B are absent, CDR-H1 ends at position 33; if only H35A is present, CDR-H1 ends at position 34; if both H35A and H35B are present, CDR-H1 ends at position 35.

[0049] According to an embodiment of the present invention, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 or LCDR3 is defined by any one system or a combination of multiple systems of Kabat, Chothia, IMGT, AbM or Contact.

[0050] In some optional embodiments of the present invention, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by the Kabat system.

[0051] In some optional embodiments of the present invention, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by the Chothia system.

[0052] In some optional embodiments of the present invention, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by the IMGT system.

[0053] In some optional embodiments of the present invention, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by the AbM system.

[0054] In some optional embodiments of the present invention, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by a Contact system.

[0055] In some optional embodiments of the present invention, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by a combination of Kabat, Chothia, IMGT, AbM or Contact systems.

[0056] According to an embodiment of the present invention, the Kabat numbering positions corresponding to the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 or LCDR3 defined by the Kabat, Chothia, AbM or IMGT systems are as follows:

[0057] CDR Kabat AbM IMGT Chothia HCDR1 H31~H35 H26~H35 H26~H33 H26~H32 HCDR2 H50~H65 H50~H58 H51~H57 H52~H56 HCDR3 H95~H102 H95~H102 H93~H102 H95~H102 LCDR1 L24~L34 L24~L34 L27~L32 L24~L34 LCDR2 L50~L56 L50~L56 L50~L51 L50~L56 LCDR3 L89~L97 L89~L97 L89~L97 L89~L97

[0058] In a second aspect, an embodiment of the present invention provides an anti-fibrin degradation product antibody, the antibody comprising HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3, the amino acid sequences of the HCDR1, HCDR2, HCDR3 comprising SEQ ID NOs: 1 to 3 in sequence, or as shown in SEQ ID NOs: 1 to 3 in sequence; the amino acid sequences of the LCDR1, LCDR2, LCDR3 comprising SEQ ID NOs: 4 to 6 in sequence, or as shown in SEQ ID NOs: 4 to 6 in sequence.

[0059] According to an embodiment of the present invention, the HCDR1, HCDR2 and HCDR3 are, respectively, the amino acid sequences of positions 31 to 35 (SEQ ID No: 1), 50 to 65 (SEQ ID No: 2), and 95 to 100B (SEQ ID No: 3) of the heavy chain variable region according to Kabat numbering; the LCDR1, LCDR2 and LCDR3 include or are, respectively, the amino acid sequences of positions 24 to 34 (SEQ ID No: 4), 50 to 56 (SEQ ID No: 5), and 89 to 95 (SEQ ID No: 6) of the light chain variable region according to Kabat numbering.

[0060] In the present invention, the term "framework region" or "FRs" refers to the region other than CDRs in the heavy chain variable region and light chain variable region of an antibody, including the heavy chain framework region and the light chain framework region. Among them, the heavy chain framework region can be further subdivided into adjacent regions separated by HCDRs, including HFR1, HFR2, HFR3 and HFR4 framework regions; the light chain framework region can be further subdivided into adjacent regions separated by LCDRs, including LFR1, LFR2, LFR3 and LFR4 framework regions. In the present invention, the heavy chain framework region is represented by HFR or HFRs; the light chain framework region is represented by LFR or LFRs.

[0061] In the present invention, the heavy chain variable region is obtained by connecting the following numbered HCDR and HFR in the following combination: HFR1-HCDR1-HFR2-HCDR2-HFR3-HCDR3-HFR4; the light chain variable region is obtained by connecting the following numbered LCDR and LFR in the following combination: LFR1-LCDR1-LFR2-LCDR2-LFR3-LCDR3-LFR4. The above-mentioned combined fragments are arranged in sequence from the upstream (N-terminus) to the downstream (C-terminus) of the sequence, and the "-" represents a covalent bond (peptide bond).

[0062] In an alternative embodiment, the antibody further comprises HFR1, HFR2, HFR3, HFR4, LFR1, LFR2, LFR3 and LFR4.

[0063] In an optional embodiment, the HFR1 to HFR4 include SEQ ID NO:7 to SEQ ID NO:10, or an amino acid sequence with at least 80% identity thereto; or, are shown in sequence as SEQ ID NO:7 to SEQ ID NO:10, or an amino acid sequence with at least 80% identity thereto; the LFR1 to LFR4 include SEQ ID NO:11 to SEQ ID NO:14, or an amino acid sequence with at least 80% identity thereto; or, are shown in sequence as SEQ ID NO:11 to SEQ ID NO:14, or an amino acid sequence with at least 80% identity thereto.

[0064] In an optional embodiment, the framework region amino acid sequence of the antibody may be at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the above-mentioned framework region.

[0065] In an optional embodiment, the amino acid sequence of HFR1 is shown in SEQ ID NO:15.

[0066] In an optional embodiment, the amino acid sequence of HFR3 is shown in SEQ ID NO:16.

[0067] In an optional embodiment, the amino acid sequence of LFR1 is shown in SEQ ID NO:17.

[0068] In a third aspect, an embodiment of the present invention provides an anti-fibrin degradation product antibody, the antibody comprising a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising a sequence structure of HFR1-HCDR1-HFR2-HCDR2-HFR3-HCDR3-HFR4, the light chain variable region comprising a sequence structure of LFR1-LCDR1-LFR2-LCDR2-LFR3-LCDR3-LFR4, the amino acid sequences of the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are the above-mentioned amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and the amino acid sequences of the HFR1, HFR2, HFR3, HFR4, LFR1, LFR2, LFR3, and LFR4 are the above-mentioned amino acid sequences of HFR1, HFR2, HFR3, HFR4, LFR1, LFR2, LFR3, and LFR4.

[0069] In the present invention, the heavy chain variable region is obtained by arranging and connecting the following numbered CDRs and FRs in the following combinations: HFR1-HCDR1-HFR2-HCDR2-HFR3-HCDR3-HFR4; the light chain variable region is obtained by arranging and connecting the following numbered CDRs and FRs in the following combinations: LFR1-LCDR1-LFR2-LCDR2-LFR3-LCDR3-LFR4.

[0070] In a fourth aspect, an embodiment of the present invention provides an anti-fibrin degradation product antibody, the antibody comprising a heavy chain variable region and / or a light chain variable region, the heavy chain variable region comprising an amino acid sequence as shown in any one of SEQ ID NOs: 18 to 21; or, consisting of an amino acid sequence as shown in any one of SEQ ID NOs: 18 to 21. In an optional embodiment, the light chain variable region comprises an amino acid sequence as shown in SEQ ID NOs: 22 or 23; or, consisting of an amino acid sequence as shown in SEQ ID NOs: 22 or 23.

[0071] In an alternative embodiment, the antibody further comprises a constant region.

[0072] In an alternative embodiment, the constant region includes a heavy chain constant region and / or a light chain constant region.

[0073] In an optional embodiment, the heavy chain constant region is selected from the heavy chain constant region of any one of IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE and IgD; and the light chain constant region is selected from the κ-type or λ-type light chain constant region.

[0074] In an optional embodiment, the species origin of the constant region is any one of cattle, horses, pigs, sheep, goats, rats, mice, dogs, cats, rabbits, donkeys, deer, minks, chickens, ducks, geese and humans.

[0075] In an alternative embodiment, the species origin of the constant region is mouse.

[0076] In an alternative embodiment, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO:24 or having at least 80% identity thereto; or, consists of an amino acid sequence as shown in SEQ ID NO:24 or having at least 80% identity thereto.

[0077] In an alternative embodiment, the light chain constant region comprises an amino acid sequence as shown in SEQ ID NO:25 or having at least 80% identity thereto; or, consists of an amino acid sequence as shown in SEQ ID NO:25 or having at least 80% identity thereto.

[0078] Specifically, the constant region sequence can have at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity with the above-mentioned constant region (SEQ ID NO: 24 or 25).

[0079] In a fifth aspect, an embodiment of the present invention provides an anti-fibrin degradation product antibody, the antibody comprising a heavy chain and / or a light chain, the antibody comprising a heavy chain and a light chain; the heavy chain comprises a sequence structure of VH-CH, the light chain comprises a sequence structure of VL-CL, and the amino acid sequences of VH, VL, CH, and CL are the amino acid sequences of VH, VL, CH, and CL described in any of the above embodiments. The above-mentioned combined fragments are arranged in sequence from upstream (N-terminus) to downstream (C-terminus) of the sequence, and the "-" represents a covalent bond (peptide bond).

[0080] On the other hand, an embodiment of the present invention provides an anti-fibrin degradation product antibody, wherein the antibody comprises a heavy chain and a light chain; the heavy chain comprises the amino acid sequence shown in any one of SEQ ID NOs: 26 to 29; or, consists of the amino acid sequence shown in any one of SEQ ID NOs: 26 to 29; the light chain comprises the amino acid sequence shown in SEQ ID NOs: 30 or 31; or, consists of the amino acid sequence shown in SEQ ID NOs: 30 or 31.

[0081] On the other hand, an embodiment of the present invention provides an anti-fibrin degradation product antibody, which binds to the same epitope in the amino acid sequence of a fibrin degradation product as the antibody described in any of the above embodiments; or, the antibody competitively binds to a fibrin degradation product with the antibody described in any of the above embodiments.

[0082] There are many methods for determining antibody affinity (KD), which can be divided into thermodynamic detection methods, kinetic detection methods and dynamic equilibrium detection methods according to the detection principle. Among them, thermodynamic detection methods are commonly used, such as isothermal titration calorimetry (ITC); kinetic detection methods are commonly used, such as surface plasmon resonance (SPR) and biomembrane interferometry (BLI); dynamic equilibrium detection methods are commonly used, such as enzyme-linked immunosorbent assay (ELISA).

[0083] In an alternative embodiment, KD is determined using a kinetic assay; preferably, a surface plasmon resonance assay, such as by using a surface plasmon resonance assay such as Biosensor system of the system.

[0084] In an alternative embodiment, the determination of KD is performed with reference to the method in the examples of the present invention.

[0085] In an alternative embodiment, the antibody has a KD ≤ 1.37 × 10 -7 The affinity of M for binding to fibrin degradation products.

[0086] In an alternative embodiment, the antibody has a KD≤10 -07 M, KD≤10 -08 M, KD≤10 -09 M, KD≤10 -10 M, KD≤10 -11 M or KD≤10 -12 The affinity of M for binding to fibrin degradation products.

[0087] In an alternative embodiment, the antibody has a KD≤7.00×10 -9 Affinity binding of M to adiponectin.

[0088] In an optional embodiment, the antibody is selected from any one of F(ab')2, Fab', Fab, Fv and scFv.

[0089] On the other hand, an embodiment of the present invention further provides an antibody conjugate, which includes the antibody described in the above embodiment.

[0090] In an optional embodiment, the antibody conjugate further comprises biotin or a biotin derivative conjugated to the antibody.

[0091] In an optional embodiment, the antibody conjugate further comprises a label coupled to the antibody.

[0092] In an optional embodiment, the above-mentioned marker refers to a class of substances with properties that can be directly observed by the naked eye or detected or detected by an instrument, such as luminescence, color development, radioactivity, etc., through which qualitative or quantitative detection of the corresponding target can be achieved.

[0093] In an optional embodiment, the marker is selected from at least one of a fluorescent dye, an enzyme, a radioactive isotope, a chemiluminescent agent and a nanoparticle marker.

[0094] In actual use, those skilled in the art can select a suitable marker according to the detection conditions or actual needs. No matter which marker is used, it belongs to the protection scope of the present invention.

[0095] In an optional embodiment, the fluorescent dye is not limited to fluorescein dyes and their derivatives (for example, including but not limited to fluorescein isothiocyanate (FITC), hydroxyfluorescein (FAM), tetrachlorofluorescein (TET), etc. or their analogs), rhodamine dyes and their derivatives (for example, including but not limited to red rhodamine (RBITC), tetramethylrhodamine (TAMRA), rhodamine B (TRITC), etc. or their analogs), Cy series dyes and their derivatives (for example, including but not limited to Cy2, Cy3, Cy3B, Cy3.5, Cy3.7, Cy3.8, Cy3.9, Cy3.10, Cy3.11, Cy3.12, Cy3.13, Cy3.14, Cy3.15, Cy3.16, Cy3.17, Cy3.18, Cy3.19, Cy3.20, Cy3.21, Cy3.22, Cy3.23, Cy3.24, Cy3.25, Cy3.26, Cy3.27, Cy3.28, Cy3.29, Cy3.30, Cy3.31, Cy3.32, Cy3.33, Cy3.34, Cy3.35, Cy3.36, Cy3.37, Cy3.38, Cy3.39, Cy3.40, Cy3.41, Cy3.42, Cy3.43, Cy3.44, Cy3.45, Cy3.46, Cy3.47, Cy3.48, Cy3.49, Cy3.50, Cy3.51, Cy3.52, Cy3.53, Cy3.54, Cy3.55, Cy3.56, Cy3.57, Cy3.58, Cy3.59, Cy3.59, Cy3.59, Cy3.59, Cy3.59, Cy3.5 y5, Cy5.5, Cy3, etc. or their analogs), Alexa series dyes and their derivatives (for example, including but not limited to AlexaFluor350, 405, 430, 488, 532, 546, 555, 568, 594, 610, 33, 647, 680, 700, 750, etc. or their analogs) and protein dyes and their derivatives (for example, including but not limited to phycoerythrin (PE), phycocyanin (PC), allophycocyanin (APC), pre-chlorophyll protein (preCP), etc.).

[0096] In alternative embodiments, the enzyme includes, but is not limited to, horseradish peroxidase, alkaline phosphatase, β-galactosidase, glucose oxidase, carbonic anhydrase, acetylcholinesterase, and 6-phosphoglucose deoxygenase.

[0097] In an optional embodiment, the radioactive isotopes include but are not limited to 212Bi, 131I, 111In, 90Y, 186Re, 211At, 125I, 188Re, 153Sm, 213Bi, 32P, 94mTc, 99mTc, 203Pb, 67Ga, 68Ga, 43Sc, 47Sc, 110mIn, 97Ru, 62Cu, 64Cu, 67Cu, 68Cu, 86Y, 88Y, 121Sn, 161Tb, 166Ho, 105Rh, 177Lu, 172Lu and 18F.

[0098] In an optional embodiment, the chemiluminescent reagent includes but is not limited to luminol and its derivatives, lucigenin, crustacean fluorescein and its derivatives, bipyridine ruthenium and its derivatives, acridinium esters and their derivatives, dioxetanes and their derivatives, lophanes and their derivatives, and peroxyoxalates and their derivatives.

[0099] In an optional embodiment, the nanoparticle markers include, but are not limited to, nanoparticles, colloids, organic nanoparticles, magnetic nanoparticles, quantum dot nanoparticles, and rare earth complex nanoparticles.

[0100] In alternative embodiments, the colloid includes, but is not limited to, colloidal metals, colloidal selenium, disperse dyes, dye-labeled microspheres, and latex.

[0101] In an optional embodiment, the colloidal metal includes but is not limited to colloidal gold or colloidal silver.

[0102] In an optional embodiment, the colloidal metal is colloidal gold.

[0103] In an optional embodiment, the antibody conjugate further comprises a solid phase carrier coupled to the antibody. In the antibody conjugate, the antibody is coupled to the solid phase carrier.

[0104] In an alternative embodiment, the solid support is selected from microspheres, plates and membranes.

[0105] In an optional embodiment, the solid phase includes, but is not limited to, magnetic microspheres, plastic microspheres, plastic microparticles, microplates, glass, capillaries, nylon, and nitrocellulose membranes.

[0106] In an optional embodiment, the solid phase carrier is a nitrocellulose membrane.

[0107] On the other hand, an embodiment of the present invention further provides a reagent or a kit, which includes the antibody as described in any of the foregoing embodiments or the antibody conjugate as described in any of the foregoing embodiments.

[0108] In an alternative embodiment, the reagent or kit has improved detection sensitivity or specificity.

[0109] On the other hand, an embodiment of the present invention further provides a method for detecting fibrin degradation products, comprising:

[0110] The antibody described in any of the preceding embodiments, or the antibody conjugate described in any of the preceding embodiments, or the reagent or kit described in any of the preceding embodiments is contacted with the fibrin degradation product in the sample to be detected to form an immune complex.

[0111] In a preferred embodiment, the immune complex further comprises a second antibody, which binds to the antibody.

[0112] In a preferred embodiment, the immune complex further comprises a second antibody, which binds to fibrin degradation products.

[0113] On the other hand, an embodiment of the present invention further provides the use of the antibody or functional fragment described in any of the preceding embodiments, or the antibody conjugate described in any of the preceding embodiments, or the reagent or kit described in any of the preceding embodiments in detecting fibrin degradation products or preparing a product for detecting fibrin degradation products.

[0114] On the other hand, an embodiment of the present invention further provides the use of the antibody or functional fragment described in any of the preceding embodiments, or the antibody conjugate described in any of the preceding embodiments, or the reagent or kit described in any of the preceding embodiments in the preparation of a product having at least one of the following uses, wherein the uses include: diagnosing or assisting in diagnosing diseases related to the metabolism of fibrin degradation products, and predicting or assisting in predicting at least one of the prognosis and efficacy of diseases related to the metabolism of fibrin degradation products.

[0115] In an optional embodiment, the fibrin degradation product metabolism-related diseases include disseminated intravascular coagulation, hypercoagulable state, thrombosis, kidney disease, uremia, liver disease, and colorectal cancer.

[0116] In an alternative embodiment, the product comprises a reagent or a kit.

[0117] On the other hand, an embodiment of the present invention further provides an isolated nucleic acid encoding the antibody described in any of the above embodiments.

[0118] On the other hand, an embodiment of the present invention further provides a vector comprising the isolated nucleic acid described in any of the above embodiments.

[0119] On the other hand, an embodiment of the present invention further provides a cell, which contains the isolated nucleic acid described in any of the foregoing embodiments or the vector described in any of the foregoing embodiments.

[0120] On the other hand, an embodiment of the present invention further provides a method for preparing the antibody as described in any of the above embodiments, comprising: culturing the cell as described in any of the above embodiments.

[0121] Based on the disclosure of the amino acid sequence of the antibody in the present invention, it is easy for those skilled in the art to conceive of using genetic engineering technology or other technologies (chemical synthesis, recombinant expression) to prepare the antibody, for example, separating and purifying the antibody from the culture product of a recombinant cell that can recombinantly express the antibody as described in any of the above items, which is easy to achieve for those skilled in the art. Based on this, no matter what technology is used to prepare the antibody of the present invention, it belongs to the protection scope of the present invention.

[0122] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0123] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those of ordinary skill in the art to which the present disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used for the practice or testing of the preparations or unit doses herein, some methods and materials are now described. Unless otherwise stated, the techniques adopted or considered herein are standard methods. Materials, methods and examples are illustrative and non-restrictive only.

[0124] The practice of the present invention will employ, unless otherwise indicated, conventional techniques of cell biology, molecular biology (including recombinant techniques), microbiology, biochemistry, and immunology, which are within the capabilities of a skilled artisan. This technique is fully explained in the literature, such as Molecular Cloning: A Laboratory Manual, 2nd Edition (Sambrook et al., 1989); Oligonucleotide Synthesis (MJ Gait, ed., 1984); Animal Cell Culture (RI Freshney, ed., 1987); Methods in Enzymology (Academic Press, Inc.); Handbook of Experimental Immunology (DM Weir and CC Blackwell, eds.); Gene Transfer Vectors for Mammalian Cells (JM Miller and MP Calos, eds., 1987); Current Protocols in Molecular Biology (FM Ausubel et al., eds., 1987); PCR: The Polymerase Chain Reaction (PCR: The Polymerase Chain Reaction) (Academic Press, Inc., 1987). Reaction" (Mullis et al., eds., 1994); and Current Protocols in Immunology (JE Coligan et al., eds., 1991), each of which is expressly incorporated herein by reference.

[0125] The features and performance of the present invention are further described in detail below in conjunction with the embodiments.

[0126] Example 1 Preparation of Anti-FDPs 5C1 Monoclonal Antibody

[0127] In this example, restriction endonucleases and Prime Star DNA polymerase were purchased from Takara. MagExtractor-RNA extraction kit was purchased from TOYOBO. BD SMART TM RACE cDNA Amplification Kit was purchased from Takara. pMD-18T vector was purchased from Takara. Plasmid extraction kit was purchased from Tiangen. Primer synthesis and gene sequencing were completed by a gene sequencing company.

[0128] 1. Expression plasmid construction

[0129] In this example, restriction endonucleases and Prime Star DNA polymerase were purchased from Takara. MagExtractor-RNA extraction kit was purchased from TOYOBO. BD SMART TM RACE cDNA Amplification Kit was purchased from Takara. pMD-18T vector was purchased from Takara. Plasmid extraction kit was purchased from Tiangen. Primer synthesis and gene sequencing were completed by a gene sequencing company.

[0130] 1.1 Anti-FDPs 5C1 antibody gene preparation

[0131] mRNA was extracted from the hybridoma cell line secreting Anti-FDPs 5C1 monoclonal antibody, and the DNA product was obtained by RT-PCR. It was inserted into the pMD-18T vector and transformed into DH5α competent cells. After the colonies grew, 4 positive clones of the Heavy Chain and Light Chain genes were taken and sent to a gene sequencing company for sequencing.

[0132] 1.2 Sequence analysis of the variable region gene of Anti-FDPs 5C1 antibody

[0133] The gene sequences obtained by the above sequencing were placed in the Kabat antibody database for analysis, and the VNTI11.5 software was used for analysis to determine that the genes amplified by the heavy chain and light chain primer pairs were correct. Among the gene fragments amplified by the Light Chain, the VL gene sequence was 336bp, preceded by a 57bp leader peptide sequence; among the gene fragments amplified by the Heavy Chain primer pair, the VH gene sequence was 360bp, belonging to the VH1 gene family, and preceded by a 57bp leader peptide sequence.

[0134] 1.3 Construction of recombinant antibody expression plasmid

[0135] pcDNA TM 3.4 vector is a constructed recombinant antibody eukaryotic expression vector, which has been modified to introduce multiple cloning restriction sites and is subsequently referred to as 3.4A expression vector; based on the sequencing results of the antibody variable region genes in the above pMD-18T, the VL and VH gene-specific primers of the Anti-FDPs5C1 antibody were designed, with restriction endonuclease sites and protective bases at both ends, respectively, and the 0.74KB Light Chain gene fragment and the 1.41kb Heavy Chain gene fragment were amplified by the PCR amplification method.

[0136] The Heavy Chain and Light Chain gene fragments were double-digested with restriction endonucleases, and the 3.4A vector was double-digested with restriction endonucleases. After the fragments and vectors were purified and recovered, the Heavy Chain gene and the Light Chain gene were respectively connected to the 3.4A expression vector to obtain the recombinant expression plasmids of the Heavy Chain and Light Chain, respectively.

[0137] 2. Recombinant Antibody Sample Preparation

[0138] Resuscitate HEK293 cells in advance and subculture them to 200 ml system to make the cell density reach 3-5×10 6 cells / ml, cell viability>95%; wash the cells by centrifugation, re-dissolve with culture medium, and adjust the cell density to 2.9×10 6 cells / ml, as cell diluent. Prepare plasmid DNA and transfection reagent diluents with culture medium respectively. Add transfection reagent diluent to plasmid DNA diluent, mix well and let stand at room temperature for 15 minutes; slowly add the mixture to cell diluent within 1 minute, mix well and take samples to count, record and observe the viability of cells after transfection, and place them in a 35℃ constant temperature incubator for culture, speed 120rmp, CO2 content 8%, and centrifuge after 13 days. The supernatant of centrifugation was affinity purified using protein A affinity chromatography column. Take 6μg of purified antibody for reducing SDS-PAGE, and the electrophoresis is shown in the figure. After reducing SDS-PAGE, two bands are shown, one Mr is 50KD (heavy chain) and the other Mr is 28KD (light chain).

[0139] 3. Affinity and activity optimization

[0140] Although the Anti-FDPs 5C1 monoclonal antibody prepared above has the ability to bind to the fibrin degradation product antigen, its affinity and antibody activity are not ideal, so the applicant carried out directed mutation of the variable region of the antibody. That is, the computer was used to simulate the structure of the antibody variable region, the structure of the antigen and antibody variable region interaction complex, the key amino acid analysis of the antibody and the mutation design, and the bidirectional primers covering the mutation site were designed and synthesized according to the mutation scheme, the primers at both ends of the target DNA were synthesized, and a high-fidelity PCR reaction was performed, and the PCR product was cloned into the vector, and then the mutant antibody was prepared according to the method of step 2 above. After screening, monoclonal antibodies with significantly improved affinity and antibody activity were obtained, and were named Anti-FDPs 5C1RMb1 to Anti-FDPs 5C1RMb7, and their heavy chain and light chain amino acid sequences are shown in the following table.

[0141] Table 2 Antibody sequences

[0142] Sample name Heavy chain number Light chain number Anti-FDPs 5C1RMb1 SEQ ID NO:26 SEQ ID NO:30 Anti-FDPs 5C1RMb2 SEQ ID NO:27 SEQ ID NO:30 Anti-FDPs 5C1RMb3 SEQ ID NO:28 SEQ ID NO:30 Anti-FDPs 5C1RMb4 SEQ ID NO:28 SEQ ID NO:31 Anti-FDPs 5C1RMb5 SEQ ID NO:29 SEQ ID NO:30 Anti-FDPs 5C1RMb6 SEQ ID NO:27 SEQ ID NO:31 Anti-FDPs 5C1RMb7 SEQ ID NO:29 SEQ ID NO:31

[0143] Example 2 Affinity Analysis

[0144] Purified antibodies were diluted in advance, and FDPs antigen (purchased from Feipeng Bio) was diluted in gradients. The binding and dissociation curves of antigen and antibody were tested on the Biacore 8K+ device using a CM5 chip pre-coupled with goat anti-mouse IgG. The instrument automatically fitted the affinity constant, binding rate, and dissociation rate. The results showed that the KD of Anti-FDPs 5C1RMb1 to FDPs 5C1RMb7 were all within 1.0×10 -8 M to 1.0×10 -11 M, better than the control (KD represents the equilibrium dissociation constant, i.e., affinity constant; ka represents the association rate; kd represents the dissociation rate).

[0145] Table 3 Affinity analysis data

[0146] Sample name KD(M) ka kd Control Antibodies 1.37E-07 4.54E+04 6.23E-03 Anti-FDPs 5C1RMb1 6.10E-10 6.83E+05 4.17E-04 Anti-FDPs 5C1RMb2 3.89E-09 9.40E+04 3.66E-04 Anti-FDPs 5C1RMb3 1.69E-09 4.89E+05 8.24E-04 Anti-FDPs 5C1RMb4 7.00E-09 4.53E+04 3.17E-04 Anti-FDPs 5C1RMb5 3.50E-09 2.92E+05 1.02E-03 Anti-FDPs 5C1RMb6 5.00E-09 1.39E+05 6.95E-04 Anti-FDPs 5C1RMb7 5.46E-09 1.82E+05 9.93E-04

[0147] Example 3 Activity Identification

[0148] The coating solution (main component NaHCO3) was diluted with FDPs antigen (purchased from Feipeng Bio) to 2ug / ml, 100uL per well, overnight at 4°C; the next day, the washing solution (main component Na2HPO4+Nacl) was used to wash twice and pat dry; the blocking solution (20% BSA+80% PBS) was added, 120uL per well, 37°C, 1h, pat dry; the diluted purified antibody and control antibody were added, 100uL / well, 37°C, 30min; the washing solution was used to wash 5 times and pat dry; the goat anti-mouse IgG-HRP was added, 100uL per well, 37°C, 30min; the washing solution was used to wash 5 times and pat dry; the color developing solution A (50uL / well) and the color developing solution B (50uL / well) were added for 10min; the stop solution was added, 50uL / well; the OD value was read at 450nm (reference 630nm) on the microplate reader, and the results showed that Anti-FDPs The activity readings of 5C1RMb1 to Anti-FDPs5C1RMb7 were all between 1.85 and 2.35, which were better than the control.

[0149] Table 4 Activity data

[0150]

[0151]

[0152] Example 4 Antibody Stability Assessment

[0153] The above antibodies were placed at 4°C (refrigerator), -80°C (refrigerator), and 37°C (constant incubator) for 21 days, and samples were taken for 7 days, 14 days, and 21 days for status observation, and the activity of the 21-day samples was tested. The results showed that the antibody Anti-FDPs5C1RMb3 did not show obvious protein state changes under the three test conditions for 21 days, and the activity did not show a downward trend with the increase of the test temperature, indicating that the expressed antibody is stable. Table 5 below shows the OD results of the enzyme immunoassay activity test for 21 days.

[0154] Table 5 Stability data

[0155] Sample concentration (ng / ml) 250 125 0 4℃, 21-day samples 1.891 1.521 0.012 -80℃, 21 days sample 1.921 1.501 0.019 37℃, 21 days sample 1.923 1.587 0.013

[0156] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

[0157] Some of the amino acid sequences involved in this application are shown in Table 6 below:

[0158]

[0159]

Claims

1. An anti-fibrin degradation product antibody, comprising HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3, characterized in that: The HCDR1 / HCDR2 / HCDR3 combination is the same as the HCDR1 / HCDR2 / HCDR3 combination contained in the heavy chain variable region shown in any one of SEQ ID NO:18 to SEQ ID NO:21, and the LCDR1 / LCDR2 / LCDR3 combination is the same as the LCDR1 / LCDR2 / LCDR3 combination contained in the light chain variable region shown in SEQ ID NO:22 or 23; the HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3 are defined by Kabat, Chothia, AbM, Contact or IMGT systems.

2. An anti-fibrin degradation product antibody, characterized in that: The antibody comprises HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3, wherein the amino acid sequences of the HCDR1, HCDR2, HCDR3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the LCDR1, LCDR2, LCDR3 are shown in SEQ ID NOs: 4 to 6, respectively.

3. The antibody according to any one of claims 1 to 2, further comprising HFR1, HFR2, HFR3, HFR4, LFR1, LFR2, LFR3 and LFR4; the HFR1 to HFR4 comprise, in sequence, SEQ ID NO: 7 to SEQ ID NO: 10 or an amino acid sequence having at least 80% identity thereto; or, are shown, in sequence, as SEQ ID NO: 7 to SEQ ID NO: 10 or an amino acid sequence having at least 80% identity thereto; the LFR1 to LFR4 comprise, in sequence, SEQ ID NO: 11 to SEQ ID NO: 14 or an amino acid sequence having at least 80% identity thereto; or, are shown, in sequence, as SEQ ID NO: 11 to SEQ ID NO: 14 or an amino acid sequence having at least 80% identity thereto.

4. An anti-fibrin degradation product antibody, characterized in that The antibody comprises a heavy chain variable region and a light chain variable region, and the heavy chain variable region and the light chain variable region comprise any combination of the following amino acid sequences: 。 5. The antibody according to any one of claims 1 to 2 and 4, characterized in that The antibody also comprises a constant region.

6. The antibody according to claim 5, characterized in that The constant region includes a heavy chain constant region and / or a light chain constant region.

7. The antibody according to claim 6, characterized in that The heavy chain constant region is selected from the heavy chain constant region of any one of IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE and IgD; the light chain constant region is selected from the κ type or λ type light chain constant region.

8. The antibody according to claim 5, characterized in that The species origin of the constant region is any one of cattle, horses, pigs, sheep, goats, rats, mice, dogs, cats, rabbits, donkeys, deer, minks, chickens, ducks, geese and humans.

9. The antibody according to claim 5, characterized in that The species origin of the constant region is mouse.

10. The antibody according to claim 6, characterized in that The heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 24 or having at least 80% identity thereto; or, consists of an amino acid sequence as shown in SEQ ID NO: 24 or having at least 80% identity thereto.

11. The antibody according to claim 6, characterized in that The light chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 25 or having at least 80% identity thereto; or, consists of an amino acid sequence as shown in SEQ ID NO: 25 or having at least 80% identity thereto.

12. An anti-fibrin degradation product antibody, characterized in that: The antibody comprises a heavy chain and a light chain; the heavy chain and the light chain comprise the following amino acid sequences in any combination: 。 13. The antibody according to any one of claims 1 to 2, 4, 6 to 12, characterized in that The antibody has a KD≤1.37×10 -7 M binds with affinity to fibrin degradation products.

14. The antibody according to any one of claims 1 to 2, 4, 6 to 12, characterized in that The antibody is selected from any one of F(ab')2, Fab', Fab, Fv and scFv.

15. An antibody conjugate against fibrin degradation products, characterized in that: It comprises the antibody according to any one of claims 1 to 14.

16. The antibody conjugate according to claim 15, characterized in that The antibody conjugate further comprises biotin or a biotin derivative conjugated to the antibody.

17. The antibody conjugate according to claim 15, characterized in that The antibody conjugate further comprises a solid phase carrier coupled to the antibody.

18. The antibody conjugate according to claim 15, characterized in that: The antibody conjugate further comprises a label coupled to the antibody.

19. The antibody conjugate according to claim 18, characterized in that The marker is selected from at least one of fluorescent dyes, enzymes, radioactive isotopes, chemiluminescent reagents and nanoparticle markers.

20. A reagent or a kit, characterized in that: It comprises the antibody according to any one of claims 1 to 14 or the antibody conjugate according to claims 15 to 19.

21. Use of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 14, the antibody conjugate according to any one of claims 15 to 19, or the reagent or kit according to claim 20 in the preparation of a product for detecting fibrin degradation products, characterized in that: It includes: The antibody according to any one of claims 1 to 14, the antibody conjugate according to any one of claims 15 to 19, or the reagent or kit according to claim 20 is contacted with the fibrin degradation product in the sample to be detected to form an immune complex.

22. The use according to claim 21, characterized in that The immune complex also includes a second antibody that binds to the antibody.

23. The use according to claim 21, characterized in that The immune complex also includes a second antibody that binds to a fibrin degradation product.

24. An isolated nucleic acid, characterized in that The nucleic acid encodes the antibody according to any one of claims 1 to 14.

25. A carrier, characterized in that The vector contains the nucleic acid according to claim 24.

26. A cell, characterized in that The cell contains the nucleic acid of claim 24 or the vector of claim 25.

27. A method for preparing the antibody according to any one of claims 1 to 14, characterized in that: The method comprises: culturing the cell of claim 26.

28. Use of the antibody according to any one of claims 1 to 14, the antibody conjugate according to any one of claims 15 to 19, or the reagent or kit according to claim 20 in the preparation of a product for detecting fibrin degradation products.

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