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WO2025113565A1 - Anticorps anti-p24 et son utilisation - Google Patents

Anticorps anti-p24 et son utilisation Download PDF

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Publication number
WO2025113565A1
WO2025113565A1 PCT/CN2024/135282 CN2024135282W WO2025113565A1 WO 2025113565 A1 WO2025113565 A1 WO 2025113565A1 CN 2024135282 W CN2024135282 W CN 2024135282W WO 2025113565 A1 WO2025113565 A1 WO 2025113565A1
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antibody
seq
amino acid
acid sequence
optionally
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Chinese (zh)
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钟冬梅
梁碧
唐丽娜
孟媛
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Fapon Biotech Inc
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Fapon Biotech Inc
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    • C07—ORGANIC CHEMISTRY
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
    • C07K16/1036—Retroviridae, e.g. leukemia viruses
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
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    • C07—ORGANIC CHEMISTRY
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    • C07K16/46—Hybrid immunoglobulins
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    • C12N5/10—Cells modified by introduction of foreign genetic material
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    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase
    • G01N33/537—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with separation of immune complex from unbound antigen or antibody
    • G01N33/539—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with separation of immune complex from unbound antigen or antibody involving precipitating reagent, e.g. ammonium sulfate
    • G01N33/541—Double or second antibody, i.e. precipitating antibody
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    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
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    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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    • G01N33/56983—Viruses
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    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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    • C07K2317/515—Complete light chain, i.e. VL + CL
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    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
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    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567—Framework region [FR]
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    • C12N2800/00—Nucleic acids vectors
    • C12N2800/10—Plasmid DNA
    • C12N2800/106—Plasmid DNA for vertebrates
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    • G—PHYSICS
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    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/08—RNA viruses
    • G01N2333/15—Retroviridae, e.g. bovine leukaemia virus, feline leukaemia virus, feline leukaemia virus, human T-cell leukaemia-lymphoma virus

Definitions

  • the present disclosure relates to the field of antibody technology, and in particular, to an anti-P24 antibody and application thereof.
  • Human immunodeficiency virus also known as AIDS, is a virus that causes human immune system defects. Human immunodeficiency virus was first discovered in the United States in 1981. It is a lentivirus that infects human immune system cells and is a type of retrovirus.
  • HIV is the pathogen of AIDS, which is mainly transmitted through sexual contact, blood and mother-to-child transmission.
  • the determination of serum HIV antibodies is a routine experimental method for diagnosing HIV infection, but the determination of HIV antibodies has limitations: more than 70% of HIV-infected people can only detect antibodies 6 months after infection. In the homosexual community, this number exceeds 80%.
  • the antibody detection method increases the risk of HIV transmission during the "window period"; in addition, it takes one year for newborns to produce antibodies after birth, and HIV antibodies from the mother will cause false positives; due to the continuous presence of HIV antibodies during the disease process, they will only disappear in the late stage of AIDS and cannot be used as a stable indicator for treatment monitoring.
  • P24 is the main structural protein of HIV virus particles and the product of the structural gene GAG. It plays an important role in the packaging and maturation of the virus.
  • the amino acid sequence of the P24 protein is highly conserved among HIV strains. The absence of P24 will cause the virus to be unable to assemble normally.
  • the P24 protein is highly specific and has no cross-reaction with most other retroviruses.
  • the first viral marker that appears in the blood of the infected person is the viral P24 protein.
  • the detection of HIV-P24 antigen has played an important role in the early diagnosis of HIV infection, the prognosis of patients, the screening and evaluation of anti-HIV drugs, and the detection of mother-to-child transmission.
  • HIV-1 P24 antigen detection adopts serological diagnosis methods, mainly including double antibody sandwich ELISA, immune complex lysis detection, ultra-sensitive EIA, enzyme-linked immunofluorescence, etc.
  • the double antibody sandwich method is widely used to detect human immunodeficiency virus P24 antigen, and obtaining anti-P24 antibodies is the key to realize the double antibody sandwich method detection.
  • the present application provides an anti-P24 antibody, which provides an important source of raw materials for the detection of P24 and has good activity or affinity.
  • an anti-P24 antibody which comprises three complementary determining regions of a heavy chain variable region having an amino acid sequence as shown in SEQ ID NO: 19 and three complementary determining regions of a light chain variable region having an amino acid sequence as shown in any one of SEQ ID NO: 21, 22, 23, and 24.
  • an anti-P24 antibody comprising the following complementary determining regions:
  • HCDR1 which comprises or consists of the amino acid sequence shown in SEQ ID NO:1;
  • HCDR2 which comprises or consists of the amino acid sequence shown in SEQ ID NO:2;
  • HCDR3 which comprises or consists of the amino acid sequence shown in SEQ ID NO:3;
  • LCDR1 which comprises or consists of the amino acid sequence shown in SEQ ID NO:4;
  • LCDR2 which comprises or consists of the amino acid sequence shown in SEQ ID NO:5;
  • LCDR3 which comprises or consists of the amino acid sequence shown in SEQ ID NO:6.
  • an anti-P24 antibody comprising a heavy chain variable region and/or a light chain variable region, wherein the amino acid sequence of the heavy chain variable region is as shown in SEQ ID NO: 19; and the amino acid sequence of the light chain variable region is as shown in any one of SEQ ID NO: 21, 22, 23, and 24.
  • an anti-P24 antibody comprising a heavy chain and/or a light chain, wherein the amino acid sequence of the heavy chain is as shown in any one of SEQ ID NO: 20 and 30; and the amino acid sequence of the light chain is as shown in any one of SEQ ID NO: 25, 26, 27 and 28.
  • an antibody conjugate is provided, wherein the antibody conjugate comprises the above antibody.
  • a reagent or a kit comprising the above-mentioned antibody or the above-mentioned antibody conjugate.
  • the seventh aspect of the present disclosure there is provided a use of the above antibodies and antibody conjugates in detecting P24, diagnosing HIV infection in a subject, preparing a product for detecting P24, or preparing a product for diagnosing whether a subject is infected with HIV.
  • a method for diagnosing whether a subject is infected with HIV comprising: a) contacting the above-mentioned antibody, antibody conjugate, reagent or kit with an ex vivo sample to be tested under conditions sufficient for an antibody/antigen binding reaction to occur to form an immune complex; and b) detecting the presence of the immune complex.
  • a method for detecting P24 comprising: a) contacting the above-mentioned antibody, antibody conjugate, reagent or kit with P24 in a sample to be detected under conditions sufficient for an antibody/antigen binding reaction to occur to form an immune complex; and b) detecting the presence of the immune complex, wherein the presence of the complex indicates the presence of the antigen in the test sample.
  • the present disclosure also provides a nucleic acid, a vector, a cell and a method for preparing the above antibody.
  • Figure 1 shows the results of reducing SDS-PAGE of Anti-P24 20C5 Rmb1 to Anti-P24 20C5 Rmb8.
  • the embodiments of the present disclosure provide an anti-P24 antibody, which comprises three complementary determining regions of a heavy chain variable region having an amino acid sequence as shown in SEQ ID NO: 19 and three complementary determining regions of a light chain variable region having an amino acid sequence of any one of SEQ ID NO: 21, 22, 23, and 24.
  • 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
  • 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.
  • the HCDR1, HCDR2, and HCDR3 are amino acid sequences consistent with the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region shown in SEQ ID NO:19; the LCDR1, LCDR2, and LCDR3 are amino acid sequences consistent with the LCDR1, LCDR2, and LCDR3 of the light chain variable region shown in SEQ ID NO:21.
  • antibody is used in the broadest sense, which may include full-length monoclonal antibodies, bispecific antibodies, multispecific antibodies, chimeric antibodies or antigen-binding fragments of antibodies, as long as they exhibit the desired antigen-binding activity.
  • Antigen-binding fragments of antibodies include any one of F(ab)2, F(ab')2, Fab', Fab, Fv and scFv, and generally have the same binding specificity as the antibody from which they are derived. It is easy for those skilled in the art to understand from the contents of the present disclosure that antigen-binding fragments of antibodies 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 disclosure, antigen-binding fragments of antibodies can be easily obtained by those skilled in the art.
  • Antigen-binding fragments of antibodies 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.
  • CDR complementarity determining region
  • CDRs refers to the highly variable region 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 play a role in the binding of an antibody or antigen-binding fragment to its recognized antigen or epitope.
  • CDRs refers to the highly variable region of the heavy and light chains of the antibody.
  • the heavy chain complementarity determining region is denoted by HCDR, which includes HCDR1, HCDR2 and HCDR3;
  • the light chain complementarity determining region is denoted by LCDR, which includes LCDR1, LCDR2 and LCDR3.
  • CDR definition methods include: Kabat definition, Chothia definition, IMGT definition, Contact definition, and AbM definition.
  • Kabat definition refers to the definition system described by Kabat et al., U.S. Dept. of Health and Human Services, "Sequence of Proteins of Immunological Interest” (1983).
  • Chothia definition refers to Chothia et al., J Mol Biol 196: 901-917 (1987).
  • CDR definition methods that may not strictly follow one of the above schemes, but will still overlap with at least a portion of the CDR region defined by Kabat, although they may be shortened or extended based on predictions or experimental results of specific residues or residue groups.
  • 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 contain a specific CDR. It should be noted that CDRs defined by other methods not limited to those in Table 1 also fall within the protection scope of the present disclosure.
  • CDR Definition 1 The numbering of all CDR definitions in Table 1 is based on the Kabat numbering system (see below), with amino acid numbers on the heavy chain represented by “H+numbers” and amino acid numbers on the light chain represented by “L+numbers".
  • Kabat numbering refers to the numbering system described in Kabat et al., U.S. Patent No. of Health and Human Services, "Sequence of Proteins of Immunological Interest" (1983).
  • 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.
  • the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by the Kabat system.
  • the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by the Chothia system.
  • the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by the IMGT system.
  • the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by the AbM system.
  • the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by a Contact system.
  • the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by a combination of Kabat, Chothia, IMGT, AbM or Contact systems.
  • the present disclosure provides an anti-P24 antibody, wherein the antibody comprises the following complementary determining regions:
  • HCDR1 which comprises or consists of the amino acid sequence shown in SEQ ID NO:1.
  • HCDR2 comprises or consists of the amino acid sequence shown in SEQ ID NO:2.
  • HCDR3 which comprises or consists of the amino acid sequence shown in SEQ ID NO:3.
  • LCDR1 which comprises or consists of the amino acid sequence shown in SEQ ID NO:4.
  • LCDR2 which comprises or consists of the amino acid sequence shown in SEQ ID NO:5.
  • LCDR3 which comprises or consists of the amino acid sequence shown in SEQ ID NO:6.
  • the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 are defined by the Kabat system.
  • framework region or "FR” region includes heavy chain framework region and light chain framework region, and refers to the region other than CDR in the heavy chain variable region and light chain variable region of the antibody; wherein the heavy chain framework region can be further subdivided into adjacent regions separated by CDR, including HFR1, HFR2, HFR3 and HFR4 framework regions; the light chain framework region can be further subdivided into adjacent regions separated by CDR, including LFR1, LFR2, LFR3 and LFR4 framework regions.
  • the heavy chain variable region is obtained by 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 connecting the following numbered CDRs and FRs in the following combinations: LFR1-LCDR1-LFR2-LCDR2-LFR3-LCDR3-LFR4.
  • the antibody of the first aspect or the second aspect further has HFR1, HFR2, HFR3, HFR4, LFR1, LFR2, LFR3 and LFR4.
  • the HFR1 comprises/is such as SEQ ID NO:7 or an amino acid sequence having at least 80% identity thereto;
  • the HFR2 comprises/is such as SEQ ID NO:8 or an amino acid sequence having at least 80% identity thereto;
  • the HFR3 comprises/is such as SEQ ID NO:9 or an amino acid sequence having at least 80% identity thereto;
  • the HFR4 comprises/is such as SEQ ID NO:10 or an amino acid sequence having at least 80% identity thereto;
  • the LFR1 comprises/is such as SEQ ID NO:11 or an amino acid sequence having at least 80% identity thereto;
  • the LFR2 comprises/is such as SEQ ID NO:12 or an amino acid sequence having at least 80% identity thereto;
  • the LFR3 comprises/is represented by SEQ ID NO:13 or an amino acid sequence having at least 80% identity thereto;
  • the LFR4 includes/is such as SEQ ID NO:14 or an amino acid sequence having at least 80% identity thereto.
  • the amino acid sequences of each framework region of the anti-P24 antibody provided by the present disclosure may 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 corresponding framework region (SEQ ID NO: 7, 8, 9, 10, 11, 12, 13 or 14).
  • the LFR3 includes/is represented by an amino acid sequence as shown in SEQ ID NO:18.
  • the LFR2 includes/is represented by an amino acid sequence as shown in SEQ ID NO:17.
  • the antibody binds P24 with an affinity of KD ⁇ 7.15 x 10 -8 M.
  • the antibody binds P24 with an affinity of KD ⁇ 10 "8M , KD ⁇ 10 “9M , KD ⁇ 10” 10M , KD ⁇ 10 "11M , or KD ⁇ 10 "12M .
  • the antibody binds P24 with an affinity of KD ⁇ 1.41 ⁇ 10 ⁇ 9 M.
  • 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).
  • ITC isothermal titration calorimetry
  • SPR surface plasmon resonance
  • BLI biomembrane interferometry
  • ELISA enzyme-linked immunosorbent assay
  • KD is determined using a kinetic assay; optionally, surface plasmon resonance, for example by using a kinetic assay such as Biosensor system of the system.
  • the embodiments of the present disclosure provide an anti-P24 antibody, comprising a heavy chain variable region and/or a light chain variable region, wherein the amino acid sequence of the heavy chain variable region is as shown in SEQ ID NO: 19, and the amino acid sequence of the light chain variable region is as shown in any one of SEQ ID NO: 21, 22, 23, and 24.
  • the antibody described in the first aspect, the second aspect, and the third aspect further comprises a constant region.
  • the constant region includes a heavy chain constant region and/or a light chain constant region.
  • the heavy chain constant region is selected from any one of the heavy chain constant regions of IgG, IgA, IgM, IgE, and IgD, or a combination of multiple constant region segments.
  • the heavy chain constant region includes CH1 of IgG, a hinge region of IgG, CH2 of IgM, CH3 of IgM and/or CH4 of IgM.
  • the IgG is selected from IgG1, IgG2, IgG3 or IgG4.
  • the light chain constant region is selected from a kappa-type or a lambda-type light chain constant region.
  • the species of origin of the constant region is cattle, horses, dairy cows, pigs, sheep, rats, mice, dogs, camels, cats, rabbits, donkeys, deer, minks, chickens, ducks, geese, turkeys, fighting cocks or humans.
  • the species origin of the constant region is human.
  • variable and constant region sequences refers to the IMGT division method, see Lefranc, and Martinez-Jean C. and Bosc N. or Ehrenmann,Patrice Duroux,Chantal Ginestoux,Gene table:house mouse(Mus musculus)IGHC,IMGT Repertoire.
  • variable regions divided by different methods may have some amino acid differences with the variable region C-terminus or constant region N-terminus divided by IMGT.
  • variable regions or constant regions divided by other methods known in the art are also within the protection scope of the present disclosure.
  • the heavy chain constant region sequence (CH) is as shown in SEQ ID NO:15 or 29, and the light chain constant region (CL) sequence is as shown in SEQ ID NO:16.
  • 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: 15 or 16).
  • the antibody comprises any one of F(ab)2, F(ab')2, Fab', Fab, Fv and scFv.
  • the present disclosure provides an anti-P24 antibody, comprising a heavy chain and/or a light chain, wherein the amino acid sequence of the heavy chain is shown in any one of SEQ ID NO: 20 and 30, and the amino acid sequence of the light chain is shown in any one of SEQ ID NO: 25, 26, 27 and 28.
  • the antibody of the first aspect, the second aspect, the third aspect or the fourth aspect comprises any combination of the following heavy chains and light chains:
  • the present disclosure provides an antibody conjugate, which comprises the above-mentioned antibody.
  • the above-mentioned antibody conjugate further comprises biotin or a biotin derivative conjugated to the antibody.
  • the antibody conjugate further comprises a label coupled to the antibody.
  • 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.
  • the label includes but is not limited to fluorescent dyes, enzymes, radioactive isotopes, chemiluminescent agents and nanoparticle labels.
  • 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.
  • 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
  • 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, Cy3.59, Cy3.59, Cy3.59, Cy3.59, Cy3.59, Cy3.59, Cy3.5 y5, Cy5.5, Cy3, etc.
  • 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
  • protein dyes and their derivatives for example, including but not limited to phycoerythrin (PE), phycocyanin (PC), allophycocyanin (APC), pre-chlorophyll protein (preCP), etc.
  • the enzyme includes, but is not limited to, horseradish peroxidase, alkaline phosphatase, ⁇ -galactosidase, glucose oxidase, carbonic anhydrase, acetylcholinesterase, and 6-phosphoglucose deoxygenase.
  • 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.
  • 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.
  • the nanoparticle markers include, but are not limited to, nanoparticles, colloids, organic nanoparticles, magnetic nanoparticles, quantum dot nanoparticles, and rare earth complex nanoparticles.
  • the colloid includes, but is not limited to, colloidal metals, colloidal carbon, disperse dyes, dye-labeled microspheres, and latex.
  • the colloidal metal includes, but is not limited to, colloidal gold, colloidal silver, and colloidal selenium.
  • the colloidal metal is colloidal gold.
  • the above-mentioned antibody conjugate further includes a solid phase carrier coupled to the antibody.
  • the solid support is selected from microspheres, plates and membranes.
  • the solid phase carrier includes but is not limited to magnetic microspheres, plastic microspheres, plastic microparticles, microwell plates, glass, capillaries, nylon and nitrocellulose membranes.
  • the present disclosure provides a reagent or a kit, wherein the reagent or the kit comprises the above-mentioned antibody or the above-mentioned antibody conjugate.
  • the antibodies in some embodiments or examples of the present disclosure can effectively bind to P24, so the reagents or kits containing the P24 antibodies can effectively detect P24 qualitatively or quantitatively.
  • the reagents or kits provided by the present disclosure can be used, for example, for detections involving the specific binding properties of P24 and its antibodies, such as immunoblotting and immunoprecipitation.
  • the antibodies in some embodiments or examples of the present disclosure have higher binding activity or affinity with P24, so the reagents or kits containing the antibodies have higher detection sensitivity or specificity.
  • products disclosed herein include but are not limited to reagents, test kits, test strips or test plates.
  • the present disclosure provides a method for detecting P24, comprising: a) contacting the above-mentioned antibody, antibody conjugate, reagent or kit with P24 in a sample to be detected to form an immune complex under conditions sufficient for an antibody/antigen binding reaction to occur; and b) detecting the presence of the immune complex, wherein the presence of the complex indicates the presence of the antigen in the test sample;
  • the immune complex further comprises a second antibody that binds to the antibody.
  • the immune complex further comprises a second antibody, which binds to P24.
  • the present disclosure provides a method for diagnosing whether a subject is infected with HIV, comprising: a) contacting the above-mentioned antibody, antibody conjugate, reagent or kit with P24 in a sample to be tested to form an immune complex under conditions sufficient for an antibody/antigen binding reaction to occur; and b) detecting the presence of the immune complex, wherein the presence of the complex indicates the presence of the antigen in the test sample;
  • the immune complex further comprises a second antibody that binds to the antibody.
  • the immune complex further comprises a second antibody, which binds to P24.
  • the present disclosure provides uses of the above-mentioned anti-P24 antibodies and antibody conjugates in detecting P24, diagnosing HIV infection in a subject, preparing products for detecting P24, or preparing products for diagnosing whether a subject is infected with HIV.
  • the present disclosure provides a nucleic acid molecule encoding the above-mentioned antibody.
  • the present disclosure provides a vector containing the above-mentioned nucleic acid molecule.
  • the present disclosure provides cells containing the above-mentioned vector.
  • the present disclosure provides a method for preparing an anti-P24 antibody, comprising: culturing the cells as described above.
  • the restriction endonucleases and Prime Star DNA polymerase in this example 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 Invitrogen. The hybridoma cell line secreting mAnti-P24 20C5 monoclonal antibody was prepared in this laboratory and revived for use.
  • mRNA was extracted from the hybridoma cell line secreting mAnti-P24 20C5 monoclonal antibody, and the DNA product was obtained by RT-PCR.
  • the product was inserted into the pMD-18T vector after A addition reaction with rTaq DNA polymerase and transformed into DH5 ⁇ competent cells. After colonies grew, Heavy Chain and Light Chain gene clones were taken and 4 clones each were sent to a gene sequencing company for sequencing.
  • 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.
  • the VL gene sequence was 330bp, and it was preceded by a 57bp leader peptide sequence
  • the VH gene sequence was 378bp, belonging to the VH1 gene family, and it was preceded by a 57bp leader peptide sequence.
  • the obtained mouse antibodies were then humanized by humanization technology to obtain humanized antibodies and sequences.
  • pcDNA TM 3.4 vector is a recombinant antibody eukaryotic expression vector constructed, which has introduced multiple cloning restriction sites such as HindIII, BamHI, and EcoRI, and is named pcDNA3.4A expression vector, hereinafter referred to as 3.4A expression vector; according to the sequence of the above humanized antibody, the VL and VH gene-specific primers of the antibody were designed, with HindIII, EcoRI restriction sites and protective bases at both ends, respectively, and the 0.71kb Light Chain gene fragment and the 1.42kb Heavy Chain gene fragment were amplified by the PCR amplification method.
  • the Heavy Chain and Light Chain gene fragments were digested with HindIII/EcoRI, and the 3.4A vector was digested with HindIII/EcoRI. After the fragments and vectors were purified and recovered, the Heavy Chain gene and Light Chain gene were connected to the 3.4A expression vector, respectively, to obtain the recombinant expression plasmids of Heavy Chain and Light Chain, respectively.
  • Anti-P24 20C5Rmb1 was mutated to obtain a mutant antibody.
  • the sequences of the heavy chain (H) and light chain (L) of the above antibody are shown in the following table:
  • the purified antibody was diluted in advance, and the P24 recombinant antigen (from Feipeng Bio) was diluted in a gradient manner; the binding and dissociation curves of the antigen and antibody were tested on the Biacore 8K+ device using the CM5 chip that had been pre-coupled with Protein A.
  • the instrument automatically fitted the affinity constant, binding rate, and dissociation rate. (KD represents the equilibrium dissociation constant, i.e., affinity constant; ka represents binding rate; kd represents dissociation rate)
  • the coating solution (main component NaHCO 3 ) was used to dilute P24 recombinant antigen (from Feipeng Bio) to 3ug/ml, 100uL per well, and incubated at 4°C overnight; the next day, the wells were washed twice with washing solution (main component Na 2 HPO 4 +NaCl), and patted dry; blocking solution (20% BSA + 80% PBS) was added, 120uL per well, 37°C, 1h, and patted dry; the diluted purified antibody and control antibody were added, 100uL/well, 37°C, 30min; the wells were washed with washing solution 5 times, and patted dry; goat anti-human IgG-HRP was added, 100uL per well, 37°C, 30min; the wells were washed with washing solution 5 times, and patted dry; color development solution A (50uL/well) and color development solution B (50uL/well) were added, 10min; stop solution was added, 50uL/well; OD
  • Solution A main ingredients: citric acid + sodium acetate + acetanilide + urea peroxide
  • Solution B main ingredients: citric acid + EDTA ⁇ 2Na + TMB + concentrated HCl
  • Stop solution EDTA ⁇ 2Na + concentrated H 2 SO 4
  • the above antibodies were placed at 4°C (refrigerator), -80°C (refrigerator), and 37°C (constant temperature box) 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 there was no obvious protein state change in the antibodies 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 above antibodies are stable.
  • Table 5 below shows the OD results of the enzyme immunoassay activity test of the antibody Anti-P24 20C5Rmb5 for 21 days.
  • Example 3 Antibody performance test (exemplary display of the performance test results of the antibody Anti-P24 20C5Rmb4)
  • Anti-P24 20C5Rmb4 and Anti-P24-B (control antibody, from Feipeng Bio) were replaced into PBS (100 mM PB, 50 mM sodium chloride, pH 8.0) using a Zeba desalting column (10K MWCO) and labeled with biotin.
  • the biotin-modified antibody was the biotin working solution and was stored at 4°C for future use.
  • the test was performed on the Yingkai shine i2910 model fully automatic chemiluminescence immunoassay analyzer using the double antibody sandwich method, that is, the instrument sequentially added 100 ⁇ L sample, 50 ⁇ L magnetic particle working solution and 50 ⁇ L biotin working solution, mixed and incubated for 10 minutes, rinsed the reaction mixture after incubation, and then added 100 uL SA-AE working solution. Mix and incubate for 10 minutes, rinsed the reaction mixture after incubation, added pre-excitation solution and excitation solution, and detected the relative luminescence intensity (RLU).
  • RLU relative luminescence intensity
  • the samples in the experiment refer to: sample diluent, positive test samples of different concentrations, positive clinical samples, negative plasma samples of different populations, and negative serum samples of different populations.

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Abstract

L'invention concerne un anticorps anti-P24 et son utilisation. L'anticorps anti-P24 comprend une région déterminant la complémentarité de chaîne lourde et une région déterminant la complémentarité de chaîne légère. L'anticorps fournit une source de matière première importante pour la détection de P24, et présente une bonne affinité ou une bonne activité.
PCT/CN2024/135282 2023-11-30 2024-11-28 Anticorps anti-p24 et son utilisation Pending WO2025113565A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995033206A1 (fr) * 1994-05-31 1995-12-07 Abbott Laboratories Detection de differents genotypes de vih utilisant un immunodosage modifie par un peptide synthetique
CN101363853A (zh) * 2007-08-06 2009-02-11 北京科美东雅生物技术有限公司 人类免疫缺陷病毒抗原/抗体化学发光免疫分析测定试剂盒及其制备方法
CN113121678A (zh) * 2019-12-31 2021-07-16 东莞市朋志生物科技有限公司 一种抗hiv-1 p24的重组抗体
CN113683688A (zh) * 2021-07-23 2021-11-23 无锡傲锐东源生物科技有限公司 抗人类免疫缺陷病毒ⅰ型p24抗原（hiv-1 p24）兔单克隆抗体及其应用
WO2022013730A1 (fr) * 2020-07-13 2022-01-20 Grifols Diagnostic Solutions Inc. Anticorps anti-virus de l'immunodéficience humaine-1 et leurs procédés d'utilisation
CN116143909A (zh) * 2021-11-20 2023-05-23 东莞市朋志生物科技有限公司 一种抗hiv-1 p24的抗体及其制备方法和用途

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995033206A1 (fr) * 1994-05-31 1995-12-07 Abbott Laboratories Detection de differents genotypes de vih utilisant un immunodosage modifie par un peptide synthetique
CN101363853A (zh) * 2007-08-06 2009-02-11 北京科美东雅生物技术有限公司 人类免疫缺陷病毒抗原/抗体化学发光免疫分析测定试剂盒及其制备方法
CN113121678A (zh) * 2019-12-31 2021-07-16 东莞市朋志生物科技有限公司 一种抗hiv-1 p24的重组抗体
WO2022013730A1 (fr) * 2020-07-13 2022-01-20 Grifols Diagnostic Solutions Inc. Anticorps anti-virus de l'immunodéficience humaine-1 et leurs procédés d'utilisation
CN113683688A (zh) * 2021-07-23 2021-11-23 无锡傲锐东源生物科技有限公司 抗人类免疫缺陷病毒ⅰ型p24抗原（hiv-1 p24）兔单克隆抗体及其应用
CN116143909A (zh) * 2021-11-20 2023-05-23 东莞市朋志生物科技有限公司 一种抗hiv-1 p24的抗体及其制备方法和用途

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