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CN-121991221-A - Antibodies against human MPC or antigen binding fragments thereof and uses thereof

CN121991221ACN 121991221 ACN121991221 ACN 121991221ACN-121991221-A

Abstract

The invention provides an antibody or antigen binding fragment thereof for resisting human MPC and application thereof, and provides an antibody or antigen binding fragment thereof for resisting mitochondrial pyruvic acid carrier (MPC) and a composition and application thereof. In particular, an anti-MPC antibody or antigen binding fragment thereof is provided that is capable of efficiently binding MPC. The invention also provides an antibody drug conjugate, a detection plate or a kit containing the antibody or the antigen binding fragment thereof, which can be applied to detection and marking of MPC protein, and further applied to structure and function research or drug development related to MPC protein, and has wide application prospect.

Inventors

  • TONG PEI
  • MA QIUYUN
  • QIAN HONGWU
  • LIU GUOYUN

Assignees

  • 合肥综合性国家科学中心大健康研究院

Dates

Publication Date
20260508
Application Date
20260120

Claims (10)

  1. 1. An anti-human MPC antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof has three complementarity determining regions HCDR for the heavy chain variable regions and three complementarity determining regions LCDR for the light chain variable regions: HCDR1 as shown in SEQ ID NO:59, HCDR2 as shown in SEQ ID NO. 60, HCDR3 as shown in SEQ ID NO. 61, LCDR1 as shown in SEQ ID NO. 63, LCDR2 as shown in SEQ ID NO. 64, and LCDR3 as shown in SEQ ID NO. 65.
  2. 2. The anti-human MPC antibody or antigen-binding fragment thereof of claim 1, wherein said heavy chain variable region and light chain variable region of said anti-human MPC antibody or antigen-binding fragment thereof are the heavy chain variable region of amino acid sequence set forth in SEQ ID No. 58 and the light chain variable region of amino acid sequence set forth in SEQ ID No. 62.
  3. 3. A recombinant protein, wherein the recombinant protein has: (1) The anti-human MPC antibody or antigen binding fragment thereof of claim 1, and (2) Optionally a tag sequence to assist expression and/or purification.
  4. 4. A polynucleotide expressing the anti-human MPC antibody or antigen-binding fragment thereof of claim 1.
  5. 5. A carrier, characterized in that, the vector contains the polynucleotide of claim 4.
  6. 6. A host cell expressing the anti-human MPC antibody or antigen-binding fragment thereof of claim 1, having a genome incorporating the polynucleotide of claim 4, or comprising the vector of claim 5.
  7. 7. An antibody drug conjugate, which is characterized in that, the antibody drug conjugate comprises: (I) An antibody moiety comprising the anti-human MPC antibody or antigen binding fragment thereof of claim 1, and (II) a coupling moiety coupled to the antibody or antigen binding fragment thereof, the coupling moiety being selected from the group consisting of a detectable label, a drug, or a combination thereof.
  8. 8. A pharmaceutical composition, characterized in that, the pharmaceutical composition comprises: (a) The anti-human MPC antibody or its antigen binding fragment of claim 1, the recombinant protein of claim 3, the polynucleotide of claim 4, the vector of claim 5, the host cell of claim 6, or the antibody drug conjugate of claim 7, and (B) A pharmaceutically acceptable carrier, diluent or excipient.
  9. 9. The use of an anti-human MPC antibody or antigen binding fragment thereof according to claim 1, a recombinant protein according to claim 3, a polynucleotide according to claim 4, a vector according to claim 5, or a host cell according to claim 6 for the preparation of reagents, assay plates, kits.
  10. 10. A method of detecting an MPC protein in a sample, said method comprising the steps of: (y 1) contacting the sample with the anti-human MPC antibody or antigen-binding fragment thereof of claim 1; (y 2) detecting whether an antigen-antibody complex is formed, wherein the presence of an MPC protein in the sample is indicated if an antigen-antibody complex is formed.

Description

Antibodies against human MPC or antigen binding fragments thereof and uses thereof Technical Field The invention belongs to the technical field of biology, in particular to the technical field of antibodies, and relates to an antibody or an antigen binding fragment thereof capable of binding human MPC, and a composition and application thereof. Background Mitochondrial pyruvate carrier (mitochondrial pyruvate CARRIER MPC), consisting of two heterodimeric membrane proteins (mitochondrial pyruvate carrier 1 (MPC 1, SLC54 A1) and mitochondrial pyruvate carrier 2 (MPC 2, SLC54 A2)), is a specific protein complex located within the mitochondrial membrane. MPCs are the only channels for transfer of pyruvate from the mitochondrial membrane stroma to the mitochondrial matrix. In the line granule, pyruvic acid is converted into acetyl-CoA under the action of the complex of pyruvic acid dehydrogenase. Acetyl-coa enters the tricarboxylic acid cycle (TCA cycle), and participates in substance metabolism and energy production. . Abnormal pyruvate metabolism due to dysfunctional MPCs is associated with cancer, heart failure and type II diabetes. In addition, the nervous system requires a large amount of energy to maintain its function, and thus the energy supply of mitochondria is closely related to the nerve function. Mitochondrial dysfunction can induce or exacerbate an intra-brain pathology. The MPC is an important target for treating related diseases, and the deep research on the functional structure and the regulation mechanism of the MPC not only reveals the action mechanism of the MPC in the related diseases, but also provides a more effective way for diagnosing and treating the related diseases. However, to date, the detection/labelling antibody libraries of existing MPC carrier proteins have been limited, and limited detection antibodies or detection methods have prevented MPC research progress. Therefore, there is a further need in the art to develop antibodies or antigen binding fragments thereof that bind MPC proteins with high specificity and affinity for further research in scientific research, diagnosis, detection, etc. Disclosure of Invention The invention aims to provide an antibody or antigen binding fragment thereof for resisting human MPC, and a composition and application thereof. In a first aspect of the invention there is provided an anti-human MPC antibody or antigen binding fragment thereof having three complementarity determining regions HCDR for the heavy chain variable region and three complementarity determining regions LCDR for the light chain variable region: (1) HCDR1 as shown in SEQ ID NO:59, HCDR2 as shown in SEQ ID NO. 60, HCDR3 as shown in SEQ ID NO. 61, LCDR1 as shown in SEQ ID NO. 63, LCDR2 as shown in SEQ ID NO. 64, and LCDR3 as shown in SEQ ID NO. 65; (2) HCDR1 as shown in SEQ ID NO. 69, HCDR2 as shown in SEQ ID NO. 70, HCDR3 as shown in SEQ ID NO:71, LCDR1 as shown in SEQ ID NO. 73, LCDR2 as shown in SEQ ID NO:74, and LCDR3 as shown in SEQ ID NO. 75. In another preferred embodiment, the antibody is a murine antibody, a chimeric antibody or a humanized antibody. In another preferred embodiment, the antigen binding fragment comprises a Fab fragment, a Fab '-SH, an Fv fragment, an scFv fragment, or a F (ab') 2 fragment. In another preferred embodiment, the heavy chain variable region and the light chain variable region of the anti-human MPC antibody or antigen binding fragment thereof are selected from the group consisting of: (a) A heavy chain variable region having an amino acid sequence shown as SEQ ID NO. 58 and a light chain variable region having an amino acid sequence shown as SEQ ID NO. 62, or (B) A heavy chain variable region having an amino acid sequence shown in SEQ ID NO. 68, and a light chain variable region having an amino acid sequence shown in SEQ ID NO. 72. In another preferred embodiment, the heavy chain of the antibody or antigen-binding fragment thereof further comprises a heavy chain constant region, and the light chain of the antibody or antigen-binding fragment thereof further comprises a light chain constant region. In another preferred embodiment, the antibody is a single chain antibody, a diabody, or an antigen-binding fragment. In another preferred embodiment, the heavy chain constant region is IgG1, igG2a, igG2b, or IgM. In another preferred embodiment, the constant regions of the heavy and light chains of the anti-human MPC antibody are the heavy and light chain constant region sequences of human IgG1, respectively. In another preferred embodiment, the constant regions of the heavy and light chains of the anti-human MPC antibody are the heavy and light chain constant region sequences of mouse IgG1, respectively. In another preferred embodiment, the heavy chain constant region is of human or murine origin. In another preferred embodiment, the light chain constant region is of human or murine origin. In another preferred embodiment, the antibody is an antibo