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CN-121991222-A - Antibody against SLC25A20 or antigen binding fragment thereof, and composition and application thereof

CN121991222ACN 121991222 ACN121991222 ACN 121991222ACN-121991222-A

Abstract

The present invention provides antibodies or antigen binding fragments thereof directed against SLC25a20 and compositions and uses thereof. In particular, an anti-SLC 25a20 antibody or antigen-binding fragment thereof is provided that is capable of efficiently binding to human SLC25a20 transmembrane protein. The invention also provides antibody drug conjugates containing the antibody or antigen binding fragment, and the like, which can be applied to the preparation of drugs for treating diseases of over-expressed SLC25A20 and have good application prospects.

Inventors

  • TONG PEI
  • LIU TAO
  • YANG JIPING
  • QIAN HONGWU

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-SLC 25a20 antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof has three complementarity determining region CDRs (HCDR) of a heavy chain variable region and three complementarity determining region CDRs (LCDR) of a light chain variable region selected from the group consisting of: (1) HCDR1 shown in SEQ ID NO. 57, HCDR2 shown in SEQ ID NO. 58, HCDR3 shown in SEQ ID NO 59, LCDR1 shown in SEQ ID NO. 61, LCDR2 as shown in SEQ ID NO. 62, LCDR3 as shown in SEQ ID NO. 63; (2) HCDR1 shown in SEQ ID NO. 67, HCDR2 shown in SEQ ID NO. 68, HCDR3 shown in SEQ ID NO. 69, LCDR1 shown in SEQ ID NO. 71, LCDR2 as shown in SEQ ID NO. 72, LCDR3 as shown in SEQ ID NO. 73.
  2. 2. The antibody or antigen-binding fragment thereof of claim 1, wherein the heavy chain variable region and the light chain variable region of the anti-SLC 25a20 antibody or antigen-binding fragment thereof are selected from the group consisting of: (a) A heavy chain variable region with an amino acid sequence shown as SEQ ID NO. 56, and a light chain variable region with an amino acid sequence shown as SEQ ID NO. 60; (b) A heavy chain variable region having an amino acid sequence shown as SEQ ID NO. 66, and a light chain variable region having an amino acid sequence shown as SEQ ID NO. 70.
  3. 3. A recombinant protein, wherein the recombinant protein has: (i) The anti-SLC 25A20 antibody or antigen-binding fragment thereof of claim 1, and (Ii) Optionally a tag sequence that facilitates expression and/or purification.
  4. 4. A nucleic acid molecule encoding the antibody or antigen-binding fragment thereof of claim 1.
  5. 5. A vector comprising the nucleic acid molecule of claim 4.
  6. 6. A host cell comprising the vector of claim 5 or having the nucleic acid molecule of claim 4 integrated into the genome.
  7. 7. An antibody drug conjugate, which is characterized in that, the antibody drug conjugate comprises: (a) An antibody moiety comprising the anti-SLC 25A20 antibody or antigen-binding fragment thereof of claim 1, and (B) A coupling moiety coupled to the antibody or antigen binding fragment thereof, the coupling moiety selected from the group consisting of a detectable label, a drug, or a combination thereof.
  8. 8. Use of the antibody or antigen binding fragment thereof of claim 1, the recombinant protein of claim 3, the antibody drug conjugate of claim 7 for the preparation of a reagent, assay plate or kit; the reagent, the detection plate or the kit is used for detecting SLC25A20 protein in a sample.
  9. 9. A method of making the anti-SLC 25a20 antibody or antigen-binding fragment thereof of claim 1, said method comprising the steps of: (a) Culturing the host cell of claim 6 under expression conditions to express said anti-SLC 25a20 antibody or antigen-binding fragment thereof; (b) Isolating and purifying the anti-SLC 25a20 antibody or antigen-binding fragment thereof of (a).
  10. 10. A method for detecting SLC25a20 protein in a sample, said method comprising the steps of: (S1) contacting the sample with the antibody or antigen-binding fragment thereof of claim 1; (S2) detecting whether an antigen-antibody complex is formed, wherein the formation of the complex indicates the presence of SLC25A20 protein in the sample.

Description

Antibody against SLC25A20 or antigen binding fragment thereof, and composition and application thereof Technical Field The invention belongs to the technical field of biology, and particularly relates to an antibody or an antigen binding fragment thereof for resisting SLC25A20, and a composition and application thereof. Background SLC25a20 (Solute CARRIER FAMILY membrane 20), also known as mitochondrial carnitine/acyl carnitine carrier Protein (CAC, CARNITINE/ACYLCARNITINE CARRIER Protein), is a key participant in the mitochondrial oxidative pathway, a multiple transmembrane Protein located on the inner membrane of the line granulocytes. In humans, SLC25A20 deficiency is a disorder of fatty acid oxidation, which on the one hand leads to the inability of long chain fatty acids to transport into mitochondria and thus to conversion into energy, accompanied by symptoms such as low ketogenic hypoglycemia, and on the other hand, fatty acids and long chain acyl carnitines accumulate in cells to damage the liver, heart and muscle, accompanied by symptoms such as liver problems, cardiomyopathy, cardiac arrhythmias, skeletal muscle injuries, etc. SLC25a20 acts as an important transporter on the mitochondrial membrane and plays a key role in regulating intracellular fatty acid metabolism and energy production. The deep research on the functional structure and the regulation mechanism of the fatty acid can better understand the physiological process of fatty acid metabolism and provide theoretical basis for the treatment and prevention of related metabolic diseases. However, the limited pool of detection/labelling antibodies for the existing SLC25a20 transporter has prevented the development of SLC25a20 research to date. Therefore, there is a need in the art to develop binding antibodies with high specificity and affinity for further research of SLC25a20 protein in scientific research, diagnosis, detection, and other techniques. Disclosure of Invention The present invention provides antibodies or antigen binding fragments thereof directed against SLC25a20 and compositions and uses thereof. In a first aspect of the invention, there is provided an anti-SLC 25a20 antibody or antigen-binding fragment thereof having three complementarity determining region CDRs (HCDR) of a heavy chain variable region and three complementarity determining region CDRs (LCDR) of a light chain variable region selected from the group consisting of: (1) HCDR1 shown in SEQ ID NO. 57, HCDR2 shown in SEQ ID NO. 58, HCDR3 shown in SEQ ID NO 59, LCDR1 shown in SEQ ID NO. 61, LCDR2 as shown in SEQ ID NO. 62, LCDR3 as shown in SEQ ID NO. 63; (2) HCDR1 shown in SEQ ID NO. 67, HCDR2 shown in SEQ ID NO. 68, HCDR3 shown in SEQ ID NO. 69, LCDR1 shown in SEQ ID NO. 71, LCDR2 as shown in SEQ ID NO. 72, LCDR3 as shown in SEQ ID NO. 73. 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 F (ab') 2 fragment, or an Fv fragment. In another preferred embodiment, the heavy and light chain variable regions of the anti-SLC 25a20 antibody or antigen-binding fragment thereof are selected from the group consisting of: (a) A heavy chain variable region with an amino acid sequence shown as SEQ ID NO. 56, and a light chain variable region with an amino acid sequence shown as SEQ ID NO. 60; (b) A heavy chain variable region having an amino acid sequence shown as SEQ ID NO. 66, and a light chain variable region having an amino acid sequence shown as SEQ ID NO. 70. 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 antibody is a humanized antibody, a murine antibody, or a chimeric antibody. 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 antibody full-length protein, or an antigen-binding fragment. In another preferred embodiment, the antibody is a monoclonal antibody. In another preferred embodiment, the antibody is a partially or fully humanized monoclonal antibody. In another preferred embodiment, the antibody further comprises a connecting peptide between the heavy chain variable region and the light chain variable region. In a second aspect of the present invention, there is provided a recombinant protein having: (i) An anti-SLC 25A20 antibody or antigen-binding fragment thereof according to the first aspect of the invention, and (Ii) Optionally a tag sequence that fa