Aldosterone antigen binding molecules and uses thereof

Abstract

The invention provides an aldosterone antigen binding molecule and application thereof, and relates to the technical field of biology. The aldosterone antigen binding molecule is selected from a first antigen binding molecule containing CDR sequences as shown in SEQ ID NO.1 and SEQ ID NO.2 or a second antigen binding molecule containing CDR sequences as shown in SEQ ID NO.3 and SEQ ID NO.4. The aldosterone antigen binding molecule can bind an aldosterone antigen, and can be used for a method or a product for detecting aldosterone based on an immunological principle; the first antigen binding molecule and the second antigen binding molecule can also form an immune complex with a double-antibody sandwich structure with aldosterone, so that aldosterone is detected by a double-antibody sandwich principle.

Claims

1. An aldosterone antigen-binding molecule, characterized in that The antigen-binding molecule comprises the complementarity determining regions HCDR1, HCDR2 and HCDR3 of the heavy chain variable region, and the complementarity determining regions LCDR1, LCDR2 and LCDR3 of the light chain variable region; the antigen-binding molecule is selected from the first antigen-binding molecule or the second antigen-binding molecule; First antigen-binding molecule: HCDR1, HCDR2, and HCDR3 of the first antigen-binding molecule comprise amino acid sequences identical to HCDR1, HCDR2, and HCDR3 of the heavy chain variable region set forth in SEQ ID NO. 1; LCDR1, LCDR2, and LCDR3 comprise amino acid sequences identical to LCDR1, LCDR2, and LCDR3 of the light chain variable region set forth in SEQ ID NO. 2; Second antigen-binding molecule: The HCDR1, HCDR2 and HCDR3 of the second antigen-binding molecule include amino acid sequences consistent with HCDR1, HCDR2 and HCDR3 of the heavy chain variable region shown in SEQ ID NO.3; the LCDR1, LCDR2 and LCDR3 include amino acid sequences consistent with LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO.

4.

2. The aldosterone antigen-binding molecule according to claim 1, wherein The HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 or LCDR3 of the aldosterone antigen binding molecule is defined by any one of the Kabat, Chothia, IMGT, ABM or Contact systems or a combination of multiple definition systems; Optionally, the first antigen-binding molecule is defined in accordance with IMGT: the amino acid sequence of the HCDR1 is shown in SEQ ID NO.13, the amino acid sequence of the HCDR2 is shown in SEQ ID NO.18, and the amino acid sequence of the HCDR3 is shown in SEQ ID NO.21; the amino acid sequence of the LCDR1 is shown in SEQ ID NO.24, the amino acid sequence of the LCDR2 is KIF, and the amino acid sequence of the LCDR3 is shown in SEQ ID NO.27; Alternatively, the second antigen-binding molecule is defined according to IMGT: the amino acid sequence of the HCDR1 is shown in SEQ ID NO.33, the amino acid sequence of the HCDR2 is shown in SEQ ID NO.38, and the amino acid sequence of the HCDR3 is shown in SEQ ID NO.41; the amino acid sequence of the LCDR1 is shown in SEQ ID NO.44, the amino acid sequence of the LCDR2 is YDS, and the amino acid sequence of the LCDR3 is shown in SEQ ID NO.

47.

3. The aldosterone antigen-binding molecule according to claim 1 or 2, characterized in that The aldosterone antigen binding molecule is an antibody or antigen binding fragment; Optionally, the antigen-binding molecule, excluding the CDR region, may have its remaining sequences derived from species selected from rabbit, cattle, horse, dairy cow, pig, sheep, goat, rat, mouse, dog, cat, camel, donkey, deer, mink, chicken, duck, goose, turkey, fighting cock, human, and mutants thereof. Optionally, the aldosterone antigen binding molecule contains at least one framework region of a heavy chain variable region, and / or contains at least one framework region of a light chain variable region; Optionally, at least one framework region of the heavy chain variable region comprises an amino acid sequence consistent with the framework region of the heavy chain variable region shown in SEQ ID NO. 1 or 3; Optionally, at least one framework region of the light chain variable region comprises an amino acid sequence consistent with the framework region of the light chain variable region shown in SEQ ID NO. 2 or 4; Optionally, the first antigen-binding molecule has an amino acid sequence as shown in SEQ ID NO.1 or a heavy chain variable region having at least 80% sequence identity with the amino acid sequence as shown in SEQ ID NO.1; and / or, the first antigen-binding molecule has an amino acid sequence as shown in SEQ ID NO.2 or a light chain variable region having at least 80% sequence identity with the amino acid sequence as shown in SEQ ID NO.2; Optionally, the second antigen-binding molecule has an amino acid sequence as shown in SEQ ID NO.3 or a heavy chain variable region having at least 80% sequence identity with the amino acid sequence as shown in SEQ ID NO.3; and / or, the second antigen-binding molecule has an amino acid sequence as shown in SEQ ID NO.4 or a light chain variable region having at least 80% sequence identity with the amino acid sequence as shown in SEQ ID NO.

4.

4. The antigen-binding molecule according to claim 3, wherein The antigen-binding molecules include F(ab')2, Fab', Fab, Fv, scFv, dsFv, bispecific antibodies, domain antibodies or antigen-binding fragments composed of one or more of them; Optionally, the antigen binding molecule further comprises part or all of a constant region; Optionally, the constant region sequence is selected from the sequence of a partial or complete constant region of any one of IgG, IgA, IgM, IgE or IgD.

5. Biomaterial, characterized in that The biological material is selected from any one of (i) to (iii): (i) a polynucleotide comprising a nucleotide sequence encoding the aldosterone antigen-binding molecule according to any one of claims 1 to 4; (ii) a vector carrying the polynucleotide described in (i). (iii) a cell, wherein the cell carries the polynucleotide described in (i), or contains the vector described in (ii), or expresses the aldosterone antigen-binding molecule; Optionally, the polynucleotide contains a fragment of a nucleotide sequence as shown in at least one of SEQ ID NOs. 5 to 8.

6. A modified aldosterone antigen-binding molecule, characterized in that The aldosterone antigen-binding molecule according to any one of claims 1 to 4 is modified with a modified substance.

7. An aldosterone antigen-binding molecule composition, characterized in that: Comprising: the first antigen-binding molecule according to any one of claims 1 to 4 and the second antigen-binding molecule according to any one of claims 1 to 4.

8. Use of the aldosterone antigen-binding molecule according to any one of claims 1 to 4, or the biomaterial according to claim 5, or the modified aldosterone antigen-binding molecule according to claim 6, or the aldosterone antigen-binding molecule composition according to claim 7 in any one of (I) to (VI): (I) Aldosterone testing for non-diagnostic and non-treatment purposes; (II) preparing products for detecting aldosterone; (III) Preparation of products for the diagnosis of at least one of aldosteronism, endocrine hypertension, hyperkalemia, and hyperchloremic metabolic acidosis; (IV) Reducing the aldosterone level of subjects for non-diagnostic and non-therapeutic purposes; (V) preparing aldosterone blockers; (VI) preparing a medicament for treating at least one of aldosteronism, endocrine hypertension, hyperkalemia and hyperchloremic metabolic acidosis.

9. A kit for detecting aldosterone, characterized in that: Comprising the aldosterone antigen-binding molecule according to any one of claims 1 to 4, or the modified aldosterone antigen-binding molecule according to claim 6, or the aldosterone antigen-binding molecule composition according to claim 7; Optionally, the kit is for immunoassay and comprises reagents for immunoassay; Optionally, the immunoassay comprises chemiluminescence assay, immunochromatographic assay, ELISA assay, immunomagnetic particle assay, immunofluorescence assay or immunoblot assay; Optionally, in the immunoassay, the first antigen binding molecule is used to capture aldosterone to form a first antigen binding molecule-aldosterone immune complex, and the second antigen binding molecule is used to bind to the first antigen binding molecule-aldosterone immune complex.

10. A pharmaceutical composition, characterized in that A pharmaceutical composition comprising the aldosterone antigen-binding molecule according to any one of claims 1 to 4, or the biomaterial according to claim 5, or the modified aldosterone antigen-binding molecule according to claim 6; the pharmaceutical composition further comprising a pharmaceutical excipient; Optionally, the pharmaceutical composition comprises the first antigen binding molecule.

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