Procollagen I N-Terminal Propeptide-Specific Antibody, Kit and Use Thereof

Patent metadata

Field	Value
Publication number	US-2024360205-A1
Application number	US-202418648572-A
Country	US
Kind code	A1
Filing date	Apr 29, 2024
Priority date	Apr 28, 2023
Publication date	Oct 31, 2024
Grant date	—

Abstract

The present application relates to a PINP-specific antibody, kit and use thereof. Specifically, the present invention provides a PINP-specific antibody, as well as a kit containing the antibody, and use thereof in detecting the presence or level of tPINP in a sample.

First claim

What is claimed is:

1 . An antibody or antigen-binding fragment thereof that specifically binds to PINP (Procollagen I N-Terminal Propeptide) or different forms of existence thereof, comprising:
a heavy chain variable region comprising the following CDRs: CDR-H1 having an amino acid sequence selected from SEQ ID NO: 1, 7, 13, 19, 25, 31 and 37 or a variant thereof, CDR-H2 having an amino acid sequence selected from SEQ ID NO: 2, 8, 14, 20, 26, 32 and 38 or a variant thereof, or CDR-H3 having an amino acid sequence selected from SEQ ID NO: 3, 9, 15, 21, 27, 33 and 39 or a variant thereof; and a light chain variable region comprising following three CDRs: CDR-L1 having an amino acid sequence selected from SEQ ID NO: 4, 10, 16, 22, 28, 34 and 40 or a variant thereof, CDR-L2 having an amino acid sequence selected from SEQ ID NO: 5, 11, 17, 23, 29, 35 and 41 or a variant thereof, or CDR-L3 having an amino acid sequence selected from SEQ ID NO: 6, 12, 18, 24, 30, 36 and 42 or a variant thereof; wherein, each variant contains an amino acid mutation, the mutation is substitution, deletion or addition of one or more amino acids as compared to an amino acid sequence from which said variant is derived.

2 . The antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody or antigen-binding fragment thereof is selected from a group consisting of:
(1a) the heavy chain variable region comprises following three CDRs: CDR-H1 having an amino acid sequence of SEQ ID NO: 1 or a variant thereof, CDR-H2 having an amino acid of SEQ ID NO: 2 or a variant thereof, and CDR-H3 having an amino acid sequence of SEQ ID NO: 3 or a variant thereof; and the light chain variable region comprising the following three CDRs: CDR-L1 having an amino acid sequence of SEQ ID NO: 4 or a variant thereof, CDR-L2 having an amino acid sequence of SEQ ID NO: 5 or a variant thereof, and CDR-L3 having an amino acid sequence of SEQ ID NO: 6 or a variant thereof, (1b) the heavy chain variable region comprises following three CDRs: CDR-H1 having an amino acid sequence of SEQ ID NO: 7 or a variant thereof, CDR-H2 having an amino acid of SEQ ID NO: 8 or a variant thereof, and CDR-H3 having an amino acid sequence of SEQ ID NO: 9 or a variant thereof; and the light chain variable region comprises following three CDRs: CDR-L1 having an amino acid sequence of SEQ ID NO: 10 or a variant thereof, CDR-L2 having an amino acid sequence of SEQ ID NO: 11 or a variant thereof, and CDR-L3 having an amino acid sequence of SEQ ID NO: 12 or a variant thereof, (1c) the heavy chain variable region comprises the following three CDRs: CDR-H1 having an amino acid sequence of SEQ ID NO: 13 or a variant thereof, CDR-H2 having an amino acid of SEQ ID NO: 14 or a variant thereof, and CDR-H3 having an amino acid sequence of SEQ ID NO: 15 or a variant thereof; and the light chain variable region comprises following three CDRs: CDR-L1 having an amino acid sequence of SEQ ID NO: 16 or a variant thereof, CDR-L2 having an amino acid sequence of SEQ ID NO: 17 or a variant thereof, and CDR-L3 having an amino acid sequence of SEQ ID NO: 18 or a variant thereof; (1d) the heavy chain variable region comprises following three CDRs: CDR-H1 having an amino acid sequence of SEQ ID NO: 19 or a variant thereof, CDR-H2 having an amino acid of SEQ ID NO: 20 or a variant thereof, and CDR-H3 having an amino acid sequence of SEQ ID NO: 21 or a variant thereof; and the light chain variable region comprises following three CDRs: CDR-L1 having an amino acid sequence of SEQ ID NO: 22 or a variant thereof, CDR-L2 having an amino acid sequence of SEQ ID NO: 23 or a variant thereof, and CDR-L3 having an amino acid sequence of SEQ ID NO: 24 or a variant thereof, (1c) the heavy chain variable region comprises three CDRs: CDR-H1 having an amino acid sequence of SEQ ID NO: 25 or a variant thereof, CDR-H2 having an amino acid of SEQ ID NO: 26 or a variant thereof, and CDR-H3 having an amino acid sequence of SEQ ID NO: 27 or a variant thereof; and the light chain variable region comprises three CDRs: CDR-L1 having an amino acid sequence of SEQ ID NO: 28 or a variant thereof, CDR-L2 having an amino acid sequence of SEQ ID NO: 29 or a variant thereof, and CDR-L3 having an amino acid sequence of SEQ ID NO: 30 or a variant thereof; (1f) the heavy chain variable region comprises following three CDRs: CDR-H1 having an amino acid sequence of SEQ ID NO: 31 or a variant thereof, CDR-H2 having an amino acid of SEQ ID NO: 32 or a variant thereof, and CDR-H3 having an amino acid sequence of SEQ ID NO: 33 or a variant thereof; and the light chain variable region comprises following three CDRs: CDR-L1 having an amino acid sequence of SEQ ID NO: 34 or a variant thereof, CDR-L2 having an amino acid sequence of SEQ ID NO: 35 or a variant thereof, and CDR-L3 having an amino acid sequence of SEQ ID NO: 36 or a variant thereof; and (1g) the heavy chain variable region comprises following three CDRs: CDR-H1 having an amino acid sequence of SEQ ID NO: 37 or a variant thereof, CDR-H2 having an amino acid of SEQ ID NO: 38 or a variant thereof, and CDR-H3 having an amino acid sequence of SEQ ID NO: 39 or a variant thereof; and the light chain variable region comprises following three CDRs: CDR-L1 having an amino acid sequence of SEQ ID NO: 40 or a variant thereof, CDR-L2 having an amino acid sequence of SEQ ID NO: 41 or a variant thereof, and CDR-L3 having an amino acid sequence of SEQ ID NO: 42 or a variant thereof.

3 . The antibody or antigen-binding fragment thereof according to claim 1 , further comprising a heavy chain constant region (CH) and a light chain constant region (CL), the heavy chain constant region (CH) is selected from a group consisting of a mouse heavy chain constant region, a human heavy chain constant region, and an IgG heavy chain constant region; the light chain constant region (CL) is selected from a group consisting of a mouse light chain constant region, a human light chain constant region, a k light chain constant region and a λ light chain constant region.

4 . The antibody or antigen-binding fragment thereof according to claim 1 , wherein, the antigen-binding fragment thereof is selected from scFv, Fab, Fab′, (Fab′) 2, Fv fragment, disulfide bond-linked Fv (dsFv), diabody, bispecific antibody and multi-specific antibody; or, the antibody is a murine antibody, chimeric antibody or humanized antibody.

5 . The antibody or antigen-binding fragment thereof according to claim 1 , further comprising a detectable label,
wherein the label is selected from the group consisting of fluorescein, chemiluminescence, enzyme, radioisotope, biotin, colloidal gold, and magnetic particles.

6 . An isolated nucleic acid molecule, which encodes the antibody or antigen-binding fragment thereof according to claim 1 .

7 . An expression vector, comprising the isolated nucleic acid molecule according to claim 1 ,
wherein the vector is a plasmid, a virus, a bacteriophage, a bacterium or a viroid.

8 . A PINP detection kit, comprising a detection sensitivity of ≤0.3 ng/ml for tPINP (total Procollagen I N-Terminal Propeptide).

9 . A PINP detection kit, wherein the PINP detection kit has a detection range of 0.3-2000 ng/ml for tPINP.

10 . A composition or PINP detection kit, comprising the antibody or antigen-binding fragment thereof, wherein the composition or PINP detection kit comprises:
a first antibody, which is selected from the antibody or antigen-binding fragment thereof according to claim 1 ; and, a second antibody, which is selected from the antibody or antigen-binding fragment thereof according to claim 1 , wherein, the first antibody and the second antibody respectively target different epitopes o

Assignees

• Shenzhen Mindray Biomedical Electronics Co Ltd
• Hytest Ltd

Inventors

• Filatov Vladimir L
• Datskevich Petr N
• Kokisheva Antonina S
• Katrukha Alexey G
• Kozlovsky Stanislav V
• Postnikov Alexander B
• Rozov Fedor N
• Tang Tao
• Zhan Chengxiong
• Wu Lingjia
• Zhu Shibo
• Li Ke
• Wu Yue

Classifications

• G01N2800/10

  Musculoskeletal or connective tissue disorders · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• G01N2333/78

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG] · CPC title

• G01N33/6893

  related to diseases not provided for elsewhere · CPC title