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Anti-ST2 antibody and use thereof

An antibody and L-CDR2 technology, applied in the direction of antibodies, applications, anti-inflammatory agents, etc., can solve the problems of differences in clinical efficacy, dosage, and biological activity of antibodies

Pending Publication Date: 2021-08-06
MABWELL (SHANGHAI) BIOSCIENCE CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the antibodies reported so far can all block the interaction between ST2 and the ligand, the biological activities produced are different
The difference in biological activity may lead to differences in the clinical efficacy and dosage of antibodies, so there is still a need in this field to provide ST2 antibodies with high affinity, high stability, and high biological activity

Method used

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  • Anti-ST2 antibody and use thereof
  • Anti-ST2 antibody and use thereof
  • Anti-ST2 antibody and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0215] Example 1: Murine Antibody Screening

[0216] 1.1 Animal immunity

[0217] CHO-K1 cells were used to express Human ST2-his, and then 6 BALB / c mice were immunized according to the routine Freund's adjuvant immunization procedure. The immunization was carried out in two batches, 3 mice in each batch, with an interval of two weeks between the two batches. Each batch of mice was immunized 4 times, and the Human ST2-his was used for ELISA detection. If the mouse serum titer was >1:100,000, the final immunization was performed, and the spleen was collected 3-4 days later.

[0218] 1.2B cell panning and culture

[0219] 2 days before the formal experiment, the feeder cells were spread into four 10cm culture dishes (Corning, cat. 430167), and the feeder cells were treated with 25 μg / mL MMC for 6 hours 1 day before the formal experiment, and then 10000 cells / The wells of a 96-well plate (Corning, cat.3599) were paved, 100 μL / well; at the same time, a 6-well plate was used ...

Embodiment 2

[0229] Example 2: Antibody engineering

[0230] 2.1 B cell sequencing

[0231] Follow PureLink TM The RNA Mini Kit manual extracts the mRNA of B cell clones, and stores in -80°C in aliquots; the extracted mRNA is used as a template using PrimeScript TM II 1st Strand cDNA Synthesis Kit protocol reverse transcribed into cDNA, and stored in -80 ℃.

[0232] Use the heavy chain VH fishing primers and light chain VL fishing primers shown in Table 1-1 and Table 1-2, use the above cDNA as a template, use Ex Taq enzyme to amplify VH and VL, and then connect to pMD18T vector for sequencing .

[0233] Table 1-1 Heavy chain VH fishing primers

[0234]

[0235]

[0236] Table 1-2 Light chain VL fishing primers

[0237]

[0238]

[0239] 2.2 Recombinant expression and screening of mouse antibody

[0240] (1) Mouse anti-recombinant expression

[0241] will come from the same clone (eg Figure 1 to Figure 5 The light and heavy chains shown in ) were combined to transfect ...

Embodiment 3

[0369] Example 3 Antibody Mouse PK

[0370] After the adaptation period, 20 mice were randomly divided into 4 groups, 5 in each group, and the administration information is shown in Table 31.

[0371] Table 31 Administration information of mice in each group

[0372] Antibody Method of administration Dosing volume A 5888-116-H0L1 5mg / kg i.p. 0.1mL / 10g B 5888-153-H0L1 5mg / kg i.p. 0.1mL / 10g C CNTO7160 5mg / kg i.p. 0.1mL / 10g D 5886-156-H1L0 5mg / kg i.p. 0.1mL / 10g

[0373] Drugs were administered according to the groups, and the time of administration was recorded. Each group of mice before administration (0hr) and after administration 4hr, 8hr, 24hr(1d), 72hr(3d), 120hr(5d), 168hr(7d), 240hr(10d), 288hr(12d), 336hr (14d) Blood was collected separately, and serum was collected and stored at -60 to -80°C.

[0374]The detection method of PK blood drug concentration in mice is as follows:

[0375] (1) Coating: Human ST2-...

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PUM

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Abstract

The invention provides an ST2-binding antibody or a fragment thereof. The antibody or a fragment thereof can specifically bind to human ST2, inhibit binding of IL-33 and the human ST2, block an IL-33 / ST2 intracellular signal pathway, and inhibit a promotion effect of different forms of IL-33 on generation of cells IL5, IL6 and IL8, and has higher biological activity compared with a known anti-ST2 antibody. The antibody can be used for preventing, treating or relieving diseases related to ST2 expression or IL-33 / ST2 pathway disorder.

Description

technical field [0001] The invention relates to the field of antibody medicine, in particular, the invention relates to an antibody against human ST2 and its use for preparing medicine. Background technique [0002] Interleukin 33 (IL-33) is a cytokine related to IL-1 and IL-18, also known as NF-HEV or IL-1F11. ST2 (ST2L, IL-1RL1, T1, Fit-1, DER-4, IL-1R4, or ST2α) is a binding receptor for IL-33, which is a member of the Toll / IL-1 receptor family and is present in many Expressed on the cell surface of immune cells, including lymphocytes, especially helper T cells that express IL-5 and IL-13, natural killer (NK) and natural killer-T (NKT) cells, and many so-called innate immune cells , such as mast cells, basophils, eosinophils, macrophages, and innate helper cells (aka nuocytes (Neill, Wong et al., 2010)). [0003] ST2 is able to downregulate the responsiveness of the Toll-like receptors TLR2, TLR4 and TLR9, but also induces type 2 cytokine release through activation by i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C12N15/13A61K39/395A61P29/00A61P37/02A61P9/04A61P11/02A61P11/00A61P11/06A61P31/00A61P1/00A61P19/02A61P25/00A61P1/12
CPCC07K16/2866A61P29/00A61P37/02A61P9/04A61P11/02A61P11/00A61P11/06A61P31/00A61P1/00A61P19/02A61P25/00A61P1/12C07K2317/92C07K2317/76C07K2317/33C07K2317/24C07K2317/56A61K2039/505C07K2319/00C07K2317/94A61P37/00G01N33/6893C07K2317/565
Inventor 熊新辉张弢仲恺吴伟黄倩卉李醒潘红
Owner MABWELL (SHANGHAI) BIOSCIENCE CO LTD
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