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Single domain antibodies binding to tetanus neurotoxin

A technology of neurotoxin and single-domain antibody, which is applied in anti-bacterial immunoglobulin, anti-vector-borne diseases, anti-animal/human immunoglobulin, etc., and can solve the problems of poor production feasibility, high cost, and low affinity

Pending Publication Date: 2020-12-25
SMIVET BV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] On top of that, there is the problem of poor production feasibility: the production of larger proteins is sometimes problematic and expensive anyway
[0017] But so far, the KD of anti-TeNT SDA does exceed 1-10nM, and even exceeds 35nM, indicating a lower affinity

Method used

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  • Single domain antibodies binding to tetanus neurotoxin
  • Single domain antibodies binding to tetanus neurotoxin
  • Single domain antibodies binding to tetanus neurotoxin

Examples

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Embodiment 3

[0234] Fourteen SVT SDAs (Table 2), eight SVG SDAs (Table 3) and six SVASDAs (Table 4) were produced by secretory yeast expression. For this purpose, the SDA coding region was amplified by PCR from phage display plasmids (Examples 3-5) and cut with PstI and BstEII for ligation with a similarly cut pUR4585 plasmid. pUR4585 is a yeast-E. coli shuttle vector suitable for expression of SDA fused to the C-terminus of C-myc and his6 tags. SDA generated in this way is indicated by the suffix "L". PUR4585-derived plasmids encoding such SDAs are indicated by the SDA name and the prefix "p" in addition to the suffix "L". In addition, three mutant SVT SDAs were generated with mutations in the FR4 region to increase production levels in yeast (see Example 3 and [11]):

[0235] SDA SVT15L-3FW4M is a derivative of SVT15L containing mutations K120Q, I122T and L123Q

[0236] SDA SVT20L-L123Q is a derivative of SVT20L containing the mutation L123Q

[0237] SDA SVT34L-L123Q is a derivative ...

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Abstract

The present invention relates to single domain antibodies (SDAs) that are capable of binding to tetanus neurotoxin. The invention further relates to polypeptide constructs comprising such an SDA as well as an SDA that is capable of binding to a serum protein, preferably to serum albumin or immunoglobulin. The invention also relates to nucleic acids encoding such SDAs or polypeptide constructs, topharmaceutical compositions comprising such SDAs or polypeptide constructs, the medical use thereof and to their use in the treatment of tetanus.

Description

technical field [0001] The present invention relates to single domain antibodies (SDA) capable of binding to tetanus neurotoxin, polypeptide constructs comprising such SDAs, compositions comprising such SDAs and / or polypeptide constructs and to encoding such SDAs and / or DNA fragments of polypeptide constructs. In addition, the present invention relates to host cells comprising such DNA fragments, methods for producing such SDA and / or polypeptide constructs, and such SDA and / or polypeptide constructs and / or compositions infecting Clostridium tetani Use in disease treatment or prevention. Background technique [0002] Tetanus, a disease caused by the bacterium Clostridium tetani, was first described in Egypt about 3,000 years ago. [0003] Tetanus toxemia is caused by a specific neurotoxin; Tetanus Neurotoxin (TeNT) produced by Clostridium tetani. Almost all mammals, including humans, are susceptible. Of all species, especially humans, horses and lambs are the most sensiti...

Claims

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Application Information

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IPC IPC(8): C07K16/12
CPCC07K16/1282C07K16/18C07K16/4241C07K2317/22C07K2317/31C07K2317/569C07K2317/76C07K16/4283C07K2317/33C07K2317/35C07K2317/92C07K2317/94
Inventor A·J·德·斯米特M·M·哈姆森
Owner SMIVET BV
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