Anti-human serum albumin single-chain antibody and method for connecting polypeptide medicine with nitrogen terminal of antibody

Abstract

The invention discloses an anti-human serum albumin single-chain antibody and a method for connecting polypeptide medicine with the nitrogen terminal of the antibody. A VL chain region has a complementary identification region (CDR) which has the following amino acid sequences of CDRs: N-SEQ-08 of CDR1, N-SEQ-09 of CDR2 and N-SEQ-010 of CDR3; a VH chain region has a complementary identification region which has the following amino acid sequences of CDRs: N-SEQ-05 of CDR1, N-SEQ-06 of CDR2 and N-SEQ-07 of CDR3; the VH chain takes the amino acid sequence shown as N-SEQ-02 as an expression form; the VH chain takes the amino acid sequence shown as N-SEQ-04 as an expression form; and the VH chain region and the VL chain region are connected through a protein hinge shown as N-SEQ-01 or N-SEQ-03. The single-chain antibody has small molecular weight, strong specificity, weak immunogenicity and high water solubility and is easily produced on a large scale in a fermentation mode. The invention also discloses a composition prepared from the single-chain antibody; and the medicine can effectively prolong the half-life period of polypeptide biological medicines.

Description

technical field [0001] The present invention relates to a single-chain antibody, in particular to an anti-human serum albumin single-chain antibody and a method for connecting polypeptide drugs to its nitrogen end. Background technique [0002] At present, peptide-based biopharmaceuticals are rapidly being promoted around the world. [0003] Peptide biopharmaceuticals have remarkable effects and can treat many genetic diseases that compound drugs cannot be effective. However, one of the biggest problems in the use of peptide biological drugs is that the attenuation period of such drugs in the human body is generally short, resulting in a relatively high frequency of drug use. Bring larger treatment cost and medication pain to patient. Therefore, prolonging the half-life of polypeptide biopharmaceuticals has become an urgent issue in the field of biopharmaceuticals. [0004] The current methods for prolonging the half-life of polypeptide biopharmaceuticals mainly include c...

AI Technical Summary

Problems solved by technology

The construction of mutants can usually reduce the sensitivity of polypeptides to hydrolytic enzymes and effectively prolong the half-life of polypeptide biopharmaceuticals. However, many mutants with longer half-lives will change the activity of drugs. To obtain a mutant that can meet the half-life requirements and at the same time Mutants that do not alter drug activity are difficult

Therefore, this technology is not suitable for widespread application in the field of protein drugs. PEGylation can improve the stability of protein drugs and reduce their immunogenicity, but it has the potential to affect the biological activity of polypeptide biopharmaceuticals. It is difficult to purify peptide biopharmaceuticals after PEGylation, which increases the difficulty and production cost in the production process

Direct fusion with human proteins with longer half-life is a feasible and effective method to extend the half-life of drugs, but this fusion method greatly increases the molecular weight of polypeptide biopharmaceuticals, which brings many problems to production and purification. Molecular weight The increase of the drug will also change some pharmacokinetic properties of the drug, which may make it difficult to reach the target position, thereby affecting the efficacy of the drug

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