Designed ankyrin repeat domains with improved stability

By designing an ankyrin repeating domain with specific amino acid sequence variations, the instability of serum albumin-binding specific proteins was addressed, improving stability during storage and at high temperatures, making it suitable for the purification and storage of recombinant binding proteins.

CN114206908BActive Publication Date: 2025-12-23MOLECULAR PARTNERS AG
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Patent Information

Application Number
CN202080055757.4
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2019-06-04
Filing Date
2020-06-03
Publication Date
2025-12-23
Estimated Expiration
2040-06-03

AI Technical Summary

Technical Problem

Existing ankyrin repeat domains with specific binding to serum albumin have shortcomings in stability, especially in storage stability and high-temperature stability, which affects the purification and storage of recombinant binding proteins.

Method used

An ankyrin repeating domain with binding specificity to serum albumin was designed, containing specific amino acid sequence variations, such as the deletion of asparagine or glutamic acid at position 77 or 78, which improves the stability of the domain. Specific amino acid sequences include KDFAGKTPLHLAAX1X2G or KDFAGKTPLHLAADAG, where X1 and X2 can be A or D, and the N-terminus can contain G, S or GS.

Benefits of technology

It improves the storage stability of the ankyrin repeat domain in liquid formulations and its stability under high-temperature heat treatment, reduces the generation of assumed degradation products, maintains the binding specificity to serum albumin, and is suitable for the purification and storage of recombinant binding proteins.

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Abstract

The present invention relates to designed ankyrin repeat domains with binding specificity for serum albumin, and in particular to such designed ankyrin repeat domains with improved stability. The invention further relates to recombinant binding proteins comprising such designed ankyrin repeat domains, nucleic acids encoding such designed ankyrin repeat domains or proteins, pharmaceutical compositions comprising such proteins, and the use of such proteins or pharmaceutical compositions in the treatment of diseases.
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