Anti-bFGF humanized double-stranded antibody with stable disulfide bond, preparation method and application thereof

US9273131B2 · kind B2 · utility

Assignee

• JINAN UNIVERSITY · CN

Inventors

• Ning Deng · Cambridge, US
• Haowu Jiang · 流花街道, CN
• Zhongkui Kang · 流花街道, CN
• Hong Wang · Beijing, CN
• Qifang Song · 流花街道, CN

Key dates

• Filing date: Aug 20, 2012
• Grant date: Mar 1, 2016
• Expiry date: Aug 20, 2032

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2317/94
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed are an anti-bFGF humanized double-stranded antibody with stable disulfide bond, the preparation method and the applications thereof. The amino acid sequence of the anti-bFGF humanized ds-Diabody is shown in SEQ ID NO.1. The nucleotide sequence of gene encoding the anti-bFGF humanized ds-Diabody is shown in SEQ ID NO.2. By site-directed mutation, two cysteine residues are introduced into VL and VH domain of anti-bFGF Diabody, thus introducing the disulfide bond and form ds-Diabody. It is shown by experiments that the obtained ds-Diabody has the following advantages: enhanced stability; better affinity when binding to the specific antigen bFGF; moderate relative molecular weight, good tumor targeting, more powerful in tumor tissue penetration, and higher blood clearance rate, showing a broad application prospects in the clinic diagnosis and tumor therapy.