Collection of HCDR3 regions and uses therefor

US8273688B2 · kind B2 · utility

Assignee

• MORPHOSYS AG · DE

Inventors

• Markus Enzelberger · Gräfelfing, DE
• Stefanie Thiel · Birkenfeld, DE
• Josef Prassler · Germering, DE
• Stefanie Urlinger · Munich, DE
• Christine Rothe · Dachau, DE

Key dates

• Filing date: Dec 15, 2006
• Grant date: Sep 25, 2012
• Expiry date: Feb 15, 2028

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2317/565
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

The present invention is directed to the preparation and use of a collection of antibody heavy chain complementarity determining region 3 (HCDR3) members, where diversity of the collection is a function of the length of the HCDR3 members. The diversity of the collection of HCDR3 regions substantially represents the natural amino acid distribution of HCDR3 in the human repertoire. This natural amino acid distribution can be represented by biasing the complete random distribution of amino acids, accordingly, in the HCDR3 encoding DNA sequence by using trinucleotide mutagenesis (TRIM) technology. A collection of HCDR3 members of the invention each can be comprised within a variable region of an antibody (or fragment thereof) to form a library of synthetic antibodies or antibody fragments. The invention also provides nucleic acid molecules encoding such diverse collection and methods of making and using the same.