high affinity, developability and functional size the holy grail of combinatorial antibody library generation高亲和力,可展性和功能性大小组合的圣杯抗体库的一代.pdfVIP

Molecules 2011, 16, 3675-3700; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review High Affinity, Developability and Functional Size: The Holy Grail of Combinatorial Antibody Library Generation Dirk Ponsel , Julia Neugebauer *, Kathrin Ladetzki-Baehs and Kathrin Tissot MorphoSys AG, Lena-Christ Strasse 48, 82152 Martinsried, Germany; E-Mails: Ponsel@ (D.P.); Ladetzki-Baehs@ (K.L.-B.); Tissot@ (K.T.) * Author to whom correspondence should be addressed; E-Mail: Neugebauer@; Tel.: +49-89-89927-179; Fax: +49-89-89927-5179. Received: 23 March 2011; in revised form: 20 April 2011 / Accepted: 22 April 2011 / Published: 3 May 2011 Abstract: Since the initial description of phage display technology for the generation of human antibodies, a variety of selection methods has been developed. The most critical parameter for all in vitro-based approaches is the quality of the antibody library. Concurrent evolution of the libraries has allowed display and selection technologies to reveal their full potential. They come in different flavors, from naïve to fully synthetic and differ in terms of size, quality, method of preparation, framework and CDR composition. Early on, the focus has mainly been on affinities and thus on library size and diversity. Subsequently, the increased awareness of developability and cost of goods as important success factors has spurred efforts to gene