Universal libraries for immunoglobulins

C - Chemistry – Metallurgy – 40 – B

Patent

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Details

C40B 40/10 (2006.01) C07K 16/00 (2006.01) C12N 15/13 (2006.01) C40B 40/08 (2006.01) C40B 50/00 (2006.01) G01N 33/53 (2006.01)

Patent

CA 2482863

Libraries of immunoglobulins of interest are described, the libraries containing mutated immunoglobulins of interest in which a single predetermined amino acid has been substituted in one or more positions in one or more complementarity-determining regions of the immunoglobulin of interest. The libraries comprise a series of subset libraries, in which the predetermined amino acid is "walked through" each of the six complementarity-determining regions (CDRs) of the immunoglobulin of interest not only individually but also for each of the possible combinatorial variations of the CDRs, resulting in subset libraries that include mutated immunoglobulins having the predetermined amino acid at one or more positions in each CDR, and collectively having the predetermined amino acid at each position in each CDR. The invention is further drawn to universal libraries containing one such library for each naturally-occurring amino acid as the single predetermined amino acid, totaling twenty libraries; and also to libraries of nucleic acids encoding the described libraries.

L'invention concerne des bibliothèques pour immunoglobulines d'intérêt, lesdites bibliothèques contenant des immunoglobulines d'intérêt mutées, dans lesquelles un aminoacide simple prédéterminé a été substitué au niveau d'au moins une position, dans au moins une région déterminant la complémentarité de l'immunoglobuline d'intérêt. Lesdites bibliothèques comprennent une série de sous-ensembles de bibliothèques, où l'aminoacide prédéterminé est <= acheminé à travers >= chacune des six régions déterminant la complémentarité (CDR) de l'immunoglobuline d'intérêt, pas uniquement individuellement, mais aussi pour chacune des variations combinatoires possibles des CDR, ce qui a pour effet de produire des sous-ensembles de bibliothèques comprenant des immunoglobulines mutées présentant l'aminoacide prédéterminé au niveau d'au moins une position de chaque CDR. L'invention concerne en outre des bibliothèques universelles contenant une telle bibliothèque pour chaque aminoacide apparaissant naturellement sous forme d'aminoacide simple prédéterminé, soit vingt bibliothèques au total, ainsi que des bibliothèques d'acides nucléiques codant les bibliothèques décrites.

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