Enrichment method for variant proteins with alterred binding...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/85 (2006.01) A61K 47/48 (2006.01) C07K 14/47 (2006.01) C07K 19/00 (2006.01) C12N 5/10 (2006.01) C12N 15/11 (2006.01) C12N 15/62 (2006.01) C12Q 1/68 (2006.01) G01N 33/554 (2006.01) G01N 33/566 (2006.01) G01N 33/74 (2006.01)

Patent

CA 2405246

A method for selecting novel proteins such as growth hormone and antibody fragment variants having altered Minding properties for their respective receptor molecules is provided. The method comprises fusing a gene encoding a protein of interest to the carboxy terminal domain of the gene III coat protein of the filamentous phage M13. The gene fusion is mutated b form a library of structurally related fusion proteins that are expressed in low quantity on the surface of a phagemid particle. Biological selection and screening are employed to identify novel ligands useful as drug candidates. Disclosed are preferred phagemid expression vectors and selected human growth hormone variants. A method for selecting novel proteins such as growth hormone and antibody fragment variants having altered bind- ing properties for their respective receptor molecules is pro- vided. The method comprises fusing a gene encoding a protein of interest to the carboxy terminal domain of the gene III coat protein of the filamentous phage M13. The gene fusion is mu- tated to form a library of ratty rotated fusion proteins that are expressed in low quantity on the surface of a phagem- id particle. Biological selection and screening are employed to identify novel ligands useful as drug candidates, Disclosed are preferred phagemid expression vectors and selected human growth hormone variants.

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