Growth hormone variants with altered binding properties
AssigneeGenentech, Inc.
InventorsSteven H. Bass, Ronald Greene, Henry B. Lowman, James A. Wells
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Abstract
A method for selecting novel proteins such as growth hormone variants having altered binding properties for a growth hormone receptor molecule is provided. The method comprises fusing a gene encoding a hormone to the carboxy terminal domain of the gene III coat protein of the filamentous phage M13. The gene fusion is mutated to 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. Disposed are preferred phagemid expression vectors and selected human growth hormone variants.
Claims28
A variant of a native human growth hormone, said variant capable of binding to human growth hormone binding protein and having a set of amino acid substitutions selected from the group consisting of:
- F10H,M14G,H18N,H21N;
- F10A,M14W,H18D,H21N;
- F10Y,M14T,H18V,H21N;
- F10I,M14N,H18I,H21N;
- and
- M14S,H18F,H21L, numbered from the N-terminus of 191-amino acid human growth hormone.
A variant of a native human growth hormone, said variant capable of binding to human growth hormone binding protein and comprising a set of amino acid substitutions selected from the group consisting of:
- F10H,M14G,H18N,H21N;
- F10A,M14W,H18D,H21N;
- F10Y,M14T,H18V,H21N;
- F10I,M14N,H18I,H21N;
- and
- M14S,H18F,H21L, numbered from the N-terminus of 191-amino acid human growth hormone.
A variant of a native human growth hormone, said variant capable of binding to human growth hormone binding protein and having a set of amino acid substitutions selected from the group consisting of:
- R167N,D171S,E174S,F176Y,I173T;
- R167E,D171S,E174S,F176Y;
- R167K,D171S,E174S,F176Y,I179L;
- R167N,D171N,E174S,F176Y,I179T;
- R167N,D171S,E174S,F176Y,I179O;
- and
- E174S,F176Y, numbered from the N-terminus of 191-amino acid human growth hormone.
A variant of a native human growth hormone, said variant capable of binding to human growth hormone binding protein and comprising a set of amino acid substitutions selected from the group consisting of:
- R167N,D171S,E174S,F176Y,I179T;
- R167E,D171S,E174S,F176Y;
- R167K,D171S,E174S,F176Y,I179L;
- R167N,D171N,E174S,F176Y,I179T;
- R167N,D171S,E174S,F176Y,I179Q;
- and
- E174S,F176Y, numbered from the N-terminus of 191-amino acid human growth hormone.
Dependencies are inferred from the claim text.