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Details for Patent: 6,022,711

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Details for Patent: 6,022,711

Title: Human growth hormone variants having enhanced affinity for human growth hormone receptor at site 1
Abstract:Growth hormone participates in the regulation of normal growth and development processes. The binding affinity of growth hormone for its target receptors is dependent upon the interaction of site 1 and site 2 domains of growth hormone with the target receptor. Embodiments of the present invention include site 1 variants of human growth hormone which bind to target receptors with a different affinity than that of the native hormone. Embodiments of the invention further include components for the production of isolated human growth hormone variants using a host cell/vector expression system.
Inventor(s): Cunningham; Brian C. (Piedmont, CA), Lowman; Henry (Hercules, CA), Wells; James A. (Burlingame, CA)
Assignee: Genentech, Inc. (South San Francisco, CA)
Filing Date:Jun 07, 1995
Application Number:08/482,137
Claims:1. A variant of a naturally occurring human growth hormone, wherein said variant has a greater affinity for human growth hormone receptor at site 1 than said naturally occurring human growth hormone, said variant differing from a naturally occurring amino acid sequence of human growth hormone in that said variant comprises a set of amino acid substitutions selected from the group consisting of:

H18D, Q22A, F25A, D26A, Q29A, E65A, K168A, E174S;

H18A, Q22A, F25A, D26A, Q29A, E65A, K168A, E174S; and

H18D, Q22A, F25A, D26A, Q29A, E65A, K168A, E174A, numbered from the mature N-terminus of 191-amino acid human growth hormone.

2. A composition comprising the human growth hormone variant of claim 1 and a pharmaceutically acceptable carrier.

3. The variant of claim 1 wherein said variant is covalently attached to a polyethylene glycol molecule.

4. A variant of a naturally occurring human growth hormone, wherein said variant has a greater affinity for human growth hormone receptor at site 1 than said naturally occurring human growth hormone, said variant differing from a naturally occurring amino acid sequence of human growth hormone in that said variant only comprises all of the amino acid substitutions selected from the group consisting of:

H18D, Q22A, F25A, D26A, Q29A, E65A, K168A, E174S;

H18A, Q22A, F25A, D26A, Q29A, E65A, K168A, E174S; and

H18D, Q22A, F25A, D26A, Q29A, E65A, K168A, E174A, numbered from the mature N-terminus of 191-amino acid human growth hormone.

5. A nucleic acid encoding a variant of a naturally occurring human growth hormone, wherein said variant has a greater affinity for human growth hormone receptor at site 1 than said naturally occurring human growth hormone, said variant differing from a naturally occurring amino acid sequence of human growth hormone in that said variant comprises a set of amino acid substitutions selected from the group consisting of:

H18D, Q22A, F25A, D26A, Q29A, E65A, K168A, E174S;

H18A, Q22A, F25A, D26A, Q29A, E65A, K168A, E174S; and

H18D, Q22A, F25A, D26A, Q29A, E65A, K168A, E174A, numbered from the mature N-terminus of 191-amino acid human growth hormone.

6. A vector comprising the nucleic acid of claim 5.

7. A host cell comprising the vector of claim 6.

8. A process for preparing a human growth hormone variant comprising:

(a) culturing the host cell of claim 7; and

(b) recovering the variant from the culture.
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