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Generated: January 21, 2018

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Title: Human growth hormone variant having enhanced affinity for human growth hormone receptor at site 1
Abstract:A human growth hormone variant including the set of amino acid substitutions H18A, Q22A, F25A, D26A, Q29A, E65A, K168A, E174A is disclosed. Also disclosed is a nucleic acid encoding this variant, along with a vector including the nucleic acid, a host cell including the vector, and a process for preparing the variant. The variant has enhanced affinity for human growth hormone receptor at site 1.
Inventor(s): Cunningham; Brian C. (Piedmont, CA), Wells; James A. (Burlingame, CA)
Assignee: Genentech, Inc. (South San Francisco, CA)
Filing Date:Jun 07, 1995
Application Number:08/487,110
Claims:1. An isolated variant of a naturally occurring human growth hormone having a greater affinity for human growth hormone receptor at site 1 than said naturally occurring human growth hormone, said variant comprising the following set of amino acid substitutions:

H18A, Q22A, F25A, D26A, Q29A, E65A, K168A, E174A.

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

3. An isolated nucleic acid encoding a human growth hormone variant having a greater affinity for human growth hormone receptor at site 1 than said naturally occurring human growth hormone, said variant comprising the following set of amino acid substitutions:

H18A, Q22A, F25A, D26A, Q29A, E65A, K168A, E174A.

4. A vector comprising a nucleic acid encoding a human growth hormone variant having a greater affinity for human growth hormone receptor at site 1 than said naturally occurring human growth hormone, said variant comprising the following set of amino acid substitutions:

H18A, Q22A, F26A, D26A, Q29A, E65A, K168A, E174A.

5. A host cell comprising a vector comprising a nucleic acid encoding a human growth hormone variant having a greater affinity for human growth hormone receptor at site 1 than said naturally occurring human growth hormone, said variant comprising the following set of amino acid substitutions:

H18A, Q22A, F25A, D26A, Q29A, E65A, K168A, E174A.

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

(a) culturing a host cell comprising a vector comprising a nucleic acid encoding a human growth hormone variant having a greater affinity for human growth hormone receptor at site 1 than said naturally occurring human growth hormone, said variant comprising the following set of amino acid substitutions:

H18A, Q22A, F25A, D26A, Q29A, E65A, K168A, E174A; and

(b) recovering the variant from the culture.
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