Modified growth hormone
First Claim
Patent Images
1. A modified growth hormone polypeptide, or an active portion thereof, comprising an amino acid replacement of Y with I in an unmodified growth hormone polypeptide at a locus corresponding to amino acid Y42 of a mature growth hormone polypeptide set forth in SEQ ID NO:
- 1, wherein the amino acid replacement is the only amino acid replacement in the polypeptide, wherein;
the active portion thereof includes the position corresponding to Y42.
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Accused Products
Abstract
Provided are modified growth hormone polypeptides, nucleic acid molecules encoding modified growth hormone polypeptides and methods of generating modified growth hormone polypeptides. Also provided are methods of treatment using modified growth hormone polypeptides.
166 Citations
32 Claims
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1. A modified growth hormone polypeptide, or an active portion thereof, comprising an amino acid replacement of Y with I in an unmodified growth hormone polypeptide at a locus corresponding to amino acid Y42 of a mature growth hormone polypeptide set forth in SEQ ID NO:
- 1, wherein the amino acid replacement is the only amino acid replacement in the polypeptide, wherein;
the active portion thereof includes the position corresponding to Y42. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
- 1, wherein the amino acid replacement is the only amino acid replacement in the polypeptide, wherein;
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17. A modified growth hormone polypeptide, comprising:
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an amino acid replacement of Y with I in an unmodified growth hormone polypeptide at a locus corresponding to amino acid Y42 of a mature growth hormone polypeptide set forth in SEQ ID NO;
1; andonly one to five further amino acid replacements at positions corresponding to F1, P2, P5, R8, L9, F10, D11, M14, R16, R19, L23, F25, D26, E30, E32, E33, P37, K38, E39, K41, L52, F54, L73, E74, R77, L80, L81, L82, W86, L87, P89, L93, F97, Y103, D107, Y111, D112, L113,L114, K115, D116, L117, E118, E119, L124, M125, R127, L128, F139, D153, D154, L156, L157, K158, L162, L163, F166, R167, K168, D169, M170, D171, K172, E174, L177, R178, F191, L6, L9, A13, L15, A17, L20, L23, A24, A105, V110, L113, L114, L117, I121, L124, L128, E56, E65, E66, E88, R94, L101, E129, P133, R134, K140, Y143, K145, D147, R183 and E186, wherein; the amino acid replacements are selected from among F1V, P2A, P5A, P5S, R8H, L9I, L9V, D11N, D11Q, M14V, R16H, R19H, L23I, L23V, F25I, F25V, D26N, D26Q, E30H, E30N, E32Q, E32H, E32N, E33Q, E33H, E33N, P37S, K38N, K38Q, E39H, K41Q, L52I, L52V, F54V, L73I, L73V, E74N, R77Q, L80V, L81V, L82V, W86H, L87V, P89A, L93I, F97V, Y103H, Y103I, D107N, D107Q, Y111H, Y111I, D112N, D112Q, L113I, L113V, L114I, K115Q, D116N, D116Q, E118N, E119Q, E119H, L124V, M125I, M125V, R127H, R127Q, L128V, F139I, D153N, D154N, D154Q, L156I, L157I, L157V, K158N, L162I, L163V, F166I, F166V, R167H, R167Q, K168N, K168Q, D169N, D169Q, M170I, M170V, D171N, D171Q, K172N, K172Q, E174Q, E174H, E174N, L177I, L177V, R178H, R178Q, F191I, F191V, L6E, L6D, L6K, L6R, L6N, L6Q, L6S, L6T, L9E, L9D, L9K, L9R, L9N, L9Q, L9S, L9T, A13E, A13D, A13K, A13R, A13N, A13Q, A13S, A13T, L15E, L15D, L15K, L15R, L15Q, L15N, L15S, L15T, A17E, A17D, A17K, A17R, A17N, A17Q, A17S, A17T, L20E, L20D, L20K, L20R, L20N, L20Q, L20S, L20T, L23E, L23D, L23K, L23R, L23N, L23Q, L23S, L23T, A24E, A24D, A24K, A24R, A24N, A24Q, A24S, A24T, A105E, A105D, A105K, A105R, A105N, A105Q, A105S, A105T, V110E, V110D, V110K, V110R, V110N, V110Q, V110S, V110T, L113E, L113D, L113K, L113R, L113N, L113Q, L113S, L113T, L114E, L114D, L114K, L114R, L114N, L114Q, L114S, L114T, L117E, L117D, L117K, L117R, L117Q, L117S, L117T, I121E, I121D, I121K, I121R, I121N, I121Q, I121S, I121T, L124E, L124D, L124K, L124R, L124N, L124Q, L124S, L124T, L128E, L128D, L128K, L128R, L128Q, L128N, L128S, L128T, E56Q, E56N, E65Q, E66Q, E66H, E88Q, R94H, L101V, L101I, E129N, P133A, R134H, R134Q, K140Q, K140N, Y143H, Y143I, K145N, D147Q, D147N, R183Q, E186Q, and E186H of a mature human growth hormone polypeptide set forth in SEQ ID NO;
1;the modified growth hormone polypeptide contains only 2 to 6 amino acid replacements; the modified growth hormone polypeptide retains an activity of the unmodified polypeptide; and the modified growth hormone polypeptide is more resistant to proteolysis to proteases in serum or the gastrointestinal tract than the unmodified polypeptide. - View Dependent Claims (18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)
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Specification