Growth hormone variants
AssigneeGenentech, Inc.
InventorsJames A. Wells, Brian C. Cunningham
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AssigneeGenentech, Inc.
InventorsJames A. Wells, Brian C. Cunningham
Estimating the term…
The invention provides methods for the systematic analysis of the structure and function of polypeptides by identifying active domains which influence the activity of the polypeptide with a target substance. Such active domains are determined by substituting selected amino acid segments of the polypeptide with an analogous polypeptide segment from an analog to the polypeptide. The analog has a different activity with the target substance as compared to the parent polypeptide. The activities of the segment-substituted polypeptides are compared to the same activity for the parent polypeptide for the target. A comparison of such activities provides an indication of the location of the active domain in the parent polypeptide. The invention also provides methods for identifying the active amino acid residues within the active domain of the parent polypeptide. The method comprises substituting a scanning amino acid for one of the amino acid residues within the active domain of the parent polypeptide and assaying the residue-substituted polypeptide so formed with a target substance. The invention further provides polypeptide variants comprising segment-substituted and residue-substituted growth hormones, prolactins and placental lactogens.
A method for identifying at least a first unknown active domain in the amino acid sequence of a parent polypeptide, said active domain interacting with a first target, said method comprising;
A method for forming a growth hormone variant, said method comprising:
A method for forming a growth hormone variant such method comprising
A method for identifying at least one active amino acid residue in a parent polypeptide, said method comprising:
A growth hormone variant comprising in order relative to the N-terminus, sequentially, at least first, second and third portions, said first portion corresponding to at least one part of the amino acid sequence of a parent growth hormone, said third portion corresponding to at least another part of the amino acid sequence of said parent growth hormone and said second portion corresponding to an analogous portion of amino acid sequence of a naturally occurring analog to said parent growth hormone.
A human growth hormone variant having an amino acid sequence not found in nature and which is derived by replacement of at least one amino acid residue of a human growth hormone with a different amino acid, said amino acid residue being selected from the group of amino acid residue of human growth hormone consisting of F10, F54, E56, I58, R64, Q68, D171, K172, E174, T175, P176, R178, C182, V185, I4, P5, L6, S7, R8, N12, M14, L15, R16, R19, S55, S57, P59, S62, N63, E66, K70, S71, K168, I179, C182, R183, G187, P2, T3, L10, H18, R64, E65, Q69, L73, R167. E174, S184, E186, S188, F191, H21, N47, P48, Q49, T50, S57, Q46, V173, R77, L80, F25, D26, Q29, E30, D169, S43, F44, P97, A98, N99, S100, L101, V102, Y103, G104, Q22, E33 and equivalents thereof.
A human growth hormone variant having amino acid sequence not found in nature and which is derived with replacement of at least one amino acid residue of a human growth hormone with a different amino acid, said amino acid residue being selected form the group of amino acid residues of human growth hormone consisting of F10, F25, D26, R167, K168, K172, E174, F176, I58, R64 and equivalents thereof.
A human growth hormone variant having amino acid sequence not found in nature and which is derived with replacement of at least one amino acid residue of a human growth hormone with a different amino acid, said amino acid residue being selected form the group of amino acid residues of human growth hormone consisting of F97, S100, L101, V102, Y103, T175 and equvalents thereof.
A human growth hormone variant having the amino acid sequence of a human growth hormone containing one or more amino acid modifications comprising the substitution, insertion or deletion of an amino acid residue in said sequence, wherein the active domains for the somatogenic receptor for said growth hormone are unmodified.
A growth hormone variant having the amino acid sequence of a human growth hormone containing one or more amino acid modifications comprising the substitution, insertion or deletion of an amino acid residue in said sequence, wherein the active amino acids for the somatogenic receptor for said growth hormone are unmodified.
A human prolactin hormone variant having an amino acid sequence not found in nature and which is derived by replacement of at least one amino acid residue of a human prolactin hormone with a different amino acid, said amino acid residue being selected from the group of amino acid residues of human prolactin consisting of H171, N175, Y176, K178, H54, S56, L58, A59, E62, D63, Q66, N71, L179, T55, K64, A67, M70, Q72, K73, D74.
The human prolactin variant of claim 74 further comprising the replacement H54F.
A human placental lactogen variant having amino acid sequence not found in nature and which is derived by the replacement of at least one amino acid residue of a placental lactogin with a different amino acid, said amino acid residue being selected from the group consisting of Q2, V4, H12, Q16, D56, M64, M179, and equivalents thereof.
Dependencies are inferred from the claim text.