Modified human growth hormone
AssigneeAmbrx, Inc.
InventorsHo Cho, Thomas Daniel, Richard DiMarchi, Anna-Maria Hays, Troy Wilson, Bee-Cheng Sim, David Litzinger
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Abstract
Modified growth hormone polypeptide and uses thereof are provided.
Claims79
A hormone composition comprising a growth hormone (GH) linked to at least one water-soluble polymer by a covalent bond, wherein the covalent bond is an oxime bond.
The hormone composition of claim 28 wherein PEG has a molecular weight between about 1 and about 100 kDa.
A hormone composition comprising a hGH linked via an oxime bond to at least one linear PEG, wherein the hGH comprises the amino acid sequence of SEQ ID NO:
- 2 and comprises at least one NEAA substituted at one or more positions selected from the group consisting of residues 1-5, 6-33, 34-74, 75-96, 97-105, 106-129, 130-153, 154-183, and 184-191.
A method of making a GH linked via an oxime bond to a water-soluble polymer comprising contacting a GH that comprises a NEAA comprising a carbonyl group with a PEG oxyamine under conditions suitable for formation of an oxime bond.
A pharmaceutical composition comprising
- (i) a hormone composition comprising a growth hormone linked by a covalent bond to at least one water-soluble polymer, wherein the covalent bond is an oxime bond;
- and
- (ii) a pharmaceutically acceptable excipient.
A method of treatment comprising administering to an individual in need of treatment an effective amount of a hormone composition comprising a growth hormone (GH) linked by covalent bond(s) to at least one water-soluble polymer, wherein the covalent bond(s) is an oxime bond.
A method of treatment comprising administering to an individual in need of treatment an effective amount of a hormone composition comprising a growth hormone (GH) linked by covalent bond(s) to at least one water-soluble polymer, wherein the water-soluble polymer is a linear polymer, and wherein the hormone composition is given at a frequency of no more than once per week, once per two weeks, or once per month.
A hormone composition comprising a GH, wherein the GH has an average serum half-life of at least about 12 hours when administered to a mammal subcutaneously.
A hormone composition comprising a GH linked via an oxime bond to a PEG, wherein the GH has an average serum half-life of at least about 7-fold the serum half-life of a composition comprising the GH without the PEG, when administered to a mammal subcutaneously.
Dependencies are inferred from the claim text.