Modified human growth hormone

A growth hormone and hormone technology, applied in the direction of growth hormone, hormone peptide, animal/human protein, etc., can solve the problems of lack of reproducibility, loss of activity, loss of protein activity, etc.

Inactive Publication Date: 2007-12-19
AMBRX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some derivatives lead to loss of protein activity by linking to sites that produce protein activity
Some derivatives are not specific for where they will be attached, which also leads to loss of desired activity and to lack of reproducibility of results

Method used

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Embodiment approach

[0207] I. Introduction

[0208] In the present invention, there is provided a GH (e.g., hGH) molecule comprising at least one unnatural amino acid. In certain embodiments of the invention, a GH (e.g., hGH) polypeptide with at least one unnatural amino acid includes at least one post-translational modification. In one embodiment, the at least one post-translational modification includes using chemical methods known to those skilled in the art to be suitable for a specific reactive group, including (but not limited to) the following: The molecule of the substance is connected to at least one unnatural amino acid containing the first reactive group: labels, dyes, polymers, water-soluble polymers, derivatives of polyethylene glycol, photocrosslinkers, radionuclides, Cytotoxic compounds, drugs, affinity labels, photoaffinity labels, reactive compounds, resins, second proteins or polypeptides or polypeptide analogs, antibodies or antibody fragments, metal chelating agents, cofactors, fa...

example

[0962] The following examples are provided to illustrate (but not limit) the claimed invention.

example 1

[0964] This example describes one of a variety of potential standard settings for selecting preferred sites for incorporation of non-naturally encoded amino acids in hGH.

[0965] This example shows how to select a preferred site in the hGH polypeptide for the introduction of non-naturally encoded amino acids. The crystal structure 3HHR consisting of hGH complexed with two molecules of the extracellular domain of the receptor (hGHbp) was used to determine the preferred position where one or more non-naturally encoded amino acids can be introduced. Use other hGH structures (e.g., 1AXI) to examine potential changes in primary and secondary structure elements between the crystal structure data sets. The coordinates of these structures can be obtained from the protein database (PDB) (Bernstein et al. J. Mol. Biol. 1997, 112, p. 535), or via www. rcsb.org Obtained at The Research Collaboratory for Structural Bioinformatics PDB. The structured model 3HHR contains a complete mature 22kDa...

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Abstract

Formulations of modified human growth hormone polypeptides are provided.

Description

[0001] Cross reference of related applications [0002] This application claims the priority of U.S. Provisional Patent Application No. 60 / 638,616 filed on December 22, 2004 and U.S. Provisional Patent Application No. 60 / 727,996 filed on October 17, 2005. The full text of the specification is incorporated into this article. Technical field [0003] The present invention relates to a growth hormone polypeptide modified with at least one non-naturally encoded amino acid. Background technique [0004] Growth hormone (GH) supergene family (Bazan, F. Immunology Today 11: 350-354 (1990); Mott, HR and Campbell, ID Current Opinion in Structural Biology 5: 114-121 (1995); Silvennoinen, O. and Ihle, JN (1996) SIGNALING BY THE HEMATOPOIETIC CYTOKINERECEPTORS) represents a group of proteins with similar structural features. Each member of this protein family contains a four-helix bundle, the general structure of which is shown in Figure 1. Although there are still many members in this family...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68C07K14/61C07H21/04A61K38/27A61K38/00A61K38/21A61K47/60C07K14/56G01N33/68G01N33/74
CPCC07H21/04A61K38/21A61K47/48215G01N33/6875G01N2500/00C07K14/475A61K38/00C07K14/61C07K14/52A61K38/27C08G65/33396A61K47/60
Inventor 丘霍松托马斯·O·丹尼尔理查德·D·迪马什安娜·玛丽亚·海斯特洛伊·E·威尔逊比·查·西姆戴维·C·利青格
Owner AMBRX
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