found some more articles:
-Department of Analytical Chemistry, Genentech Inc., South San Francisco, CA 94080, USA.
[email protected]
The clinical development of methionyl human growth hormone, with particular emphasis on immunogenicity and the effects of antibody development, are summarized. In an animal model in rhesus monkeys, the immunogenicity of dinical preparations was reduced by the inclusion of additional purification steps in the manufacturing process. The immunogenic response in patients was also decreased by these improvements.
No safety consequences related to antibody formation were observed and the occurrence of growth attenuation due to antibodies was found to be extremely low (<0.1%). The data suggest that the immunogenicity was not due to the N-terminal methionine or E. coli protein impurities: rather it was probably caused by small amounts of growth hormone with subtle structural alterations whose nature remains unknown.
PMID: 12434920 [PubMed - indexed for MEDLINE]
-The use of an animal immunogenicity model in the development of Protropin somatrem (methionyl human growth hormone).
Jones AJ.
Department of Analytical Chemistry, Genentech Inc., South San Francisco, CA 94080, USA.
[email protected]
The clinical development of methionyl human growth hormone, with particular emphasis on immunogenicity and the effects of antibody development, are summarized. In an animal model in rhesus monkeys, the immunogenicity of dinical preparations was reduced by the inclusion of additional purification steps in the manufacturing process. The immunogenic response in patients was also decreased by these improvements.
No safety consequences related to antibody formation were observed and the occurrence of growth attenuation due to antibodies was found to be extremely low (<0.1%). The data suggest that the immunogenicity was not due to the N-terminal methionine or E. coli protein impurities: rather it was probably caused by small amounts of growth hormone with subtle structural alterations whose nature remains unknown.
-The molecular basis of recombinant DNA technology is described, and the principles of genetically engineered proteins developed. The production of hGH by such methods utilizes a strain of Escherichia coli as host and a vector plasmid containing the appropriate information. Fermentation and purification of the hGH produced gives a preparation of high purity, containing only 1-2 ppm of E. coli polypeptide (ECP). This somatrem (Somatonorm) is identical to pituitary hGH except for an additional methionine residue at the N-terminal. Monoclonal antibodies fail to distinguish between pituitary hGH and somatrem.
Preclinical studies of a variety of pharmacological and toxicological parameters indicate that the two hGH preparations have identical biological effects; no toxicological or mutagenic effects of somatrem have been detected
Monoclonal antibodies to human growth hormone can distinguish between pituitary and genetically engineered forms.
Aston R, Cooper L, Holder A, Ivanyi J, Preece M.
Monoclonal antibodies (MABs) prepared against human pituitary growth hormone (hGH) have been compared for their binding to pituitary-derived and genetically engineered methionyl growth hormone (met-hGH). The antibodies bind to four non-overlapping epitopes of which two are completely shared with human choronic somatomammotropin (hCS). The determinant defined by MAB NA27 was expressed on met-hGH to a lesser degree than on hGH of pituitary origin. However, another antibody, QA68, which binds to a determinant closely related to NA27, failed to discriminate between hGH and met-hGH. A further two MABs (EB1 and NA71) were similarly ineffective in distinguishing between the two forms of the hormone. The determinant recognized by antibody EB2 was equally represented on hGH and met-hGH when assessed by a liquid-phase radioimmunoassay: however, measurement of the binding in a solid-phase assay resulted in a two-four-fold lower binding to met-hGH. Bioactivity assessed by both an in vitro cell proliferation assay and an in vivo cartilage sulphation bioassay failed to distinguish between the two hormones.
It is therefore concluded that the NH2-terminal methionine on bacterially derived growth hormone results in altered antigenicity of the hormone without any measurable effect on bioactivity
Thus the bioactivity of met-hgh is the same as HGH
Most studies are performed on people with GHD, they allready have a very high anti-body level to HGH...Another problem is that most antibodies that were measured in those studies is based on antibodies to Escherichia coli proteins and not the antibodies to met-HGH..