# 191aa vs 192aa: Informative Article



## PRIDE (Jan 8, 2013)

Those of you who have some knowledge of GH and have been using have heard of the 191 amino acid vs. 192 amino acid makeup of different brands of GH...Here are some articles to shed some light on the debate:

*191AA (Humatrope):*

As with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. During the first 6 months of Humatrope therapy in 314 naive patients, only 1.6% developed specific antibodies to Humatrope (binding capacity ≥0.02 mg/L). None had antibody concentrations which exceeded 2 mg/L. Throughout 8 years of this same study, two patients (0.6%) had binding capacity >2 mg/L. Neither patient demonstrated a decrease in growth velocity at or near the time of increased antibody production. It has been reported that growth attenuation from pituitary-derived growth hormone may occur when antibody concentrations are
>1.5 mg/L.

*192AA (Protropin):*

As with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. Growth hormone antibody binding capacities below 2 mg/L have not been associated with growth attenuation. In some cases when binding capacity exceeds 2 mg/L, growth attenuation has been observed. In clinical studies and postmarketing experience of patients treated with 192 amino acid for injection, approximately 0.4 percent of patients screened for antibody production developed antibodies with binding capacities > 2 mg/L at six months. Out of approximately 26,000 patients who have been treated with 192 amino acid residues , 5 (=0.02%)patients have had growth deceleration associated with binding capacities > 2 mg/L. If growth deceleration is observed that is not attributable to another cause, the patient should be tested for antibodies to growth hormone. Although no evidence exists to indicate that the methionine on the N-terminus of 192 amino acid residues causes antibodies to growth hormone, the physician should consider transferring the patient to somatropin (rDNA origin) for injection, if a patient has antibody binding capacity > 2 mg/L, and has exhibited growth attenuation.

*Most 192AA is reconstituted with bac. water which includes BA and most 191AA with sterile water. Some people are sensitive to the benzyl alcohol and develop red welts from it. Its not the 192AA.*

*Department of Analytical Chemistry, Genentech Inc., South San Francisco, CA 94080, USA.*

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).*

*Department of Analytical Chemistry, Genentech Inc., South San Francisco, CA 94080, USA.* 

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..


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## Ironbuilt (Jan 8, 2013)

So in laymans terms did I understand some people have antibodies to both kids which means no growth? This is chemistry and I failed it badly..


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## ASHOP (Jan 11, 2013)

Ironbuilt said:


> So in laymans terms did I understand some people have antibodies to both kids which means no growth? This is chemistry and I failed it badly..



In laymans terms,,,just stick with 191aa and you should be fine.


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