Designing a Long-Acting Human Growth Hormone (hGH) by Fusing the Carboxyl-Terminal Peptide of Human Chorionic Gonadotropin β-Subunit to the Coding Sequence of hGH

Q2 · MEDICINE

Article

Author: Fuad Fares ; Ahuva Bar-Ilan ; Yana Felikman ; Rachel Guy ; Eyal Fima

Chimeric genes were constructed by fusing of human GH (hGH) cDNA to one, two, or three cassettes of the carboxyl-terminal peptide (CTP) of human chorionic gonadotropin (hCG)-beta-subunit. hGH variant genes were inserted into the pCI-DHFR plasmid, transfected into DG44 cells, and stable clones were selected. Bioactivity and pharmacokinetic studies were performed in hypophysectomized Sprague Dawley derived male rats. The results indicated that sc injections of GH-wild-type (WT), Biotropin (commercial), GH-CTP, or CTP-GH (0.6 mg/kg) once every 5 d for 11 d (total dose of 1.2 mg/kg) resulted in an increased weight gain by 4, 4.9, 5.1, and 7 g, respectively. Treatment with CTP-GH-CTP-CTP (GH-LA) or CTP-GH-CTP (0.6 mg/kg) once every 5 d for 11 d or with Biotropin (0.12 mg/kg) daily for 11 d (total dose 1.2 mg/kg) resulted in a dramatic increase in weight gain of 16.5, 16.8, and 17 g, respectively. Repeated injections with different doses of GH-LA, 0.6, 1.8 mg/kg every 4 d or daily injection of 0.12 mg/kg of Biotropin increased the weight gain by 16, 28, and 18 gr, respectively. In addition, the cumulative serum levels of IGF-I after injection of GH-LA was significantly higher than that detected after injection of Biotropin. Pharmacokinetic studies indicated that the half-life, mean residence time, area under the curve, time of maximal plasma concentration, and maximal plasma concentration of GH-LA are dramatically increased compared with Biotropin. This may suggest that the mechanism of GH metabolic clearance is affected by the presence of CTP. These data establish a rationale for using this chimera as a long-acting GH analog.

01 Jan 2003·Polish journal of veterinary sciencesQ4 · AGRICULTURAL & FORESTRY SCIENCE

Immunity against viruses in chickens after applying natural and synthetic immunity stimulator.

Q4 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Swiecicka-Grabowska, G ; Wójcik, R

Comparing the action of biotropin, which is a natural immunomodulator, with a synthetic one--levamisole, leads to the conclusion that biotropin acts as a strong stimulator, both of specific humoral immunity, which manifests itself in higher titres of antibodies HI and SN, and of non-specific humoral immunity, whose feature is a higher activity of lysozyme in comparison with the other groups. Similarly, biotropin increases the phagocytal activity of leucocytes, expressed as the phagocytar index and the percentage of non-phagocyting cells, more effectively than levamisole. However, the specific cell immunity, assessed by the BT and LMI tests, was slightly better stimulated by biotropin immediately after infection and by levamisole in the remaining time.

100 Deals associated with Somatropin biosimilar(Laboratorios Chalver de Colombia SA)

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Indication	Country/Location	Organization	Date
Growth hormone deficiency	Colombia	Laboratorios Chalver de Colombia SAS	01 Oct 2012

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