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CTP Scientific Papers
The CTP technology enhances the potency and increases the biological longevity of short half-life commercial therapeutic proteins. This is achieved by fusing the heavily glycosylated C-terminal peptide region of the human chorionic gonadotropin beta subunit to the C or N terminals of the target molecule. This region is important to maintain the prolonged plasma half-life of human CG dimer.
The fused proteins expressed in mammalian cells (CHO), have been shown to have up to 10x longer biological half life time as compared to the commercial non fused molecule and thus, can increase the efficacy of the treatment as well as reduce patient discomfort caused by frequent injections (Fares et al, PNAS, 89,4304-4308). The mechanism of the extended half life and biopotency of the CTP bound protein analogue is the result of the four O-linked glycosylation sites present on the CTP moiety.
Please open any of the following scientific papers by clicking a paper's name:
A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol (Phase III, FSH-CTP) P. Devroey et al., Human Reproduction, Vol.24, No.12 pp. 3063–3072, 2009
Induction of multiple follicular development by a single dose long-acting recombinant follicle-stimulating hormone (FSH-CTP, Corifollitropin Alfa) for controlled ovarian stimulation before in vitro fertilization P. Devroey et al., The Journal of Clinical Endrocrinology and Metabolism, 89(5): 2062-70 (2004)
A randomized dose-finding trial to establish the ovarian response of a single injection of Org 36286 for sustained follicular stimulation. P. Devroey et al., abstract of the 22nd Annual Meeting of the ESHRE, Session 45-ART, Prague, Czech Republic (18-21 June 2006)
First human exposure to FSH-CTP in hypogonadotrophic hypogonadal males P.M.G. Bouloux et al., Hum. Reprod. 16(8): 1592-1597 (2001)
Development of a Long-Acting Erythropoietin by Fusing the Carboxyl-Terminal Peptide of Human Chorionic Gonadotropin {beta}-Subunit to the Coding Sequence of Human Erythropoietin F. Fares et al., Endocrinology, 148(10): 5081 – 5087 (October, 2007).
First live birth after ovarian stimulation using a chimeric long-acting human recombinant follicle-stimulating hormone (FSH) agonist (recFSH-CTP) for in vitro fertilization Neckers NG et al., Fertil Steril. 79(3): 621-3 (2003)
Design of a long-acting follitropin agonist by fusing the C-terminal sequence of the chorionic gonadotropin ß subunit to the follitropin ß subunit Fuad A. Fares et al., Proc. Natl. Acad. Sci. USA, 89: 4304-08 (1992).
Pharmacokinetics and pharmacodynamics of single-chain recombinant human follicle-stimulating hormone containing the human chorionic gonadotropin carboxyterminal peptide in the rhesus monkey J. Klein et al., Fertil Steril. 77(6):1248-55 (Jun 2002)
Single dose pharmacokinetics and effects on follicular growth and serum hormones of a long-acting recombinant FSH preparation (FSH-CTP) in healthy pituitary-suppressed females. I. J. Duijkers et al., Hum Reprod. 17(8):1987-93 (Aug 2002)
Novel recombinant gonadotropin molecules in human reproductive dysfunction B. Mannaerts et al., Endocrine Abstracts, 11: S29 (2006)
Engineering a Potential Antagonist of Human Thyrotropin and Thyroid-stimulating Antibody Fuad A. Fares et al., J. Biol. Chem., 276( 7): 4543-48, February 16, 2001