Technology

CTP Technology

Carboxyl Terminal Peptide (CTP) is a naturally-occurring human peptide evolved to provide the Human Chorionic Gonadotropin (hCG) with the longevity required for maintaining pregnancy. hCG has a long half-life due to a unique CTP comprised of 28 amino acids and four potential O-linked oligosaccharides. These O-linked oligosaccharides add flexibility to the fused protein and decrease its hydrophobicity, enabling lower renal and hepatic clearance and increased circulatory half-life.

Preclinical and Clinical studies show that the CTP technology appears to be safe and effective in extending the serum half-life of all proteins tested to date. The safety and efficacy of CTP have also been validated by the marketing approval of Merck’s long-acting fertility drug Elonva® (FSH-CTP) in 2010 for the European market and the recently approved OPKO Biologics long-acting hGH, NGENLA,for the treatment of children and adolescents. Both drugs replace daily injections with a single weekly treatment, improving patients’ quality of life and compliance.

CTP was discovered by researchers at Washington University in St. Louis and is exclusively licensed to OPKO Biologics for all proteins and peptides, except for four endocrine hormones that are licensed to Merck & Co. OPKO applies this technology to successfully extend protein half-life, and to reduce the frequency of biotherapeutic injections.

Reversible PEGylation Technology

Reversible PEGylation is a synthetic chemistry-based technology for extending the half-life of injectable therapeutic peptides and small molecules, exclusively licensed from the Weizmann Institute of Science. The technology is based on the formation of a conjugate between a drug that contains a primary amine group and a polyethylene glycol (PEG) chain through a proprietary bi-functional hydrolysable linker.

Once the conjugate enters the bloodstream, the linker hydrolyses in a controlled manner and the intact drug is gradually released. Using a hydrolysable linker bypasses the disadvantages of using a non-reversible PEGylated molecule; for example, the potential for steric hindrance that limits function, and the limited ability to cross cellular membranes. This technology is especially suitable for drugs with a short half-life which are required to cross highly selective membranes, such as the blood-brain barrier.

Stabilizer-based Technology

OPKO Biologics develops new drug candidates utilizing native stabilizer proteins that can reversibly bind to the drug of interest via non-covalent interactions. This surrogate protein approach can increase drug longevity by reducing renal clearance and increasing drug stability, leading to higher systemic exposure. This technology is currently undergoing proof-of-concept studies and is being applied for both peptides and recombinant proteins.