Anti-Human RANKL (Denosumab)

Purified Recombinant Human RANKL

This biosimilar antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration.

Liquid

Recombinant biosimilar antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates.

Functional grade biosimilar antibodies may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at -80°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only (RUO). Non-Therapeutic.

2-8°C Wet Ice

Denosumab activity is directed against human RANKL (receptor activator of NFκB ligand).

Osteoporosis is a disease of bone microarchitecture deterioration commonly seen in postmenopausal women¹. Estrogen deficiency leads to low bone mass and increased bone fragility due to bone resorption increasing more than formation. Those affected have an increased risk of fracture. RANKL (receptor activator of NFκB ligand) is a TNF family member that acts as a key bone resorption protein by mediating osteoclast formation, activation, and survival via activating its receptor RANK^1,2.

Denosumab, a fully human monoclonal antibody originally generated using transgenic Xenomouse technology, selectively and with high affinity binds to and inhibits human RANKL, thus preventing interaction with and activation of its receptor RANK on the surface of osteoclasts and their precursors². This blocking activity inhibits the formation, function, and survival of osteoclasts, resulting in reduced bone resorption and consequently reduces the risk of vertebral, nonvertebral and hip fractures. Denosumab increases bone mineral density (BMD) and trabecular and cortical bone strength, with continued antifracture and BMD benefits over 10 years of therapy. Bone resorption is inhibited in cynomolgus monkeys and humans, but not normal mice or rats.

Unlike bisphosphonates, denosumab is not incorporated into bone and its effects on bone turnover markers, BMD and histomorphometric measures are generally reversed upon its discontinuation¹.

RANKL binds to its receptor RANK, which is located on osteoclasts and osteoclast precursors.

RANK/RANKL

1. Deeks ED. Drugs Aging. 35(2):163-173. 2018.
2. Kostenuik PJ, Nguyen HQ, McCabe J, et al. J Bone Miner Res. 24(2):182-195. 2009.
3. Cummings SR, San Martin J, McClung MR, et al. N Engl J Med. 361(8):756-765. 2009.
4. Eastell R, Christiansen C, Grauer A, et al. J Bone Miner Res. 26(3):530-537. 2011.
5. Simon JA, Recknor C, Moffett AH Jr, et al. Menopause. 20(2):130-137. 2013.
6. Bone HG, Wagman RB, Brandi ML, et al. Lancet Diabetes Endocrinol. 5(7):513-523. 2017.