Anti-Human Sclerostin (SOST) (Romosozumab)

Scl-AbII is the murine IgG1 parent. Immunogen unknown.

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.

To protect mouse colonies from infection by pathogens and to assure that experimental preclinical data is not affected by such pathogens, all of Leinco’s recombinant biosimilar antibodies are tested and guaranteed to be negative for all pathogens in the IDEXX IMPACT I Mouse Profile.

Functional grade preclinical 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 ≤ -70°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only

2 – 8° C Wet Ice

This non-therapeutic biosimilar antibody uses the same variable region sequence as the therapeutic antibody Romosozumab. AMG 785 (Romosozumab) activity is directed against human and cynomolgus monkey sclerostin (SOST).

SOST (sclerostin) is a secreted glycoprotein that acts as a negative regulator of bone growth via inhibition of Wnt signaling¹. SOST functions by blocking LRP5/6 co-receptors and binding to LRP4². SOST is expressed in the developing embryo, where it is involved in limb patterning¹. Dysregulation of SOST is associated with numerous diseases including postmenopausal osteoporosis², osteoarthritis¹, ankylosing spondylitis, and rheumatoid arthritis. Mutations are also associated with inherited high bone mass conditions involving excessive bone formation, such as sclerosteosis, craniodiaphyseal dysplasia, and Van Buchem Disease². SOST has also been observed in bone tumors and bone cancer cell lines¹. Monoclonal antibodies can be used to target SOST and promote new bone formation.

AMG 785 (Romosozumab) is a humanized monoclonal antibody against SOST that was developed for the treatment of osteoporosis³. Romosozumab was generated as a high-affinity PEGylated antibody fragment against SOST using the Selected Lymphocyte Antibody Method (SLAM) along with proprietary antibody fragment technologies. Scl-AbII is the murine IgG1 SOST-neutralizing parent antibody. The humanized version Scl-AbIV induces a dose-dependent increase in bone mineral density in cynomolgus monkeys⁴. Additionally, Romosozumab leads to increased bone mineral density in humans^5,6,7,8.

SOST production at the protein level has been confirmed in osteocytes, osteosarcomas, osteoclasts, hypertrophic chondrocytes, articular cartilage-osteoarthritis, cementocytes, multiple myeloma (MM) patient CD138⁺ plasma cells and human MM cell lines, breast cancer cell line MDA-MB-231, prostate cancer, and aortic valves in areas adjacent to calcification in hemodialysis patients.

LRP4, LRP5, LRP6, PKHF2

1 Weivoda MM, Youssef SJ, Oursler MJ. Bone. 96:45-50. 2017.
2 Martínez-Gil N, Roca-Ayats N, Cozar M, et al. Int J Mol Sci. 22(2):489. 2021.
3 Markham A. Drugs. 79(4):471-476. 2019.
4 Ominsky MS, Vlasseros F, Jolette J, et al. J Bone Miner Res. 25(5):948-959. 2010.
5 Padhi D, Jang G, Stouch B, et al. J Bone Miner Res. 26(1):19-26. 2011.
6 McClung MR, Grauer A, Boonen S, et al. N Engl J Med. 370(5):412-420. 2014.
7 Cosman F, Crittenden DB, Adachi JD, et al. N Engl J Med. 375(16):1532-1543. 2016.
8 Langdahl BL, Libanati C, Crittenden DB, et al. Lancet. 390(10102):1585-1594. 2017.