Anti-Human VEGF-A (Brolucizumab)

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 Brolucizumab. RTH-258 (Brolucizumab) binds and inhibits the three major isoforms of VEGF-A (VEGF110, VEGF121, VEGF165). Brolucizumab also binds cynomolgus monkey VEGF-A.

Vascular endothelial growth factor (VEGF), a potent proangiogenic cytokine¹, is the key signal used by oxygen-hungry cells to promote the growth of blood vessels. VEGF binds to specialized receptors on the surfaces of endothelial cells and directs them to build new vessels². VEGF are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angiogenesis). Abnormal VEGF function is associated with inflammatory diseases including atherosclerosis and hyperthyroidism^3,4,5,6. VEGF-A is a member of the VEGF gene family, and several isoforms can be generated by alternative splicing⁷. Additionally, VEGF-A is a major mediator of angiogenesis and plays a key role in various ophthalmic conditions, including age-related macular degeneration⁸.

RTH-258 (Brolucizumab) is a low molecular weight, humanized single-chain variable antibody fragment that inhibits the three major isoforms of VEGF-A⁹. Brolucizumab prevents the interaction of VEGF-A with its receptors VEGFR-1 and VEGFR-2, thereby suppressing endothelial cell proliferation, neovascularization, and vascular permeability.

Brolucizumab was developed for the treatment of wet age-related macular degeneration and macular edema⁹. It is formerly known as ESBA1008¹⁰.

VEGF-A is a secreted protein produced by diverse cell types, including aortic vascular smooth muscle cells, keratinocytes, macrophages, and many tumor cells. Expression begins during embryogenesis and declines after birth. VEGF-A expression is relatively low in most adult organs, except for the brain choroid plexus, lung alveoli, kidney glomeruli, and heart vascular beds. VEGF-A is also up-regulated during the development of the endocrine corpus luteum in pregnancy, wound healing, and tissue repair as well as during disease related neovascularization.

Binds to FLT1/VEGFR1, KDR/VEGFR2, DEAR/FBXW7-AS1and NRP1/neuropilin-1 receptors, heparan sulfate and heparin

1. Fainaru O, Adini I, Benny O, et al. FASEB J. 22(10):3728-3735. 2008.
2. Goodsell DS. Oncologist. 7(6):569-570. 2002.
3. Matsumoto T, Mugishima H. J Atheroscler Thromb. 13(3):130-135. 2006.
4. Shibuya M, Claesson-Welsh L. Exp Cell Res. 312(5):549-560. 2006.
5. Cross MJ, Dixelius J, Matsumoto T, et al. Trends Biochem Sci. 28(9):488-494. 2003.
6. Hicklin DJ, Ellis LM. J Clin Oncol. 23(5):1011-1027. 2005.
7. Holmes DI, Zachary I. Genome Biol. 6(2):209. 2005.
8. Ferrara N, Damico L, Shams N, et al. Retina. 26(8):859-870. 2006.
9 Markham A. Drugs. 79(18):1997-2000. 2019.
10 Holz FG, Dugel PU, Weissgerber G, et al. Ophthalmology. 123(5):1080-1089. 2016.