Anti-Human VEGF-A (Ranibizumab) – Fc Muted™

Derived from murine monoclonal anti-VEGF antibody, original 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 Ranibizumab. RG-3645 (Ranibizumab) activity is directed against human and cynomolgus monkey VEGF-A. The antibody targets all VEGF-A isoforms.

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.

Ranibizumab is a high-affinity recombinant, humanized antibody that neutralizes all isoforms of VEGF-A^8,9. Ranibizumab was derived from a murine monoclonal anti-VEGF antibody¹⁰and consists of a nonbinding human sequence and a high affinity murine binding epitope¹¹. When injected intravitreously, ranibizumab can penetrate the internal limiting membrane and access the subretinal space. Ranibizumab reduces the proliferation of endothelial cells as well as vascular permeability and formation of new blood vessels by preventing VEGF-A from interacting with its receptors on the endothelial cell surface⁹. Ranibizumab is also able to inhibit human umbilical vein endothelial cell proliferation in vitro. Ranibizumab does not bind to mouse VEGF-A in vitro by Western blot, nor does it have a measurable biological effect after intraperitoneal or intravitreal injection in oxygen-induced-retinopathy mouse models¹². Intravitreal injections of ranibizumab in cynomolgus monkeys reduces choroidal neovascularization¹¹.

Ranibizumab is also known as RhuFab V2 in the literature¹⁰.

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, tissue repair, as well as during disease- related neovascularization.

Binds to: FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin, NRP1/neuropilin-1 receptor

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. Blick SK, Keating GM, Wagstaff AJ. Drugs. 67(8):1199-1206. 2007.
10. Eter N, Krohne TU, Holz FG. BioDrugs. 20(3):167-179. 2006.
11. Krzystolik MG, Afshari MA, Adamis AP, et al. Arch Ophthalmol. 120(3):338-346. 2002.
12. Ichiyama Y, Matsumoto R, Obata S, et al. PLoS One. 17(12):e0278951. 2022.