Anti-Human IL-12/23 (Ustekinumab) – Fc Muted™

p40 subunit of IL-12/23

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 Ustekinumab. CNTO-1275 (Ustekinumab) activity is directed against the p40 subunit of IL-12 and IL-23.

IL-12 and IL-23 play a role in the differentiation and proliferation of type 1 T-helper cells (Th1)¹. IL-12 stimulates IFN-γ and TNF-α production via Th1 differentiation, whereas IL-23 causes activation of IL-17-producing T cells². IL-12 and IL-23 are members of the IL-12 cytokine family³. Members of the IL-12 family form soluble heterodimers consisting of α and β subunits. IL-12 and IL-23 both have a p40 subunit, and either p40 can bind to the IL-12 β1 receptor^1,2,4. IL-23 consists of IL-12p40 and IL-23p19³. IL-12 consists of IL-12p40 and IL-12p35.

IL-23 is associated with various autoimmune inflammatory diseases and is particularly highly expressed in psoriasis skin lesions^1,2. Furthermore, IL-23 is suspected to play a role in tumorigenesis³. Anti-IL12/23 p40 antibodies antagonize key pathways in inflammatory autoimmune diseases, such as arthritis and colitis^1,2.

Ustekinumab was developed from transgenic mice as an antibody against the p40 subunits of IL- 12/23^1,2. Ustekinumab binds with high affinity and specificity to p40, preventing interaction with the IL-12 β1 receptor found on natural killer cells or T cells and blocking downstream signaling, differentiation, and cytokine production^1,2,4. Additionally, ustekinumab inhibits up-regulation of cutaneous lymphocyte antigen, IL-2, IL-2Rα, and IL-12R as well as secretion of IFN-γ, TNF-α, and IL-17A.

Ustekinumab is used in clinical settings to treat plaque psoriasis, Crohn’s disease, and ulcerative colitis.

IL-12 is produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells. IL-23 is mainly secreted by activated dendritic cells, macrophages, or monocytes. Both are produced by activated antigen-presenting cells.

IL-12 β1 receptor

IL-12: P29460
IL-23: Q9NPF7

1. Reich K, Yasothan U, Kirkpatrick P. Nat Rev Drug Discov. 8(5):355-356. 2009.
2. Cingoz O. MAbs. 1(3):216-221. 2009.
3. Floss DM, Moll JM, Scheller J. Cells. 9(10):2184. 2020.
4. Kauffman CL, Aria N, Toichi E, et al. J Invest Dermatol. 123(6):1037-1044. 2004.
5. Toichi E, Torres G, McCormick TS, et al. J Immunol. 177(7):4917-4926. 2006.
6. Reddy M, Davis C, Wong J, et al. Cell Immunol. 247(1):1-11. 2007.
7. Krueger GG, Langley RG, Leonardi C, et al. N Engl J Med. 356(6):580-592. 2007.
8. Feagan BG, Sandborn WJ, Gasink C, et al. N Engl J Med. 375(20):1946-1960. 2016.
9. Brok HP, van Meurs M, Blezer E, et al. J Immunol. 169(11):6554-6563. 2002.