Human IL-12 & IL-23 p40 Antibody - Ustekinumab Biosimilar

Anti-human IL-12/IL-23 - Ustekinumab biosimilar - CAS #815610-63-0

Binding of anti-IL-12/IL-23 mAb

Anti-hIL-12/IL-23-p40-hIgG1 is a biosimilar antibody of Ustekinumab targeting the shared p40 subunit of interleukins IL-12 and IL-23. Ustekinumab inhibits the activity of IL-12 and IL-23 by preventing their binding to the IL-12 receptor β1 (L-12Rβ1). Ustekinumab is FDA-approved for treating autoimmune disorders such as Crohn's disease, ulcerative colitis, plaque psoriasis, and psoriatic arthritis.

 More details

Anti-hIL-12/IL-23-p40-hIgG1 comprises the variable region of Ustekinumab and the IgG1 constant region of Ustekinumab for high effector functions. 

This antibody can be used together with recombinant human IL-12 for screening and neutralization assays to block IL-12 signaling in HEK-Blue™ IL-12 cells. It can also be used together with recombinant human IL-23 for screening and neutralization assays to block IL-23 signaling in HEK-Blue™ IL-23 cells​ (see figures).

Key features

• Each lot is functionally tested and validated
• The complete sequence of the antibody construct has been verified
• Absence of endotoxins determined by the EndotoxDetect assay

InvivoGen’s products are for research use only, and not for clinical or veterinary use.

Figures

Dose-dependent inhibition of HEK-Blue™ IL-12 or HEK-Blue™ IL-23 cells response using Ustekinumab biosimilar. Increasing concentrations of Anti-hIL-12/IL-23-p40-hIgG1 (0.3 ng/ml - 30 µg/ml) were incubated with recombinant human (h)IL-12 (3 ng/ml) or hIL-23 (300 ng/ml) for 1 h before the addition of either HEK-Blue™ IL-12 cells (A) or HEK-Blue™ IL-23 cells (B). After overnight incubation, SEAP activity in the cell culture supernatant was assessed using QUANTI-Blue™ Solution. Data are shown in percentage of activity (%) (mean ± SEM).

Specifications

Application: Neutralization assay, ELISA

Isotype:  Human IgG1, kappa

Recommended isotype control: Human IgG1

Target: Human IL-12, Human IL-23

Species reactivity: Human

Clone: Ustekinumab

Cas number: 815610-63-0

Sterility: 0.2 µm filtration

Source: CHO cells 

Production: Animal-free

Purification: Protein A

Molecular weight: 146 kDa

Physical form: Lyophilized

Formulation buffer: Sodium phosphate buffer with glycine, saccharose, and stabilizing agents

Preservative: Azide-free

Reconstitution buffer: Sterile water (not provided)

Purity: ≥ 95 %

Quality control: Each lot is functionally tested and validated

Contents

Anti-hIL-12/IL-23-p40-hIgG1 purified monoclonal antibody is provided azide-free and lyophilized. It is available in two quantities:

• hil12p40-mab1​: 100 µg
• hil12p40-mab1-03: 3 x 100 µg

 The product is shipped at room temperature.

 Upon receipt, store lyophilized antibody at -20 °C.

 Lyophilized product is stable for at least 1 year.

 Avoid repeated freeze-thaw cycles.

Details

Ustekinumab background

Ustekinumab is a fully human IgG1 monoclonal antibody (mAb) targeting the shared p40 subunit of interleukin 12 (IL-12) and IL-23 [1]. These cytokines are critical in driving inflammatory and autoimmune responses associated with various diseases [1-2]. By binding to the p40 subunit, Ustekinumab blocks the interaction of IL-12 and IL-23 with the IL-12 receptor β1 (IL-12Rβ1 or CD212) found on the surface of natural killer cells and T cells [1]. Importantly, Ustekinumab does not bind to endogenous IL-12 or IL-23 already complexed with the receptor, making it unlikely to mediate Fc effector functions, such as antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) [1].

Upon binding, Ustekinumab neutralizes IL-12-mediated responses, including STAT4 phosphorylation, cell surface marker expression, and IFNγ cytokine production. Similarly, it inhibits IL-23-driven responses, such as STAT3 phosphorylation and the production of cytokines IL-17A, IL-17F, and IL-22 [1]. By blocking these pathways, Ustekinumab suppresses the activation and differentiation of CD4+ T cells and inhibits Th1 and Th17 signaling cascades, leading to a significant reduction in inflammation [1-2]. These mechanisms underlie its clinical efficacy in treating several immune-mediated disorders. Ustekinumab is FDA-approved for the treatment of moderate to severe plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis [3].

References:

1. Benson, J.M, et al., 2011. Discovery and mechanism of ustekinumab: a human monoclonal antibody targeting interleukin-12 and interleukin-23 for treatment of immune-mediated disorders. MAbs 3(6):535-545.
2. Montepaone M, et al. 2014. Profile of ustekinumab and its potential in the treatment of active psoriatic arthritis. Open Access Rheumatol. ;6:7-13.
3. FDA website accessed in Nov 2024: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761044s013lbl.pdf#page=37