Anti-IL-4 [SB240683 (Pascolizumab, humanized 3B9)]

Absolute Antibody

Anti-IL-4 [SB240683 (Pascolizumab, humanized 3B9)]

7

The original mouse version of this antibody can recognize recombinant human IL-4 in an ELISA and is also capable of inhibiting IL-4 dependent T-cell proliferation in vitro (PMID: 7517357). Binding of this humanized antibody completely blocks the binding of IL-4 to IL-4R. An in vitro study demonstrated that pascolizumab effectively neutralized IL-4 bioactivity in human cell lines including inhibited the proliferation of human T cells, human B cells and TF-1 cells, inhibition of interleukin-4-dependent IgE production by human PBMCs and up-regulation of FcRII. It also inhibited the early events of asthma including TH2 cell differentiation, eosinophilia and IgE up-regulation. In vivo pharmacokinetic and chronic safety testing in cynomolgus monkeys demonstrated that pascolizumab was well tolerated without inducing adverse clinical responses (PMID:12296858). The pharmacokinetics of the human version of this antibody in the male Sprague Dawley rat was studied and the half life of the antibody was determined to be 11 days (US5914110A). A Phase I trial with a single intravenous dose in mild to moderate asthma demonstrated that it was well tolerated and had an elimination half-life of more than 2 weeks (Shames et al., 2001). However, a subsequent large-scale, multidose phase II trial in steroid-naive subjects with asthma was terminated because preliminary data showed that pascolizumab did not provide clinical benefit (clinical trials: NCT00024544).

Functional Assay, ELISA, Neutralisation/Blocking

ELISA, Inhibit; Block; therapeutic; functional assay

Research Use Only

Monoclonal

SB240683 (Pascolizumab, humanized 3B9)

IL4

interleukin 4

B cell growth factor 1; B_cell stimulatory factor 1; BCGF1; BCGF-1; binetrakin; BSF1; BSF-1; IL-4; interleukin 4 variant 2; interleukin-4; lymphocyte stimulatory factor 1; pitrakinra

Human

IgG1

Interleukin-4

Human, cynomolgus monkeys

The original mouse antibody was generated by immunizing F1 hybrids of Balb/c and C57BL/6 mice with recombinant human IL-4 in Freunds complete adjuvant. The humanized version was generated by grafting CDRs of murine parent antibody onto human IgG1 kappa heavy- and light-chain frameworks.

-20°C,2°C to 8°C

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