Obiltoxaximab is a recombinant, affinity-enhanced, de-immunized chimeric IgG1 kappa (IgG1κ) monoclonal antibody directed against the protective antigen (PA) component of Bacillus anthracis toxin. It binds free protective antigen and prevents the toxin complex from interacting with host-cell receptors.
Obiltoxaximab is a biologic drug substance with an approximate glycosylated molecular mass of 148.1–148.6 kDa, according to the EMA assessment. It contains two heavy chains and two kappa light chains, with N-linked glycosylation at Asn-299 on the heavy chain.
The FDA describes obiltoxaximab as an affinity-enhanced, de-immunized IgG1κ monoclonal antibody with an approximate molecular weight of 148 kDa.
Unlike conventional chemical APIs, obiltoxaximab does not have a practically useful small-molecule-style structural formula for routine pharmaceutical specification purposes. WHO describes it as an immunoglobulin G1-kappa anti-Bacillus anthracis protective-antigen chimeric monoclonal antibody with defined heavy- and light-chain sequences.
The antibody contains human constant-region sequences together with de-immunized murine variable-region sequences derived from the murine 14B7 antibody.
Obiltoxaximab binds the protective antigen component of Bacillus anthracis toxin. By binding free protective antigen, it prevents PA from binding to cellular receptors and consequently interferes with intracellular delivery of the lethal factor and edema factor components of anthrax toxin.
Obiltoxaximab is used as an anthrax antitoxin in combination with appropriate antibacterial therapy for treatment of inhalational anthrax and for post-exposure prophylaxis when alternative therapies are not appropriate or available.
As a monoclonal antibody, obiltoxaximab requires biologic-specific analytical characterization. EMA states that the active-substance specification was established according to ICH Q6B and includes controls for:
The potency of the active substance is evaluated using a functional Lethal Toxin Neutralisation Assay (LNA), with neutralizing activity expressed using EC50 and relative potency against a qualified reference standard.
The marketed U.S. product ANTHIM is supplied as 600 mg/6 mL, equivalent to 100 mg/mL obiltoxaximab. The finished-product solution has a pH of 5.5 and is described as clear to opalescent and colorless to pale yellow/pale brownish-yellow. These values apply to the finished drug product, not necessarily to the isolated drug substance.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 10 ppm |
| Individual Impurity | NMT 0.1% |
| Water Content | NMT 5.0% |