I. Project Background

The target molecule is an IgM-form neutralizing antibody against SARS-CoV-2. It needs to be developed as a multi-dose nasal spray liquid formulation to provide mucosal protection. The project timeline is tight, requiring completion of the entire process from R&D to scale-up within an extremely short timeframe.

II. Technical Challenges

IgM antibodies typically exhibit low expression levels, and enhancing expression is challenging. There is a risk of expressing a high proportion of hexamer impurities. Difficulties include virus filtration and removal of aggregates. The intended use under ambient conditions, combined with the nasal spray device, poses significant challenges to formulation stability. Analytical characterization of IgM antibodies is also challenging.  

III. IgMax® Vector Platform Addressing Expression Challenges

• Typical IgM expression levels are below 1 g/L.
• Hanteng's proprietary IgMax® vector platform significantly increases IgM expression, achieving levels up to 8 g/L or higher.
• The expressed IgM exhibits homogeneous conformation, with the pentamer proportion approaching 100%.

IV. Downstream Process Optimization Addressing Process Challenges

• IgM antibody has a large molecular weight (970 kDa) and a particle size of 20–30 nm, which approaches or even exceeds the pore size of conventional virus removal filters, making filtration difficult.
• Through virus filter screening combined with process optimization, high-yield, high-capacity virus filtration for large-molecular-weight proteins has been achieved. Validated LRV > 4 log₁₀ and capacity testing have been performed.

• High aggregate ratio, difficult to remove.
• Hydrophobic interaction chromatography (HIC) presents challenges in IgM elution, resulting in low recovery.