Discrepancies in the phase behaviors of therapeutic antibodies

BIOT 230

Branden Salinas, Branden.Salinas@Colorado.EDU1, Sathish Hasige1, Chris Allan2, Steven Bishop2, Ambarish Shah2, John F. Carpenter, john.carpenter@uchsc.edu3, and Theodore W. Randolph, Theodore.Randolph@colorado.edu4. (1) Department of Chemical and Biological Engineering, University of Colorado, Boulder, Boulder, CO 80309, (2) MedImmune, Inc, Gaithersburg, MD 20878, (3) Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, (4) Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309
Monoclonal antibodies (mAbs) have become popular drug candidates. Since antibodies produced in the same manner have high sequence identities it is often thought they will exhibit similar phase behavior. This study is concerned with two therapeutically relevant mAbs that provide an example to the contrary. There is a difference of an order of magnitude in the mAbs solubility's at their pIs.

A combination of static light scattering (SLS), membrane osmometry, differential scanning calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR) are utilized to analyze colloidal and structural non-idealities at wide range of protein concentrations. Along with the aforementioned solubility difference, the results have illuminated a reversible association in solution for one of the two mAbs. Furthermore, both events are buffer type and salt concentration dependent. This work reveals likely sources of these non-idealities and suggests that certain buffer types disrupt domain-domain interactions leading to intermolecular attraction and associations.

 

Biophysical and Biomolecular Symposium: Protein Aggregation
3:00 PM-5:20 PM, Wednesday, August 22, 2007 BCEC -- 108, Oral

Division of Biochemical Technology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007