Momenta Pharmaceuticals, Inc. (MNTA)

[floblu14]

Additional IVG report -

Proceedings of the National Academy of Sciences of the United States of America PNAS - received for review November 24, 2014

Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity

Research Department, Momenta Pharmaceuticals, Cambridge, MA 02142; and Institute of Genetics, Department of Biology, University of Erlangen-Nürnberg, 91058 Erlangen, Germany


Significance

IgG fragment crystallizable domain (Fc) sialylation has emerged as an important but controversial concept for regulating anti-inflammatory activity of antibodies. Moreover, translating this concept to potent anti-inflammatory therapeutics has been hampered by the difficulty of generating suitable sialylated products for human use. We describe for the first time, to our knowledge, the development of a robust, scalable process to generate a sialylated intravenous immunoglobulin (IVIg) drug candidate with maximum Fc sialylation devoid of unwanted modifications. By using a wide panel of physicochemical analytics and in vivo models, we have validated the quality and potent anti-inflammatory activity of this clinical candidate. This report not only confirms the controversial anti-inflammatory activity of IgG-Fc sialylation, it also represents the first sialylated IVIg preparation, to our knowledge, with consistent anti-inflammatory potency suitable for clinical development.

Abstract (Excerpt)

To our knowledge, this candidate represents the first s4-IVIg suitable for clinical use; it is also a valuable therapeutic alternative with more consistent and potent anti-inflammatory activity.

http://www.pnas.org/content/early/2015/02/26/1422481112.abstract