Characterization of Co-Formulated High-Concentration Broadly Neutralizing Anti-HIV-1 Monoclonal Antibodies for Subcutaneous Administration

Monoclonal Antibodies

by Vaneet K. Sharma 1,†OrcID,Bijay Misra 2,†,Kevin T. McManus 3,Sreenivas Avula 1,Kaliappanadar Nellaiappan 2OrcID,Marina Caskey 4,Jill Horowitz 4,Michel C. Nussenzweig 4,5,Michael S. Seaman 3,Indu Javeri 2 andAntu K. Dey 1,*OrcID

1 IAVI, 125 Broad Street, New York, NY 10004, USA
2 CuriRx, Inc., 205 Lowell Street, Wilmington, MA 01887, USA
3 Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
4 Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
5 Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA
* Author to whom correspondence should be addressed.

Both authors contributed equally to the work.

Antibodies 20209(3), 36; (registering DOI)
Received: 26 June 2020 / Revised: 21 July 2020 / Accepted: 23 July 2020 / Published: 29 July 2020
(This article belongs to the Special Issue Monoclonal Antibody-Directed Therapy)
The discovery of numerous potent and broad neutralizing antibodies (bNAbs) against Human Immunodeficiency Virus type 1 (HIV-1) envelope glycoprotein has invigorated the potential of using them as an effective preventative and therapeutic agent. The majority of the anti-HIV-1 antibodies, currently under clinical investigation, are formulated singly for intra-venous (IV) infusion. However, due to the high degree of genetic variability in the case of HIV-1, a single broad neutralizing antibody will likely not be sufficient to protect against the broad range of viral isolates. To that end, delivery of two or more co-formulated bnAbs against HIV-1 in a single subcutaneous (SC) injection is highly desired. We, therefore, co-formulated two anti-HIV bnAbs, 3BNC117-LS and 10-1074-LS, to a total concentration of 150 mg/mL for SC administration and analyzed them using a panel of analytical techniques. Chromatographic based methods, such as RP-HPLC, CEX-HPLC, SEC-HPLC, were developed to ensure separation and detection of each antibody in the co-formulated sample. In addition, we used a panel of diverse pseudoviruses to detect the functionality of individual antibodies in the co-formulation. We also used these methods to test the stability of the co-formulated antibodies and believe that such an approach can support future efforts towards the formulation and characterization of multiple high-concentration antibodies for SC delivery. View Full-Text