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

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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