A droplet microfluidics-based platform for generating target-specific, natively-paired immune libraries and identifying potent and developable antibodies

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Author notes

1. Sarah A. Clark

   Present address: Arcellx, Rockville, MD, 20850, USA

2. Partha S. Chowdhury

   Present address: Johnson & Johnson R&D Center, Springhouse, PA, 19477, USA

3. Anusuya Ramasubramanian

   Present address: Dana-Farber Cancer Institute, Boston, MA, 02215, USA

4. Kevin Kramer

   Present address: Paragon Therapeutics, Waltham, MA, 02453, USA

5. Nikolai Suslov

   Present address: Alloy Therapeutics Inc., Waltham, MA, 02453, USA

6. Sambasiva Rao Pemmaraju

   Present address: Takeda Pharmaceuticals, Cambridge, MA, 02142, USA

7. These authors contributed equally: Brendan T. Deveney and Sarah A. Clark.

Authors and Affiliations

1. Large Molecule Research Platform USA, Sanofi R&D, 350 Water Street, Cambridge, MA, 02141, USA

   Anusuya Ramasubramanian, Sarah A. Clark, Paula Boutin, Saleh Riahi, Taotao Lao, Megan Salemi, Sagar Kathuria, Leighton Marcovici, Joern Hopke, Jocelyn Newton, Kalie Mix, Kevin Kramer, Nikolai Suslov, Ankit Mahendra, Sambasiva Rao Pemmaraju & Partha S. Chowdhury

2. Large Molecule Research Platform France, Sanofi R&D, 13 Quai Jules Guesde, 94403, Vitry-sur-Seine, France

   Hélène Erasimus & Guillaume Mottet

3. Large Molecule Research Platform Germany, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt am Main, Germany

   Pep Amengual-Rigo, Dilyana Dimova & Norbert Furtmann

4. Experimental Soft Condensed Matter Group, School of Engineering and Applied Sciences (SEAS), Harvard University, Cambridge, MA, 02138, USA

   Anusuya Ramasubramanian, Brendan T. Deveney, Kayla Keepseagle, David A. Weitz & John A. Heyman

Contributions

A.R., J.A.H., B.D., S.A.C., P.S.C, and D.A.W. designed the initial research study. A.R., B.D., S.A.C, P.B., K.K., T.L., M.S., S.K., P.A-R, D.D., L.M., J.H., J.N., K.M. and K.K. performed the experiments outlined in the manuscript. A.R., S.R., S.A.C, P.A-R, D.D. and J.A.H collated, analyzed and interpreted antibody sequencing. A.R., B.D., S.A.C, N.F., H.E., G.M., N.S., A.M. and S.R.P. and J.A.H interpreted and discussed the data. A.R. and J.A.H wrote the paper and all authors participated in manuscript review and revisions.

Corresponding authors

Correspondence to Anusuya Ramasubramanian or John A. Heyman.

Competing interests

A.R, S.A.C, P.B., S.R., T.L, M.S., S.K., P.A-R, D.D., L.M., J.H., J.N., K.M., K.K, H.E., N.F., G.M., N.S., A.M., S.R.P. and P.S.C. are or were previously affiliated with Sanofi. All work was completed at Sanofi and Harvard University. As such, the work was not conducted at J&J or any of the other current author affiliations, and does not reflect the opinions of J&J, its affiliates or any other current author affiliations. In accordance with Taylor & Francis policy and our ethical obligations as researchers, B.D., D.A.W. and J.A.H. report being inventors on the patent describing “the film-forming surfactant” used in this work titled: Copolymers for stabilizing fluorocarbon emulsions and forming interfacial films therein: Inventors: Dave Weitz, Joerg Gerd Werner, Julie V. Brouchon, John A Heyman and Brendan Deveney. Pat. Apl. Ser. No.: 62/852,750. B.D., J.A.H. and D.A.W. have no other potential competing interests. All other authors declare no other competing interests.

Ethics approval for animal experimentation

All experiments were reviewed, approved and conducted in an Association for Assessment and Accreditation of Laboratory Care International (AAALACi)-approved animal facility, the Sanofi Genzyme Institutional Animal Care and Use Committee. All methods were performed in accordance with the relevant Sanofi institutional guidelines and regulations. Further, all authors complied with ARRIVE guidelines.

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