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The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies.
Copin, Richard; Baum, Alina; Wloga, Elzbieta; Pascal, Kristen E; Giordano, Stephanie; Fulton, Benjamin O; Zhou, Anbo; Negron, Nicole; Lanza, Kathryn; Chan, Newton; Coppola, Angel; Chiu, Joyce; Ni, Min; Wei, Yi; Atwal, Gurinder S; Hernandez, Annabel Romero; Saotome, Kei; Zhou, Yi; Franklin, Matthew C; Hooper, Andrea T; McCarthy, Shane; Hamon, Sara; Hamilton, Jennifer D; Staples, Hilary M; Alfson, Kendra; Carrion, Ricardo; Ali, Shazia; Norton, Thomas; Somersan-Karakaya, Selin; Sivapalasingam, Sumathi; Herman, Gary A; Weinreich, David M; Lipsich, Leah; Stahl, Neil; Murphy, Andrew J; Yancopoulos, George D; Kyratsous, Christos A.
  • Copin R; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Baum A; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Wloga E; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Pascal KE; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Giordano S; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Fulton BO; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Zhou A; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Negron N; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Lanza K; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Chan N; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Coppola A; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Chiu J; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Ni M; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Wei Y; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Atwal GS; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Hernandez AR; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Saotome K; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Zhou Y; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Franklin MC; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Hooper AT; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • McCarthy S; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Hamon S; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Hamilton JD; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Staples HM; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
  • Alfson K; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
  • Carrion R; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
  • Ali S; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Norton T; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Somersan-Karakaya S; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Sivapalasingam S; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Herman GA; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Weinreich DM; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Lipsich L; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Stahl N; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Murphy AJ; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Yancopoulos GD; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Kyratsous CA; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA. Electronic address: christos.kyratsous@regeneron.com.
Cell ; 184(15): 3949-3961.e11, 2021 07 22.
Article in English | MEDLINE | ID: covidwho-1252550
ABSTRACT
Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. Because rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment-induced emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of virus variants in SARS-COV-2 isolates found in COVID-19 patients treated with the two-antibody combination REGEN-COV, as well as in preclinical in vitro studies using single, dual, or triple antibody combinations, and in hamster in vivo studies using REGEN-COV or single monoclonal antibody treatments. Our study demonstrates that the combination of non-competing antibodies in REGEN-COV provides protection against all current SARS-CoV-2 variants of concern/interest and also protects against emergence of new variants and their potential seeding into the population in a clinical setting.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal / Mutation Type of study: Prognostic study / Randomized controlled trials Topics: Variants Limits: Animals / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.06.002

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 / Antibodies, Monoclonal / Mutation Type of study: Prognostic study / Randomized controlled trials Topics: Variants Limits: Animals / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.06.002