SARS-CoV-2 variant nanobodies and constructs comprising such nanobodies

Patent · Tue Sep 17 04:00:00 EDT 2024

OSTI ID:2542601

Harmon, Brooke Nicole; Pham, Le; McIlroy, Peter Riches; Light, Yooli Kim

A large and highly diverse nanobody library was constructed and screened against multiple variants of SARS-COV-2 to find nanobodies with high sensitivity and specificity for the variants. Four rounds of positive selection against a panel of six diverse SARS-COV-2 variant RBDs was performed with our high-diversity. At least 59 of these nanobodies were found to work well against Alpha, Beta, Gamma, Delta, Kappa, Lambda and Mu with some overlap efficacy against other variants. These nanobodies have efficacy as stand-alone nanobodies and as a construct comprising nanobodies linked to the human IgG1 constant fragment (Fc) (nanobody-hFc constructions or nb-hFcs) to make enhanced humanized sdAbs with all the attributes of nanobodies with improved half-life and optimized effector functions. Several promising nanobodies that neutralize the original SARS-COV-2 and several of its variants have been identified, including Delta, with high efficacy. In particular, a subset of these nanobodies bind to the Omicron RBD.

• Research Organization: Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)
• Sponsoring Organization: USDOE National Nuclear Security Administration (NNSA)
• DOE Contract Number: NA0003525
• Assignee: National Technology & Engineering Solutions of Sandia, LLC (Albuquerque, NM)
• Patent Number(s): 12,091,446
• Application Number: 17/849,928
• OSTI ID: 2542601
• Country of Publication: United States
• Language: English