SARS-CoV-2 variant nanobodies and constructs comprising such nanobodies
| DWPI Title: New nanobody or construct comprising nanobody that comprises first binding domain, where nanobody or construct comprising nanobody comprises polypeptide sequence comprising amino acids, and first binding domain binds to spike protein of coronavirus or receptor-binding domain of coronavirus |
| Abstract: 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. |
| Use: Nanobody or construct. |
| Advantage: Nanobodies or construct has 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 single domain antibodies (sdAbs) with all the attributes of nanobodies with improved half-life and optimized effector functions, and neutralizes the original SARS-COV-2 and several of its variants have been identified including Delta with high efficacy. |
| Novelty: Nanobody or construct comprising a nanobody that comprises a first binding domain, is new, where the nanobody or construct comprising the nanobody comprises a polypeptide sequence comprising 119-122 amino acids (SEQ ID NOs: 340-398), given in the specification. The first binding domain binds to a spike protein of a coronavirus or a receptor-binding domain of a coronavirus. |
| Filed: 6/27/2022 |
| Application Number: US17849928A |
| Tech ID: SD 16033.0 |
| This invention was made with Government support under Contract No. DE-NA0003525 awarded by the United States Department of Energy/National Nuclear Security Administration. The Government has certain rights in the invention. |
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