HIV Antibody Variants with Enhanced Solubility
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapies for HIV infection, such as antiretroviral therapies, while reducing AIDS-related deaths, do not adequately address the ongoing health issue of HIV infections, necessitating the development of more effective treatments or preventive measures.
Innovation Solution
Development of antibody variants, like PGT121, and their antigen-binding fragments with specific mutations in the heavy and light chain variable domains, which retain the ability to neutralize HIV-1, offering improved biophysical properties and potential therapeutic or preventive applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antiretroviral therapies are used to treat HIV infection, then AIDS-related deaths are reduced, but the ability to adequately address ongoing HIV infections is insufficient
Solution Approach 1:
The patent introduces specific amino acid mutations in the antibody variable domains (such as A27G, D31E, D31S, R39Q, S40P, D56E, D56S, N68T, V78F, S81K, V83S, A84S, K92V, N124Q in heavy chain and S1P, D2S, E9Q, H30Q, S37V, P58S, P61G, S72G, D87E, T101K in light chain) to modify the antibody's biophysical properties and neutralization capabilities, enabling it to effectively address ongoing HIV infections while maintaining treatment reliability
2Reliability
If native PGT121 antibody is used to neutralize HIV-1, then viral neutralization capability is achieved, but biophysical properties such as solubility and stability are insufficient
Solution Approach 1:
The patent applies specific amino acid substitutions and modifications in the antibody variable domains to improve biophysical properties such as solubility and stability while preserving the essential viral neutralization capability. These parameter changes in the molecular structure enable the antibody to maintain therapeutic effectiveness with improved physical and chemical characteristics
Data Source
AI summary
Featured are PGT121 variant antibodies or fragments thereof, which can be administered, e.g., as antibody therapies for treating human immunodeficiency virus (HIV) infection. In particular, featured are methods of treating subjects infected with HIV and/or blocking HIV infections in subjects at risk of HIV transmission using the PGT121 variant antibodies or fragments thereof.