Anti-CMV Neutralizing Antibodies Blocking Viral Entry
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for effective vaccines or therapies to prevent or treat cytomegalovirus (CMV) infections, particularly in immunocompromised individuals and pregnant women, as CMV can cause severe morbidity and birth defects.
Innovation Solution
Development of anti-CMV antigen binding proteins, including monoclonal antibodies, that specifically bind to and neutralize CMV, blocking its entry into cells and preventing viral replication.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for CMV infection, then general immune support is provided, but severe morbidity and birth defects cannot be prevented in immunocompromised individuals and pregnant women
Solution Approach 1:
The patent uses a humanized antibody (pavacolimab) as an intermediary substance that specifically binds to the CMV gH-gL pentameric complex, blocking viral entry into cells. This mediator provides targeted neutralization of CMV without requiring the patient's own immune system to function, thereby preventing severe morbidity and birth defects in immunocompromised individuals and pregnant women where conventional immune-based treatments fail.
2Reliability
If vaccines or therapies are developed to prevent CMV, then protection against viral entry and replication is achieved, but the complexity of identifying effective neutralizing epitopes increases
Solution Approach 1:
The patent employs preliminary action by using phage display technology to pre-screen and identify antibody variants that bind to the CMV gH-gL pentameric complex before in vivo administration. This preliminary identification of effective neutralizing epitopes in a controlled in vitro system simplifies the subsequent therapeutic application, as the effective binding sites have already been characterized and selected for humanization.
Solution Approach 2:
The patent uses phage display to create copies of antibody variable regions that can be screened and selected for their ability to bind CMV. These copied and selected binding sites are then humanized and used in the therapeutic antibody, allowing identification of effective epitopes through copying and screening rather than direct de novo design.
3Reliability
If monoclonal antibodies are engineered to bind CMV, then specific neutralization is achieved, but the manufacturing complexity and cost increase
Solution Approach 1:
The patent applies parameter changes by humanizing the antibody sequence - changing the amino acid composition and structural parameters of the antibody to be predominantly human-derived while maintaining the critical CDR regions for CMV binding. This parameter change from fully non-human to humanized architecture simplifies manufacturing by reducing immunogenicity concerns and enabling production in standard mammalian cell cultures without requiring exotic production systems.
Data Source
Figure 1A
Figure 1B
Figure 1C~1D
AI summary
The present invention is directed to antigen binding proteins including, but not limited to, monoclonal antibodies and antigen binding fragments thereof, that specifically bind to and preferably neutralize human cytomegalovirus (CMV). The antigen binding proteins of the invention are useful as a prophylactic and/or therapeutic agent for preventing and/or treating CMV infections in a patient in need thereof. Also encompassed by the invention are pharmaceutical compositions comprising the antigen binding proteins of the invention and a pharmaceutically acceptable carrier. The invention further relates to methods of using the antigen binding proteins and pharmaceutical compositions of the invention for the prevention or treatment of CMV infection in patients in need thereof.