SARS-CoV-2 Antibodies to Treat or Diagnose COVID-19

This invention includes multiple high affinity, human antibodies that selectively target the SARS-CoV-2 virus which is responsible for COVID-19. Each antibody was identified by screening an internally developed human single chain variable fragment (scFv) library against different components of the SARS-CoV-2 virus particle. Successful screening protocols yielded three different antibodies; one against the receptor binding domain (RBD) of the spike protein (S-protein), one against the membrane protein (M-protein), and one against the envelope protein (E-protein). These novel high affinity antibodies can be used as theranostic tools individually or in combination to treat or diagnose COVID-19.     

 

Stage of Development

 

In vitro data: The S-protein scFv has been integrated into a full-length human IgG1 and displays a final binding affinity of 132 pM. The full-length S-protein targeted IgG demonstrates successful binding against 2 different spike protein constructs and the RBD specifically. Additionally, neutralization studies revealed that this antibody effectively neutralized SARS-CoV-2 by preventing the binding to the ACE2 receptor. The M-protein and E-protein scFvs were recently identified and are currently undergoing structure-guided optimization to further improve their binding affinity.

 

Competitive Landscape

 

There are currently more than 1,500 assets in development for COVID-19 and is segmented into two different categories, therapeutics and vaccines (i.e. prophylactics). Furthermore, the therapeutics segment is primarily composed of two different therapeutic strategies, the antivirals which inhibit viral function (entry, replication, etc.) and antibodies which alter the host’s immune system activation in response to pathogens. For the human body, the most effective and efficient way to resist viral infection is to neutralize the virus with antibodies so that it is unable to infect and damage healthy cells within the host.  However, in order for antibodies to be effective against SARS-CoV-2, they must demonstrate high binding affinities to compete against the binding affinity of SARS-CoV-2 to the host’s ACE2 receptor (KD =15 nM). Many of the antibodies in development display similar binding affinities between 1-50 nM. As a result, many of these antibodies display some level of neutralization, but not complete neutralization. Our S-protein antibody, which displays a binding affinity of 132 pM allows for complete neutralization of the SARS-CoV-2 virus in vitro and demonstrates significant promise for applications in vivo. Additionally, our M-protein and E-protein targeted antibodies present new opportunities for combination therapies or diagnostic applications. 

 

Competitive Advantages

 

•       High binding affinity

•       Complete neutralization of SARS-CoV-2

•       Potential for combination approach

 

Patent Information:
Licensing Contact
Paige Glumac
pglumac@houstonmethodist.org

Inventors:
Xian Li
Xiaohua Lou