Discovering the Next Greatest Diagnostic…
The year 2020 will go down in history as the year in which the biopharmaceutical field mobilized with unprecedented speed and innovation to develop tools and treatments to corral a devastating pandemic. Following the outbreak of the Severe Acute Respiratory Syndrome – Coronavirus 2 (SARS-CoV-2), an unrivaled wave of scientific research and initiative came forth. The development of reliable and sensitive SARS-CoV-2 diagnostics has been and remains to be of vital importance necessary to contain and eradicate the disease. Early in the pandemic, Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID) and a key member of the White House Coronavirus Task Force, estimated that the United States was conducting close to two million diagnostic tests a week. The US will need to “have enough tests to respond to the outbreaks that will inevitably occur as you try and ease your way back into the different phases”. Without a proper test, suspected infectious individuals cannot be diagnosed, quarantined, or treated.
Coming up with an effective technology is no easy task…
Apollos Diagnostics, a subsidiary of Folium BioMed, LLC (Seattle, WA), was established to design, develop, and commercialize a rapid test for SARS-CoV-2. This new diagnostic test would have to fulfill several classic and indispensable criteria. “It must be portable, accessible, manufacturable, accurate…” said John Alderete, PhD, MBA, Founder and President of Folium Biomed, LLC.
The idea, a tried-and-true diagnostic platform: the lateral flow assay (LFA). Using the same concept as an over-the-counter pregnancy test, the ‘sandwiching’ of SARS-CoV-2 viral particles by two different antibodies that bind to distinct viral epitopes produces a visual line indicating a positive diagnosis.
“Wall of Strips”: test strips representing different combinations of SARS-CoV-2 antibodies discovered at LakePharma enabling the detection of the SARS-CoV-2 virus
“We appreciate the power antibodies have when it comes to their diagnostic capability … The core of an effective LFA test is access to specific antibodies against the viral target. While other test developers were re-purposing SARS-CoV antibodies that were cross-reactive to SARS-CoV-2 … Apollos opted to reveal the most immunologically relevant epitopes from SARS-CoV-2 that would ultimately lead to highly sensitive and specific antibodies to the virus”.
LakePharma (San Carlos, CA), leading U.S.-based contract research, development, and manufacturing organization (CRDMO), was chosen for the development of this new diagnostic. Not long after conceptualizing the novel LFA idea, antibody discovery scientists at LakePharma immunized a cohort of PentaMiceTM, a proprietary, royalty-free platform comprising 5 unique strains of immunologically diverse wild-type mice.
The immune system will reveal what is important…
Over the years, several modes of antibody discovery have come to fruition, from hybridoma (the “bread and butter” of antibody discovery from which close to ninety percent of therapeutic and diagnostic antibodies are derived), phage and yeast display, to the more recent single B cell cloning. What drew Apollos to hybridomas was familiarity. “We know it works … and we trusted their (the Discovery Immunology Team at LakePharma) expertise,” said Alderete.
Armed with PentaMice and the experience of well over one hundred individual antibody campaigns, the Discovery Immunology Team got to work. After several immunizations with heat-inactivated SARS-CoV-2 virus, blood titer checks showed a robust antibody response against the spike (S) and nucleocapsid (N) viral surface proteins, enabling the scientists to move forward with the hybridoma generation process (visit for more on the history, technology, and utility of hybridoma-based antibody discovery).
Following a standard ten x 384-well plate ELISA primary screen, hundreds of lead antibodies were discovered and advanced for specificity analysis against SARS-CoV-2 proteins (e.g., S vs. N) as well as viral proteins present in other coronaviruses known to infect humans.
“The discovered antibodies were truly remarkable in terms of sensitivity, specificity, and binning,” said Kathleen Kennedy, Ph.D., Director of Research and Development, Apollos Diagnostics LLC (Seattle, WA).
Epitope binning is of the utmost importance when developing a diagnostic to determine whether the discovered antibodies bind to the same or different epitopes on the targeted antigen. One antibody enables the capture of the SARS-CoV-2 viral particle while another, which binds to a completely distinct epitope, allows for viral identification, ultimately providing the patient with the proper diagnosis.
Bring to Life…
Beyond its reputation, “what compelled us to go with LakePharma was the continuity… from discovery to commercialization” shared Alderete. With a companywide workflow that consists of up-front due diligence in developing a strategy for maximal success for the antibody discovery campaign to lead candidate characterization and engineering, to GMP process development and manufacturing, LakePharma scientists are there every step of the way.
“As a small company we have to thread the needle. Between the regular process and what we needed to move forward, LakePharma satisfied many of our requests”. The next step: manufacturing the antibodies at a large enough scale to meet demand. GMP production of Apollos’ diagnostic antibodies is currently ongoing at LakePharma’s Hayward, California facility. GMP biomanufacturing of plasmid DNA, protein therapeutics, and vaccines is performed at LakePharma’s Hopkinton, Massachusetts site.
Your Success is Our Success…
CROs often refer to their clientele as “customers”. At LakePharma, we pride ourselves in seeing our clients not simply as customers but as valued partners and collaborators, focusing on alignment with project goals from the get-go and working in parallel towards ultimate success.
"LakePharma is nothing short of a true partner with Apollos Diagnostics. We will continue to work with LakePharma as a partner for all of our future antibody development campaigns!"
- John Alderete, Ph.D., MBA; Founder and President of Folium Biomed, LLC
As of today, Apollos has completed its antibody campaign and LFA development program and will be submitting its FDA Emergency Use Authorization (EUA) application soon in Q1 of 2021.