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Alicanto: Proteogenomic discovery of single chain antibodies in llama

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44AI141046-02
Agency Tracking Number: R44AI141046
Amount: $1,096,486.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NIAID
Solicitation Number: PA19-272
Timeline
Solicitation Year: 2019
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-07-21
Award End Date (Contract End Date): 2022-06-30
Small Business Information
3210 Merryfield Row
San Diego, CA 92121-1126
United States
DUNS: 031092123
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 STEFANO BONISSONE
 (888) 416-9305
 stefano@digitalproteomics.com
Business Contact
 NATALIE CASTELLANA
Phone: (703) 727-0820
Email: ncastell@gmail.com
Research Institution
N/A
Abstract

Heavy chain-only antibodies (HCAbs) are a unique class of antibodies only produced in
camelids and cartilagenous fish. Unlike conventional antibodies that consist of two heavy
chains and two light chains, HCAbs consist only of heavy chains. The antigen-binding portion of
the camelid HCAb, called the VHH, is a polypeptide fragment with wide utility across
crystallography, imaging, and therapeutics. The small size and comparatively simple structure
of the VHH as compared to conventional antibodies makes them economical to produce and
structurally stable at a wider pH and temperature range.Growing evidence suggests that the epitopes targeted by HCAbs are distinct from those
targeted by conventional antibodies. Concave domains, such as enzyme active sites, are one
category that are preferentially targeted by HCAbs than conventional antibodies. This is in part
due to the ability of VHHs to produce convex conformations which enables targeting of sites
that are inaccessible to conventional antibodies.Phage display is the predominant method for discovering novel VHHs. HCAb transcripts
are cloned into phagemids, and phages that express a VHH that binds the target are enriched
through the process of panning. Attrition at cloning, panning, or final selection reduces the
accessible diversity of the immune system, and delivers antibodies that may not be as diverse
as the response mounted by the original host organism.In contrast to display-based methods, Alicanto combines next-generation sequencing
and mass spectrometry to directly identify antigen-specific circulating HCAbs from camelids.
Assessment of circulating HCAbs in serum is the primary method by which an immunization is
determined to be successful. While the serum is discarded after screening in the phage display
workflow, Alicanto uses mass spectrometry to identify the individual HCAbs comprising the
target-specific circulating antibodies. This enables Alicanto to discover low abundance
antibodies against challenging targets such as peptides and small molecules. By constructing
an in silico library of HCAb sequences using next-generation sequencing, Alicanto precludes the
need to clone into an intermediate host such as phages. Through direct analysis of the immune
response of llamas, Alicanto will deliver more, high affinity VHHs for use in research,
diagnostics, and therapeutics.Single chain antibodies derived from camelids are a unique class of molecules ideally suited for
a broad range of applications including therapeutics, structural biology, and histology. Alicanto
is a novel platform for discovering single chain antibodies from llamas that rapidly delivers more,
high affinity single chain antibodies than currently available technologies. Alicanto will enable
broader use of these unique molecules across research, diagnostics, and therapeutics.

* Information listed above is at the time of submission. *

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