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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: 1R43AI141046-01
Agency Tracking Number: R43AI141046
Amount: $170,108.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NIAID
Solicitation Number: PA17-302
Timeline
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-08-20
Award End Date (Contract End Date): 2019-07-31
Small Business Information
4519 49TH ST
San Diego, CA 92115-3238
United States
DUNS: 031092123
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 STEFANO BONISSONE
 (518) 210-8049
 stefano@digitalproteomics.com
Business Contact
 NATALIE CASTELLANA
Phone: (619) 752-4821
Email: natalie@digitalproteomics.com
Research Institution
N/A
Abstract

Antibodies are a key component of the adaptive immune systemreleased in response to disease
in order to target foreign molecular surfacesDue to their capacity for high target affinity and
specificitythey ve become one of the fastest growing classes of therapeutic molecules addressing a
range of disease including infectious diseasesauto immune diseasesand cancerCamelidsincluding
llamascamelsand alpacasproduce a unique repertoire of antibodies that includes both dual chain
antibodies and single chain antibodiesSingle chain antibodiesdue to their comparative structural
simplicityare simpler to express and develop at the scale required for therapeuticsIn additionsingle
chain antibodies are able to bind to small epitopessuch as enzyme active sitesthat would be hidden to
largerdual chain antibodiesThe binding domain of the single chain antibody may be small enough to
infiltrate traditionally difficult to access tissuesincluding crossing the blood brain barrierCurrent approaches to single chain antibody discovery require the collection of cells that encode
the antibody genesincluding memory B cells and plasma cellsTarget specific antibodies are selected
after the antibody transcripts are cloned into a display systemsuch as phage or yeastWhile memory
B cells and plasma cells represent only a minute fraction of the cells located in peripheral bloodtargetspecific antibodies are present in high concentration in blood after an infectionEach plasma cell can
secrete thousands of antibodies per minuteDigital Proteomics is developing Alicantoa technology
that utilizes the antibodies circulating in blood to identify target specific antibodiesAlicanto integrates two sources of information about the antibody repertoireFirstAlicanto
constructs a database of potential antigen specific antibodies by performing next generation sequencing
of antibody transcriptsNextAlicanto enriches for target specific antibodies from the blood using
affinity chromatography and subjects the antibodies to tandem mass spectrometryFinallyAlicanto
uses machine learning models to integrate the sequencing and mass spectrometry data to derive a
collection of target specific antibody candidatesFor single chain antibody discoveryAlicanto will use
specialized primers and enrichment techniques to isolate only the subset of the antibody repertoire that
contains the single chain antibodiesAlicanto will be used to discover high affinitysingle chain
antibodies for development as therapeutic molecules Antibodies are produced natively in humans to fight disease and the molecules have garnered
significant attention due to their therapeutic potentialSingle chain antibodieswhich are smaller than
conventional antibodiesrepresent a new frontier for antibody based therapeutics due to their ability to
target molecular surfaces that would be hidden to larger antibodiesas well as the relative simplicity of
their developmentDigital Proteomics is developing Alicanto to discover single chain antibodies in
llama that can be developed into human therapies

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

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