Antibodiesareidealdrugcandidatesduetotheirhighspecificityfortarget molecules.Monoclonalantibodiesrepresentoneofthefastestgrowingsegmentsof thedrugmarket,however,recentattentionhasfocusedonpolyclonalantibodies andmonoclonalmixturestoreducetheopportunityforadiseasetobecomedrug resistant.Polyclonalantibodiessampledfromdiseasesurvivorsorimmunized hostsofferawealthofnewdrugcandidates.Currentpipelinesforinvestigatingthe immuneresponserelyonhybridomatechnology,whichistime-?consuminganddoes notcomeclosetomimickingthediversityofantibodiespresentintheorganism. NextgenerationsequencingofB-?cellscandeeplyinterrogatetheimmuneresponse, however,thistechnologyfallsshortofprovidinginsightintothebestantibodydrug candidates. WeproposethedevelopmentofValens-?Poly,whichwillintegratemass spectrometry-?basedproteomicsdatawithnextgenerationsequencingofB-?cells,an emergingfieldcalledimmunoproteogenomics.Byinterrogatingtheimmune responseattheprotein-?level,Valens-?Polywillbeabletorankantibodysequences basedontheirabundance,whichisaproxyforspecificitytotheantigenofinterest. ItisimpossibletosequenceallmemoryB-?cellsinahostorganism,thereforethe antibodysequencesreportedwouldonlyrepresentasmallfractionoftheantibodies thatcouldbepresent.Usingourpatentedspectralnetworkapproach,pioneeredin ourmonoclonalantibodysequencingtool,Valens,wewillbeabletorecover complementarity-?definingregions(CDRs)ofantibodiesevenwhentheB-?cellwas notcapturedfornextgenerationsequencing. Finally,wewillcharacterizethebroadspectrumofantibodiesproducedas partoftheimmuneresponse,calledtheantibodyrepertoire.Identifyingchangesin germlinegeneusageandtrackingcloneabundanceandlineageinresponseto immunizationoracrosspatientsisanimportantcomponentofcharacterizing diseasesandguidingdrugdiscovery.

Public Health Relevance

Characterizationoftheantibodyresponsetoaninfectionisanimportantprecursor toantibody-?baseddrugdevelopment.Hereweproposeatool,Valens-?Poly,which identifyabundantantibodyspeciesbyintegratingmassspectrometryand nucleotidesequencingofmatureB-?cells.Ourtechnologywillcircumventtheneed forhybridomadevelopmentsavingoveramonthofdevelopmenttime,andwill consequentlyenablenoveldrugdiscoveriesandshortendrugdevelopment timelines.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
1R44GM122102-01
Application #
9254618
Study Section
Special Emphasis Panel (ZRG1-IMST-K (14)B)
Program Officer
Marino, Pamela
Project Start
2017-02-16
Project End
2019-01-31
Budget Start
2017-02-16
Budget End
2018-01-31
Support Year
1
Fiscal Year
2017
Total Cost
$388,404
Indirect Cost
Name
Digital Proteomics, LLC
Department
Type
Domestic for-Profits
DUNS #
031092123
City
La Jolla
State
CA
Country
United States
Zip Code
92037