Production and Characterization of Human Immunoglobulin Producing Goats for Diagnostic Reagents and Therapeutics

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R42AI131823-02
Agency Tracking Number: R42AI131823
Amount: $758,090.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA18-575
Timeline
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-04-18
Award End Date (Contract End Date): 2021-03-31
Small Business Information
935 E EAGLEWOOD DR, North Salt Lake, UT, 84054-3302
DUNS: 080197308
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 HUA WU
 (605) 679-6985
 hwu@sabbiotherapeutics.com
Business Contact
 PETER BOEREMA
Phone: (605) 231-8058
Email: pboerema@sabbiotherapeutics.com
Research Institution
 UTAH STATE UNIVERSITY
 1415 Old main Hill Old Main Room 64
LOGAN, UT, 84329
 Nonprofit college or university
Abstract
Project Summary Abstract The ultimate goal of this phase II STTR proposal is to expand the capabilities of SABandapos s diversitAbplatform by continuing advanced development of Transchromosomic goatsTcGsThis will be accomplished by producing male and female goat endogenous immunoglobulin gene knockout cell lines that contain SAB Capraandapos s human artificial chromosomeHACwhich encodes the entire repertoire of the germline human antibody genes thereby greatly improving the production efficiency of fully human antibodies in TcGsTo further advance the TcG platform towards commercial production of therapeutic and diagnostic antibody productsoptimization of the antibody purification processdevelopment of quality control assaysand further development of a purified TcGderived pandemic influenza antibody product targeting H Nby completing in vitro and in vivo evaluation is also proposedTo accomplish these goalsendogenous immunoglobulin gene knockouts will be facilitated utilizing the CRISPR Cassystem in domestic Nubian Boar goat fetal fibroblastGFFcellsand transfer of the SABdesigned HAC into the knockout cells will be accomplished by microcell mediated chromosome transferMMCTHAC containing knockout GFF cells will be used to produce embryos by somatic cell nuclear transferSCNTAfter gestation and birth of multiple TcGsmolecular characterization will be completedpresence of the knockouts and HAC will be confirmedand human IgG production will be confirmed and evaluatedTwo of these TcGs will then be hyperimmunized with a plasmid DNA vaccine targeting H NPlasma will be collected from the hyperimmunized TcGsand anti H Nfully human IgG will be purified from the TcG plasmaThe in vitro potency and in vivo efficacy of the purified TcG derived anti H Nhuman IgG product will then be evaluatedOptimization of established purification procedures will be undertaken to ensure efficient and effective purification of TcG derived human IgG from plasmaand development of quality control assays to evaluate product identitypurityand potency will be completedSABandapos s diversitAbplatform for human antibody production is currently utilized in transchromosomic bovines against a wide range of antigens including virusesbacteriaoncology targetsrecombinant proteinsand DNA vaccinesThis proven technology has the advantages of scalabilitysimplicityand broad applicabilityThe addition of TcGs to the platform allows for simpler and cheaper rapid response production of small volume targeted products as well as diagnostic reagents for serological testing of emerging infectious diseases Project Narrative The research proposed in this application seeks to expand the capabilities of SABandapos s diversitAbplatform by continuing advanced development of Transchromosomic goatsTcGsthat express human polyclonal antibodies for use as targeted immunotherapies and or diagnostic reagents for serological testingImmunotherapy products derived from TcGs will combine the beneficial effects of current animal derived antibody products with improved efficacy and safety while eliminating the risk of anaphylaxis and serum sickness associated with xenobiotic IgG administrationA TcG derived anti H Nfully human IgG product will also be developed through this proposalpotentially addressing the global need for highly effective therapeutics against avian lineage influenza virus infections in humans

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

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