Ungulate-derived polyclonal immunoglobulin specific for coronavirus protein and uses thereof
Inventors
Luke, Tom • BAUSCH, Christoph L. • SULLIVAN, Eddie J. • Wu, Hua • EGLAND, Kristi A.
Assignees
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Publication Number
US-11975066-B2
Publication Date
2024-05-07
Expiration Date
Abstract
Provided are human polyclonal immunoglobulin products for use in treating or preventing coronavirus disease. Further provided are methods for making such compositions in a transgenic ungulate, e.g. using a transchromosomic bovine (TcB) system.
Core Innovation
The invention relates to a method of making polyclonal human immunoglobulin for treatment of COVID-19. A transgenic ungulate is used for production, where the transgenic ungulate is a bovine comprising an artificial chromosome with a human heavy chain immunoglobulin (IgH) locus and a human immunoglobulin kappa (IgK) locus, and wherein a bovine immunoglobulin locus has been knocked out.
The method includes administering coronavirus antigens to the transgenic bovine, including an antigen comprising a polynucleotide encoding a full-length SARS-CoV-2 spike (S) protein with an amino acid sequence of SEQ ID NO: 19. The spike antigen includes a deletion of a polybasic S1/S2 cleavage site corresponding to residues 682 to 685 of SEQ ID NO: 19, amino acid substitutions of K986P and/or V987P relative to SEQ ID NO: 19 that stabilize an ectodomain of SARS-CoV-2 S protein, and a T4 foldon trimerization domain.
After the antigen administrations, a population of human immunoglobulins is purified from serum or plasma of the transgenic ungulate. The population comprises fully human immunoglobulin G (IgG), and the resulting polyclonal human immunoglobulin is made for treatment of COVID-19.
Claims Coverage
The claim coverage describes one independent workflow for making polyclonal human IgG for COVID-19 using a transgenic bovine and SARS-CoV-2 spike antigens, followed by purification from serum or plasma. It centers on 4 inventive features.
Transgenic bovine with human IgH/IgK artificial chromosome
A transgenic ungulate that is a bovine comprising an artificial chromosome with a human heavy chain immunoglobulin (IgH) locus and a human immunoglobulin kappa (IgK) locus, with a bovine immunoglobulin locus knocked out.
SARS-CoV-2 spike polynucleotide antigen with defined S1/S2 deletion and stabilizing substitutions
Administering an antigen comprising a polynucleotide encoding a full-length SARS-CoV-2 spike (S) protein comprising SEQ ID NO: 19, with a deletion of a polybasic S1/S2 cleavage site corresponding to residues 682 to 685 of SEQ ID NO: 19, amino acid substitutions of K986P and/or V987P relative to SEQ ID NO: 19, and a T4 foldon trimerization domain.
Additional administration of SARS-CoV-2 S protein or antigenic fragment
Administering an antigen comprising a SARS-CoV-2 S protein or an antigenic fragment thereof to the transgenic ungulate.
Purification of fully human IgG from serum or plasma
Purifying a population of human immunoglobulins from serum or plasma of the transgenic ungulate after antigen administration, wherein the population comprises fully human immunoglobulin G (IgG), to make the polyclonal human immunoglobulin for treatment of COVID-19.
The inventive features combine the transgenic bovine platform, defined SARS-CoV-2 spike antigen administrations, and purification of fully human IgG from serum or plasma for COVID-19 treatment.
Stated Advantages
Provides polyclonal fully human immunoglobulin G for treatment of COVID-19.
Documented Applications
Treatment of coronavirus disease 2019 (COVID-19) using the made polyclonal human immunoglobulin comprising fully human IgG.
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