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59 results about "Immunoglobulin region" patented technology

The variable region is the region of the immunoglobulin (Ig) which varies greatly in amino acid sequence among different immunoglobulins of the same class. Each immunoglobulin molecules is a tetramer of two identical light chains and two identical heavy chains linked by disulfide bonds.

Episomal Expression of Potent Immunoglobulins Derived from Human Blood or Convalescent Plasma to Enable Short term Vaccination / Immunization to COVID, COVID-19 and Mutants and Other Pandemic and non-Pandemic Viruses designed from Rapid FDA approval.

The present invention provides methods, immunoglobulin compositions and vector constructs as a general approach to provide episomal based immune protection from the 2019 novel coronavirus (COVID-19), its variants / mutants and other pandemic and even non-pandemic viruses. The immunoglobulin compositions include the heavy chain variable, diversity and joining (VDJ or Variable Heavy Region genes) segment immunoglobulin DNA and / or polypeptide sequence from humans identified to have developed high affinity immunoglobulins (ideally antibodies with nanomolar to picomolar dissociation constants to virus proteins with additional emphasis on cell surface proteins and further emphasis on the Spike protein as related to COVID-19) against the virus of interest and either to use the exact immunoglobulin composition identified from the donor or to combine that variable immunoglobulin region for both heavy and light chains with a non-divergent well-conserved amino acid sequence for the constant regions especially, Hinge region, Constant Heavy 2 (CH2) and Constant Heavy 3 (CH3) for the immunoglobulin heavy chain polypeptide with optional use of donor based Constant Heavy 1 (CH1) or non-divergent well conserved CH1 heavy chain constant region and optional use of hinge region peptides. The immunoglobulin light chain will use either entirely donor based amino acid sequence or donor based light chain variable and joining (VJ or Variable light region genes) segments immunoglobulin polypeptide sequence with a well-conserved non-divergent constant light (CL) chain region for immunoglobulin Kappa locus (κ) or immunoglobulin lambda locus (λ) light chain. The resulting antibodies can either be used as a monoclonal or polyclonal mix of (Immunoglobulin Class G subclass1) IgG1, IgG3 and other subclasses, IgA1 monomer and IgA2 monomer and dimeric IgA1 (dIgA1) immunoglobulins (as identified by the potency of associated memory B-cells) to be expressed via intramuscular administration, intravenous or proximal to lymph nodes. The immunoglobulins will be expressed in the vaccine / immunization recipient via an episome. The vector will be ideally delivered in a recombinant Adeno Associated Virus (rAAV) with preference for AAV serotype 8 (AAV8) containing a single-stranded Deoxyribonucleic acid (ssDNA) non-viral vector or lentivirus virion containing double stranded DNA as a non-viral vector. A single non-viral vector will code for the entire immunoglobulin and J-chain expression for dIgA1 where expression will occur with a single start codon and stop codon for the amino acid sequence and in some embodiments a second start codon for J chain expression. The specific DNA of the immune donor can be identified as follows: Cluster of Differentiation 27+ (CD27+) IgG+ and CD27+ IgA+ memory B cells or other CD memory B-cells will be isolated from serum using established methods. Each resulting isotype of memory B-cell will be subjected to a competitive binding assay using flow cytometry methods such as Fluorescence Activated Cell Sorting (FACS) to identify the memory B-cells with the greatest binding affinity to the COVID-19 antigens of interest. Isolated memory B-cells will have their DNA sequenced to identify the genetic sequence of their cell surface IgG+ or IgA+ receptor. That information and potentially other sources of immunoglobulin genetic information will be used to create vector construct coding for antibodies to be further evaluative for potency and safety and then to be incorporated into a vector construct for episomal immunoglobulin expression. Episomes will be designed to express IgG1, IgG3, IgA1, IgA2 and dIgA1 with potent binding to COVID antigens or antigens of other viruses. A central part of this patent application is the method used to identify the high affinity immunoglobulins expressed by those that were exposed to COVID or other virus of interest.
Owner:SWARTZ ROGER B
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