# US 12,108,745 B2 · Rat model of IgA nephropathy induced with a multimeric recombinant IgA fragment > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,108,745 B2 - Document ID: US12108745B2 - Status: Granted - Kind: B2 - Application number: 17/155,870 - Filed: 2021-01-22 - Published: 2021-11-25 - Granted: 2024-10-08 - Earliest claimed: 2020-01-23 - Assignees: Northwestern University - Applicants: Northwestern University - Inventors: Jing Jin; Xinfang Xie - Web page: https://patentgrep.com/patent/US12108745B2 ## CPC - A01K 67/027: New or modified breeds of vertebrates - A61P 13/12: of the kidneys - C07K 14/36: from Actinomyces; from Streptomyces (G) - C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies - C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes} - G01N 33/5088: {of vertebrates} - G01N 33/6857: {Antibody fragments} - A01K 2207/10: Animals modified by protein administration, for non-therapeutic purpose - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C07K 2317/41: Glycosylation, sialylation, or fucosylation - C07K 2317/52: Constant or Fc region; Isotype - C07K 2317/53: Hinge - C07K 2317/90: characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin - C07K 2319/70: containing domain for protein-protein interaction - G01N 2800/347: Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy - A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Recombinant poly-IgA oligomers that form high-order oligomers resembling poly-IgA of IgA nephropathy are provided. Injection of recombinant IgA oligomers in an animal model produces prominent renal glomerular mesangial deposition of recombinant poly IgA oligomer, as in IgA nephropathy patients. Thus, producing a model of IgAN pathology that is able to provide screening and evaluation of therapeutic drugs and diagnostic tests. ## Claims ### Claim 1 A method of inducing IgA nephropathy in a subject comprising: providing a polymeric complex of unglycosylated IgA CH2-CH3 oligomeric fragments, wherein each of the IgA CH2-CH3 oligomeric fragments comprises a biotin moiety at the N-terminus of the IgA CH2-CH3 and the polymeric complex is formed by the addition of streptavidin to a mixture of biotinylated IgA CH2-CH3 oligomeric fragments; and daily, intravenous administering to a subject the polymeric complex of unglycosylated IgA CH2-CH3 oligomeric fragments, wherein the daily administration of the polymeric complex to the subject for a period of twelve consecutive days induces in the subject kidney glomerulus mesangial deposition of the polymeric complex of unglycosylated IgA fragments and induction of renal and systemic responses toward clearance of the polymeric complex from the kidney, the deposition of IgA polymers and renal and systemic responses toward clearance of IgA polymers being indicators of a IgA nephropathy, wherein the subject is a rodent. ### Claim 2 (depends on 1) The method of claim 1 wherein the polymeric complex is homo-oligomeric. ### Claim 3 (depends on 1) The method of claim 1 wherein the polymeric complex is about 200 kDa to about 800 kDa in size. ### Claim 4 (depends on 1) The method of claim 1, wherein the polymeric complex comprises two, three, four or seven IgA CH2-CH3 oligomeric fragments. ### Claim 5 (depends on 1) The method of claim 1, wherein the subject having induced IgA nephropathy demonstrates histologic changes of the glomerulus comprising mesangial hypercellularity, matrix expansion, narrowing of capillary loops, or a combination thereof. ### Claim 6 (depends on 5) The method of claim 5 further comprising determining the efficacy of a therapeutic agent for IgA nephropathy in a subject comprising: treating the subject having induced IgA nephropathy with a therapeutic agent; and evaluating glomerulus mesangial deposition of the polymeric complex of unglycosylated IgA oligomeric fragments or histologic changes after treatment with the therapeutic agent thereby determining the efficacy of the therapeutic agent. ### Claim 7 (depends on 5) The method of claim 5 further comprising, determining the efficacy of a diagnostic method of IgA nephropathy in a subject comprising: applying a diagnostic method to the subject having induced IgA nephropathy; and evaluating IgA indicators including glomerulus mesangial deposition of the polymeric complex of unglycosylated IgA oligomeric fragments or histologic changes in the subject to obtain a correlation between the diagnostic method and IgA indicators, thereby determining the efficacy of the diagnostic method. ### Claim 8 A method for producing an IgA nephropathy animal model comprising: providing a polymeric complex of unglycosylated IgA CH2-CH3 oligomeric fragments, wherein each of the IgA CH2-CH3 oligomeric fragments comprises a biotin moiety at the N-terminus of the IgA CH2-CH3 and the polymeric complex is formed by the addition of streptavidin to a mixture of biotinylated IgA CH2-CH3 oligomeric fragments and daily, intravenous administering to a subject the polymeric complex of unglycosylated IgA CH2-CH3 oligomeric fragments, wherein the daily administration of the polymeric complex to the subject for a period of twelve consecutive days induces in the animal kidney glomerulus mesangial deposition of the polymeric complex of unglycosylated IgA fragments thus inducing renal and systemic responses toward clearance of the polymeric complex from the kidney, thereby producing an animal model of IgA nephropathy, wherein the animal model is a rodent.