# US 10,869,906 B2 · Method of reducing titers of antibodies specific for a therapeutic agent > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,869,906 B2 - Document ID: US10869906B2 - Status: Granted - Kind: B2 - Application number: 15/796,137 - Filed: 2017-10-27 - Published: 2018-05-03 - Granted: 2020-12-22 - Earliest claimed: 2010-05-06 - Assignees: Duke University - Applicants: Duke University - Inventors: Priya S. Kishnani; Suhrad G. Banugaria; Dwight D. Koeberl; Sean N. Prater - Web page: https://patentgrep.com/patent/US10869906B2 ## CPC - A61K 38/05: Dipeptides - A61K 31/00: Medicinal preparations containing organic active ingredients - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61K 31/69: Boron compounds - A61K 38/1722: {Plasma globulins, lactoglobulins} - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 16/2887: {against CD20} - A61K 2039/505: {comprising antibodies} - A61K 2039/545: {characterised by the dose, timing or administration schedule} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - 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) - 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) ## Abstract The present invention relates, in general, to a method of treating patients undergoing enzyme replacement therapy (ERT) or other therapy involving the administration of a proteinaceous therapeutic agent as well gene replacement therapy with non-viral or viral vectors, or other therapeutic modality or modalities, used alone or in combination, which involve the administration of exogenous substances for potential therapeutic benefit, including, but not limited to DNA vaccines, siRNA, splice-site switching oligomers (SSOs) as well as RNA-based nanoparticles (RNPs) and nanovaccines. The invention further relates to compounds and compositions suitable for use in such methods. ## Claims ### Claim 1 A method for reducing titers of antibodies against a therapeutic protein in a patient treated with the therapeutic protein by administration of a nucleic acid comprising a nucleotide sequence encoding the therapeutic protein in expressible form, said administration able to elicit said antibodies, wherein the therapeutic protein is a proteinaceous replacement for acid alpha-glucosidase (GAA), comprising administering to the patient a proteasome inhibitor in an amount and under conditions that the antibody titers are reduced. ### Claim 2 (depends on 1) The method of claim 1, wherein the nucleic acid is present in a vector. ### Claim 3 (depends on 2) The method of claim 2, wherein the vector is a viral vector. ### Claim 4 A method for reducing titers of antibodies elicited by administration of a viral vector comprising a nucleotide sequence encoding a therapeutic protein in expressible form in a patient treated with the viral vector comprising administering to the patient a proteasome inhibitor in an amount and under conditions that the antibody titers are reduced. ### Claim 5 (depends on 1) The method of claim 1, wherein the patient suffers from Pompe disease, a mucopolysaccharide storage disorder, Fabry disease, Gaucher disease, gangliosidosis, alkaline hypophosphatasia, cholesterol ester storage disease, hyperuricemia, hemophilia, diabetes, growth hormone deficiency, or renal anemia. ### Claim 6 (depends on 1) The method of claim 1, wherein the patient suffers from Pompe disease and the therapeutic protein is acid alpha-glucosidase (GAA). ### Claim 7 (depends on 1) The method of claim 1, wherein the method further comprises administering to the patient a compound that targets or alters antigen presentation or humoral or cell mediated immune response. ### Claim 8 (depends on 1) The method of claim 1, wherein the method further comprises administering to the patient a compound that exerts a therapeutic effect against B cells and a compound that targets or alters antigen presentation or humoral or cell mediated immune response. ### Claim 9 (depends on 1) The method of claim 1, wherein the proteosome inhibitor is bortezomib. ### Claim 10 (depends on 1) The method of claim 1, wherein the method further comprises administering to said patient rituximab, methotrexate, and intravenous gamma globulin. ### Claim 11 (depends on 3) The method of claim 3, wherein the viral vector is an adenovirus vector or an adeno-associated virus vector. ### Claim 12 A method to reduce or prevent the production of antibodies elicited against a therapeutic agent in a patient treated with the therapeutic agent, wherein the therapeutic agent is a viral vector, wherein the viral vector comprises a nucleic acid encoding a therapeutic protein in expressible form, said treatment comprising administration of said therapeutic agent, and said therapeutic agent able to elicit said antibodies, the method comprising administering to the patient, prior to administration of the therapeutic agent, an amount of a proteasome inhibitor sufficient to effect said reduction or prevention. ### Claim 13 (depends on 12) The method of claim 12, wherein the method further comprises administering to the patient a compound that targets or alters antigen presentation or humoral or cell mediated immune response. ### Claim 14 (depends on 12) The method of claim 12, wherein the patient suffers from Pompe disease, a mucopolysaccharide storage disorder, Fabry disease, Gaucher disease, gangliosidosis, alkaline hypophosphatasia, cholesterol ester storage disease, hyperuricemia, hemophilia, diabetes, growth hormone deficiency, or renal anemia. ### Claim 15 (depends on 12) The method of claim 12, wherein the method further comprises administering to said patient rituximab, methotrexate, and intravenous gamma globulin. ### Claim 16 (depends on 12) The method of claim 12, wherein the viral vector is an adenovirus vector or an adeno-associated virus vector. ### Claim 17 (depends on 4) The method of claim 4, wherein the viral vector is an adenovirus vector or an adeno-associated virus vector.