# US 12,110,333 B2 · Methods to manipulate alpha-fetoprotein (AFP) > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,110,333 B2 - Document ID: US12110333B2 - Status: Granted - Kind: B2 - Application number: 16/284,005 - Filed: 2019-02-25 - Published: 2020-01-09 - Granted: 2024-10-08 - Earliest claimed: 2014-04-25 - Assignees: The Brigham and Women's Hospital, Inc. - Applicants: The Brigham and Women's Hospital, Inc. - Inventors: Richard S. Blumberg; Kristi Baker; Michal Pyzik; Amit Gandhi - Web page: https://patentgrep.com/patent/US12110333B2 ## CPC - C07K 16/283: {against Fc-receptors, e.g. CD16, CD32, CD64 (CD23 C07K16/2851)} - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids} - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C07K 2317/77: Internalization into the cell - 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) - 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 ## Abstract As demonstrated herein, soluble human FcRn binds to AFP with affinities greater than observed with albumin, and is able to interfere with FcRn-mediated protection of and functional associations with IgG. Accordingly, provided herein, in some aspects, are compositions and methods to inhibit FcRn and AFP interactions in diseases or disorders where elevated AFP levels are associated with immunosuppression. Also provided herein, in some aspects, are compositions and methods to enhance or potentiate FcRn and AFP interactions in diseases or disorders with decreased AFP levels or diseases or disorders where increasing AFP levels increasing with immunosuppression. ## Claims ### Claim 1 A method to inhibit or reduce FcRn and alpha-fetoprotein (AFP) interactions in a disease or disorder associated with elevated AFP levels comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising an inhibitor of AFP-FcRn and a pharmaceutically acceptable carrier, wherein said inhibitor of AFP-FcRn inhibits binding between alpha-fetoprotein (AFP) and FcRn, wherein the inhibitor of AFP-FcRn inhibits or blocks the AFP binding site on FcRn, wherein the inhibitor of AFP-FcRn is an antibody or antigen-binding fragment thereof, wherein the inhibitor of AFP-FcRn is an anti-FcRn ADM31 antibody, and wherein the subject has or has been diagnosed with cancer. ### Claim 2 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment thereof is a chimeric, humanized, or completely human antibody or antigen-binding fragment thereof. ### Claim 3 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between Y521 and/or V522 of AFP and R42 of FcRn. ### Claim 4 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between P492 of AFP and R69 of FcRn. ### Claim 5 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between Q441 and/or V493 of AFP and E44 of FcRn. ### Claim 6 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between H534 and/or E589 of AFP and N173 of FcRn. ### Claim 7 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between the hydrophobic core of AFP and FcRn. ### Claim 8 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between L484, V493, V497, and/or F512 of AFP and V57, W59, and/or W61 of FcRn. ### Claim 9 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between T443 of AFP and E62 and/or W59 of FcRn. ### Claim 10 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between D529 of AFP and S230 of FcRn. ### Claim 11 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between S527 and/or D528 of AFP and E50 and/or 67Y of β2m complexed with FcRn. ### Claim 12 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between R604 of AFP and the carbonyl oxygen at E50 of β2m complexed with FcRn. ### Claim 13 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between Q597 of AFP and E69 of β2m complexed with FcRn. ### Claim 14 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between E106 of AFP and H161 of FcRn. ### Claim 15 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between S135 of AFP and H161 of FcRn. ### Claim 16 (depends on 1) The method of claim 1, wherein the inhibitor of AFP-FcRn inhibits binding between F531, F533, F552, and/or F575 of AFP and W53 of FcRn. ### Claim 17 (depends on 1) The method of claim 1, further comprising administering an anticancer therapy or agent to the subject. ### Claim 18 (depends on 1) The method of claim 1, wherein the subject has or has been diagnosed with a cancer or tumor of primitive origin, a tumor of liver origin, a hepatoma, a tumor of biliary origin, cholangiocarcinoma, stomach cancer, pancreatic cancer, or a teratocarcinoma. ### Claim 19 A method to inhibit or reduce FcRn and alpha-fetoprotein (AFP) interactions in a disease or disorder associated with elevated AFP levels comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising an inhibitor of AFP-FcRn and a pharmaceutically acceptable carrier, wherein said inhibitor of AFP-FcRn inhibits binding between alpha-fetoprotein (AFP) and FcRn, wherein the inhibitor of AFP-FcRn inhibits or blocks the AFP binding site on FcRn, wherein the inhibitor of AFP-FcRn is an antibody or antigen-binding fragment thereof, wherein the inhibitor of AFP-FcRn is a chimeric anti-FcRn ADM31 antibody or a humanized anti-FcRn ADM31 antibody, and wherein the subject has or has been diagnosed with cancer.