# US 12,595,310 B2 · Compositions and methods for transferrin receptor 1 targeting > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,595,310 B2 - Document ID: US12595310B2 - Status: Granted - Kind: B2 - Application number: 17/775,167 - Filed: 2020-11-06 - Published: 2022-12-29 - Granted: 2026-04-07 - Earliest claimed: 2019-11-06 - Assignees: The Regents of the University of California - Applicants: The Regents of the University of California - Inventors: Manuel L. Penichet; Tracy R. Wells; Pierre V. Candelaria; Juan C. Almagro - Web page: https://patentgrep.com/patent/US12595310B2 ## CPC - C07K 16/2881: {against CD71} - 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 31/14: for RNA viruses - A61P 35/00: Antineoplastic agents - A61K 2039/505: {comprising antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance - 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 Aspects of the disclosure relate to transferrin receptor 1 (TfR1)-binding proteins. In some cases, humanized TfR1-binding proteins are described. Embodiments include methods for treating one or more conditions, for example cancer, using a humanized TfR1-binding protein. In some embodiments, the disclosed methods and compositions involve one or more antibodies that are capable of binding TfR1. Certain aspects relate to humanized antibodies and antibody-like molecules comprising one or more amino acid substitutions (e.g., backmutations). Additional aspects relate to combination treatments with TfR1-binding proteins and one or more additional therapeutics. ## Claims ### Claim 1 A transferrin receptor 1 (TfR1)-binding protein comprising: (a) a light chain variable region comprising SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10, wherein the light chain variable region comprises an arginine, a lysine, or a histidine at amino acid position 45 and a tryptophan, a phenylalanine, a methionine, a valine, an isoleucine, a glycine, or an alanine at amino acid position 46; and (b) a heavy chain variable region comprising SEQ ID NO: 18 or SEQ ID NO: 20. ### Claim 2 (depends on 1) The TfR1-binding protein of claim 1, wherein the light chain variable region comprises an arginine at position 45 relative to SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10. ### Claim 3 (depends on 1) The TfR1-binding protein of claim 1, wherein the light chain variable region comprises a tryptophan at position 46 relative to SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10. ### Claim 4 (depends on 1) The TfR1-binding protein of claim 1, wherein the light chain variable region comprises SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10. ### Claim 5 (depends on 1) The TfR1-binding protein of claim 1, wherein the heavy chain variable region comprises SEQ ID NO: 18 or SEQ ID NO: 20. ### Claim 6 (depends on 1) The TfR1-binding protein of claim 1, wherein the light chain variable region comprises SEQ ID NO: 7 and the heavy chain variable region comprises SEQ ID NO: 18. ### Claim 7 (depends on 1) The TfR1-binding protein of claim 1, wherein the light chain variable region comprises SEQ ID NO: 9 and the heavy chain variable region comprises SEQ ID NO: 18. ### Claim 8 (depends on 1) The TfR1-binding protein of claim 1, wherein the light chain variable region comprises SEQ ID NO: 9 and the heavy chain variable region comprises SEQ ID NO: 20. ### Claim 9 (depends on 1) The TfR1-binding protein of claim 1, wherein the light chain variable region comprises SEQ ID NO: 10 and the heavy chain variable region comprises SEQ ID NO: 20. ### Claim 10 A TfR1-binding protein comprising: (a) a light chain variable region comprising SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10; and (b) a heavy chain variable region comprising SEQ ID NO: 18 or SEQ ID NO: 20. ### Claim 11 (depends on 1) A cell comprising the TfR1-binding protein of claim 1. ### Claim 12 (depends on 11) The cell of claim 11, wherein the cell comprises the TfR1-binding protein and wherein the cell secretes the TfR1-binding protein outside the cell. ### Claim 13 (depends on 11) The cell of claim 11, wherein the cell comprises the TfR1-binding protein and wherein the TfR1-binding protein is attached to a surface of the cell. ### Claim 14 (depends on 1) A method for treating cancer in a subject comprising providing to the subject a therapeutically effective amount of the TfR1-binding protein of claim 1. ### Claim 15 (depends on 14) The method of claim 14, wherein the cancer is a brain cancer. ### Claim 16 (depends on 14) The method of claim 14, wherein the cancer is a blood cancer. ### Claim 17 (depends on 16) The method of claim 16, wherein the blood cancer is a B-cell malignancy. ### Claim 18 (depends on 17) The method of claim 17, wherein the B-cell malignancy is multiple myeloma or non-Hodgkin lymphoma (NHL). ### Claim 19 (depends on 14) The method of claim 14, wherein the TfR1-binding protein comprises SEQ ID NO: 7 and SEQ ID NO: 18, SEQ ID NO: 9 and SEQ ID NO:18, SEQ ID NO: 9 and SEQ ID NO: 20, or SEQ ID NO: 10 and SEQ ID NO: 20. ### Claim 20 (depends on 14) The method of claim 14, wherein the TfR1-binding protein comprises SEQ ID NO: 7 and SEQ ID NO:18.