# US 10,479,835 B2 · Agent, uses and methods for treatment > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,479,835 B2 - Document ID: US10479835B2 - Status: Granted - Kind: B2 - Application number: 15/743,549 - Filed: 2016-07-12 - Published: 2018-10-25 - Granted: 2019-11-19 - Earliest claimed: 2015-07-13 - Assignees: H. Lundbeck A/S - Applicants: H. Lundbeck A/S - Inventors: Lars Christian Biilmann Rønn; Ibrahim John Malik; Jeffrey B. Stavenhagen; Søren Christensen; Jan Egebjerg; Arnout Gerritsen; Edward Van Den Brink; Paul Parren; Rob De Jong - Web page: https://patentgrep.com/patent/US10479835B2 ## CPC - C07K 16/286: {against neuromediator receptors, e.g. serotonin receptor, dopamine receptor} - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - A61K 2039/505: {comprising antibodies} - C07K 2317/20: characterized by taxonomic origin - C07K 2317/21: from primates, e.g. man - 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 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - 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 The present invention relates to monoclonal anti-Sortilin antibodies which have been found useful in correcting a deficient level of progranulin (PGRN). In particular, these antibodies can be used in the treatment of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). ## Claims ### Claim 1 An antibody, or an antigen-binding fragment thereof, comprising: a) a light chain variable domain L-CDR1 comprising SEQ ID NO: 17; b) a light chain variable domain L-CDR 2 comprising SEQ ID NO: 18: c) a light chain variable domain L-CDR 3 comprising SEQ ID NO: 19: d) a heavy chain variable domain H-CDR 1 comprising SEQ ID NO: 20: e) a heavy chain variable domain H-CDR 2 comprising SEQ ID NO: 21: and f) a heavy chain variable domain H-CDR 3 comprising SEQ ID NO: 22. ### Claim 2 (depends on 1) The antibody, or antigen-binding fragment thereof, of claim 1, wherein said antibody or antigen-binding fragment thereof binds to the D Region of Sortilin as defined by SEQ ID NO:170. ### Claim 3 (depends on 1) The antibody, or antigen-binding fragment thereof of claim 1 wherein said antibody or antigen-binding fragment thereof binds to at least 3 consecutive amino acids within the D Region of Sortilin as defined in SEQ ID NO: 170. ### Claim 4 (depends on 1) The antibody, or antigen-binding fragment thereof, or claim 1, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable domain comprising SEQ ID NO:24. ### Claim 5 (depends on 1) The antibody, or antigen-binding fragment thereof, of claim 1, wherein said antibody or antigen-binding fragment thereof comprises a light chain variable domain comprising SEQ ID NO:23. ### Claim 6 (depends on 1) The antibody, or antigen-binding fragment thereof of claim 1 wherein the antibody or antigen-binding fragment thereof comprises both the heavy chain variable domain of SEQ ID NO: 24 and light chain variable domain of SEQ ID NO: 23. ### Claim 7 (depends on 1) The antibody, or antigen-binding fragment thereof of claim 1, wherein the antigen-binding fragment is selected from the group consisting of an Fv fragment and a Fab-like fragment. ### Claim 8 (depends on 1) The antibody, or antigen-binding fragment thereof, of claim 1, wherein the antibody is selected from the group consisting of: an antibody of subtype IgG1, IgG2, IgG3 or IgG4. ### Claim 9 (depends on 1) The antibody, or antigen-binding fragment thereof, of claim 1, wherein the antibody or antigen-binding fragment thereof is a human, humanized, recombinant or chimeric antibody. ### Claim 10 (depends on 1) The antibody, or antigen-binding fragment thereof of claim 1 wherein the antibody or antigen-binding fragment exhibits one or more of the following properties: a) a binding affinity (KD) for Sortilin between 0.5-10 nM; b) capability to reduce and/or inhibit PGRN binding to Sortilin; c) capability to reduce and/or inhibit clearance of PGRN by Sortilin-expressing cells; d) capability to reduce and/or inhibit the endocytosis of PGRN by Sortilin-expressing cells; e) capability to increase the amount and/or concentration of PGRN in the brain, and/or f) capability to increase the amount and/or concentration of PGRN in the plasma in human-Sortilin-expressing knock-in mice. ### Claim 11 (depends on 1) A pharmaceutical composition comprising an antibody, or an antigen binding fragment thereof of claim 1 and a pharmaceutically-acceptable carrier. ### Claim 12 (depends on 1) A kit comprising an antibody, or antigen-binding fragment thereof of claim 1. ### Claim 13 (depends on 1) A nucleotide sequence encoding an antibody or antibody binding fragment of claim 1. ### Claim 14 (depends on 13) A cell line comprising the nucleotide sequence of claim 13. ### Claim 15 (depends on 1) A method of treating a disease associated with decreased PGRN levels in the brain of a patient, comprising administering an effective dosage of an antibody, or an antigen-binding fragment thereof of claim 1. ### Claim 16 (depends on 15) The method according to claim 15, wherein the disease is frontotemporal dementia, amyotrophic lateral sclerosis or Alzheimer's disease.