# US 11,306,146 B2 · Method of treating bone metastasis diseases, medicaments therefore, and a method of predicting the clinical outcome of treating bone metastasis diseases > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,306,146 B2 - Document ID: US11306146B2 - Status: Granted - Kind: B2 - Application number: 16/518,174 - Filed: 2019-07-22 - Published: 2019-11-07 - Granted: 2022-04-19 - Earliest claimed: 2014-09-17 - Assignees: Merck Patent GmbH - Applicants: Merck Patent GmbH - Inventors: Josef Straub; Eike Staub - Web page: https://patentgrep.com/patent/US11306146B2 ## CPC - C07K 16/2848: {against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61} - A61K 38/09: Luteinising hormone-releasing hormone [LHRH] {, i.e. Gonadotropin-releasing hormone [GnRH]}; Related peptides - A61K 39/39558: {against tumor tissues, cells, antigens} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 13/08: of the prostate - A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease - A61P 35/04: specific for metastasis - G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites} - G01N 33/57585: {involving compounds identifiable in body fluids} - 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 - C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - 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 - 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) ## Abstract A method is used for treating bone metastasis diseases in subjects. The method preferably depends on whether the subject shows certain specific proteins levels in one or more body fluids prior to or during treatment. The treatment includes the administration of at least one pan αv integrin inhibitor to a subject, a medicament for use in said new methods, and a method of predicting the outcome of a treatment with at least one pan αv integrin inhibitor based on the specific protein levels in one or more body fluids of the subject. ## Claims ### Claim 1 A method of treating a bone metastasis disease in a subject, wherein said subject is characterized by: a) a high level of one or more proteins in at least one body fluid of said subject, wherein said one or more proteins are selected from the group consisting of: DCN (UniProt ID: P07585), F5 (UniProt ID: P12259), ICAM3 (UniProt ID: P32942), PIGR (UniProt ID: P01833), STK17B (UniProt ID: 094768), STX1A (UniProt ID: Q16623), and TEK (UniProt ID: Q02763), and/or b) a low level of one or more proteins in at least one body fluid of said subject, wherein said one or more proteins are selected from the group consisting of: ANG (UniProt ID: P03950), IL1B (UniProt ID: P01584), LEPR (UniProt ID: P48357), MAP2K2 (UniProt ID: P36507), MAPK11 (UniProt ID: Q15759), RGMB (UniProt ID: Q6NW40), and TNFRSF17 (UniProt ID: Q02223); said method comprising: administering to said subject at least one pan αv integrin inhibitor; wherein a level of a specific protein of said one or more proteins in at least one body fluid of said subject is a) classified as high, if the level of the specific protein of said one or more proteins in said body fluid is at least 2% higher than a median threshold determined for the specific protein, and/or b) classified as low, if the level of the specific protein of said one or more proteins in said body fluid is at least 2% lower than said median threshold for the specific protein; and wherein a threshold or median threshold for the specific protein is determined from the body fluid of a plurality of subjects being part of a diseased subject population suffering from the bone metastasis disease. ### Claim 2 (depends on 1) The method according to claim 1, wherein said at least one pan αv integrin inhibitor comprises Abituzumab. ### Claim 3 (depends on 1) The method according to claim 1, wherein said at least one pan αv integrin inhibitor is Abituzumab. ### Claim 4 (depends on 1) The method according to claim 1, wherein said subject is characterized by a high level of the protein STX1A (UniProt ID: Q16623) and/or a protein having at least 80% sequence homology to said protein. ### Claim 5 (depends on 1) The method according to claim 1, wherein said subject is characterized by the respective levels of one or more proteins having at least 80% sequence homology to said one or more proteins. ### Claim 6 (depends on 1) The method according to claim 1, wherein said body fluid is selected from the group consisting of blood plasma, blood serum and whole blood. ### Claim 7 (depends on 1) The method according to claim 1, wherein said high levels and/or low levels of one or more of said proteins are present and/or determined prior to administering said at least one pan αv integrin inhibitor. ### Claim 8 (depends on 1) The method according to claim 1, wherein said high levels and/or low levels of one or more of said proteins are present and/or determined during or after administering said at least one pan αv integrin inhibitor. ### Claim 9 (depends on 1) The method according to claim 1, wherein the bone metastasis disease is cancer or is derived from cancer. ### Claim 10 (depends on 1) The method according to claim 1, wherein the bone metastasis disease is derived from prostate cancer, breast cancer and/or lung cancer. ### Claim 11 (depends on 1) The method according to claim 1, wherein said at least one pan αv integrin inhibitor is administered to said subject in an amount of 100 mg to 3000 mg per month. ### Claim 12 (depends on 1) The method according to claim 1, wherein said at least one pan αv integrin inhibitor comprises or is Abituzumab, and wherein the Abituzumab is administered to said subject in an amount of 500 to 2000 mg every week, every second week every or every fourth week. ### Claim 13 (depends on 1) The method according to claim 1, wherein said at least one pan αv integrin inhibitor comprises or is Abituzumab, and wherein the Abituzumab is administered to said subject in an amount of about 500 mg per week, about 750 mg per week, about 1000 mg per week or about 1500 mg per week. ### Claim 14 (depends on 1) The method according to claim 1, wherein said at least one pan αv integrin inhibitor is administered in combination with one or more agents or chemotherapeutic agents, a) selected from the group consisting of Leuproreline, Leuproreline acetate, bicalutamide, nilutamide, triptoreline, gosereline, flutamide, cyproterone, busereline and degarelix, b) selected from the group consisting of Zoledronic acid, Pamidronic acid, Clodronate disodium, Alendronic acid and Ibandronic acid, and/or c) selected from the group consisting of Abiraterone, Abiraterone acetate, Prednisone, Enzalutamide, Radium Ra 223 dichloride, Docetaxel, Sipuleucel-T, Cabazitaxel and Mitoxantrone; and/or the pharmaceutically acceptable derivatives and/or salts thereof. ### Claim 15 (depends on 1) The method according to claim 1, wherein said at least one pan αv integrin inhibitor is administered in combination with, or additionally in combination with, one or more chemotherapeutic agents, selected from the group consisting of cetuximab, Panitumumab, irinotecan, vinorelbine, capecitabine, leucovorine, oxaliplatin, cisplatin, carboplatin, 5-fluorouracil (5-FU), bevacizumab, aflibercept and regorafenib. ### Claim 16 (depends on 1) The method according to claim 1, wherein said at least one pan αv integrin inhibitor is administered in combination with one or more agents or chemotherapeutic agents, selected from the group consisting of a) Leuproreline, Leuproreline acetate, bicalutamid, nilutamide, triptoreline, gosereline, flutamide, cyproterone, busereline and degarelix, and/or the pharmaceutically acceptable derivatives and/or salts thereof; and/or b) Zoledronic acid, Pamidronic acid, Clodronate disodium, Alendronic acid and Ibandronic acid, and/or the pharmaceutically acceptable derivatives and/or salts thereof.