# US 8,784,811 B2 · Method of treating cancer using antibodies to a non-ligand binding region of NOTCH1 > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,784,811 B2 - Document ID: US8784811B2 - Status: Granted - Kind: B2 - Application number: 13/773,921 - Filed: 2013-02-22 - Published: 2013-09-26 - Granted: 2014-07-22 - Earliest claimed: 2006-06-13 - Assignees: OncoMed Pharmaceuticals, Inc. - Applicants: OncoMed Pharmaceuticals, Inc. - Inventors: John A. Lewicki; Austin Gurney; Timothy Hoey; Wan-ching Yen; Sanjeev Satyal - Web page: https://patentgrep.com/patent/US8784811B2 ## CPC - C07K 16/30: from tumour cells - A61K 39/39558: {against tumor tissues, cells, antigens} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61N 5/10: X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence) - A61P 35/00: Antineoplastic agents - C07K 16/18: against material from animals or humans - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - C07K 16/3015: {Breast} - C07K 16/3046: {Stomach, Intestines} - A61K 2039/505: {comprising antibodies} - A61K 2039/507: {Comprising a combination of two or more separate antibodies} - 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 2317/31: multispecific - 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 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - C07K 2317/734: Complement-dependent cytotoxicity [CDC] - 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) - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides an antibody that specifically binds to a non-ligand binding region of the extracellular domain of a human NOTCH receptor and inhibits growth of tumor cells. The present invention further provides a method of treating cancer, the method comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding region of the extracellular domain of a human NOTCH receptor protein and inhibits growth of tumor cells. ## Claims ### Claim 1 A method of treating breast cancer or colon cancer, the method comprising administering a therapeutically effective amount of a monoclonal antibody that specifically binds to a non-ligand binding region of the extracellular domain of human NOTCH1, wherein the non-ligand binding region comprises epidermal growth factor (EGF) repeats 1-10 or EGF repeats 13-36. ### Claim 2 (depends on 1) The method of claim 1, wherein the antibody is a chimeric antibody. ### Claim 3 (depends on 1) The method of claim 1, wherein the antibody is a humanized antibody. ### Claim 4 (depends on 1) The method of claim 1, wherein the antibody is a human antibody. ### Claim 5 (depends on 1) The method of claim 1, wherein the antibody inhibits growth of tumor cells. ### Claim 6 (depends on 1) The method of claim 1, wherein the antibody is an antagonist of human NOTCH 1. ### Claim 7 (depends on 1) The method of claim 1, wherein the non-ligand binding region comprises EGF repeats 1-10. ### Claim 8 (depends on 7) The method of claim 7, wherein the non-ligand binding region comprises EGF repeat 4. ### Claim 9 (depends on 1) The method of claim 1, wherein the non-ligand binding region comprises EGF repeats 13-36. ### Claim 10 (depends on 9) The method of claim 9, wherein the non-ligand binding region comprises EGF repeat 13. ### Claim 11 (depends on 1) The method of claim 1, wherein the antibody comprises: (a) a heavy chain CDR1 comprising SSYTMS (SEQ ID NO:12), a heavy chain CDR2 comprising YIDYGGDFTSYSDAIRG (SEQ ID NO:13), and a heavy chain CDR3 comprising RRYDAMDY (SEQ ID NO:14); and (b) a light chain CDR1 comprising SASQAISNYLN (SEQ ID NO:15), a light chain CDR2 comprising YTTNLHS (SEQ ID NO:16), and a light chain CDR3 comprising QQYSKFPWT (SEQ ID NO:17). ### Claim 12 (depends on 1) The method of claim 1, wherein the antibody is 13M57. ### Claim 13 (depends on 1) The method of claim 1, wherein the antibody is conjugated to a cytotoxic moiety. ### Claim 14 (depends on 1) The method of claim 1, wherein the antibody is administered with at least one additional therapeutic agent. ### Claim 15 (depends on 14) The method of claim 14, wherein the additional therapeutic agent is a chemotherapeutic agent. ### Claim 16 (depends on 15) The method of claim 15, wherein the chemotherapeutic agent is paclitaxel, oxaliplatin, or irinotecan. ### Claim 17 (depends on 14) The method of claim 14, wherein the additional therapeutic is a second antibody. ### Claim 18 (depends on 1) The method of claim 1, wherein the antibody is administered with radiation therapy.