# US 9,518,121 B2 · Anti-Jagged1 antibodies and methods of use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,518,121 B2 - Document ID: US9518121B2 - Status: Granted - Kind: B2 - Application number: 14/619,930 - Filed: 2015-02-11 - Published: 2015-09-10 - Granted: 2016-12-13 - Earliest claimed: 2014-02-12 - Assignees: Genentech, Inc. - Applicants: Genentech, Inc. - Inventors: Yvonne Chinn; Julie Q. Hang; Christian W. Siebel; Yan Wu - Web page: https://patentgrep.com/patent/US9518121B2 ## CPC - C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere} - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant} - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 11/00: Drugs for disorders of the respiratory system - A61P 11/06: Antiasthmatics - A61P 35/00: Antineoplastic agents - A61P 37/00: Drugs for immunological or allergic disorders - A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - 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 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/56: variable (Fv) region, i.e. VH and/or VL - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - 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 invention provides anti-Jagged1 antibodies and methods of using the same. ## Claims ### Claim 1 An isolated antibody that binds to human Jagged 1, wherein the antibody comprises an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 35 or 78; an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 28 or 36; an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 55 or 59, wherein X is any amino acid other than S; an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16 or 40. ### Claim 2 (depends on 1) The isolated antibody of claim 1, wherein the antibody comprises: a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 55; or b) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 59; or c) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 28; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 59. ### Claim 3 (depends on 1) The isolated antibody of claim 1, wherein the antibody comprises: a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 40; or b) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16. ### Claim 4 (depends on 1) The isolated antibody of claim 1, wherein the antibody comprises: a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 55; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 40; or b) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 59; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16; or c) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 28; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 59; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16. ### Claim 5 (depends on 1) The isolated antibody of claim 1, wherein the antibody comprises a VH sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 54, 58, or 62. ### Claim 6 (depends on 1) The isolated antibody of claim 1, wherein the antibody comprises a VL sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 10, 26, or 34. ### Claim 7 (depends on 1) The isolated antibody of claim 1, wherein the antibody comprises: a) a VH sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 54 and a VL sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 34; or b) a VH sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 58 and a VL sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 10; or c) a VH sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 62 and a VL sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 26. ### Claim 8 An isolated antibody that binds human Jagged1, comprising: a) a VH sequence of SEQ ID NO: 54, wherein X is any amino acid other than S, and a VL sequence of SEQ ID NO: 34; or b) a VH sequence of SEQ ID NO: 58, wherein X is any amino acid other than S, and a VL sequence of SEQ ID NO: 10; or c) a VH sequence of SEQ ID NO: 62, wherein X is any amino acid other than S, and a VL sequence of SEQ ID NO: 26. ### Claim 9 (depends on 8) The isolated antibody of claim 8, wherein the antibody comprises a VH sequence of SEQ ID NO: 54 and a VL sequence of SEQ ID NO: 34. ### Claim 10 (depends on 9) The isolated antibody of claim 9, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 56 and the light chain comprises the amino acid sequence of SEQ ID NO: 53. ### Claim 11 (depends on 9) The isolated antibody of claim 9, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 57 and the light chain comprises the amino acid sequence of SEQ ID NO: 53. ### Claim 12 (depends on 1) The isolated antibody of claim 1, wherein X is any amino acid other than S or H. ### Claim 13 (depends on 1) The isolated antibody of claim 1, wherein X is selected from A, D, E, G, I, K, L, N, Q, R T, and V. ### Claim 14 (depends on 1) The isolated antibody of claim 1, wherein X is T. ### Claim 15 An isolated antibody that binds human Jagged1, comprising: a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 37; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 40; or b) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 64; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16; or c) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 28; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 64; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16. ### Claim 16 (depends on 15) The isolated antibody of claim 15, wherein the antibody comprises: a) a VH sequence of SEQ ID NO: 33 and a VL sequence of SEQ ID NO: 34; or b) a VH sequence of SEQ ID NO: 65 and a VL sequence of SEQ ID NO: 10; or c) a VH sequence of SEQ ID NO: 66 and a VL sequence of SEQ ID NO: 26. ### Claim 17 An isolated antibody that binds human Jagged1, wherein the antibody comprises a VH sequence of SEQ ID NO: 33 and a VL sequence of SEQ ID NO: 34. ### Claim 18 (depends on 1) The isolated antibody of claim 1, which is a full length IgG1 antibody. ### Claim 19 (depends on 18) The isolated antibody of claim 18, wherein the antibody substantially lacks effector function. ### Claim 20 (depends on 18) The isolated antibody of claim 18, wherein the heavy chain comprises a N297G or N297A mutation. ### Claim 21 An isolated antibody that binds human Jagged1, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 51 and the light chain comprises the amino acid sequence of SEQ ID NO: 53. ### Claim 22 An isolated antibody that binds human Jagged1, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 52 and the light chain comprises the amino acid sequence of SEQ ID NO: 53. ### Claim 23 (depends on 16) The isolated antibody of claim 16, wherein the antibody comprises: a) a heavy chain comprising the amino acid sequence of SEQ ID NO: 69 and a light chain comprising the amino acid sequence of SEQ ID NO: 75; or b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 70 and a light chain comprising the amino acid sequence of SEQ ID NO: 76; or c) a heavy chain comprising the amino acid sequence of SEQ ID NO: 79 and a light chain comprising the amino acid sequence of SEQ ID NO: 75; or d) a heavy chain comprising the amino acid sequence of SEQ ID NO: 80 and a light chain comprising the amino acid sequence of SEQ ID NO: 76. ### Claim 24 (depends on 1) The isolated antibody of claim 1, wherein the antibody is an antagonist of Jagged1-mediated signaling. ### Claim 25 (depends on 1) The isolated antibody of claim 1, wherein the antibody does not bind human Jagged2. ### Claim 26 (depends on 1) The isolated antibody of claim 1, wherein the antibody does not bind human DLL4. ### Claim 27 (depends on 1) The isolated antibody of claim 1, wherein the antibody does not bind human DLL1. ### Claim 28 (depends on 1) The isolated antibody of claim 1, wherein the antibody does not bind murine Jagged2, murine DLL4, and/or murine DLL1. ### Claim 29 (depends on 1) The isolated antibody of claim 1, wherein the antibody reduces tumor growth in a mouse xenograft model without causing weight loss. ### Claim 30 (depends on 29) The isolated antibody of claim 29, wherein the mouse xenograft model is a liver cancer xenograft model. ### Claim 31 (depends on 30) The isolated antibody of claim 30, wherein tumor growth is reduced by at least 50, at least 60, at least 70, at least 80, or at least 90 AUC/day TGI %. ### Claim 32 An immunoconjugate comprising an antibody, wherein the antibody comprises an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 35 or 78; an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 28 or 36; an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 55 or 59, wherein X is any amino acid other than S; an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16 or 40, and a cytotoxic agent. ### Claim 33 A pharmaceutical formulation comprising an antibody, wherein the antibody comprises an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 35 or 78; an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 28 or 36; an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 55 or 59, wherein X is any amino acid other than S; an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16 or 40, and a pharmaceutically acceptable carrier. ### Claim 34 (depends on 32) A pharmaceutical formulation comprising the immunoconjugate of claim 32 and a pharmaceutically acceptable carrier. ### Claim 35 (depends on 1) The isolated antibody of claim 1 conjugated to a label. ### Claim 36 An isolated antibody that binds human Jagged1, comprising: HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 37; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 40. ### Claim 37 An isolated antibody that binds human Jagged1, comprising: HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 36; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 64; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16. ### Claim 38 An isolated antibody that binds human Jagged1, comprising: HVR-H1 comprising the amino acid sequence of SEQ ID NO: 78; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 28; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 64; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 38; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 16.