# US 10,500,276 B2 · Antibodies binding AXL > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,500,276 B2 - Document ID: US10500276B2 - Status: Granted - Kind: B2 - Application number: 16/270,317 - Filed: 2019-02-07 - Published: 2019-05-30 - Granted: 2019-12-10 - Earliest claimed: 2014-07-11 - Assignees: Genmab A/S - Applicants: Genmab A/S - Inventors: Esther Breij; David Satijn; Edward Norbert Van Den Brink; Dennis Verzijl; Rob N. De Jong; Paul Parren; Riemke Van Dijkhuizen Radersma - Web page: https://patentgrep.com/patent/US10500276B2 ## CPC - A61K 39/39558: {against tumor tissues, cells, antigens} - A61K 47/6801: {Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent} - A61K 47/6855: {the tumour determinant being from breast cancer cell} - A61K 47/6857: {the tumour determinant being from lung cancer cell} - A61K 47/6869: {the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate} - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes - A61P 7/00: Drugs for disorders of the blood or the extracellular fluid - A61P 11/00: Drugs for disorders of the respiratory system - A61P 13/10: of the bladder - A61P 13/12: of the kidneys - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 17/00: Drugs for dermatological disorders - A61P 19/04: for non-specific disorders of the connective tissue - A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease - A61P 21/00: Drugs for disorders of the muscular or neuromuscular system - A61P 25/00: Drugs for disorders of the nervous system - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 16/2863: {against receptors for growth factors, growth regulators} - C07K 16/3061: {Blood cells} - A61K 2039/505: {comprising antibodies} - A61K 2121/00: Preparations for use in therapy - 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 2317/56: variable (Fv) region, i.e. VH and/or VL - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - C07K 2317/77: Internalization into the cell - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - 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 - 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) ## Abstract The present invention relates to anti-AXL antibodies, immunoconjugates, compositions and method of treatment of cancer with such anti-AXL antibodies, immunoconjugates, or compositions. ## Claims ### Claim 1 An immunoconjugate comprising (a) an antibody which binds to AXL (SEQ ID NO: 130) and comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 36, 37, and 38, respectively, and the VL region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 39, the amino acid sequence GAS, and SEQ ID NO: 40, respectively, (b) a mc-vc-PAB linker, and (c) a cytotoxic agent, which is MMAE. ### Claim 2 (depends on 1) The immunoconjugate of claim 1, wherein the VH and VL regions comprise the amino acid sequences of SEQ ID NOs: 1 and 2, respectively. ### Claim 3 (depends on 1) The immunoconjugate of claim 1, wherein MMAE is linked to the antibody via the mc-vc-PAB linker, wherein the cytotoxic agent and the linker have the chemical structure; wherein MAb is the antibody. ### Claim 4 (depends on 1) The immunoconjugate according to claim 1, wherein the MMAE is conjugated to the antibody via a cysteine thiol or a lysine. ### Claim 5 (depends on 1) The immunoconjugate of claim 1, wherein cytotoxic agent loading (p) is 1 to 8. ### Claim 6 (depends on 1) The immunoconjugate of claim 1, wherein cytotoxic agent loading (p) is 10 to 30. ### Claim 7 (depends on 1) The immunoconjugate of claim 1, wherein said antibody comprises a heavy chain of an isotype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4. ### Claim 8 (depends on 1) The immunoconjugate of claim 1, wherein the antibody is a full-length monoclonal antibody. ### Claim 9 (depends on 1) The immunoconjugate of claim 1, wherein the antibody is a full-length monoclonal IgG1,κ antibody. ### Claim 10 (depends on 1) The immunoconjugate of claim 1, wherein the antibody is a monovalent antibody. ### Claim 11 (depends on 1) The immunoconjugate of claim 1, wherein the antibody is an antigen-binding fragment of an immunoglobulin molecule. ### Claim 12 (depends on 1) The immunoconjugate of claim 1, wherein the antibody is a single-chain antibody. ### Claim 13 (depends on 1) The immunoconjugate of claim 1, wherein the antibody is a human antibody. ### Claim 14 (depends on 1) A pharmaceutical composition comprising the immunoconjugate of claim 1, and a pharmaceutical acceptable carrier. ### Claim 15 (depends on 1) A kit comprising the immunoconjugate of claim 1. ### Claim 16 (depends on 6) The immunoconjugate of claim 6, wherein cytotoxic agent loading (p) is 1 to 20. ### Claim 17 (depends on 6) The immunoconjugate of claim 6, wherein cytotoxic agent loading (p) is 2 to 6. ### Claim 18 (depends on 6) The immunoconjugate of claim 6, wherein cytotoxic agent loading (p) is 2 to 4. ### Claim 19 An immunoconjugate comprising (a) an antibody which binds to AXL (SEQ ID NO: 130) and comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the VH region comprises the amino acid sequence of SEQ ID NO: 1 and the VL region comprises the amino acid sequence of SEQ ID NO: 2, (b) a mc-vc-PAB linker, and (c) a cytotoxic agent, which is MMAE. ### Claim 20 (depends on 19) The immunoconjugate of claim 19, wherein the combination of the MMAE and the mc-vc-PAB linker has the chemical structure; wherein MAb is the antibody. ### Claim 21 (depends on 19) The immunoconjugate according to claim 19, wherein the MMAE is conjugated to the antibody via a cysteine thiol or a lysine. ### Claim 22 (depends on 19) The immunoconjugate of claim 19, wherein cytotoxic agent loading (p) is 1 to 8. ### Claim 23 (depends on 19) The immunoconjugate of claim 19, wherein cytotoxic agent loading (p) is 10 to 30. ### Claim 24 (depends on 19) The immunoconjugate of claim 19, wherein said antibody comprises a heavy chain of an isotype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4. ### Claim 25 (depends on 19) The immunoconjugate of claim 19, wherein the antibody is a full-length monoclonal antibody. ### Claim 26 (depends on 19) The immunoconjugate of claim 19, wherein the antibody is a full-length monoclonal IgG1,κ antibody. ### Claim 27 (depends on 19) The immunoconjugate of claim 19, wherein the antibody is a monovalent antibody. ### Claim 28 (depends on 19) The immunoconjugate of claim 19, wherein the antibody is a single-chain antibody. ### Claim 29 (depends on 19) The immunoconjugate of claim 19, wherein the antibody is an antigen-binding fragment of an immunoglobulin molecule. ### Claim 30 (depends on 19) The immunoconjugate of claim 19, wherein the antibody is a human antibody. ### Claim 31 (depends on 19) A pharmaceutical composition comprising the antibody of claim 19, and a pharmaceutical acceptable carrier. ### Claim 32 (depends on 19) A kit comprising the immunoconjugate of claim 19. ### Claim 33 (depends on 19) The immunoconjugate of claim 19, wherein cytotoxic agent loading (p) is 1 to 20. ### Claim 34 (depends on 19) The immunoconjugate of claim 19, wherein cytotoxic agent loading (p) is 2 to 6. ### Claim 35 (depends on 19) The immunoconjugate of claim 19, wherein cytotoxic agent loading (p) is 2 to 4.