# US 11,028,169 B2 · Antibody molecules for cancer treatment > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,028,169 B2 - Document ID: US11028169B2 - Status: Granted - Kind: B2 - Application number: 15/598,356 - Filed: 2017-05-18 - Published: 2017-11-23 - Granted: 2021-06-08 - Earliest claimed: 2016-05-18 - Assignees: Boehringer Ingelheim International GmbH - Applicants: Boehringer Ingelheim International GmbH - Inventors: Markus Zettl; Ivo Lorenz; Otmar Schaaf; Melanie Wurm; Jean-Francois Fortin; Scott Ronald Brodeur; Keith A. Canada; Lukasz Chlewicki; Priyanka Gupta; Rocío K. Pérez; Joseph Robert Woska; Haiguang Xiao; Danlin Yang - Web page: https://patentgrep.com/patent/US11028169B2 ## CPC - C07K 16/2803: {against the immunoglobulin superfamily} - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 16/2818: {against CD28 or CD152} - C07K 16/2827: {against B7 molecules, e.g. CD80, CD86} - A61K 2039/505: {comprising antibodies} - A61K 2039/507: {Comprising a combination of two or more separate antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - 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 2317/565: 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 present invention relates to novel anti-PD1 and anti-LAG3 antibody molecules. The invention also relates to nucleic acids encoding such antibody molecules; to methods for preparing such antibody molecules; to host cells expressing or capable of expressing such antibody molecules; to compositions comprising such antibody molecules; and to uses of such antibody molecules or such compositions, in particular for therapeutic purposes in the field of cancer diseases. ## Claims ### Claim 1 An anti-PD1 antibody molecule comprising a heavy chain variable domain comprising heavy chain CDRs comprising the amino acid sequence of SEQ ID NO:13 (hcCDR1), SEQ ID NO:14 (hcCDR2) and SEQ ID NO:15 (hcCDR3) and a light chain variable domain comprising light chain CDRs comprising the amino acid sequence of SEQ ID NO:16 (lcCDR1), SEQ ID NO:17 (lcCDR2) and SEQ ID NO:18 (lcCDR3). ### Claim 2 (depends on 1) The anti-PD1 antibody molecule of claim 1, wherein said antibody molecule is a humanized antibody molecule. ### Claim 3 (depends on 1) The anti-PD1 antibody molecule of claim 1, wherein said antibody molecule is selected from the group consisting of a monoclonal antibody molecule, a Fab, a F(ab′)2, a Fv and an scFv. ### Claim 4 (depends on 1) The anti-PD1 antibody molecule of claim 1 which comprises a heavy chain constant region selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE constant regions. ### Claim 5 (depends on 4) The anti-PD1 antibody molecule of claim 4, wherein the heavy chain constant region is a human heavy chain constant region of an IgG4 with a S241P mutation. ### Claim 6 (depends on 1) The anti-PD1 antibody molecule of claim 1, wherein the antibody molecule comprises a light chain constant region selected from the group consisting of kappa and lambda. ### Claim 7 (depends on 1) The anti-PD1 antibody molecule of claim 1, wherein said antibody molecule comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 23. ### Claim 8 (depends on 1) The anti-PD1 antibody molecule of claim 1, wherein said antibody molecule comprises a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 24. ### Claim 9 (depends on 1) The anti-PD1 antibody molecule of claim 1, wherein said antibody molecule has a heavy chain comprising the amino acid sequence of SEQ ID NO: 33. ### Claim 10 (depends on 1) The anti-PD1 antibody molecule of claim 1, wherein said antibody molecule has a light chain comprising the amino acid sequence of SEQ ID NO: 34. ### Claim 11 An anti-PD1 antibody molecule, wherein said antibody molecule comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 23 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 24. ### Claim 12 An anti-PD1 antibody molecule, wherein said antibody molecule has a heavy chain comprising the amino acid sequence of SEQ ID NO: 33 and a light chain comprising the amino acid sequence of SEQ ID NO:34. ### Claim 13 (depends on 1) An isolated nucleic acid molecule encoding the heavy chain variable domain and the light chain variable domain of an antibody molecule of claim 1. ### Claim 14 (depends on 13) The nucleic acid molecule of claim 13 which has the nucleotide sequence of SEQ ID NO: 75 encoding the heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 23. ### Claim 15 (depends on 13) The nucleic acid molecule of claim 13 which has the nucleotide sequence of SEQ ID NO: 76 encoding the light chain variable domain comprising the amino acid sequence of SEQ ID NO: 24. ### Claim 16 (depends on 1) An expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding the heavy chain variable domain and the light chain variable domain of an antibody molecule of claim 1. ### Claim 17 (depends on 16) The expression vector of claim 16 comprising a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 75 and SEQ ID NO: 76. ### Claim 18 (depends on 16) The expression vector of claim 16, wherein said nucleic acid molecule further comprises a nucleotide sequence encoding heavy chain constant domains and light chain constant domain, respectively, linked to the nucleotide sequence encoding the heavy chain variable domain and the light chain variable domain, respectively. ### Claim 19 (depends on 1) A host cell comprising an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain variable domain of an antibody molecule of claim 1, and an expression vector comprising a nucleic acid molecule comprising the nucleotide sequence encoding a light chain variable domain of an antibody molecule of claim 1. ### Claim 20 (depends on 19) The host cell of claim 19, wherein the cell is a mammalian cell. ### Claim 21 (depends on 1) A method of manufacturing an antibody molecule of claim 1 comprising the steps of: culturing a host cell comprising an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain variable domain of an antibody molecule of claim 1, and an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a light chain variable domain of an antibody molecule of claim 1 under conditions that allow formation of an antibody molecule according to claim 1; and, recovering said antibody molecule. ### Claim 22 (depends on 21) The method of claim 21, further comprising the step of purifying said antibody molecule. ### Claim 23 (depends on 21) The method of claim 21, further comprising the step of formulating said antibody molecule into a pharmaceutical composition. ### Claim 24 (depends on 1) A pharmaceutical composition comprising an anti-PD1 antibody of claim 1 and a pharmaceutically acceptable carrier. ### Claim 25 (depends on 1) A method of treating cancer comprising administering to a patient having cancer a therapeutically effective amount of the anti-PD1 antibody molecule of claim 1. ### Claim 26 (depends on 25) The method of claim 25, wherein said cancer is a solid tumor cancer or a cancer of the hematopoietic system. ### Claim 27 (depends on 25) The method of claim 25, wherein the antibody molecule is administered in combination with one or more further therapeutic agents or procedures. ### Claim 28 (depends on 27) The method of claim 27, wherein the one or more further therapeutic agents or procedures is selected from chemotherapy, a targeted anti-cancer therapy, an oncolytic drug, a cytotoxic agent, an immune-based therapy, a cytokine, surgical procedure, a radiation procedure, an activator of a costimulatory molecule, an inhibitor of an inhibitory molecule, a vaccine, and a cellular immunotherapy. ### Claim 29 (depends on 11) A host cell comprising an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain variable domain of an antibody molecule of claim 11, and an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a light chain variable domain of an antibody molecule of claim 11. ### Claim 30 (depends on 29) The host cell of claim 29, wherein the cell is a mammalian cell. ### Claim 31 (depends on 11) A method of manufacturing an antibody molecule of claim 11 comprising the steps of: culturing a host cell comprising an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain variable domain of an antibody molecule of claim 11, and an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a light chain variable domain of an antibody molecule of claim 11 under conditions that allow formation of an antibody molecule according to claim 11; and, recovering said antibody molecule. ### Claim 32 (depends on 31) The method of claim 31, further comprising the step of purifying said antibody molecule. ### Claim 33 (depends on 31) The method of claim 31, further comprising the step of formulating said antibody molecule into a pharmaceutical composition. ### Claim 34 (depends on 11) A pharmaceutical composition comprising an anti-PD1 antibody of claim 11 and a pharmaceutically acceptable carrier. ### Claim 35 (depends on 12) A host cell comprising an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain variable domain of an antibody molecule of claim 12, and an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a light chain variable domain of an antibody molecule of claim 12. ### Claim 36 (depends on 35) The host cell of claim 35, wherein the cell is a mammalian cell. ### Claim 37 (depends on 12) A method of manufacturing an antibody molecule of claim 12 comprising the steps of: culturing a host cell comprising an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain variable domain of an antibody molecule of claim 12, and an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a light chain variable domain of an antibody molecule of claim 12 under conditions that allow formation of an antibody molecule according to claim 12; and, recovering said antibody molecule. ### Claim 38 (depends on 37) The method of claim 37, further comprising the step of purifying said antibody molecule. ### Claim 39 (depends on 37) The method of claim 37, further comprising the step of formulating said antibody molecule into a pharmaceutical composition. ### Claim 40 (depends on 12) A pharmaceutical composition comprising an anti-PD1 antibody of claim 12 and a pharmaceutically acceptable carrier. ### Claim 41 An anti-PD-1 antibody molecule, wherein said antibody molecule has a heavy chain, wherein the amino acid sequence of said heavy chain consists of the amino acids of SEQ ID NO: 33, and a light chain, wherein the amino acid sequence of said light chain consists of the amino acids of SEQ ID NO:34. ### Claim 42 (depends on 41) A host cell comprising an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain variable domain of an antibody molecule of claim 41, and an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a light chain variable domain of an antibody molecule of claim 41. ### Claim 43 (depends on 42) The host cell of claim 42, wherein the cell is a mammalian cell. ### Claim 44 (depends on 41) A method of manufacturing an antibody molecule of claim 41 comprising the steps of: culturing a host cell comprising an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain variable domain of an antibody molecule of claim 41, and an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a light chain variable domain of an antibody molecule of claim 41 under conditions that allow formation of an antibody molecule according to claim 41; and, recovering said antibody molecule. ### Claim 45 (depends on 44) The method of claim 44, further comprising the step of purifying said antibody molecule. ### Claim 46 (depends on 44) The method of claim 44, further comprising the step of formulating said antibody molecule into a pharmaceutical composition. ### Claim 47 (depends on 41) A pharmaceutical composition comprising an anti-PD1 antibody of claim 41 and a pharmaceutically acceptable carrier. ### Claim 48 (depends on 11) A method of treating cancer comprising administering to a patient having cancer a therapeutically effective amount of the anti-PD1 antibody molecule of claim 11. ### Claim 49 (depends on 48) The method of claim 48, wherein said cancer is a solid tumor cancer or a cancer of the hematopoietic system. ### Claim 50 (depends on 48) The method of claim 48, wherein the antibody molecule is administered in combination with one or more further therapeutic agents or procedures. ### Claim 51 (depends on 50) The method of claim 50, wherein the one or more further therapeutic agents or procedures is selected from chemotherapy, a targeted anti-cancer therapy, an oncolytic drug, a cytotoxic agent, an immune-based therapy, a cytokine, surgical procedure, a radiation procedure, an activator of a costimulatory molecule, an inhibitor of an inhibitory molecule, a vaccine, and a cellular immunotherapy. ### Claim 52 (depends on 12) A method of treating cancer comprising administering to a patient having cancer a therapeutically effective amount of the anti-PD1 antibody molecule of claim 12. ### Claim 53 (depends on 52) The method of claim 52, wherein said cancer is a solid tumor cancer or a cancer of the hematopoietic system. ### Claim 54 (depends on 52) The method of claim 52, wherein the antibody molecule is administered in combination with one or more further therapeutic agents or procedures. ### Claim 55 (depends on 54) The method of claim 54, wherein the one or more further therapeutic agents or procedures is selected from chemotherapy, a targeted anti-cancer therapy, an oncolytic drug, a cytotoxic agent, an immune-based therapy, a cytokine, surgical procedure, a radiation procedure, an activator of a costimulatory molecule, an inhibitor of an inhibitory molecule, a vaccine, and a cellular immunotherapy. ### Claim 56 (depends on 41) A method of treating cancer comprising administering to a patient having cancer a therapeutically effective amount of the anti-PD1 antibody molecule of claim 41. ### Claim 57 (depends on 56) The method of claim 56, wherein said cancer is a solid tumor cancer or a cancer of the hematopoietic system. ### Claim 58 (depends on 56) The method of claim 56, wherein the antibody molecule is administered in combination with one or more further therapeutic agents or procedures. ### Claim 59 (depends on 58) The method of claim 58, wherein the one or more further therapeutic agents or procedures is selected from chemotherapy, a targeted anti-cancer therapy, an oncolytic drug, a cytotoxic agent, an immune-based therapy, a cytokine, surgical procedure, a radiation procedure, an activator of a costimulatory molecule, an inhibitor of an inhibitory molecule, a vaccine, and a cellular immunotherapy. ### Claim 60 (depends on 1) The anti-PD1 antibody molecule of claim 1 which comprises a human heavy chain constant region selected from the group consisting of IgG1, IgG2, IgG3, and IgG4 constant regions. ### Claim 61 (depends on 1) The anti-PD1 antibody molecule of claim 1, wherein the antibody molecule comprises a human light chain constant region selected from the group consisting of kappa and lambda. ### Claim 62 (depends on 1) An isolated nucleic acid molecule encoding the heavy chain variable domain or the light chain variable domain of an antibody molecule of claim 1. ### Claim 63 (depends on 62) The nucleic acid molecule of claim 62 which has the nucleotide sequence of SEQ ID NO: 75 encoding the heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 23. ### Claim 64 (depends on 62) The nucleic acid molecule of claim 62 which has the nucleotide sequence of SEQ ID NO: 76 encoding the light chain variable domain comprising the amino acid sequence of SEQ ID NO: 24. ### Claim 65 (depends on 1) An expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding the heavy chain variable domain or the light chain variable domain of an antibody molecule of claim 1. ### Claim 66 (depends on 65) The expression vector of claim 65 comprising a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 75 or SEQ ID NO: 76. ### Claim 67 (depends on 65) The expression vector of claim 65, wherein said nucleic acid molecule further comprises a nucleotide sequence encoding heavy chain constant domains or light chain constant domain, respectively, linked to the nucleotide sequence encoding the heavy chain variable domain or the light chain variable domain, respectively.