# US 11,111,292 B2 · Anti-IL-5 antibodies > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,111,292 B2 - Document ID: US11111292B2 - Status: Granted - Kind: B2 - Application number: 15/848,090 - Filed: 2017-12-20 - Published: 2018-07-05 - Granted: 2021-09-07 - Earliest claimed: 2016-12-23 - Assignees: Cephalon, Inc. - Applicants: Cephalon, Inc. - Inventors: Mark Terence Liddament; Anthony Doyle; Adam Clarke; David Jose Simon Laine; Bridget Ann Cooksey - Web page: https://patentgrep.com/patent/US11111292B2 ## CPC - C07K 16/244: {Interleukins [IL]} - A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) - A61K 2039/505: {comprising 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 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/54: F(ab')2 - C07K 2317/55: Fab or Fab' - C07K 2317/56: variable (Fv) region, i.e. VH and/or VL - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/622: Single chain antibody (scFv) - C07K 2317/75: Agonist effect on antigen - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract Disclosed herein are fully human antibody molecules that immunospecifically bind to human IL-5. The antibody molecules can bind to human IL-5 with an equilibrium affinity constant (KD) of at least about 40 pM as determined by surface plasmon resonance. ## Claims ### Claim 1 A human antibody molecule that immunospecifically binds to human IL-5 with an equilibrium affinity constant (KD) of at least about 40 pM as determined by surface plasmon resonance, wherein the human antibody molecule comprises: a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 comprising the amino acid sequence of SEQ ID NOs: 5, 21, 24, 27, 30, 33, 36, 39, or 66, a light chain CDR2 comprising the amino acid sequence of SEQ ID NOs: 7, 42, or 45, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NOs: 15, 48, 51, 54, 57, 60, or 63. ### Claim 2 (depends on 1) The antibody molecule of claim 1, wherein the antibody molecule comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, and a. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15; b. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15; c. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 24, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15; d. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15; e. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 30, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15; f. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 33, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15; g. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 36, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15; h. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 39, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15; i. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 66, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15; j. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 42, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15; k. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 45, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15; l. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 48; m. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 51; n. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 54; o. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 57; p. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 60; or q. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 63; wherein the position of the amino acid residues of the CDR is determined according to AbM. ### Claim 3 (depends on 2) The antibody molecule of claim 2, wherein the antibody molecule comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15. ### Claim 4 (depends on 1) The antibody molecule of claim 1, wherein the antibody is an IgG molecule comprising: a. a S228P mutation in the hinge region; b. a M252Y mutation, a S254T mutation, and a T256E mutation in the CH2 domain of the heavy chain; c. a deletion of a heavy chain C-terminal lysine residue; or d. any combination of a to c. ### Claim 5 (depends on 4) The antibody molecule of claim 4, wherein the antibody molecule comprises a S228P mutation and a deletion of a heavy chain C-terminal lysine residue. ### Claim 6 (depends on 4) The antibody molecule of claim 4, wherein the antibody molecule comprises a S228P mutation, a M252Y mutation, a S254T mutation, a T256E mutation, and a deletion of a heavy chain C-terminal lysine residue. ### Claim 7 (depends on 1) The antibody molecule of claim 1, wherein the antibody molecule comprises an IgG4 heavy chain constant region and a lambda light chain constant region. ### Claim 8 (depends on 1) The antibody molecule of claim 1, wherein the antibody molecule comprises a heavy chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 18 and a. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19; b. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 23; c. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 26; d. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 29; e. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 32; f. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 35; g. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 38; h. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 41; i. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 44; j. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 47; k. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 50; l. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 53; m. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 56; n. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 59; o. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 62; p. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 65; or q. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 68. ### Claim 9 (depends on 1) The antibody molecule of claim 1, wherein the antibody molecule comprises a heavy chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 20 and a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19. ### Claim 10 (depends on 1) The antibody molecule of claim 1, wherein the antibody molecule is a Fab fragment, a Fab2 fragment, or a single chain antibody. ### Claim 11 (depends on 1) The antibody molecule of claim 1, wherein the antibody molecule has one or more of the following properties: a. reduces binding of IL-5 to the IL-5 receptor; b. has a serum half-life of at least about 20 days; or c. binds human and cynomolgus monkey IL-5 but not mouse, rat, or guinea pig IL-5. ### Claim 12 (depends on 1) A pharmaceutical composition comprising the antibody molecule of claim 1. ### Claim 13 (depends on 1) A nucleic acid molecule encoding the antibody molecule of claim 1. ### Claim 14 (depends on 13) A vector comprising the nucleic acid molecule of claim 13. ### Claim 15 (depends on 1) A cell transformed to express the antibody molecule of claim 1. ### Claim 16 (depends on 1) A method of treating a subject having eosinophilic asthma, hypereosinophilic syndrome, nasal polyposis with eosinophilic involvement, eosinophilic granulomatosis with polyangiitis, atopic dermatitis or eosinophilic esophagitis comprising: administering to the subject a therapeutically effective amount of the antibody molecule of claim 1 to treat the eosinophilic asthma, hypereosinophilic syndrome, nasal polyposis with eosinophilic involvement, eosinophilic granulomatosis with polyangiitis, atopic dermatitis or eosinophilic esophagitis. ### Claim 17 (depends on 1) The antibody molecule of claim 1, wherein the antibody molecule comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16 and a. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 17; b. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 22; c. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 25; d. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 28; e. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 31; f. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 34; g. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 37; h. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 40; i. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 43; j. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 46; k. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 49; l. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 52; m. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55; n. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 58; o. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 61; p. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 64; or q. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 67. ### Claim 18 (depends on 17) The antibody molecule of claim 17, wherein the antibody molecule comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 17. ### Claim 19 (depends on 17) The antibody molecule of claim 17, wherein the antibody molecule comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 22. ### Claim 20 (depends on 17) The antibody molecule of claim 17, wherein the antibody molecule comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 25. ### Claim 21 (depends on 17) The antibody molecule of claim 17, wherein the antibody molecule comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 28. ### Claim 22 (depends on 1) The antibody molecule of claim 1, wherein the antibody molecule comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15. ### Claim 23 (depends on 1) The antibody molecule of claim 1, wherein the antibody molecule comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 24, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15. ### Claim 24 (depends on 1) The antibody molecule of claim 1, wherein the antibody molecule comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15.