# US 2014/0154267 A1 · Use of interleukin-4 antagonists and compositions thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0154267 A1 - Document ID: US20140154267A1 - Status: Published application - Kind: A1 - Application number: 14/175,943 - Filed: 2014-02-07 - Published: 2014-06-05 - Earliest claimed: 2001-05-01 - Assignees: Immunex Corporation - Applicants: Immunex Corporation - Inventors: Richard J. ARMITAGE; Jose Carlos ESCOBAR; Arvia E. MORRIS; John D. PLUENNEKE - Web page: https://patentgrep.com/patent/US20140154267A1 ## CPC - C07K 16/2866: {against receptors for cytokines, lymphokines, interferons} - A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum - A61P 11/06: Antiasthmatics - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 31/04: Antibacterial agents - A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) - C07K 14/7155: {for interleukins [IL]} - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - A01K 2217/05: Animals comprising random inserted nucleic acids (transgenic) - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K 2039/505: {comprising antibodies} - C07K 2317/21: from primates, e.g. man - C07K 2317/56: variable (Fv) region, i.e. VH and/or VL - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - 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 - A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS ## Abstract Methods for treating medical conditions induced by interleukin-4 involve administering an IL-4 antagonist to a patient afflicted with such a condition. Suitable IL-4 antagonists include, but are not limited to, IL-4 receptors (such as a soluble human IL-4 receptor), antibodies that bind IL-4, antibodies that bind IL-4R, IL-4 muteins that bind to IL-4R but do not induce a biological response, molecules that inhibit IL-4-induced signal transduction, and other compounds that inhibit a biological effect that results from the binding of IL-4 to a cell surface IL-4R. Particular antibodies provided herein include human monoclonal antibodies generated by procedures involving immunization of transgenic mice. Such human antibodies may be raised against human IL-4 receptor. Certain of the antibodies inhibit both IL-4-induced and IL-13-induced biological activities. ## Claims ### Claim 1 An isolated antibody that competes with a reference antibody for binding to human IL-4 receptor, wherein: a. the light chain of said reference antibody comprises the amino acid sequence of SEQ ID NO:14 and the heavy chain of said reference antibody comprises the amino acid sequence of SEQ ID NO:16; or b. the light chain of said reference antibody comprises the amino acid sequence of SEQ ID NO:18 and the heavy chain of said reference antibody comprises the amino acid sequence of SEQ ID NO:20; or c. the light chain of said reference antibody comprises the amino acid sequence of SEQ ID NO:22 and the heavy chain of said reference antibody comprises the amino acid sequence of SEQ ID NO:24. ### Claim 2 (depends on 1) The isolated antibody of claim 1, wherein when said reference antibody is bound to human IL-4 receptor, binding of said isolated antibody to said human IL-4 receptor is inhibited. ### Claim 3 (depends on 1) The isolated antibody of claim 1, wherein when said isolated antibody is bound to human IL-4 receptor, binding of said reference antibody to said human IL-4 receptor is inhibited. ### Claim 4 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody inhibits the binding of human IL-4 to human IL-4 receptor. ### Claim 5 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody inhibits the binding of human IL-13 to human IL-4 receptor. ### Claim 6 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody inhibits human IL-4 signaling through human IL-4 receptor. ### Claim 7 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody inhibits human IL-13 signaling through human IL-4 receptor. ### Claim 8 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody binds to human IL-4 receptor with a binding affinity (Ka) of at least 1×108. ### Claim 9 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody binds to human IL-4 receptor with a binding affinity (Ka) of at least 1×109. ### Claim 10 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody binds to human IL-4 receptor with a binding affinity (Ka) of at least 1×1010. ### Claim 11 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody is a human, partially human, humanized, or chimeric antibody. ### Claim 12 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody is a full-length antibody. ### Claim 13 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody is an IgA antibody, an IgD antibody, an IgE antibody, IgG antibody, an IgG1 antibody, an IgG2 antibody, an IgG3, antibody, an IgG4 antibody, or an IgM antibody. ### Claim 14 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody is a fragment of an antibody. ### Claim 15 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody is a fusion protein. ### Claim 16 (depends on 1) The isolated antibody of claim 1, wherein said isolated antibody is a single chain antibody (scFv). ### Claim 17 (depends on 1) The isolated antibody of claim 1, wherein: a. the light chain variable domain of said isolated antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:14 and the heavy chain variable domain of said isolated antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:16; or b. the light chain variable domain of said isolated antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:18 and the heavy chain variable domain of said isolated antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:20; or c. the light chain variable domain of said isolated antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:22 and the heavy chain variable domain of said isolated antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:24. ### Claim 18 (depends on 1) The isolated antibody of claim 1, wherein: a. the light chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:14; or b. the heavy chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:16; or c. the light chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:18; or d. the heavy chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:20; or e. the light chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:22; or f. the heavy chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:24. ### Claim 19 (depends on 1) The isolated antibody of claim 1, wherein: a. the light chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:14 and the heavy chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:16; or b. the light chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:18 and the heavy chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:20; or c. the light chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:22 and the heavy chain of said isolated antibody comprises the amino acid sequence of SEQ ID NO:24. ### Claim 20 (depends on 1) An isolated nucleic acid, wherein said isolated nucleic acid comprises a sequence encoding: a. light chain variable domain of said isolated antibody of claim 1; or b. the heavy chain variable domain of said isolated antibody of claim 1; or c. light chain variable domain of said isolated antibody of claim 1 and the heavy chain variable domain of said isolated antibody of claim 1. ### Claim 21 (depends on 20) A vector, wherein said vector comprises said isolated nucleic acid of claim 20. ### Claim 22 (depends on 21) The vector of claim 21, wherein said vector is an expression vector. ### Claim 23 (depends on 20) An isolated cell, wherein said cell comprises said isolated nucleic acid of claim 20. ### Claim 24 (depends on 23) The isolated cell of claim 23, wherein said isolated cell expresses said isolated antibody. ### Claim 25 (depends on 1) A method of reducing IL-4 receptor-dependent signaling in a subject, comprising administering to said subject an effective amount of said isolated antibody of claim 1. ### Claim 26 (depends on 25) The method of claim 25, wherein said method suppresses a TH2-type immune response. ### Claim 27 (depends on 25) The method of claim 25, wherein said subject has, or is at risk of developing, a condition responsive to inhibition of IL-4R signaling. ### Claim 28 (depends on 27) The method of claim 27, wherein said condition is an inflammatory condition. ### Claim 29 (depends on 27) The method of claim 27, wherein said condition is an IgE mediated condition. ### Claim 30 (depends on 27) The method of claim 27, wherein said condition is an allergic condition. ### Claim 31 (depends on 27) The method of claim 27, wherein said condition is a condition in which IL-4 mediated epithelial barrier disruption plays a role. ### Claim 32 (depends on 27) The method of claim 27, wherein said condition is asthma, COPD, pulmonary fibrosis, or septic arthritis. ### Claim 33 (depends on 23) A method of making an antibody, comprising incubating said cell of claim 23 under conditions that allow it to express said isolated antibody. ### Claim 34 (depends on 1) A composition comprising said isolated antibody of claim 1 and a pharmaceutically acceptable diluent, buffer, or excipient. ### Claim 35 (depends on 1) A kit comprising said isolated antibody of claim 1.