# US 11,028,183 B2 · HER2/neu-specific antibodies and methods of using same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,028,183 B2 - Document ID: US11028183B2 - Status: Granted - Kind: B2 - Application number: 16/156,382 - Filed: 2018-10-10 - Published: 2019-08-01 - Granted: 2021-06-08 - Earliest claimed: 2008-04-02 - Assignees: MacroGenics, Inc. - Applicants: MacroGenics, Inc. - Inventors: Leslie S. Johnson; Ling Huang; Nadine Tuaillon; Ezio Bonvini - Web page: https://patentgrep.com/patent/US11028183B2 ## CPC - C07K 16/32: against translation products of oncogenes - A61K 39/39558: {against tumor tissues, cells, antigens} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - A61P 35/04: specific for metastasis - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K 2039/505: {comprising antibodies} - A61K 2039/54: {characterised by the route of administration} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1 - C07K 2317/515: Complete light chain, i.e. VL + CL - C07K 2317/71: Decreased effector function due to an Fc-modification - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - 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 This invention relates to antibodies that specifically bind HER2/neu, and particularly chimeric 4D5 antibodies to HER2/neu, which have reduced glycosylation as compared to known 4D5 antibodies. The invention also relates to methods of using the 4D5 antibodies and compositions comprising them in the diagnosis, prognosis and therapy of diseases such as cancer, autoimmune diseases, inflammatory disorders, and infectious disease. ## Claims ### Claim 1 A method of treating a HER2/neu-expressing cancer in a patient in need thereof having a CD16A Fc Receptor comprising a Phe at position 158, comprising administering to said patient a therapeutically effective amount of an antibody that binds human HER2/neu and comprises: (A) an immunoglobulin light chain comprising an amino acid sequence of SEQ ID NO: 2; and (B) an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13. ### Claim 2 (depends on 1) The method of claim 1, wherein said antibody is administered by intravenous infusion. ### Claim 3 (depends on 1) The method of claim 1, comprising the further step of administering a second therapeutic agent simultaneously or sequentially with said antibody. ### Claim 4 (depends on 3) The method of claim 3, wherein said second therapeutic agent and said antibody are administered no more than 12 hours apart, or no more than 24 hours apart, or no more than 96 hours apart. ### Claim 5 (depends on 3) The method of claim 3, wherein said second therapeutic agent is selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic agent, a chemotherapeutic agent, and a cytotoxic agent. ### Claim 6 (depends on 3) The method of claim 3, wherein said second therapeutic agent is selected from the group consisting of an anti-mitotic agent, a hormone therapy agent, and an aromatase inhibitor. ### Claim 7 (depends on 1) The method of claim 1, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 8 (depends on 2) The method of claim 2, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 9 (depends on 3) The method of claim 3, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 10 (depends on 4) The method of claim 4, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 11 (depends on 5) The method of claim 5, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 12 (depends on 6) The method of claim 6, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 13 A method of treating a HER2/neu-expressing cancer in a patient in need thereof having a CD16A Fc Receptor comprising a Phe at position 158, comprising administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising an antibody that binds human HER2/neu and comprises: (A) an immunoglobulin light chain comprising an amino acid sequence of SEQ ID NO: 2; and (B) an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13; and (C) a pharmaceutically acceptable carrier and/or an excipient. ### Claim 14 (depends on 13) The method of claim 13, further comprising the steps of: providing said pharmaceutical composition as a sterile liquid in a hermetically sealed container; and extracting said pharmaceutical composition from said hermetically sealed container prior to said administering step. ### Claim 15 (depends on 14) The method of claim 14 wherein the concentration of said antibody in said sterile liquid is at least 1 mg/ml. ### Claim 16 (depends on 13) The method of claim 13, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 17 (depends on 14) The method of claim 14, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 18 (depends on 15) The method of claim 15, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 19 (depends on 14) The method of claim 14, wherein the concentration of said antibody in said sterile liquid is at least 2.5 mg/ml. ### Claim 20 (depends on 14) The method of claim 14, wherein the concentration of said antibody in said sterile liquid is at least 5 mg/ml. ### Claim 21 (depends on 14) The method of claim 14, wherein the concentration of said antibody in said sterile liquid is at least 8 mg/ml. ### Claim 22 (depends on 14) The method of claim 14, wherein the concentration of said antibody in said sterile liquid is at least 10 mg/ml. ### Claim 23 (depends on 14) The method of claim 14, wherein the concentration of said antibody in said sterile liquid is at least 15 mg/ml. ### Claim 24 (depends on 14) The method of claim 14, wherein the concentration of said antibody in said sterile liquid is at least 25 mg/ml. ### Claim 25 (depends on 14) The method of claim 14, wherein the concentration of said antibody in said sterile liquid is at least 50 mg/ml. ### Claim 26 (depends on 14) The method of claim 14, wherein the concentration of said antibody in said sterile liquid is at least 100 mg/ml. ### Claim 27 (depends on 14) The method of claim 14, wherein the concentration of said antibody in said sterile liquid is at least 150 mg/ml. ### Claim 28 (depends on 14) The method of claim 14, wherein the concentration of said antibody in said sterile liquid is at least 200 mg/ml. ### Claim 29 (depends on 19) The method of claim 19, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 30 (depends on 20) The method of claim 20, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 31 (depends on 21) The method of claim 21 wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 32 (depends on 22) The method of claim 22, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 33 (depends on 23) The method of claim 23, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 34 (depends on 24) The method of claim 24, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 35 (depends on 25) The method of claim 25, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 36 (depends on 26) The method of claim 26, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 37 (depends on 27) The method of claim 27, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11. ### Claim 38 (depends on 28) The method of claim 28, wherein said antibody comprises an immunoglobulin heavy chain comprising an amino acid sequence of SEQ ID NO: 11.