# US 2019/0375835 A1 · Use of monoclonal antibodies for the treatment of inflammation and bacterial infections > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0375835 A1 - Document ID: US20190375835A1 - Status: Published application - Kind: A1 - Application number: 16/436,537 - Filed: 2019-06-10 - Published: 2019-12-12 - Earliest claimed: 2012-12-17 - Assignees: Laboratoire Francais Du Fractionnement Et Des Biotechnologies - Applicants: Laboratoire Francais Du Fractionnement Et Des Biotechnologies - Inventors: Christophe De Romeuf - Web page: https://patentgrep.com/patent/US20190375835A1 ## CPC - C07K 16/241: {Tumor Necrosis Factors} - 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 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 5/14: of the thyroid hormones, e.g. T3, T4 - A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents - A61P 7/06: Antianaemics - A61P 13/12: of the kidneys - A61P 17/00: Drugs for dermatological disorders - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease - A61P 21/04: for myasthenia gravis - A61P 25/00: Drugs for disorders of the nervous system - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 37/02: Immunomodulators - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 16/22: against growth factors {; against growth regulators} - C07K 16/24: against cytokines, lymphokines or interferons - A61K 2039/505: {comprising antibodies} - C07K 2317/41: Glycosylation, sialylation, or fucosylation - C07K 2317/52: Constant or Fc region; Isotype - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance - 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 A composition includes monoclonal antibodies directed against a circulating proinflammatory cytokine, the antibodies having a high affinity for the FcγRIIIa receptor (CD16), in particular the fucose level of all of the antibodies of the composition being less than 60%, and preferably less than 50%, and in particular, the galactosylation level of all of the antibodies of the composition being at least 60%, for the use thereof in the context of the prevention or treatment of the early phases of inflammation. A composition including monoclonal antibodies directed against a circulating bacterial toxin, having an improved affinity for the FcγRIIIa receptor (CD16) with respect to antibodies directed against the bacterial toxin, produced in the CHO cell line, for the use thereof in the context of the prevention or treatment of the early phases of a bacterial infection linked to the release of the toxin is also described. ## Claims ### Claim 1 A method for the prevention or treatment of the early phases of inflammation comprising administering to a patient in need thereof a composition comprising monoclonal antibodies directed against a circulating proinflammatory cytokine, said antibodies have a high affinity for the FcγRIIIa receptor (CD16). ### Claim 2 (depends on 1) The method according to claim 1, wherein said antibodies of said composition have an affinity of at least equal to 2×106 M−1, at least equal to 2×107 M−1, 2×108 M−1 or 2×109 M−1, as determined by Scatchard analysis or BIAcore technology (Label-free surface plasmon resonance based technology) or competition assay with an anti-CD16 antibody 3G8. ### Claim 3 (depends on 1) The method according to claim 1, wherein the fucose level of all of the antibodies of said composition is less than 60%, and preferably less than 50%. ### Claim 4 (canceled) ### Claim 5 (depends on 1) The method according to claim 1, wherein the fucose level of all of the antibodies of said composition is less than 60%, and preferably less than 50%, and wherein each of the antibodies of said composition has, on the glycosylation site in position 297 of its heavy chains, one of the biantennary glycan forms selected from the following structures: ### Claim 6 (depends on 5) The method according to claim 5, wherein the G0F+G1F forms of the antibodies of said composition represent less than 50% of the glycan structures borne by the glycosylation site in position 297 of the heavy chain (Asn 297). ### Claim 7 (canceled) ### Claim 8 (depends on 1) The method according to claim 1, wherein the fucose level of all of the antibodies of said composition is less than 60%, and preferably less than 50%, and wherein each monoclonal antibody of said composition has an affinity for the FcγRIII receptors at least 1.5 times greater than that of a natural antibody directed against said circulating proinflammatory cytokine. ### Claim 9 (depends on 1) The method according to claim 1, wherein the fucose level of all of the antibodies of said composition is less than 60%, and preferably less than 50%, and wherein said proinflammatory cytokine is selected from the group consisting of: TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12, IL-17 IL-18, and GM-CSF. ### Claim 10 (depends on 1) The method according to claim 1, wherein the fucose level of all of the antibodies of said composition is less than 60%, and preferably less than 50%, and wherein said antibody of said composition has no properties of neutralization of said circulating proinflammatory cytokine. ### Claim 11 (depends on 1) The method according to claim 1, wherein the fucose level of all of the antibodies of said composition is less than 60%, and preferably less than 50%, and wherein said antibody of said composition is used in doses varying from 0.05 mg/m2 to 2000 mg/m2. ### Claim 12 (depends on 1) The method according to claim 1, wherein the fucose level of all of the antibodies of said composition is less than 60%, and preferably less than 50%, and wherein said antibody of said composition is in injectable form, or in spray form. ### Claim 13 (depends on 1) The method according to claim 1, wherein the fucose level of all of the antibodies of said composition is less than 60%, and preferably less than 50%, and wherein said antibody of said composition is combined with a pharmaceutically acceptable vehicle. ### Claim 14 (depends on 1) The method according to claim 1, wherein the fucose level of all of the antibodies of said composition is less than 60%, and preferably less than 50%, and wherein said composition is in combination with at least one anti-inflammatory agent. ### Claim 15 (depends on 1) The method according to claim 1, wherein the galactosylation level of all of the antibodies of said composition is at least 60%. ### Claim 16 (depends on 1) The method according to claim 1, wherein the galactosylation level of all of the antibodies of said composition is at least 60%, and wherein the galactosylation level of all of the antibodies of said composition is at least 70%. ### Claim 17 (depends on 1) The method according to claim 1, wherein the galactosylation level of all of the antibodies of said composition is at least 60%, and wherein the galactosylation level of all of the antibodies of said composition is at least 80%. ### Claim 18 (depends on 1) The method according to claim 1, wherein the galactosylation level of all of the antibodies of said composition is at least 60%, and wherein the fucosylation level of all of the antibodies of said composition is at least 50%. ### Claim 19 (depends on 1) The method according to claim 1, wherein the galactosylation level of all of the antibodies of said composition is at least 60%, and wherein the fucosylation level of all of the antibodies of said composition is at least 60%. ### Claim 20 (depends on 1) The method according to claim 1, wherein the galactosylation level of all of the antibodies of said composition is at least 60%, and wherein the antibodies of said composition comprise mono-galactosylated N-glycans. ### Claim 21 (depends on 1) The method according to claim 1, wherein the galactosylation level of all of the antibodies of said composition is at least 60%, and wherein the antibodies of said composition which comprise bi-galactosylated N-glycans. ### Claim 22 (depends on 1) The method according to claim 1, wherein the galactosylation level of all of the antibodies of said composition is at least 60%, and wherein the ratio of the galactosylation level of the antibodies of said composition to the fucosylation level of the antibodies of said composition is from 1.0 to 1.4. ### Claim 23 (depends on 1) The method according to claim 1, wherein the galactosylation level of all of the antibodies of said composition is at least 60%, and wherein at least 35% of the antibodies of said composition comprise bi-galactosylated N-glycans and at least 25% of the antibodies comprise mono-galactosylated N-glycans. ### Claim 24 (depends on 1) The method according to claim 1, wherein the antibody of said composition is produced in the mammary epithelial cells of a non-human mammal. ### Claim 25 (depends on 1) The method according to claim 1, wherein the antibody of said composition is produced in a transgenic non-human mammal, in particular in a goat, a sheep, a bison, a camel, a cow, a pig, a rabbit, a buffalo, a horse, a rat, a mouse or a llama. ### Claim 26 (depends on 1) The method according to claim 1, wherein said composition also comprises milk. ### Claim 27 (depends on 1) The method according to claim 1, wherein said composition also comprises a pharmaceutically acceptable vehicle. ### Claim 28 (depends on 1) The method according to claim 1, wherein the antibodies of said composition contain an oligomannose. ### Claim 29 (depends on 1) The method according to claim 1, wherein the antibodies of said composition contain an oligomannose, and wherein at least 30% of the antibodies of said composition contain at least one oligomannose. ### Claim 30 (depends on 1) The method according to claim 1, wherein the antibodies of said composition contain an oligomannose, and wherein the N-glycans of the antibodies of said composition have a highly mannosylated glycosylation profile. ### Claim 31 (depends on 1) The method according to claim 1, wherein the antibodies of said composition contain an oligomannose, and wherein the N-glycans of the antibodies of said composition have a highly mannosylated glycosylation profile, and at least one chain of the antibodies of said composition contains an oligomannose and is not fucosylated. ### Claim 32 (depends on 1) The method according to claim 1, wherein the antibodies of said composition contain an oligomannose, and wherein a major N-glycan of the antibodies is not fucosylated. ### Claim 33 (depends on 1) The method according to claim 1, wherein the antibodies of said composition contain an oligomannose, and wherein a major N-glycan of the antibodies of said composition is not fucosylated, and said major N-glycan of the antibodies of said composition is a non-fucosylated oligomannose. ### Claim 34 (depends on 1) The method according to claim 1, wherein the antibodies of said composition contain an oligomannose, and wherein a major N-glycan of the antibodies of said composition is not fucosylated, and said major N-glycan of the antibodies of said composition is a non-fucosylated Man5. ### Claim 35 (depends on 1) The method according to claim 1, wherein the antibodies of said composition contain an oligomannose, and wherein less than 40% of the N-glycans of the antibodies of said composition contain fucose. ### Claim 36 (depends on 1) The method according to claim 1, wherein the antibodies of said composition contain an oligomannose, and wherein the antibodies of said composition contain no fucose. ### Claim 37 (depends on 1) The method according to claim 1, wherein the antibodies of said composition contain an oligomannose, and wherein at least 60% of the N-glycans of the antibodies of said composition contain a non-fucosylated oligomannose, and less than 40% of the N-glycans of the antibodies of said composition contain fucose. ### Claim 38 (depends on 1) The method according to claim 1, wherein the fucose level of all of the antibodies of said composition is less than 60%, and preferably less than 50%, and wherein each of the antibodies of said composition has, on the glycosylation site in position 297 of its heavy chains, one of the biantennary glycan forms selected from the following structures: the GlcNAc represented by in the above G0 and G1 structures being capable of being fucosylated. ### Claim 39 (depends on 38) The method according to claim 38, wherein the G0+G1+G0F+G1F forms of the antibodies of said composition represent more than 60% of said glycan structures and preferably more than 80% of the glycan structures borne by the glycosylation site in position 297 of the heavy chain (Asn 297).