# US 11,077,204 B2 · Compositions comprising antibody-duocarmycin drug conjugates > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,077,204 B2 - Document ID: US11077204B2 - Status: Granted - Kind: B2 - Application number: 15/743,413 - Filed: 2016-07-08 - Published: 2018-07-19 - Granted: 2021-08-03 - Earliest claimed: 2015-07-10 - Assignees: Byondis B.V. - Applicants: Byondis B.V. - Inventors: Niels Jaap Osinga; Ernst Johannes Bernardus Van Bockxmeer - Web page: https://patentgrep.com/patent/US11077204B2 ## CPC - A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame} - A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} - A61K 31/4184: condensed with carbocyclic rings, e.g. benzimidazoles - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61K 47/6803: {Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates} - A61K 47/6809: {Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin} - A61K 47/6851: {the antibody targeting a determinant of a tumour cell} - A61P 35/00: Antineoplastic agents - C07K 16/2863: {against receptors for growth factors, growth regulators} - C07K 16/30: from tumour cells - C07K 16/32: against translation products of oncogenes - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - 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 - 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) ## Abstract The present invention relates to lyophilized compositions comprising antibody-duocarmycin drug conjugates. ## Claims ### Claim 1 A lyophilized composition comprising an antibody-drug conjugate of formula (I), a buffering agent, a lyoprotectant, and a surfactant wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-3,200 to 1, wherein mAb is a monoclonal antibody. ### Claim 2 (depends on 1) The composition according to claim 1 wherein the lyoprotectant is a non-reducing saccharide. ### Claim 3 (depends on 2) The composition according to claim 2, wherein the lyoprotectant is sucrose, trehalose or a mixture thereof. ### Claim 4 (depends on 1) The composition according to claim 1, wherein the buffering agent is histidine, citrate or succinate. ### Claim 5 (depends on 1) The composition according to claim 1, wherein the surfactant is an alkyl glycoside, poloxamer or polysorbate. ### Claim 6 (depends on 1) The composition according to claim 1, wherein the monoclonal antibody is an anti-HER2 antibody. ### Claim 7 (depends on 1) The composition according to claim 1, consisting essentially of an antibody-drug conjugate of formula (I), a buffering agent, a lyoprotectant, and a surfactant wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-3,200 to 1. ### Claim 8 (depends on 1) The composition according to claim 1, wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-2,000 to 1. ### Claim 9 (depends on 8) The composition according to claim 8, wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-1,800 to 1. ### Claim 10 (depends on 1) A process for the preparation of the composition according to claim 1, comprising the steps of a) freezing a pre-lyophilization aqueous solution of a composition of claim 1, b) primary drying at a product temperature below the collapse temperature of the composition at a pressure below atmospheric pressure, and c) secondary drying at a product temperature above 0° C. and below the glass transition temperature of the composition at a pressure below atmospheric pressure. ### Claim 11 (depends on 10) The process of claim 10 wherein the freezing step a) comprises an annealing step, wherein the annealing step is performed for 0.5 to 6 hours at a shelf temperature in the range of −25° C. to −10° C. ### Claim 12 A composition comprising an antibody-drug conjugate of formula (I), a buffering agent, a lyoprotectant, a surfactant, and water, wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-3,200 to 1, wherein mAb is a monoclonal antibody. ### Claim 13 (depends on 12) The composition according to claim 12 wherein the lyoprotectant is a non-reducing saccharide. ### Claim 14 (depends on 13) The composition according to claim 13, wherein the lyoprotectant is sucrose, trehalose or a mixture thereof. ### Claim 15 (depends on 12) The composition according to claim 12, wherein the buffering agent is histidine, citrate or succinate. ### Claim 16 (depends on 12) The composition according to claim 12, wherein the surfactant is an alkyl glycoside, poloxamer or polysorbate. ### Claim 17 (depends on 12) The composition according to claim 12, wherein the monoclonal antibody is an anti-HER2 antibody. ### Claim 18 (depends on 12) The composition according to claim 12, consisting essentially of an antibody-drug conjugate of formula (I), a buffering agent, a lyoprotectant, and a surfactant wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-3,200 to 1. ### Claim 19 (depends on 12) The composition according to claim 12, wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-2,000 to 1. ### Claim 20 (depends on 19) The composition according to claim 19, wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-1,800 to 1. ### Claim 21 (depends on 12) The composition according to claim 12, wherein the antibody-drug conjugate is present in a concentration of 1-30 mg/ml. ### Claim 22 (depends on 12) The composition according to claim 12, wherein the buffering agent is present in a concentration of 2.5-25 mM. ### Claim 23 (depends on 12) The composition according to claim 12, wherein the composition has a pH of 5.3-6.0. ### Claim 24 (depends on 12) The composition according to claim 12, comprising an antibody-drug conjugate of formula (II), histidine, trehalose, and polysorbate 20, wherein the molar ratio of trehalose to antibody-drug conjugate is about 1,605 to 1, and wherein the antibody-drug conjugate is present in an amount of about 10 mg/ml, the concentration of histidine is about 5 mM, the amount of polysorbate 20 is about 0.01% (mass/volume), and the pH is about 5.7. ### Claim 25 (depends on 24) The composition according to claim 24 consisting essentially of an antibody-drug conjugate of formula (II), histidine, trehalose, and polysorbate 20, wherein the molar ratio of trehalose to antibody-drug conjugate is about 1,605 to 1, and the antibody-drug conjugate is present in an amount of about 10 mg/ml, the concentration of histidine is about 5 mM, the amount of polysorbate 20 is about 0.01% (mass/volume), and the pH is about 5.7.