WO2024023762A1 - Composition liquide stable d'ocrélizumab - Google Patents

Composition liquide stable d'ocrélizumab Download PDF

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Publication number
WO2024023762A1
WO2024023762A1 PCT/IB2023/057644 IB2023057644W WO2024023762A1 WO 2024023762 A1 WO2024023762 A1 WO 2024023762A1 IB 2023057644 W IB2023057644 W IB 2023057644W WO 2024023762 A1 WO2024023762 A1 WO 2024023762A1
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antibody
ocrelizumab
liquid composition
stable liquid
stable
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PCT/IB2023/057644
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English (en)
Inventor
Kiran Suresh AVADHANI
Kaushal JOSHI
Chandramauli RAWAL
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Kashiv Biosciences, Llc
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Publication of WO2024023762A1 publication Critical patent/WO2024023762A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39591—Stabilisation, fragmentation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered

Definitions

  • the present invention relates to a stable liquid composition comprising Ocrelizumab antibody. More specifically the present invention further provides stable liquid composition does not comprise a hyaluronidase enzyme.
  • CD20 molecule is a transmembrane protein expressed on most of the cells of human B-cell lineage. CD20 is also found related to B-cell derived malignancies such as non- Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL) (Anderson et al., Blood, 63(6): 1424-1433 (1984) and B cells involved in immune disorders, inflammatory and autoimmune disease. Chemical agents or radioactive labels are often used to destroy CD20 expressing tumor cells along with such agents can be conjugated to the anti-CD20 antibody such that the agent is specifically "delivered" to the neoplastic B cells.
  • B-cell derived malignancies such as non- Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL) (Anderson et al., Blood, 63(6): 1424-1433 (1984) and B cells involved in immune disorders, inflammatory and autoimmune disease.
  • Multiple sclerosis is a disabling disease relates to brain and spinal cord (central nervous system) wherein the immune system attacks the protective sheath (myelin) and causes permanent damage or deterioration of the nerves.
  • Ocrelizumab (Ocrevus®) is a humanized anti-CD20 monoclonal antibody approved for the treatment of adults with relapsing forms of multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS) (Lamb YN. Ocrelizumab: A Review in Multiple Sclerosis. Drugs. 2022 Feb;82(3):323-334).
  • anti-CD20 antibody that depletes circulating immature and mature B cells but spares CD20- negative plasma cells.
  • the effector mechanisms of anti-CD20 antibodies are complementdependent cytotoxicity and antibody-dependent cellular cytotoxicity.
  • Stable liquid formulations comprising antibodies with suitable excipients being popular and it is always preferred to prepare high concentrated stable pharmacologically active antibody formulation and the next generation antibody therapeutics for delivering formulation includes prefilled syringe, Pen-PFS, autoinjector and on-body injectors. Moreover, in view of patient as well as physician compliance, these delivery devices are more in demand.
  • the present invention relates to a preparation of stable liquid composition comprising an anti-CD20 antibody with suitable pharmaceutically acceptable excipients.
  • the present invention provides a stable liquid formulation comprising high concentrated pharmacologically active anti-CD20 antibody.
  • the present invention relates to stable liquid formulation comprising high concentrated pharmacologically anti-CD20 antibody having concentration 30 mg/ml or above with suitable pharmaceutically acceptable excipients.
  • the invention provides a stable liquid composition comprising ocrelizumab having concentration 50 mg/ml or above with pharmaceutically acceptable excipients.
  • the invention relates to a stable liquid formulation comprising high concentrated pharmacologically anti-CD20 antibody having concentration 50 mg/ml or above with suitable pharmaceutically acceptable excipients selected from anti aggregation agent, suitable buffer and suitable surfactant.
  • aggregation inhibitors selected from L-arginine, L-lysine, L-methionine, L- glycine, L-histidine, L-methionine and suitable salt thereof.
  • the invention provides a stable formulation comprises a suitable buffer selected from sodium phosphate, citrate, phosphate-citrate, L-histidine and acetate.
  • the invention provides a stable formulation comprises a surfactant selected from polysorbate or poloxamer.
  • a stable liquid formulation comprising ocrelizumab antibody having concentration 30mg/ml, 40mg/ml, 50mg/ml, 60mg/ml, 70mg/ml, 80mg/ml, 90mg/ml, lOOmg/ml, HOmg/ml, 120mg/ml, 130 mg/ml, 140mg/ml, 150mg/ml, 160mg/ml, 170mg/ml, 180mg/ml, 190mg/ml, 200mg/ml.
  • a stable liquid composition comprises: a) ocrelizumab antibody concentration selected from about 50 mg/ml to about 150 mg/ml; b) a buffering agent selected from phosphate, citrate, glycine, lysine phosphate-citrate, succinate, histidine, acetate, arginine, gluconate, methionine, glutamate, aspartate or combination salt thereof; c) an aggregation inhibitor selected from sugar, polyol, amino acid or combination thereof; d) optionally, cyclodextrin; e) a non-ionic surfactant ranging from about 0.01 % to about 0.2%; f) pH selected from about 5.0 to about 7.0. wherein the composition does not comprise hyaluronidase enzyme.
  • a stable liquid composition comprises: a) ocrelizumab antibody concentration selected from about 30 mg/ml to about 200 mg/ml; b) a buffering agent selected from group comprising salt, amino acid or combination thereof; c) an aggregation inhibitor selected from group comprising sugar, polyol, amino acid or combination thereof; d) a non-ionic surfactant ranging from about 0.01 % to about 0.2%; e) composition pH ranging from about 5.0 to about 7.0. wherein the composition does not comprise hyaluronidase enzyme.
  • the invention provides a stable liquid formulation for subcutaneous administration.
  • the present invention utilizes an antibody formulation in injector device for subcutaneous administration.
  • the invention provides antibody formulation can be supplied in auto-injector or on-body injector.
  • formulation comprises an anti-CD20 antibody selected from Rituximab, Ofatumumab, Veltuzumab, Ocartuzumab, Ocrelizumab, Ibritumomab, Tositumomab, Obinutuzumab.
  • the formulation of the present invention possesses advantageous properties such as low viscosity, low aggregation and low osmolarity.
  • the present invention provides a stable liquid formulation comprising high concentrated pharmacologically active anti-CD20 antibody.
  • the present invention relates to stable liquid formulation comprising high concentrated pharmacologically anti-CD20 antibody having concentration 30 mg/ml or above with suitable pharmaceutically acceptable excipients.
  • the invention provides a stable liquid composition comprising ocrelizumab having concentration 50 mg/ml or above with pharmaceutically acceptable excipients.
  • antibody refers to anti-CD20 antibody i.e., ocrelizumab expressed in mammalian cells specifically binds to CD20 antigen and exhibit therapeutic activity in multiple sclerosis and other auto immune diseases.
  • composition or “stable composition” or “stable liquid composition” are used herein are interchangeable.
  • stable liquid composition refers to a mixture that usually contains an active ingredient, and carrier, such as a pharmaceutically acceptable carrier or excipient comprises buffer, amino acid, salts, isotonicity agents, aggregation inhibitors, surfactants, additives etc., suitable for administration into a subject for therapeutic, diagnostic, or prophylactic purposes.
  • carrier such as a pharmaceutically acceptable carrier or excipient comprises buffer, amino acid, salts, isotonicity agents, aggregation inhibitors, surfactants, additives etc.
  • pharmaceutically acceptable carrier or “suitable pharmaceutically acceptable excipients” used herein refers to a non-toxic solid, semisolid or liquid filler, diluent, encapsulating material, formulation auxiliary, or excipient of any conventional type.
  • a pharmaceutically acceptable carrier is non-toxic to recipients at the dosages and concentrations employed and is compatible with other ingredients of the formulation.
  • stable or “stabilized” used herein with respect to long-term storage is understood to mean that Ocrelizumab contained in the pharmaceutical composition remains physically and chemically active.
  • the formulation remains liquid at a temperature of at least about 2 to about 8° C.
  • the liquid composition is stable at room temperature.
  • the liquid composition is stable at 2°C to 8°C.
  • the liquid composition is stable at 37°C for at least 15 days or preferably 30 days.
  • the pharmaceutical composition does not lose more than 20%, or more preferably 15%, or even more preferably 10%, and most preferably 5% of its activity relative to activity of the composition at the beginning of storage.
  • Size variants refers to LMW, HMW or aggregates.
  • High molecular weight refers to product-related impurities that contribute to the size heterogeneity of antibody products.
  • the formation of HMW species within a therapeutic antibody drug product as a result of protein aggregation can potentially compromise both drug efficacy and safety (e.g. eliciting unwanted immunogenic response).
  • HMW is considered critical quality attributes that are routinely monitored during drug development and as part of release testing of purified drug product during manufacturing.
  • LMW Low molecular weight
  • buffer or “buffering agent” used herein refers to a buffering agent providing pH about 5+2.0 to the solution it resists changes in pH by the action of its acid/base conjugate components.
  • suitable buffer selected from sodium phosphate, citrate, phosphate-citrate, L-histidine, and acetate.
  • aggregation inhibitor or “stabilizer” used herein refers to excipient which prevent aggregation of anti-20 antibody such as Ocrelizumab. Aggregation inhibitor is generally useful to stabilize when used in high concentration in the formulation.
  • the aggregation inhibitors such as amino acids selected from L-arginine, L-lysine, L-methionine, L-glycine, L- ornithine, L-glutamine, L-asparagine, L-histidine, L-glutamic acid, L-asparagic acid, L-isoleucine, L-leucine, L-alanine, L-phenylalanine, L-tyrosine, L-tryptophan, L-serine, L-proline.
  • amino acids selected from L-arginine, L-lysine, L-methionine, L-glycine, L- ornithine, L-glutamine, L-asparagine, L-histidine, L-glutamic acid, L-asparagic acid, L-isoleucine, L-leucine, L-alanine, L-phenylalanine, L-tyrosine, L-tryptophan, L-ser
  • the aggregation inhibitors such as sugar or polyol selected from sucrose, trehalose mannitol, sorbitol, inositol, glucose, fructose, lactose, xylose, mannose, maltose, raffinose.
  • concentration of sugar or polyol selected from about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, and about 20%,
  • the selection of aggregation inhibitor in combination with suitable excipients such as buffer, surfactant and pH provide desirable result.
  • cyclodextrin refers to complexing agents used in drug compositions for increasing bioavailability and to improve stability of compounds. Cyclodextrins are non-reducing cyclic glucose oligosaccharides produced from starch, cyclodextrins have 6, 7 or 8 glucose units. In an embodiment, cyclodextrin selected from a- cyclodextrin, P- cyclodextrin, and y-cyclodextrin.
  • the cyclodextrin selected from hydroxylpropyl-P-cyclodextrin, 2- hydroxypropyl-b-CyD (HP-b-CyD), O-carboxymethyl-O-ethyl-b-CyD, SBE-b-CyD, SBE6.6-P- cyclodextrin, SBE6.7-P-cyclodextrin, SBE6.8-P-cyclodextrin, SBE4.1-P-cyclodextrin, and SBE4.6Et3.5-P-cyclodextrin, SBE4.3-y-cyclodextrin, SBE4.6-y-cyclodextrin, SBE5.2-y- cyclodextrin, and SBE5.6Et6.3-y-cyclodextrin, glucuronyl-glucosyl-b-CyD (GUG-b-CyD), heptakis(2,6-di-O-methyl-3-O-ace
  • Methylated b-CyD Hydroxyalkylated b-CyD, Branched b-CyD, Alkylated b-CyD, Acylated b-CyD (C2 — Cl 8), Anionic b-CyD, CME-b-CyD, hydroxypropyl cyclodextrin (e.g., HP4.3-P-cyclodextrin, HP5.5-P- cyclodextrin, HP7.6-P-cyclodextrin, and HP4.5-y-cyclodextrin), hydroxyethyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin (i.e.
  • the concentration of cyclodextrin selected from about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14% and about 15%. In another embodiment, the concentration of cyclodextrin selected from about 5mM to about 300mM.
  • the concentration of cyclodextrin selected from 5mM, about lOrnM, about 20mM, about 30mM, about 40mM, about 50mM, about 60mM, about 70mM, about 80mM, about 90mM, about lOOmM, about l lOmM, about 120mM, about 130mM, about 140mM, about 150mM, about 160mM, about 170mM, about 180mM, about 190mM, about 200mM, about 210mM, about 220mM, about 230mM, about 240mM, about 250mM, about 260mM, about 270mM, about 280mM, about 290mM, and about 300mM.
  • non-ionic surfactant refers to an excipient used in biotherapeutic formulation that prevents physical damage to antibody polypeptide during operational steps and upon storage.
  • the non-ionic surfactant selected from polyglycerol alkyl ethers, glucosyl dialkyl ethers, crownethers, ester-linked surfactants, polyoxyethylene alkyl ethers, BYK- 110, Polysorbate 20 (PS 20), Polysorbate 40 (PS 40), Polysorbate (PS 60), Polysorbate 80 (PS 80), Poloxamer 188 (Pl 88), Poloxamer 237 (P237), Poloxamer (P338), Poloxamer (P407) and Nonidet-P40 (nonylphenoxypoly ethoxy ethanol).
  • ultrafiltering refers to using synthetic semi-permeable membranes, with appropriate physical and chemical properties, to discriminate between molecules in the mixture, primarily on the basis of molecular size and shape, and accomplish separation of different molecules or accomplish concentration of like molecules.
  • diafiltering or “diafiltration” or “diafiltered” or “diafiltrating” or “DF” used herein refers to using an ultrafiltration membrane to remove, replace, or lower the concentration of salts or solvents from solutions or mixtures containing proteins, peptides, nucleic acids, or other biomolecules.
  • Tangential flow filtration or “cross flow filtration” or “TFF” used herein refers to a mode of filtration in which the solute-containing solution passes tangentially across the UF membrane and lower molecular weight salts or solutes are passed through by applying pressure.
  • the formulation of the present invention comprises high concentration of pharmacologically active antibody, buffer, aggregation inhibitor and surfactant.
  • the invention relates to a stable liquid formulation comprising high concentrated pharmacologically anti-CD20 antibody having concentration 50 mg/ml or above with suitable pharmaceutically acceptable excipients selected from anti aggregation agent, suitable buffer and suitable surfactant.
  • suitable pharmaceutically acceptable excipients selected from anti aggregation agent, suitable buffer and suitable surfactant.
  • aggregation inhibitors selected from L-arginine, L-lysine, L-methionine, L- glycine, and suitable salt thereof.
  • the invention provides a stable liquid formulation comprises a suitable buffer selected from phosphate, citrate, phosphate-citrate, L-histidine, and acetate.
  • the invention provides a stable liquid formulation comprises a surfactant selected from polysorbate or poloxamer.
  • the invention provides high concentrated pharmacologically anti-CD20 antibody having concentration 30mg/ml, 40mg/ml, 50mg/ml, 60mg/ml, 70mg/ml, 80mg/ml, 90mg/ml, lOOmg/ml, HOmg/ml, 120mg/ml, 130 mg/ml, 140mg/ml, 150mg/ml, 160mg/ml, 170mg/ml, 180mg/ml, 190mg/ml, 200mg/ml.
  • the ocrelizumab concentration selected from about 30mg/ml, about 40mg/ml, about 50mg/ml, about 60mg/ml, about 70mg/ml, about 80mg/ml, about 90mg/ml, about lOOmg/ml, about llOmg/ml, about 120mg/ml, about 130 mg/ml, about 140mg/ml, about
  • a stable liquid composition comprises: a) ocrelizumab antibody concentration selected from about 50 mg/ml to about 150 mg/ml; b) a buffering agent selected from phosphate, citrate, glycine, lysine phosphate-citrate, succinate, histidine, acetate, arginine, gluconate, methionine, glutamate, aspartate or combination salt thereof; c) an aggregation inhibitor selected from sugar, polyol, amino acid or combination thereof; d) optionally, cyclodextrin; e) a non-ionic surfactant ranging from about 0.01 % to about 0.2%; f) pH selected from about 5.0 to about 7.0. wherein the composition does not comprise hyaluronidase enzyme.
  • a stable liquid composition comprises: a) ocrelizumab antibody concentration selected from about 30 mg/ml to about 200 mg/ml; b) a buffering agent selected from group comprising salt, amino acid or combination thereof; c) an aggregation inhibitor selected from group comprising sugar, polyol, amino acid or combination thereof; d) optionally, comprises cyclodextrin; e) a non-ionic surfactant ranging from about 0.01 % to about 0.2%; f) composition pH ranging from about 5.0 to about 7.0. wherein the composition does not comprise hyaluronidase enzyme.
  • the invention provides; a) high concentration of anti-CD20 antibody comprising about 30mg/ml to about 200mg/ml b) aggregation inhibitor; c) buffer; d) surfactant; and e) pH 5.0 to 7.0
  • the invention provides; a) high concentration of anti-CD20 antibody comprising about 30mg/ml to about 200mg/ml b) arginine as aggregation inhibitor; c) L-histidine as buffer; d) polysorbate as stabilizer; e) pH 5.0 to 7.0
  • the invention provides; a) high concentration of anti-CD20 antibody comprising about 30mg/ml to about 200mg/ml b) arginine as aggregation inhibitor; c) L-histidine and/or Phosphate as buffer; d) polysorbate as stabilizer; e) pH 5.0 to 7.0
  • the invention provides a stable liquid formulation for subcutaneous administration.
  • the present invention utilizes an antibody formulation in injector device for subcutaneous administration.
  • the invention provides antibody formulation can be supplied in auto-injector or on-body injector.
  • formulation comprises an anti-CD20 antibody selected from Rituximab, Ofatumumab, Veltuzumab, Ocartuzumab, Ocrelizumab, Ibritumomab, Tositumomab, Obinutuzumab.
  • the formulation of the present invention possesses advantageous properties such as low viscosity, low aggregation and low osmolarity.
  • the present invention is stable at room temperature. In an embodiment, the formulation of the present are stable at 2°C to 8 °C.
  • the formulation of the present invention optionally comprise Ca+2 or Mg+2 salt.
  • the formulation of the present invention comprises additives.
  • the pharmacologically active antibody is selected from IgGl, IgG2, IgG3, IgG4 or fragment thereof. In an embodiment, the pharmacology active antibody binds to CD20 to treat CD20 mediated disease. In an embodiment the pharmacology antibody is an anti-CD20 antibody.
  • the formulation of the present invention are mainly useful for the treatment of CD20 mediated disease, but not limited to, relapsing forms of multiple sclerosis or primary progressive MS, Non-Hodgkin’s Lymphoma (NHL), Leukemia, Rheumatoid Arthritis (RA), Granulomatosis with Polyangiitis (GPA), Pemphigus Vulgaris (PV), and other autoimmune diseases.
  • NHL Non-Hodgkin’s Lymphoma
  • Leukemia Leukemia
  • RA Rheumatoid Arthritis
  • GPA Granulomatosis with Polyangiitis
  • PV Pemphigus Vulgaris
  • the pharmacological antibody is present in high concentration selected form 10 mg/ml to 300 mg/ml. In another embodiment, the pharmacological antibody is present in high concentration selected form 50 mg/ml to 480 mg/ml. In another embodiment, the pharmacological antibody is present in high concentration selected form 100 mg/ml to 600 mg/ml. In another embodiment the pharmacological antibody is present in high concentration selected form 150 mg/ml to 500 mg/ml. In an embodiment, the pharmacological antibody is present in high concentration selected form about lOOmg/ml to about 300 mg/ml.
  • the invention provides a stable liquid formulation comprises a suitable buffer selected from phosphate, citrate, phosphate-citrate, L-histidine and acetate and salt thereof.
  • the invention provides a stable liquid formulation comprises more than one buffer.
  • L-histidine can also be used in its salt form such as L-histidine hydrochloride.
  • the buffer is presented in the concentration of at least 5mM. In another embodiment, the buffer is presented in the range of 5mM to 20mM.
  • the concentration of buffer selected from about 5mM, about 6mM, about 7mM, about 8mM, about 9mM, about lOmM, about l lmM, about 12mM, about 13mM, about 14mM, about 15mM, about 16mM, about 17mM, about 18mM, about 19mM, about 20mM, about 21mM, about 22mM, about 23mM, about 24mM, about 25mM, about 26mM, about 27mM, about 28mM, about 29mM, about 30mM, about 31mM, about 32mM, about 33mM, about 34mM, about 35mM, about 36mM, about 37mM, about 38mM, about 39mM, about 40mM, about 41mM, about 42mM, about 43mM, about 44mM, about 45mM, about 46mM, about 47mM, about 48mM, about 49mM, and about 50mM,
  • the aggregation inhibitors selected from L-arginine, L-lysine, L-methionine, L- glycine & suitable salt thereof.
  • the buffer is presented in the concentration of at least Img/ml. In another embodiment, the buffer is presented in the range of Img/ml to lOmg/ml. In another embodiment the buffer is presented in the range of 10 mg/ml to 50 mg/ml.
  • Lysine and/or arginine can be used in its salt form such as lysine hydrochloride or arginine hydrochloride.
  • the aggregation inhibitors are presented in the concentration of at least 5mM. In another embodiment, the aggregation inhibitors are presented in the range of 50mM to 200mM.
  • the concentration of aggregation inhibitors selected from about 50mM, about 60mM, about 70mM, about 80mM, about 90mM, about lOOmM, about l lOmM, about 120mM, about 130mM, about 140mM, about 150mM, about 160mM, about 170mM, about 180mM, about 190mM, and about 200mM.
  • the aggregation inhibitors are present in the concentration of at least 1 mg/ml. In certain embodiment, the aggregation inhibitors are present in the range of 1 mg/ml to 75 mg/ml. In certain embodiment, the aggregation inhibitors are present in the range of 10 mg/ml to 50mg/ml. In certain embodiment, the aggregation inhibitors are present in range of 20mg/ml to 50mg/ml. In certain embodiment, the aggregation inhibitors are present in range of 30 mg/ml to 45 mg/ml.
  • the surfactant is selected from polysorbate and poloxamer 188. In another embodiment, the surfactant is selected from different grades of polysorbate such as but not limited to polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80 or mixture thereof can be used. In certain embodiment, the surfactant is poloxamer 188. In certain embodiment, the surfactant is polysorbate 20.
  • the surfactant concentration selected from about 0.0001% to about 2.0%. In another embodiment, the surfactant concentration selected from about 0.01% to about 0.1%. In an embodiment, the surfactant is present in the amount from 0.01% to 0.20%. In another embodiment, the surfactant concentration selected from about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, and about 2%.
  • the surfactant is present in the amount from O.lmg/ml to 0.5mg/ml.In an embodiment, the surfactant is present in the concentration at least about 1 mg/ml. In another embodiment, the surfactant is present in concentration from about 1 mg/ml to about 20 mg/ml.
  • the surfactant is present in concentration selected from about 1 mg/ml, about 2 mg/ml about 3 mg/ml, about 4 mg/ml, about 5 mg/ml, about 6 mg/ml, about 7 mg/ml, about 8 mg/ml, about 9 mg/ml, about 10 mg/ml, about 11 mg/ml, about 12 mg/ml, about 13 mg/ml, about 14 mg/ml, about 15 mg/ml, about 16 mg/ml, about 17 mg/ml, about 18 mg/ml, about 19 mg/ml, and about 20 mg/ml.
  • the Ca+2 or Mg+2 salt is used to achieve desired osmolality.
  • the Ca+2 or Mg+2 salt according to present invention are. Calcium chloride or Magnesium chloride.
  • the additives or ionic stabiliser used in composition selected from sodium chloride, mannitol, sucrose, proline, glycine, sodium acetate, sodium citrate, sodium succinate, sodium phosphate and sodium sulphate.
  • the additives are presented in the range of 50mM to 200mM.
  • the additive is in the concentration of at least about 50g/L. In another embodiment, the additive is present in the range of about 50g/L to about 200g/L. In another embodiment, the additive is present in the range selected from about 60g/L to about 70g/L, about 70g/L to about 80g/L, about 80g/L to about 90g/L, about 90g/L to about lOOg/L, about HOg/L to about 120g/L, about 120g/L to about 130g/L, about 130g/L to about 140g/L, about 140g/L to about 150g/L, about 150g/L to about 160g/L, about 160g/L to about 170g/L, about 170g/L to about 180g/L, about 180g/L to about 190g/L, and about 190g/L to about 200g/L. In an embodiment, the formulation of the present invention has pH 5 to pH 7. In another embodiment, the formulation of the present invention has pH 5 to pH 6.
  • the formulation has viscosity of at least about 5 cps. In another embodiment, the formulation has viscosity of about 5 cps to about 20 cps, In one aspect of such embodiment, the viscosity of formulation is about 5 cps, about 6 cps, about 7 cps, about 8 cps, about 9 cps, about 10 cps, about 11 cps, about 12 cps, about 13 cps, about 14 cps, about 15 cps, about 16 cps, about 17 cps, about 18 cps, about 19 cps, and about, about 20 cps.
  • the viscosity of stable liquid composition is not more than 11 cps.
  • the formulation of present invention has osmolality selected from about 300 mOsm/kg to about 900 mOsm/kg. In another embodiment, the formulation of present invention has osmolality selected from about 330 mOsm/kg to about 850 mOsm/kg. In another embodiment, the formulation of present invention has osmolality selected from about 350 mOsm/kg to about 800 mOsm/kg.
  • the osmolality of the formulation is about 300 mOsm/kg, about 350 mOsm/kg, about 400 mOsm/kg, about 450 mOsm/kg, about 500 mOsm/kg, about 550 mOsm/kg, about 600 mOsm/kg, about 650 mOsm/kg, about 700 mOsm/kg, about 750 mOsm/kg, about 800 mOsm/kg, about 850 mOsm/kg, and about 900 mOsm/kg.
  • the liquid composition is stable at room temperature.
  • the liquid composition is stable at 2°C to 8°C.
  • the liquid composition is stable at 37°C for at least 15 days or preferably 30 days.
  • the stable liquid composition the ocrelizumab concentration selected from about 50mg/ml, about 60mg/ml, about 70mg/ml, about 80mg/ml, about 90mg/ml, about lOOmg/ml, about l lOmg/ml, about 120mg/ml, about 130 mg/ml, about 140mg/ml, and about 150mg/ml.
  • the stable liquid composition comprise buffering agent concentration selected from about 5mM to about 150mM.
  • the stable liquid composition the buffering agent concentration selected from about 5mM, about lOrnM, about 20mM, about 30mM, about 40mM, about 50mM, about 60mM, about 70mM, about 80mM, about 90mM, about lOOmM, about 1 lOrnM, about 120mM, about 130mM, about 140mM, and about 150mM.
  • the stable liquid composition comprises the aggregation inhibitor sugar or polyol selected from sucrose, trehalose mannitol, sorbitol, inositol, glucose, fructose, lactose, xylose, mannose, maltose, raffinose.
  • the sugar or polyol concentration selected from about 1 %, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, and about 20%.
  • the stable liquid composition sugar or polyol concentration selected from about 50mM to about 200mM.
  • the stable liquid composition sugar or polyol concentration selected from about 50mM, about 60mM, about 70mM, about 80mM, about 90mM, about lOOmM, about l lOmM, about 120mM, about 130mM, about 140mM, about 150mM, about 160mM, about 170mM, about 180mM, about 190mM, and about 200mM.
  • the stable liquid composition comprises aggregation inhibitor amino acid selected from L-arginine, L-lysine, L-histidine, L-methionine, L-glycine.
  • the stable liquid composition the amino acid concentration selected from about 50mM to about 200mM.
  • the stable liquid composition the amino acid concentration selected from about 50mM, about 60mM, about 70mM, about 80mM, about 90mM, about lOOmM, about l lOmM, about 120mM, about 130mM, about 140mM, about 150mM, about 160mM, about 170mM, about 180mM, about 190mM, and about 200mM.
  • the stable liquid composition comprises cyclodextrin selected from Alphacyclodextrin, beta- cyclodextrin, and gamma-cyclodextrin.
  • the stable liquid composition the concentration of cyclodextrin selected from about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14% and about 15%.
  • the stable liquid composition comprises surfactant is selected from polysorbate or poloxamer 188.
  • the stable liquid composition pH selected from about 5.0, about 5.1, about 5.2 about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2 about 6.3, about 6.4, about 6.5, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, and about 7.5.
  • the pharmaceutically stable antibody composition comprises; a) about 50 mg/mL ocrelizumab; b) aggregation inhibitor about 100 mM arginine; c) phosphate buffer about 10 mM; d) 0.02 % Poloxamer 188; e) pH about 5.0 to about 7.0
  • the pharmaceutically stable antibody composition comprises; a) about 50 mg/mL ocrelizumab; b) aggregation inhibitor about 100 mM Lysine; c) phosphate buffer about 10 mM; d) 0.02 % Poloxamer 188; e) pH about 5.0 to about 7.0
  • the pharmaceutically stable antibody composition comprises; a) about 50 mg/mL ocrelizumab; b) aggregation inhibitor about 100 mM Lysine; c) histidine buffer about 10 mM; d) 0.02 % Poloxamer 188; e) pH about 5.0 to about 7.0
  • the pharmaceutically stable antibody composition comprises; a) about 100 mg/mL ocrelizumab; b) aggregation inhibitor about 150 mM Arginine HC1; c) histidine buffer about 15 mM; d) 0.04 % Poloxamer 188; e) pH about 5.0 to about 7.0
  • the pharmaceutically stable antibody composition comprises; a) about 150 mg/mL ocrelizumab; b) aggregation inhibitor about 200 mM Arginine HC1 and sucrose 150mM; c) phosphate buffer about 20 mM; d) 0.04 % Poloxamer 188; e) pH about 5.0 to about 7.0
  • the pharmaceutically stable antibody composition comprises; a) about 150 mg/mL ocrelizumab; b) aggregation inhibitor about 200 mM Lysine; c) histidine buffer about 20 mM; d) 0.04 % Poloxamer 188; e) pH about 5.0 to about 7.0
  • the pharmaceutically stable antibody composition comprises; a) about 150 mg/mL ocrelizumab; b) aggregation inhibitor about 200 mM Arginine; c) phosphate buffer about 20 mM; d) 0.04 % Poloxamer 188; e) pH about 6.0 to about 7.0
  • the present invention provides a pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer comprising L-Histidine or L-Histidine HC1; c) suitable aggregation inhibitor Lysine HCL; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody in an amount of about lOOmg/ml to 300 mg/ml; b) suitable buffer comprising L-Histidine or L-Histidine HC1 in an amount of at least about 20 mM or 200mM; c) suitable aggregation inhibitor Lysine or Lysine HC1; d) polysorbate 20 and/or poloxamer e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer comprising sodium phosphate; c) suitable aggregation inhibitor Arginine or Arginine HC1; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer comprising sodium Citrate; c) suitable aggregation inhibitor Arginine or Arginine HC1; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer comprising sodium citrate; c) suitable aggregation inhibitor Arginine or Arginine HCL; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer comprising L-Histidine or L-Histidine HC1; c) suitable aggregation inhibitor L- Arginine or L- Arginine HCL; d) Polysorbate and e) pH 5.0 to 7.0
  • suitable additive comprising NaCl, Mannitol, Sucrose, Proline, and Glycine.
  • the present invention provides novel pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer comprising L-Histidine or L-Histidine HC1; c) suitable aggregation inhibitor L- Arginine or L- Arginine or Aspartic acid; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer comprising L-Histidine or L-Histidine HC1; c) suitable aggregation inhibitor L- Arginine or L- Arginine HC1; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer comprising L-Histidine or L-Histidine HC1; c) suitable aggregation inhibitor L- Arginine HC1; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer comprising L-Histidine or L-Histidine HC1; c) suitable aggregation inhibitor L- Arginine or L- Arginine HC1; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer comprising L-Histidine or L-Histidine HC1; c) suitable aggregation inhibitor L- Arginine HC1; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer comprising L-Histidine or L-Histidine HC1; c) suitable aggregation inhibitor L- Arginine HC1; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is L-methionine; c) suitable aggregation inhibitor L- Arginine HC1; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is L- methionine; c) suitable aggregation inhibitor L- Arginine HC1; d) Poloxamer 188 and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is phosphate; c) suitable aggregation inhibitor Arginine HC1; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is L-methionine and phosphate; c) suitable aggregation inhibitor L- Arginine HC1; d) Poloxamer 188 and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is L- histidine; c) suitable aggregation inhibitor is L- lysine HC1; d) Poloxamer 188 and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is L-histidine and/or phosphate; c) suitable aggregation inhibitor is L-lysine or L-lysine HC1; d) Poloxamer 188 and e) pH 6.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is L-histidine or L-histidine HC1; c) suitable aggregation inhibitor is L-glycine; d) Poloxamer 188 and e) pH 6.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is L-histidine and/or phosphate; c) suitable aggregation inhibitor is L-glycine; d) Poloxamer 188 and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is L-Histidine or L-Histidine HC1; c) suitable aggregation inhibitor is L- Arginine and L-Lysine; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is L-histidine and/or phosphate; c) suitable aggregation inhibitor is L- Arginine HC1 and L-Lysine HC1; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is L-histidine and/or Citrate; c) suitable aggregation inhibitor is L- Arginine HC1 and L-Lysine HC1; d) Polysorbate and e) pH 5.0 to 7.0
  • the present invention provides pharmaceutically stable formulation comprising; a) high concentration of pharmacologically active anti-CD20 antibody; b) suitable buffer is L-histidine and and/or Sodium Acetate; c) suitable aggregation inhibitor is L- Arginine HC1 and L-Lysine; d) Polysorbate and e) pH 5.0 to 7.0
  • Table 1 Composition of Rituximab (anti-CD20 antibody) injection
  • Table 4 Composition of Ofatumumab (anti-CD20 antibody) injection
  • Table 5 Composition of Ofatumumab (anti-CD20 antibody) injection
  • L-Lysine 50mM-200mM
  • 10 mM of dibasic sodium phosphate anhydrous 10 mM of monobasic sodium phosphate monohydrate to get clear buffer solution using WFI.
  • Poloxamer 188 (0.1-0.20 %)
  • Sucrose 50mM-150mM
  • Table 6 Composition of Ofatumumab (anti-CD20 antibody) injection
  • Table 7 Composition of ocrelizumab (anti-CD20 antibody) injection
  • Table 8 Composition of ocrelizumab (anti-CD20 antibody) injection
  • Table 9 Composition of ocrelizumab (anti-CD20 antibody) injection
  • Table 10 Composition of ocrelizumab (anti-CD20 antibody) injection
  • Table 11 Composition of ocrelizumab (anti-CD20 antibody) injection
  • Table 12 Composition of ocrelizumab (anti-CD20 antibody) injection
  • L- Arginine (lOOmM) was added into phosphate buffer (10 mM) to get clear buffer solution using WFI. Further, Poloxamer 188 (0.02 %) was added into buffer solution. About 50 mg/ml of Ocrelizumab (anti-CD20 antibody) was added into placebo solution to get 10 mL of clear drug product solution of Ocrelizumab (anti-CD20 antibody). 10 mL drug solution was filtered through 0.2 pm PES syringe filter to get the sterile solution of Ocrelizumab (anti-CD20 antibody). 1 mL of Ocrelizumab (anti-CD20 antibody) solution was filled into 1 mL clear glass (USP type 1) PFS using flurotec coated rubber stoppers. The stable formulations were analyzed at 5°C, 25°C and 40°C and the results are shown in the table below.
  • Table 13 Composition of ocrelizumab (anti-CD20 antibody) injection
  • Lysine HC1 (lOOmM) was added into phosphate buffer (10 mM) to get clear buffer solution using WFI. Further, Poloxamer 188 (0.02 %) was added into buffer solution. About 50 mg/ml of Ocrelizumab (anti-CD20 antibody) was added into placebo solution to get 10 mL of clear drug product solution of Ocrelizumab (anti-CD20 antibody). 10 mL drug solution was filtered through 0.2 pm PES syringe filter to get the sterile solution of Ocrelizumab (anti-CD20 antibody). 1 mL of Ocrelizumab (anti-CD20 antibody) solution was filled into 1 mL clear glass (USP type 1) PFS using flurotec coated rubber stoppers. The stable formulations were analyzed at 5°C, 25°C and 40°C and the results are shown in the table below.
  • Table 14 Composition of ocrelizumab (anti-CD20 antibody) injection
  • L-Lysine (lOOmM) was added into L-Histidine buffer (10 mM) to get clear buffer solution using WFI. Further, Polysorbate 20 (0.02 %) was added into buffer solution. About 50 mg/ml of Ocrelizumab (anti-CD20 antibody) added added into placebo solution to get 10 mL of clear drug product solution of Ocrelizumab (anti-CD20 antibody). 10 mL drug solution was filtered through 0.2 pm PES syringe filter to get the sterile solution of Ocrelizumab (anti-CD20 antibody). 1 mL of Ocrelizumab (anti-CD20 antibody) solution was filled into 1 mL clear glass (USP type 1) PFS using flurotec coated rubber stoppers. The stable formulations were analyzed at 5°C, 25°C and 40°C and the results are shown in the table below.
  • Table 15 Composition of ocrelizumab (anti-CD20 antibody) injection
  • Arginine HC1 150 mM was added into L- Histidine buffer (15 mM) to get clear buffer solution using WFI. Further, Poloxamer 188 (0.04 %) was added into buffer solution. About 100 mg/ml of Ocrelizumab (anti-CD20 antibody) was added into placebo solution to get 10 mL of clear drug product solution of Ocrelizumab (anti-CD20 antibody). 10 mL drug solution was filtered through 0.2 pm PES syringe filter to get the sterile solution of Ocrelizumab (anti-CD20 antibody). 1 mL of Ocrelizumab (anti-CD20 antibody) solution was filled into 1 mL clear glass (USP type 1) PFS using flurotec coated rubber stoppers. The stable formulations were analyzed at 5°C, 25°C and 40°C and the results are shown in the table below.
  • Table 16 Composition of Ocrelizumab (anti-CD20 antibody) injection
  • L-Arginine 200mM was added into 10 mM of dibasic sodium phosphate anhydrous and 10 mM of monobasic sodium phosphate monohydrate to get clear buffer solution using WFI. Further, Poloxamer 188 (0.20 %) and Sucrose (50mM-150mM) was into buffer solution. About 150 mg/ml of Ocrelizumab (anti-CD20 antibody) was into placebo solution to get 10 mL of clear drug product solution of Ocrelizumab (anti-CD20 antibody). 10 mL drug solution was filtered through 0.2 pm PES syringe filter to get the sterile solution of Ocrelizumab (anti-CD20 antibody).
  • Ocrelizumab anti-CD20 antibody
  • USP type 1 clear glass
  • the stable formulations were analyzed at 5°C, 25°C and 40°C and the results are shown in the table below.
  • Table 17 Composition of ocrelizumab (anti-CD20 antibody) injection
  • Table 18 Composition of ocrelizumab (anti-CD20 antibody) injection
  • Arginine HC1 (200mM) was added into Phosphate buffer (20 mM) to get clear buffer solution using WFI. Further, Poloxamer 188 (0.04 %) was added into buffer solution. About 150 mg/ml of Ocrelizumab (anti-CD20 antibody) was added into placebo solution to get 10 mL of clear drug product solution of Ocrelizumab (anti-CD20 antibody). 10 mL drug solution was filtered through 0.2 pm PES syringe filter to get the sterile solution of Ocrelizumab (anti-CD20 antibody). 1 mL of Ocrelizumab (anti-CD20 antibody) solution was filled into 1 mL clear glass (USP type 1) PFS using flurotec coated rubber stoppers. The stable formulations were analyzed at 5°C, 25°C and 40°C and the results are shown in the table below.

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Abstract

La présente invention concerne une composition liquide stable comprenant un anticorps ocrélizumab. Plus spécifiquement, la présente invention concerne en outre une composition liquide stable ne comprenant pas d'enzyme hyaluronidase.
PCT/IB2023/057644 2022-07-27 2023-07-27 Composition liquide stable d'ocrélizumab WO2024023762A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8956611B2 (en) * 2007-10-16 2015-02-17 Zymogenetics, Inc. Combination of BLyS inhibition and anti-CD 20 agents for treatment of autoimmune disease
AU2013266987B2 (en) * 2009-09-11 2016-11-10 F. Hoffmann-La Roche Ag Highly concentrated pharmaceutical formulations comprising anti - CD20 antibody
US20180333493A1 (en) * 2017-05-16 2018-11-22 Bhami's Research Laboratory, Pvt. Ltd. High concentration protein formulations with reduced viscosity

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8956611B2 (en) * 2007-10-16 2015-02-17 Zymogenetics, Inc. Combination of BLyS inhibition and anti-CD 20 agents for treatment of autoimmune disease
AU2013266987B2 (en) * 2009-09-11 2016-11-10 F. Hoffmann-La Roche Ag Highly concentrated pharmaceutical formulations comprising anti - CD20 antibody
US20180333493A1 (en) * 2017-05-16 2018-11-22 Bhami's Research Laboratory, Pvt. Ltd. High concentration protein formulations with reduced viscosity

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