WO2024257040A1 - Composition et formulations liquides stables comprenant des anticorps monoclonaux humanisés anti-récepteurs de l'interleukine 6 humaine (il-6) - Google Patents

Composition et formulations liquides stables comprenant des anticorps monoclonaux humanisés anti-récepteurs de l'interleukine 6 humaine (il-6) Download PDF

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Publication number
WO2024257040A1
WO2024257040A1 PCT/IB2024/055846 IB2024055846W WO2024257040A1 WO 2024257040 A1 WO2024257040 A1 WO 2024257040A1 IB 2024055846 W IB2024055846 W IB 2024055846W WO 2024257040 A1 WO2024257040 A1 WO 2024257040A1
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Prior art keywords
formulation
buffer
antibody
composition
salt
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PCT/IB2024/055846
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Inventor
Nildip CHAUHAN
Abijar BHORI
Kinnari DAVE
Himanshu Gadgil
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Enzene Biosciences Ltd
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Enzene Biosciences Ltd
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    • 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
    • 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
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/26—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Definitions

  • the present disclosure relates to a pharmaceutical compositions comprising a humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody.
  • IL-6 humanized anti-human interleukin 6
  • the present disclosure relates to a composition comprising a humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody, succinate buffer, and combination of amino acid and salt; and stable, isotonic formulations thereof.
  • Interleukin-6 is an essential cytokine in particular involved in the regulation of immune cell proliferation and differentiation. IL-6 is strongly overproduced during inflammatory processes, and this overproduction is observed in many diseases such as infections, acute or chronic inflammatory diseases, and cancer.
  • IL-6 thus appears to be the driving signal in several inflammatory diseases.
  • Preclinical studies in animal models of human diseases have shown that blocking IL-6 activity alleviates symptoms or even completely prevents the onset of the disease.
  • IL-6R blocker tocilizumab the first monoclonal antibody developed against the IL-6 pathway, is now approved for the treatment of moderate to severe active rheumatoid arthritis (RA) in adults.
  • RA rheumatoid arthritis
  • High concentration monoclonal antibody formulations are manufactured using various technology such as ultrafiltration and diafiltration (UF/DF), lyophilization and then reconstituting monoclonal antibody powder to prepare high concentration liquid solution prior to subcutaneous injection.
  • UF/DF ultrafiltration and diafiltration
  • monoclonal antibody powder to prepare high concentration liquid solution prior to subcutaneous injection.
  • UF/DF ultrafiltration and diafiltration
  • instabilities may reduce the potency and/or increase the immunogenicity of the antibody.
  • a stable formulation to ensure that the antibody remains therapeutically active and safe until the administration is needed.
  • none of the present approaches provide a desired solution. Such formulations suffer from severe limitations in terms of stability, high viscosity.
  • buffer systems comprising acetate and amino acid such as histidine is used.
  • buffers such as acetate and histidine have certain limitations.
  • Acetate buffer cannot be utilized for lyophilized products due to the risk of a flash-off, while histidine offers a poor buffering capacity.
  • Histidine buffer With respect to its physical appearance, in case of histidine buffer, change in color is observed under accelerated temperature condition and acidic pH extract iron from stainless steel vessels during manufacturing operation or storage condition.
  • most of the biologies formulation contains anionic surfactant either polysorbate 20 or polysorbate 80 in the formulation to prevent aggregation during long term storage.
  • polysorbate 20 or polysorbate 80 degradation in the presence of a histidine buffer system because of imidazole group present in to the histidine.
  • ester hydrolysis leads to the degradation of polysorbate 20 or polysorbate 80 in a formulation containing histidine buffer.
  • Polysorbate 20 or polysorbate 80 degradation by hydrolysis results in the accumulation of free fatty acids, which can lead to particle formation and oxidation.
  • Other challenges with the high concentration antibody injections include pain inflicted to a patient, swelling and induration risk due to the high break loose force and glide force; while administration with syringe having thin wall needle or prefdled delivery devices.
  • the primary objective of the present invention is to provide a composition comprising a humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody for a stable, isotonic formulation.
  • IL-6 humanized anti-human interleukin 6
  • Another objective of the present invention is to provide stable, isotonic, high concentration monoclonal antibody formulations which are suitable for subcutaneous injection.
  • Another objective of the present invention is to provide a monoclonal antibody formulation wherein the viscosity of the formulation is between 2-20 cps for betterment of injectability.
  • Another objective of the present invention is to provide a monoclonal antibody formulations that reduce pain during subcutaneous administration.
  • the technical problem to be solved by the present invention is to provide a composition comprising a humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody for a stable, isotonic formulation that can be delivered with delivery device such as prefdled syringe having safety needle guard or two step auto injectors.
  • the present invention is directed to provide a high concentration monoclonal antibody formulation that is stable, isotonic, and suitable for subcutaneous injection with a desirable low break loose force and glide force for easy flow during administration from the syringe that reduce pain, swelling and induration risk.
  • a composition comprising a humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody.
  • the composition comprises: a. a monoclonal antibody; b. a buffer system; c. a viscosity reducing agent; d. a stabilizer; and e. pharmaceutically acceptable excipients.
  • a composition comprising a. a humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody; b. a succinate buffer; c. a viscosity reducing agent comprising an amino acid; d. a solution of sodium chloride; and e. pharmaceutically acceptable excipients.
  • IL-6 humanized anti-human interleukin 6
  • the present disclosure provides a stable, isotonic, high concentration monoclonal antibody formulations comprising a. a monoclonal antibody; b. a buffer system; c. a viscosity reducing agent; d. a stabilizer; and e. pharmaceutically acceptable excipients.
  • the present disclosure provides a stable, isotonic, high concentration monoclonal antibody formulations comprising a. a humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody; b. a succinate buffer; c. a viscosity reducing agent comprising an amino acid; d. a solution of sodium chloride; and e. pharmaceutically acceptable excipients.
  • IL-6 humanized anti-human interleukin 6
  • Figure 1 illustrates a representation flow chart of manufacturing process of the finished formulation.
  • Figure 2 is a graph elucidating the density of the formulation in accordance with one of the exemplary embodiment of the present disclosure and the comparative formulation of the marketed product.
  • Figure 3 is a graph elucidating the viscosity of the formulation in accordance with one of the exemplary embodiment of the present disclosure and the comparative formulation of the marketed product.
  • Figure 4 is a graph elucidating the glide force of different make syringes filled with a formulation in accordance with one of the exemplary embodiment of the present disclosure and the comparative formulation of the marketed product.
  • Figure 5 is a graph elucidating the Break loose force of different make syringes filled with a formulation in accordance with one of the exemplary embodiment of the present disclosure and the comparative formulation of the marketed product.
  • Figure 6 is a graph elucidating the functionality testing showing the Break loose force and glide force of syringe of make 2 filled with the formulation in accordance with one of the exemplary embodiment of the present disclosure.
  • Figure 7 is a graph elucidating the functionality testing showing the Break loose force and glide force of syringe of make 2 filled with the comparative formulation of the marketed product.
  • inventive subject matter provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus, if one embodiment comprises elements A, B, and C, and a second embodiment comprises elements B and D, then the inventive subject matter is also considered to include other remaining combinations of A, B, C, or D, even if not explicitly disclosed.
  • formulation refers to a composition that maintains the biological activity of the active component in an effective manner and does not contain other components that are unacceptably toxic to the subject. Such preparations are sterile.
  • sterile refers to the absence of live bacteria or the absence or substantial absence of all live microorganisms and their spores.
  • a “stable” formulation refers to a formulation in which the active component retains substantially its physical stability and/or chemical stability, and/or biological activity after storage. Preferably, the formulation retains substantially its physical and chemical stability, as well as its biological activity after storage.
  • the terms “patient” or “subject” are used interchangeably and refer to any mammal suffering from a condition or disease in accordance with the present invention. Preferably, human.
  • buffer refers to a buffer solution that resists pH changes through the action of its conjugate acid-base pairs.
  • surfactant refers to a surface active agent.
  • Protein "stability" can be assessed qualitatively and/or quantitatively after storage at selected temperatures for selected periods in some different ways, including assessment of aggregate formation (e.g. using size exclusion chromatography, measuring turbidity, and/or by visual inspection); assessment of charge heterogeneity using cation exchange chromatography, image capillary isoelectric focusing (icIEF) or capillary zone electrophoresis; analysis of aminoterminal or carboxy-terminal sequence; mass spectrometry; SDS-PAGE analysis to compare reduced and intact antibodies; peptide mapping (e.g., trypsin or LYS-C) analysis; assessment of biological activity or antigen-binding function of antibodies; etc.
  • aggregate formation e.g. using size exclusion chromatography, measuring turbidity, and/or by visual inspection
  • icIEF image capillary isoelectric focusing
  • capillary zone electrophoresis analysis of aminoterminal or carboxy-terminal sequence
  • mass spectrometry SDS-PAGE analysis to compare
  • antibody refers to an immunoglobulin molecule and refers to any form of antibody that exhibits the desired biological activity. These include, but are not limited to, monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies and multi-specific antibodies (e.g., bispecific antibodies), and even antibody fragments.
  • the full-length antibody structure preferably contains four polypeptide chains, two heavy (H) chains, and two light (L) chains, typically interconnected by disulfide bonds. Each heavy chain contains a heavy chain variable region and a heavy chain constant region. Each light chain contains a light chain variable region and a light chain constant region.
  • the structure also includes other derivative forms.
  • chimeric antibody refers to an antibody in which a portion of the heavy and/or light chain is derived from a specific source or species and the remainder is derived from a different source or species. “Humanized antibodies” are a subset of “chimeric antibodies”.
  • humanized antibody or “humanized antigen-binding fragment” is defined herein as an antibody or antibody fragment that: (i) antibodies derived from a non-human source (e.g., a transgenic mouse carrying a heterologous immune system) and based on a human germline sequence; or (ii) chimeric antibodies in which the variable region is of non- human origin and the constant region is of human origin; or (iii) CDR grafts in which the CDR in the variable region is of non-human origin and one or more of the framework regions in the variable region is of human origin and the constant region, if any, is of human origin.
  • a non-human source e.g., a transgenic mouse carrying a heterologous immune system
  • chimeric antibodies in which the variable region is of non- human origin and the constant region is of human origin
  • CDR grafts in which the CDR in the variable region is of non-human origin and one or more of the framework regions in the variable region is of human origin and the constant region, if
  • humanization is to eliminate the immunogenicity of nonhuman origin antibodies in humans while retaining the greatest possible affinity. It is advantageous to select the human framework region sequence that is most similar to the framework region sequence of the non-human source antibody as the template for humanization. In some cases, it may be necessary to replace one or more amino acids in the human framework region sequence with the corresponding residues in the nonhuman framework region to avoid loss of affinity.
  • the term "monoclonal antibody” refers to an antibody derived from a substantially homogeneous population of antibodies, i.e., every single antibody comprised in the population is identical except for possible mutations (e.g., natural mutations) that may be present in very small amounts. Thus, the term “monoclonal” indicates the nature of said antibodies, i.e., not a mixture of unrelated antibodies. In contrast to polyclonal antibody preparations, which usually include different antibodies against different antigenic determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a separate antigenic determinant. In addition to their specificity, monoclonal antibody preparations have the advantage that they are usually not contaminated with other antibodies. The term “monoclonal” should not be construed as requiring any particular method of producing said antibody. The term monoclonal antibody specifically includes chimeric antibodies, humanized antibodies, and human antibodies.
  • the present invention relates to a composition comprising a humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody for a stable, isotonic formulation.
  • IL-6 humanized anti-human interleukin 6
  • the present disclosure provides a composition
  • a composition comprising: a. a monoclonal antibody; b. a buffer system; c. a viscosity reducing agent; d. a stabilizer; and e. pharmaceutically acceptable excipients.
  • a monoclonal antibody formulation comprising: a. a monoclonal antibody; b. a buffer system; c. a viscosity reducing agent; d. a stabilizer; and e. pharmaceutically acceptable excipients.
  • the viscosity of the formulation is between 2-20 cps, preferably 5-12 for betterment of injectability.
  • the monoclonal antibody is anti-IL-6 antibody.
  • the monoclonal antibody is lyophilized antibody.
  • the present disclosure provides a composition
  • a composition comprising: a. an anti-IL-6 antibody; b. a buffer system; c. a viscosity reducing agent; d. a stabilizer; and e. pharmaceutically acceptable excipients.
  • an anti-IL-6 antibody formulation comprising: a. an anti-IL-6 antibody; b. a buffer system; c. a viscosity reducing agent; d. a stabilizer; and e. pharmaceutically acceptable excipients.
  • the buffer is selected from one or more of succinate buffer, citric acid buffer, acetate buffer, and glycine buffer.
  • the viscosity reducing agent is selected from one or more of amino acids or their salts thereof.
  • the stabilizer is isotonic solution of a salt.
  • the present disclosure provides a composition
  • a composition comprising: a. an anti-IL-6 antibody; b. a buffer system selected from one or more of succinate buffer, citric acid buffer, acetate buffer, and glycine buffer; c. a viscosity reducing agent selected from an amino acid or salt thereof; d. an isotonic solution of a salt; and e. pharmaceutically acceptable excipients.
  • an anti-IL-6 antibody formulation comprising: a. an anti-IL-6 antibody; b. a buffer system selected from one or more of succinate buffer, citric acid buffer, acetate buffer, and glycine buffer; c. a viscosity reducing agent selected from an amino acid or salt thereof; d. an isotonic solution of a salt; and e. pharmaceutically acceptable excipients.
  • the salt for isotonic solution is selected from but not limiting to sodium chloride, sodium acetate or the like or the combination thereof.
  • the amino acid and salt is in a ratio ranging from 1 : 0.2 to 1: 12, preferably ranging from 1:0.4 to 1: 10.
  • the amino acid and salt can be in a ratio of 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1: 1, 1: 1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:95 or 1: 10.
  • the stabilizer is NaCl. In some embodiments NaCl is used as the stabilizer as well as the viscosity reducing agent.
  • the buffering system is succinate buffer.
  • the viscosity reducing agent is selected from one or more of valine, methionine, histidine, lysine, proline or their salts thereof.
  • the viscosity reducing agent is lysine HC1.
  • the anti-IL-6 antibody is selected from sarilumab, olokizumab, elsilimomab, clazakizumab, sirukumab, levilimab, and gerilimzumab.
  • the anti -IL-6 antibody is tocilizumab.
  • the present disclosure provides a composition
  • a composition comprising: a. tocilizumab; b. succinate buffer; c. lysine; d. an isotonic solution of salt; and e. pharmaceutically acceptable excipients.
  • a monoclonal antibody formulation comprising: a. tocilizumab; b. succinate buffer; c. lysine; d. an isotonic solution of salt; and e. pharmaceutically acceptable excipients.
  • the pharmaceutically acceptable excipients include but not limited to antioxidants, surfactants, a carrier, a diluent, a preservative and combinations thereof.
  • the surfactant is selected from but not limiting to polysorbate 80, polysorbate 20 and poloxamer 188.
  • the antioxidant is selected from but not limiting to methionine, citric acid and ascorbic acid.
  • the pH in some embodiments, is in the range from pH 5.0 to 7.0.
  • the purity of the sample after storage of the selected time period is detected by molecular exclusion high performance liquid chromatography : separation and quantification according to the different molecular sizes, and thus information on the amount of the sample monomers, aggregates, and fragments is obtained; charge isomers are detected by cation exchange high performance liquid chromatography (CE-HPLC): separation and quantification according to the different protein charges, and thus information on the charge heterogeneity of the sample is obtained; or the charge isomers are detected by imaging capillary isoelectric focusing electrophoresis (IEF): separation and quantification based on the different isoelectric points of the proteins, thus obtaining information on the amount of acidic and basic proteins in the sample; determination of the "biological activity" of the sample by reporter gene assay.
  • CE-HPLC cation exchange high performance liquid chromatography
  • CE-HPLC cation exchange high performance liquid chromatography
  • the charge isomers are detected by imaging capillary isoelectric focusing electrophoresis (IEF): separation
  • the present invention provides a composition comprising a humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody for a stable, isotonic formulation that can be delivered with delivery device such as prefilled syringe having safety needle guard or two step auto injectors.
  • delivery device such as prefilled syringe having safety needle guard or two step auto injectors.
  • the present advantageously provides a high concentration monoclonal antibody formulation that is stable, isotonic, and suitable for subcutaneous injection with a desirable low break loose force and glide force for easy flow during administration from the syringe that reduce pain, swelling and induration risk.
  • CEX HPLC Cation Exchange High performance liquid chromatography RP HPLC : Reverse phase High performance liquid chromatography HMW : High molecular weight
  • Tm melting temperature mg/mL : milligram/milliliter
  • Manufacturing process started with the thawing of drug substance Tocilizumab stored at lower temperature, followed by preparation of equilibration buffer/formulation buffer, concentration of the Tocilizumab NLT 200mg/mL by using 50 KDA cassette. The concentrated product was diluted to target concentration of 180mg/ml for formulated bulk solution preparation. Addition of Polysorbate 20, fdtration, fdling and stoppering, visual inspection and labelling was done. Table 1: Formulations
  • Viscosity was checked using Brookfield cone and plate viscometer using small spindle size at different rpm and torque at room temperature condition. Viscosity of the formulation on average was found to be in the range of 10 to 12 cPs.
  • Prefdled syringe of 27 G regular wall and 27 G thin wall both can be used for administration, more preferably 27 G thin wall syringe can be used for administration of solution for injection.
  • Table 2 Glide force and Break loose force data of the formulation of the present invention and comparative formulation
  • Stability study of the formulation Fl (present invention formulation prepared in accordance with the present invention), performed to check product quality for a period of time at different condition, real time, accelerated and stress. Real time and accelerated condition stability was carried out up to 3M and stress stability was carried out up to 4 weeks. No changes in Physicochemical parameters are observed during stability. Monomer purity of the formulation was checked using size exclusion HPLC and Cation exchange chromatography. Potency of the formulation was checked by In vitro bioassay. Overall stability data shows protein stability in current formulations. The stability data mentioned in the below
  • the present invention provides a stable, isotonic, high concentration monoclonal antibody formulations which are suitable for subcutaneous injection.
  • the present invention provides a monoclonal antibody formulations wherein the viscosity of the formulation is between 5-12 cps for betterment of injectability.
  • the present invention provides a monoclonal antibody formulations that reduce pain during subcutaneous administration.

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Abstract

La présente invention concerne une composition comprenant une combinaison unique des anticorps monoclonaux anti-récepteurs de l'interleukine 6 humaine (IL-6) avec un tampon, un agent réducteur de viscosité, un agent stabilisant/isotonique et des tensioactifs, qui est stable, a un pH d'isotonicité 6,0 et une plage de viscosité appropriée pour une administration sous-cutanée à un sujet sans infliger de douleur qui est habituellement observée avec une formulation d'anticorps à viscosité élevée pendant l'administration.
PCT/IB2024/055846 2023-06-14 2024-06-14 Composition et formulations liquides stables comprenant des anticorps monoclonaux humanisés anti-récepteurs de l'interleukine 6 humaine (il-6) Pending WO2024257040A1 (fr)

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Application Number Priority Date Filing Date Title
IN202321040621 2023-06-14
IN202321040621 2023-06-14

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010106812A1 (fr) * 2009-03-19 2010-09-23 Chugai Seiyaku Kabushiki Kaisha Formulation pharmaceutique contenant des molécules d'anticorps améliorées
WO2018067987A1 (fr) * 2016-10-06 2018-04-12 Amgen Inc. Formulations pharmaceutiques de protéines à viscosité réduite
WO2018078162A1 (fr) * 2016-10-31 2018-05-03 Ares Trading S.A. Composition pharmaceutique liquide

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010106812A1 (fr) * 2009-03-19 2010-09-23 Chugai Seiyaku Kabushiki Kaisha Formulation pharmaceutique contenant des molécules d'anticorps améliorées
WO2018067987A1 (fr) * 2016-10-06 2018-04-12 Amgen Inc. Formulations pharmaceutiques de protéines à viscosité réduite
WO2018078162A1 (fr) * 2016-10-31 2018-05-03 Ares Trading S.A. Composition pharmaceutique liquide

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