An aqueous solution composition of pH in the range 4.0-8.5 comprising:
an antibody construct comprising an Fc domain;
optionally one or more buffers being substances having at least one ionisable group with a pKa in the range 3.0 to 9.5 and which pKa is within 2 pH units of the pH of the composition;
optionally one or more neutral amino acids; and
an uncharged tonicity modifier;
wherein the buffers are present in the composition at a total concentration of 0-5 mM; and
wherein the total ionic strength of the composition excluding the contribution of the engineered protein construct is less than 20 mM.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
There is provided inter alia a storage stable aqueous solution composition comprising vancomycin or a pharmaceutically acceptable salt thereof, at a concentration of 1-10 mg/mL; D-lactic acid or a pharmaceutically acceptable salt thereof; and a polyol selected from the group consisting of propylene glycol, sucrose, glycerol, trehalose, lactose, glucose, sorbitol and mannitol, or a mixture thereof; wherein the osmolarity of the composition is 400-1250 mOsm/L.
There is provided inter alia an injection pen system comprising an injector mechanism and a reservoir comprising an aqueous liquid pharmaceutical composition for delivery by means of said injector mechanism to a mammal wherein the composition comprises (i) an insulin compound, (ii) ionic zinc and (ii) an alkyl glycoside as a non-ionic surfactant.
A storage stable aqueous solution composition comprising vancomycin or a pharmaceutically acceptable salt thereof, at a concentration of 25-75 mg/mL; D-lactic acid or a pharmaceutically acceptable salt thereof; a cosolvent selected from propylene glycol and a mixture of propylene glycol and glycerol; and an inorganic salt containing a metal cation.
The present invention relates inter alia to an aqueous liquid pharmaceutical formulation comprising (i) an insulin compound, (ii) ionic zinc, (iii) a nicotinic compound (iv) a non-ionic surfactant; and (v) a salt selected from the salts formed between Group 1 metals and a mono or divalent anion. It also provides related methods, uses and pharmaceutical compositions.
There is provided, inter alia, an aqueous solution composition of pH in the range 4.0-7.5 comprising: a peptide therapeutic agent; optionally one or more buffers being substances having at least one ionisable group with a pK a in the range 3.0 to 8.5 and which pk a is within 2 pH units of the pH of the composition; and a stabilizer; wherein the peptide therapeutic agent does not contain ionisable groups with pk a in the range 3.0 to 8.5, and wherein the buffers are present in the composition at a total concentration of 0-5 mM.
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
7.
AQUEOUS SOLUTION COMPOSITIONS FOR INCREASING STABILITY OF ENGINEERED DIMERIC PROTEINS
The present application relates to aqueous solution compositions of engineered dimeric proteins comprising monomers that comprise at least one human serpin polypeptide operably linked to a human immunoglobulin Fc polypeptide or a polypeptide that is derived from an immunoglobulin Fc polypeptide, at low buffer concentrations and low ionic strength and containing a neutral amino acid. The aqueous solution compositions increase the stability of the an Fc domain in aqueous solution compositions, and in particular increase the stability of an engineered dimeric protein.
There is provided inter alia a storage stable liquid solution composition comprising carfilzomib or a pharmaceutically acceptable salt thereof and a solvent consisting of (a) an organic solvent component comprising propylene glycol optionally together with polyethylene glycol (PEG), present at a total concentration of at least about 65% (v/v based on the total volume of the composition) and (b) water at a concentration of no more than about 15% (v/v based on the total volume of the composition); and a neutral amino acid, wherein the pH of the storage stable liquid solution composition is in the range 2.5 to 4.0.
There is provided inter alia a storage stable liquid composition concentrate comprising bendamustine or a pharmaceutically acceptable salt thereof and a liquid solvent in which said bendamustine or a pharmaceutically acceptable salt thereof is dissolved;
wherein said composition comprises:
(i) a mixture of two or more different polyethylene glycol (PEG) polymers, wherein each polyethylene glycol has an average molecular weight in the range 150-650 Da; and
(ii) 5-20% (v/v) of water.
There is provided inter alia an aqueous solution composition of pH in the range of about 4.0 to about 8.5 comprising: —an engineered protein construct comprising an Fc domain; —optionally one or more buffers being substances having at least one ionisable group with a pKa in the range of about 3.0 to about 9.5 and which pKa is within 2 pH units of the pH of the composition; —optionally one or more neutral amino acids; and—an uncharged tonicity modifier; wherein the buffers are present in the composition at a total concentration in the range of about 0 mM to about 10 mM; and wherein the total ionic strength of the composition excluding the contribution of the engineered protein construct is less than 20 mM.
There is provided, inter alia, an aqueous solution comprising an antibody protein and a stabilizing amount of (i) a chelating agent which is a multi-anion; and (ii) a C3 polyol.
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
inter aliainter alia a storage stable aqueous solution composition comprising vancomycin or a pharmaceutically acceptable salt thereof, at a concentration of 1-10 mg/mL; D-lactic acid or a pharmaceutically acceptable salt thereof; and a polyol selected from the group consisting of propylene glycol, sucrose, glycerol, trehalose, lactose, glucose, sorbitol and mannitol, or a mixture thereof; wherein the osmolarity of the composition is 400-1250 mOsm/L.
A storage stable aqueous solution composition comprising vancomycin or a pharmaceutically acceptable salt thereof, at a concentration of 25-75 mg/mL; D-lactic acid or a pharmaceutically acceptable salt thereof; a cosolvent selected from propylene glycol and a mixture of propylene glycol and glycerol; and an inorganic salt containing a metal cation.
There is provided, inter alia, an aqueous solution comprising (i) an antibody protein; and (ii) a antibody protein stabilizing mixture of arginine, methionine, and a C3 polyol.
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
The present invention relates to novel liquid pharmaceutical compositions of adalimumab, which include adalimumab or a biosimilar thereof, arginine and/or methionine, and a small polyol stabiliser such as glycerol. Such a combination of components furnishes formulations having a stability (e.g. on storage and when exposed to stress) which is comparable to or an improvement upon those known in the art, and with fewer ingredients. Such advances will help adalimumab treatments to become more widely available at lower cost, and prolong the viability of pre-loaded delivery devices (e.g. pre-filled syringes) to reduce unnecessary waste of the drug.
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
There is provided inter alia a storage stable liquid composition concentrate comprising bendamustine or a pharmaceutically acceptable salt thereof and a liquid solvent in which said bendamustine or a pharmaceutically acceptable salt thereof is dissolved; wherein said composition comprises: (i) a mixture of two or more different polyethylene glycol (PEG) polymers, wherein each polyethylene glycol has an average molecular weight in the range 150-650 Da; and (ii) 5-20 % (v/v) of water.
There is provided, inter alia, an aqueous liquid pharmaceutical formulation comprising (i) a fast acting insulin analogue; (ii) ionic zinc; and (ill) citrate, said formulation being substantially free of a zinc binding species having a logK with respect to zinc ion binding of greater than 12.3 at 25° C.; for use in the treatment of a human subject suffering from diabetes mellitus by administration by subcutaneous injection or subcutaneous infusion at or close to a meal-time wherein the administration of 0.3 U/kg of the formulation leads to one or more specified pharmacokinetic and/or pharmacodynamic parameters.
An aqueous solution composition of pH in the range 4.0-8.5 comprising: an antibody construct comprising an Fc domain; optionally one or more buffers being substances having at least one ionisable group with a pKa in the range 3.0 to 9.5 and which pKa is within 2 pH units of the pH of the composition; optionally one or more neutral amino acids; and an uncharged tonicity modifier; wherein the buffers are present in the composition at a total concentration of 0-5 mM; and wherein the total ionic strength of the composition excluding the contribution of the engineered protein construct is less than 20 mM.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The present application relates to aqueous solution compositions of engineered dimeric proteins comprising monomers that comprise at least one human serpin polypeptide operably linked to a human immunoglobulin Fc polypeptide or a polypeptide that is derived from an immunoglobulin Fc polypeptide, at low buffer concentrations and low ionic strength and containing a neutral amino acid. The aqueous solution compositions increase the stability of the an Fc domain in aqueous solution compositions, and in particular increase the stability of an engineered dimeric protein.
The present application relates to aqueous solution compositions of engineered dimeric proteins comprising monomers that comprise at least one human serpin polypeptide operably linked to a human immunoglobulin Fc polypeptide or a polypeptide that is derived from an immunoglobulin Fc polypeptide, at low buffer concentrations and low ionic strength and containing a neutral amino acid. The aqueous solution compositions increase the stability of the an Fc domain in aqueous solution compositions, and in particular increase the stability of an engineered dimeric protein.
aa in the range of about 3.0 to about 9.5 and which pKa is within 2 pH units of the pH of the composition; - optionally one or more neutral amino acids; and - an uncharged tonicity modifier; wherein the buffers are present in the composition at a total concentration in the range of about 0 mM to about 10 mM; and wherein the total ionic strength of the composition excluding the contribution of the engineered protein construct is less than 20 mM.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
There is provided, inter alia, an aqueous solution formulation comprising: (i) an Fc fusion protein; and (ii) sulfate ions at a concentration of 5-200 mM to stabilise the Fc fusion protein; which formulation is free of amino acids selected from arginine, lysine and proline, and salts thereof, and which formulation is free of magnesium ions.
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 9/00 - Medicinal preparations characterised by special physical form
The invention provides inter alia an aqueous solution composition of pH in the range 4.0-6.0 comprising: —terlipressin or a salt thereof; —optionally one or more buffers being substances having at least one ionisable group with a pKa in the range 3.0 to 7.0 and which pKa is within 1 pH unit of the pH of the composition; —optionally an amino acid; and—optionally a tonicity modifier wherein the buffers are present in the composition at a total concentration of 0-5 mM.
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
There is provided inter alia an aqueous solution composition of pH in the range 5.0 to 8.0 comprising: —daptomycin or an analogue thereof, or a salt thereof; —a divalent metal cation; and —optionally one or more buffers being substances having at least one ionisable group with a pKa in the range 3.0 to 9.0 and which pKa is within 2 pH units of the pH of the composition; wherein the buffers are present at a total concentration of 0-5 mM.
The invention provides inter alia an aqueous solution composition of pH in the range 6.0 to 8.0 comprising: —daptomycin or an analogue thereof, or a salt thereof; —a divalent metal cation; and —one or more salts which are not divalent metal cation salts or amino acid salts or buffer salts at a total concentration of 300 mM or more.
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Medical preparations; medicinal products; pharmaceuticals;
biopharmaceuticals. Medical and pharmacological research services; consultancy
in the field of pharmaceutical research and development;
development of pharmaceutical preparations and medicines;
pharmaceutical product evaluation & development; research
and development of vaccines and medicines.
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Medical preparations; medicinal products; pharmaceuticals;
biopharmaceuticals. Medical and pharmacological research services; consultancy
in the field of pharmaceutical research and development;
development of pharmaceutical preparations and medicines;
pharmaceutical product evaluation & development; research
and development of vaccines and medicines.
inter aliainter alia, an aqueous liquid pharmaceutical formulation comprising (i) a fast acting insulin analogue; (ii) ionic zinc; and (ill) citrate, said formulation being substantially free of a zinc binding species having a logK with respect to zinc ion binding of greater than 12.3 at 25 °C; for use in the treatment of a human subject suffering from diabetes mellitus by administration by subcutaneous injection or subcutaneous infusion at or close to a meal-time wherein the administration of 0.3 U/kg of the formulation leads to one or more specified pharmacokinetic and/or pharmacodynamic parameters.
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Medical preparations, namely, diagnostic preparations for medical purposes, preparations for the treatment of viral, metabolic, endocrine, musculoskeletal, cardiovascular, metabolic, immune-oncology, oncology, anti-infective, neuroscience, cardiopulmonary, genitourinary, sexual dysfunction, oncological, hepatological, ophthalmology, respiratory, neurological, gastrointestinal, hormonal, dermatological, psychiatric and immune system related diseases and disorders, rare diseases, autoimmune, inflammatory, immunology, pain, infectious diseases, renal, reproductive health and childbirth, blood disorders, vaccines, haematological related diseases and disorders; Medicinal products, namely, pharmaceutical products for the treatment of viral, metabolic, endocrine, musculoskeletal, cardiovascular, metabolic, immune-oncology, oncology, anti-infective, neuroscience, cardiopulmonary, genitourinary, sexual dysfunction, oncological, hepatological, ophthalmology, respiratory, neurological, gastrointestinal, hormonal, dermatological, psychiatric and immune system related diseases and disorders, rare diseases, autoimmune, inflammatory, immunology, pain, infectious diseases, renal, reproductive health and childbirth, blood disorders, vaccines, haematological related diseases and disorders; Pharmaceuticals, namely, preparations and substances for the treatment of viral, metabolic, endocrine, musculoskeletal, cardiovascular, metabolic, immune-oncology, oncology, anti-infective, neuroscience, cardiopulmonary, genitourinary, sexual dysfunction, oncological, hepatological, ophthalmology, respiratory, neurological, gastrointestinal, hormonal, dermatological, psychiatric and immune system related diseases and disorders, rare diseases, autoimmune, inflammatory, immunology, pain, infectious diseases, renal, reproductive health and childbirth, blood disorders, vaccines, haematological related diseases and disorders; Biopharmaceuticals, namely, preparations and substances for the treatment of viral, metabolic, endocrine, musculoskeletal, cardiovascular, metabolic, immune-oncology, oncology, anti-infectives, neuroscience, cardiopulmonary, genitourinary, sexual dysfunction, oncological, hepatological, ophthalmology, respiratory, neurological, gastrointestinal, hormonal, dermatological, psychiatric and immune system related diseases and disorders, rare diseases, autoimmune, inflammatory, immunology, pain, infectious diseases, renal, reproductive health and childbirth, blood disorders, vaccines, haematological related diseases and disorders Medical and pharmacological research services; consultancy in the field of pharmaceutical research and development; development of pharmaceutical preparations and medicines; pharmaceutical product evaluation and development; research and development of vaccines and medicines
42 - Scientific, technological and industrial services, research and design
Goods & Services
Medical and pharmacological research services; consultancy in the field of pharmaceutical research and development; development of pharmaceutical preparations and medicines; pharmaceutical product evaluation and development; research and development of vaccines and medicines
31.
MEDICAL INFUSION PUMP SYSTEM FOR THE DELIVERY OF AN INSULIN COMPOUND
There is provided inter alia medical infusion pump system comprising a pump and a reservoir comprising an aqueous liquid pharmaceutical composition for delivery by means of said pump to a mammal wherein the composition comprises (i) an insulin compound at a concentration of 400 U/mL or more, (ii) ionic zinc and (iii) a non-ionic surfactant and wherein the said pump delivers the composition in pulses wherein the volume of the pulse is 0.5 μL or less.
There is provided inter alia medical infusion pump system comprising a pump and a reservoir comprising an aqueous liquid pharmaceutical composition for delivery by means of said pump to a mammal wherein the composition comprises (i) an insulin C compound, (ii) ionic zinc and (iii) an alkyl glycoside as a non-ionic surfactant.
An aqueous solution composition of pH in the range 4.0-8.5 comprising: an antibody construct comprising an Fc domain; optionally one or more buffers being substances having at least one ionisable group with a pKa in the range 3.0 to 9.5 and which pKa is within 2 pH units of the pH of the composition; optionally one or more neutral amino acids; and an uncharged tonicity modifier; wherein the buffers are present in the composition at a total concentration of 0-5 mM; and wherein the total ionic strength of the composition excluding the contribution of the engineered protein construct is less than 20 mM.
There is provided inter alia an injection pen system comprising an injector mechanism and a reservoir comprising an aqueous liquid pharmaceutical composition for delivery by means of said injector mechanism to a mammal wherein the composition comprises (i) an insulin compound, (ii) ionic zinc and (iii) an alkyl glycoside as a non-ionic surfactant.
inter alia inter alia, an aqueous solution formulation comprising: (i) an Fc fusion protein;and (ii) sulfate ions at a concentration of 5-200 mM to stabilise the Fcfusion protein; which formulation is free of amino acids selected from arginine, lysineand proline, and salts thereof,and which formulationis free of magnesium ions.
C07K 14/715 - ReceptorsCell surface antigensCell surface determinants for cytokinesReceptorsCell surface antigensCell surface determinants for lymphokinesReceptorsCell surface antigensCell surface determinants for interferons
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
The invention provides inter alia an aqueous solution composition of pH in the range 4.0-6.0 comprising: - terlipressin or a salt thereof; - optionally one or more buffers being substances having at least one ionisable group with a pKa in the range 3.0 to 7.0 and which pKa is within 1 pH unit of the pH of the composition; - optionally an amino acid; and - optionally a tonicity modifier wherein the buffers are present in the composition at a total concentration of 0-5 mM.
inter aliainter alia an aqueous solution composition of pH in the range 6.0 to 8.0 comprising: -daptomycin or an analogue thereof, or a salt thereof; -a divalent metal cation; and -one or more salts which are not divalent metal cation salts or amino acid salts or buffer salts at a total concentration of 300 mM or more.
The present invention provides an aqueous solution comprising an antibody protein at a concentration of at least about 10 mg/mL and an oligomer of ethyleneimine, wherein the number of repeating units of ethyleneimine (n) in the oligomer is in the range of n=2-12.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present invention relates inter alia to an aqueous liquid pharmaceutical formulation comprising (i) an insulin compound, (ii) ionic zinc, (iii) a nicotinic compound (iv) a non-ionic surfactant; and (v) a salt selected from the salts formed between Group 1 metals and a mono or divalent anion. It also provides related methods, uses and pharmaceutical compositions.
The present invention relates inter alia to an aqueous liquid pharmaceutical formulation comprising: (i) an insulin compound; (ii) ionic zinc; (iii) a zinc binding species at a concentration of 1 mM or more selected from species having a log K with respect to zinc ion binding in the range 4.5-10 at 25° C.; (iv) a zinc binding species selected from species having a log K with respect to zinc ion binding of more than 12.3 at 25° C. at a concentration of less than about 0.3 mM; and (v) a non-ionic surfactant. It also provides related methods, uses and pharmaceutical compositions.
There is provided, inter alia, an aqueous solution comprising (i) an antibody protein; and (ii) a antibody protein stabilizing mixture of arginine, methionine, and a C3 polyol.
The present invention relates to novel liquid pharmaceutical compositions of adalimumab, which include adalimumab or a biosimilar thereof, arginine and/or methionine, and a small polyol stabiliser such as glycerol. Such a combination of components furnishes formulations having a stability (e.g. on storage and when exposed to stress) which is comparable to or an improvement upon those known in the art, and with fewer ingredients. Such advances will help adalimumab treatments to become more widely available at lower cost, and prolong the viability of pre-loaded delivery devices (e.g. pre-filled syringes) to reduce unnecessary waste of the drug.
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
The present invention relates to novel liquid pharmaceutical compositions of adalimumab, which include adalimumab or a biosimilar thereof, EDTA, and a small polyol stabiliser such as glycerol. Such a combination of components furnishes formulations having a stability (e.g. on storage and when exposed to stress) which is comparable to or an improvement upon those known in the art, and with fewer ingredients. Such advances will help adalimumab treatments to become more widely available at lower cost, and prolong the viability of pre-loaded delivery devices (e.g. pre-filled syringes) to reduce unnecessary waste of the drug.
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
45.
MEDICAL INFUSION PUMP SYSTEM FOR THE DELIVERY OF AN INSULIN COMPOUND
inter aliainter alia medical infusion pump system comprising a pump and a reservoir comprising an aqueous liquid pharmaceutical composition for delivery by means of said pump to a mammal wherein the composition comprises (i) an insulin compound, (ii) ionic zinc and (iii) an alkyl glycoside as a non-ionic surfactant.
There is provided inter aliaa medical infusion pump system comprising a pump and a reservoir comprising an aqueous liquid pharmaceutical composition for delivery by means of said pump to a mammal wherein the composition comprises (i) an insulin compound at a concentration of 400 U/mLor more, (ii) ionic zinc and (iii) a non-ionic surfactant and wherein the said pump delivers the composition in pulses wherein the volume of the pulse is 0.5 µLor less.
inter aliainter alia an injection pen system comprising an injector mechanism and a reservoir comprising an aqueous liquid pharmaceutical composition for delivery by means of said injector mechanism to a mammal wherein the composition comprises (i) an insulin compound, (ii) ionic zinc and (iii) an alkyl glycoside as a non-ionic surfactant.
There is provided inter alia an aqueous liquid pharmaceutical formulation comprising (i) an insulin compound, (ii) ionic zinc, (iii) a zinc binding species at a concentration of 1 mM or more selected from species having a log K with respect to zinc ion binding in the range 4.5-12.3 at 25° C., and (iv) a non-ionic surfactant which is an alkyl glycoside; and wherein the formulation is substantially free of EDTA and any other zinc binding species having a log K with respect to zinc ion binding of more than 12.3 at 25° C.
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/34 - 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
A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
There is provided inter alia an aqueous liquid pharmaceutical formulation comprising (i) an insulin compound at a concentration of 500-1000 U/ml, (ii) ionic zinc, (iii) a zinc binding species at a concentration of 1 mM or more selected from species having a logK with respect to zinc ion binding in the range 4.5-12.3 at 25° C., and (iv) a non-ionic surfactant; and wherein the formulation is substantially free of EDTA and any other zinc binding species having a logK with respect to zinc ion binding of more than 12.3 at 25° C.
A61K 31/194 - Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/34 - 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
A61M 5/315 - PistonsPiston-rodsGuiding, blocking or restricting the movement of the rodAppliances on the rod for facilitating dosing
A61M 5/32 - NeedlesDetails of needles pertaining to their connection with syringe or hubAccessories for bringing the needle into, or holding the needle on, the bodyDevices for protection of needles
There is provided, inter alia, an aqueous solution composition of pH in the range 4.0-7.5 comprising: a peptide therapeutic agent; optionally one or more buffers being substances having at least one ionisable group with a pKa in the range 3.0 to 8.5 and which pKa is within 2 pH units of the pH of the composition; and a stabilizer; wherein the peptide therapeutic agent does not contain ionisable groups with pKa in the range 3.0 to 8.5, and wherein the buffers are present in the composition at a total concentration of 0-5 mM.
The present invention relates inter alia to an aqueous liquid pharmaceutical formulation comprising (i) an insulin compound, (ii) ionic zinc, (iii) a nicotinic compound (iv) a non-ionic surfactant; and (v) a salt selected from the salts formed between Group 1 metals and a mono or divalent anion. It also provides related methods, uses and pharmaceutical compositions.
The present invention relates inter alia to an aqueous liquid pharmaceutical formulation comprising: (i) an insulin compound; (ii) ionic zinc; (iii) a zinc binding species at a concentration of 1 mM or more selected from species having a logK with respect to zinc ion binding in the range 4.5-10 at 25 °C; (iv) a zinc binding species selected from species having a logK with respect to zinc ion binding of more than 12.3 at 25 °C at a concentration of less than about 0.3 mM; and (v) a non-ionic surfactant. It also provides related methods, uses and pharmaceutical compositions.
The present invention relates inter alia to an aqueous liquid pharmaceutical formulation comprising (i) an insulin compound other than insulin glargine, (ii) ionic zinc, (iii) a zinc binding species selected from diethylenetriamine (DETA) and triethylenetetramine (TETA), and (iv) a non-ionic surfactant. It also provides related methods, uses and pharmaceutical compositions.
The present invention relates to novel liquid pharmaceutical compositions of adalimumab, which include adalimumab or a biosimilar thereof, arginine and/or methionine, and a small polyol stabiliser such as glycerol. Such a combination of components furnishes formulations having a stability (e.g. on storage and when exposed to stress) which is comparable to or an improvement upon those known in the art, and with fewer ingredients. Such advances will help adalimumab treatments to become more widely available at lower cost, and prolong the viability of pre-loaded delivery devices (e.g. pre-filled syringes) to reduce unnecessary waste of the drug.
The present invention relates to novel liquid pharmaceutical compositions of adalimumab, which include adalimumab or a biosimilar thereof, EDTA, and a small polyol stabiliser such as glycerol. Such a combination of components furnishes formulations having a stability (e.g. on storage and when exposed to stress) which is comparable to or an improvement upon those known in the art, and with fewer ingredients. Such advances will help adalimumab treatments to become more widely available at lower cost, and prolong the viability of pre-loaded delivery devices (e.g. pre-filled syringes) to reduce unnecessary waste of the drug.
The present invention relates to novel liquid pharmaceutical compositions of adalimumab, which include adalimumab or a biosimilar thereof, EDTA, and a small polyol stabiliser such as glycerol. Such a combination of components furnishes formulations having a stability (e.g. on storage and when exposed to stress) which is comparable to or an improvement upon those known in the art, and with fewer ingredients. Such advances will help adalimumab treatments to become more widely available at lower cost, and prolong the viability of pre-loaded delivery devices (e.g. pre-filled syringes) to reduce unnecessary waste of the drug.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
The present invention relates to novel liquid pharmaceutical compositions of adalimumab, which include adalimumab or a biosimilar thereof, arginine and/or methionine, and a small polyol stabiliser such as glycerol. Such a combination of components furnishes formulations having a stability (e.g. on storage and when exposed to stress) which is comparable to or an improvement upon those known in the art, and with fewer ingredients. Such advances will help adalimumab treatments to become more widely available at lower cost, and prolong the viability of pre-loaded delivery devices (e.g. pre-filled syringes) to reduce unnecessary waste of the drug.
There is provided, inter alia, an aqueous solution comprising (i) an antibody protein; and (ii) a stabilizing mixture of arginine, methionine and a C3 polyol.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
There is provided, inter alia, an aqueous solution comprising an antibody protein and a stabilizing mixture of (i) a chelating agent which is a multi-anion; and (ii) a C3 polyol.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
There is provided, inter alia, an aqueous solution composition comprising a GLP-1 receptor agonist as an active ingredient and multivalent anions having a charge of at least minus 2 as stabilising agent, wherein the total concentration of multivalent anions in the composition having a charge of at least minus 2 is at least 15 mM.
There is provided inter aliaan aqueous liquid pharmaceutical formulation comprising (i) an insulin compound, (ii) ionic zinc, (iii) a zinc binding species at a concentration of mM or more selected from species having a logK with respect to zinc ion binding in 5 the range 4.5-12.3 at 25 °C, and (iv) a non-ionic surfactant which is an alkyl glycoside; and wherein the formulation is substantially free of EDTA and any other zinc binding species having a logK with respect to zinc ion binding of more than 12.3 at 25 °C.
There is provided inter aliaan aqueous liquid pharmaceutical formulationcomprising (i) an insulincompound at a concentration of 500-1000 U/ml, (ii) ionic zinc, (iii) a zinc binding species at a concentration of 1 mM or more selected from species having a logK with respect to zinc ion binding in the range 4.5-12.3 at 25 °C, and (iv) a non- ionic surfactant; and wherein the formulation is substantially free of EDTA and any other zinc binding species havinga logK with respect to zinc ion binding of more than 12.3at 25 °C.
According to the invention there is provided inter alia an aqueous liquid pharmaceutical formulation comprising insulin or an insulin analogue, ionic zinc, a chelating agent and polysorbate 80.
A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests
There is provided inter alia an aqueous solution composition comprising insulin glargine as an active ingredient and an amino acid selected from aspartic acid and glutamic acid as a stabilising agent, wherein the amino acid is present at a concentration of 1-50 mM.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 47/00 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
There is provided inter alia an aqueous solution composition comprising insulin glargine as an active ingredient and triethylenetetramine (TETA) as a stabilising agent.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 47/00 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
There is provided inter alia an aqueous solution composition having pH between 4 and 7 comprising: (i) glucagon at a concentration of 1 mg/mL or more; (ii) a cationic surfactant selected from benzalkonium salts and benzethonium salts at a concentration of 2.5 mg/mL or less; and (iii) a polyol at a concentration of 0.5 M or more, wherein the polyol is selected from 1,2-propanediol and glycerol; and wherein the ratio of glucagon to cationic surfactant (mg/mL:mg/mL) is 2: 1 or more.
According to the invention there is provided inter alia an aqueous liquid pharmaceutical formulation comprising insulin or an insulin analogue, ionic zinc, a chelating agent and polysorbate 80.
A61M 5/00 - Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular wayAccessories therefor, e.g. filling or cleaning devices, arm rests
The present invention is based on the surprising discovery that the inclusion of an anionic polymer in the adenovirus formulation enhances long-term stability of the vector composition. An aqueous formulation comprising an adenovirus vector and at least one anionic polymer is provided, together with methods of the preparation of a storage stable adenovirus aqueous formulation.
The present invention provides an aqueous solution comprising an antibody protein at a concentration of at least about 10 mg/mL and an oligomer of ethyleneimine, wherein the number of repeating units of ethyleneimine (n) in the oligomer is in the range n=2-12.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present invention is based on the surprising discovery that the inclusion of an anionic polymer in the adenovirus formulation enhances long-term stability of the vector composition. An aqueous formulation comprising an adenovirus vector and at least one anionic polymer is provided, together with methods of the preparation of a storage stable adenovirus aqueous formulation.
The present invention is based on the surprising discovery that the inclusion of an anionic polymer in the adenovirus formulation enhances long-term stability of the vector composition. An aqueous formulation comprising an adenovirus vector and at least one anionic polymer is provided, together with methods of the preparation of a storage stable adenovirus aqueous formulation.
There is provided according to the invention an aqueous composition having pH between 4 and 7 comprising (i) glucagon at a concentration of 0.05% w/v or more and (ii) a cationic surfactant selected from benzalkonium salts and benzethonium salts as solubilizing agent in an amount sufficient to dissolve the glucagon in the composition.
The present invention provides an aqueous solution comprising an antibody protein at a concentration of at least about 10 mg/mL and an oligomer of ethyleneimine, wherein the number of repeating units of ethyleneimine (n) in the oligomer is in the range n = 2-12.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
There is provided according to the invention an aqueous composition having pH between (4) and (7) comprising (i) glucagon at a concentration of 0.05 % w/v or more and (ii) a cationic surfactant selected from benzalkonium salts and benzethonium salts as solubilising agent in an amount sufficient to dissolve the glucagon in the composition.
There is provided according to the invention an aqueous composition having pH between (4) and (7) comprising (i) glucagon at a concentration of 0.05 % w/v or more and (ii) a cationic surfactant as solubilising agent in an amount sufficient to dissolve the glucagon in the composition, wherein the overall concentration of charged species, other than those originating from glucagon and the cationic surfactant, in the composition is less than 150 mM.
The present invention provides an aqueous solution comprising an antibody protein at a concentration of at least about 10 mg/m L and a stabilizing amount of polyethyleneimine.
The invention allows substantial improvements in stability of coagulation Factor IX in aqueous compositions. An aqueous composition sealed in a non-glass container comprising Factor IX in a buffer and calcium ions is provided, together with methods of stabilizing an aqueous Factor IX composition comprising storing said composition in a non-glass container for at least 7 days.
The invention relates to the discovery that the addition of aromatic carboxylate ions inhibit protein instability caused by aromatic preservatives. Thus, the invention relates to compositions, preferably aqueous compositions, comprising a protein, an aromatic preservative and aromatic carboxylate ions. The proteins remain stable and suitable for storage at ambient temperatures or lower, even in aqueous form. Preferably, the aqueous composition comprises a protein, a phenolic preservative and benzoate ions, wherein the pH of the composition is at least 1 unit greater than the pKa of benzoic acid. The invention also provides methods of reducing protein degradation by aromatic preservatives in an aqueous formulation of a protein susceptible to such degradation, comprising the step of adding aromatic carboxylate ions to the formulation wherein the formulation is maintained at a pH that is at least 1 unit greater than the pKa of the corresponding aromatic carboxylic acid.
An aqueous composition which comprises a protein or other biological molecule and also (i) optionally comprises one or more metal ions at a concentration of 0.01 to 20 mM; (ii) comprises excipients which are weak ligands; and (iii) is substantially free of excipients which are medium-strength ligands, and is substantially free of excipients which are strong ligands in free form.
A composition comprises a biological molecule that is susceptible to aggregation, dimerization or hydrolysis, wherein the ionic strength is less than 40 mM.
There is provided inter alia a cell culture medium for recombinant Factor VIII production characterized in that the culture medium contains calcium ions and a strong ligand such as EDTA.
The invention relates inter alia to a composition which is storage-stable at 25°C for a minimum of 18 weeks comprising a therapeutically effective amount of Factor VIII and an aqueous medium having a Factor VIII potency after 18 weeks of storage at 25° C of at least 90% of the Factor VIII potency of a Control Composition.
A dry composition for use in therapy or diagnosis, obtainable by drying an aqueous composition comprising a protein and one or more displacement buffers, such as TRIS, lactate, lysine and histidine wherein the pH of the aqueous composition is such that the protein is stable, wherein the or each displacement buffer has a pKa that is at least 1 unit greater or less than the pH of the aqueous composition, and wherein the aqueous composition is substantially free of a conventional buffer having a pKa that is within one pH unit of the pH of the aqueous composition.
An aqueous composition comprising a therapeutic protein further characterized in that (i) the pH of the composition is adjusted to be between about 5.9 and 6.3, preferably about 6.1; (ii) the composition comprises at least one displaced buffer having a pKa within 1 to 3 pH units of the pH of the composition such as lactate and TRIS; (iv) the osmolarity of the composition is between 150 - 500 mOsm/L.
A composition comprises a biological molecule that is susceptible to aggregation, dimerisation or hydrolysis, wherein the ionic strength is less than 40 mM.
An aqueous composition which comprises a protein or other biological molecule and also (i) optionally comprises one or more metal ions at a concentration of 0.01 to 20 mM; (ii) comprises excipients which which are weak ligands; and (iii) is substantially free of excipients which are medium-strength ligands or strong ligands.
An aqueous composition having increased protein stability is obtained by : a. determining a pH at which the protein has stability at the desired temperature; b. adding to the composition at least one displacement buffer wherein the displacement buffer has a pKa that is at least 1 unit greater or less than the pH of step (a); and c. adjusting the pH of the composition to the pH of step (a); wherein the aqueous composition does not comprise a conventional buffer at a concentration greater than about 2 mM and wherein the conventional buffer has a pKa that is within 1 unit of the pH of step (a).
A method of sterilising a protein, comprises exposing to ionising radiation an at least substantially dry composition comprises a protein and a protective compound or combination of protective compounds having both of the following characteristics: (i) a rate of reaction with singlet oxygen greater than 1 x 10 ^7 L mol^-1 s^-1; (ii) being a reducing agent whilst at the same time containing a proton dissociable group with a pKa no more than 3 units from the pH of the composition. The compound having characteristic (i) is selected from histidine, thiamine and tryptophan, the compound having characteristic (ii) is selected from methionine, malate, citrate, lactate and tiron. The radiation is gamma radiation or electron beam, whereby the preferred dose is 15 - 40 kGy.
An aqueous vaccine composition comprises a protein adsorbed on a solid and one or more stabilising agents, wherein the one or more stabilising agents have ionisable groups capable of exchanging protons with the protein and with the ionised products of water dissociation, and wherein the ionisable groups include first groups that are positively charged when protonated and uncharged when deprotonated, and second groups that are uncharged when protonated and negatively charged when deprotonated.
