WO2023140807A1 - Pharmaceutical compositions of trastuzumab - Google Patents

Pharmaceutical compositions of trastuzumab Download PDF

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Publication number
WO2023140807A1
WO2023140807A1 PCT/TR2022/050040 TR2022050040W WO2023140807A1 WO 2023140807 A1 WO2023140807 A1 WO 2023140807A1 TR 2022050040 W TR2022050040 W TR 2022050040W WO 2023140807 A1 WO2023140807 A1 WO 2023140807A1
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Prior art keywords
pharmaceutical composition
lyophilized powder
powder pharmaceutical
trastuzumab
composition according
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PCT/TR2022/050040
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French (fr)
Inventor
Yuksel TOPALOGLU
Ali Ihsan SECKIN
Turgay KACAR
Emine Yilmaz
Original Assignee
Arven Ilac Sanayi Ve Ticaret Anonim Sirketi
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Application filed by Arven Ilac Sanayi Ve Ticaret Anonim Sirketi filed Critical Arven Ilac Sanayi Ve Ticaret Anonim Sirketi
Priority to PCT/TR2022/050040 priority Critical patent/WO2023140807A1/en
Publication of WO2023140807A1 publication Critical patent/WO2023140807A1/en

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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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • 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
    • A61K47/16—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
    • A61K47/06—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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • 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
    • 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

  • This invention relates to stable pharmaceutical compositions of trastuzumab for injection.
  • Such compositions comprising in addition to trastuzumab, at least one stabilizer or a combination of two or more stabilizers, a buffering agent, a nonionic surfactant and water for injection to overcome the stability problems that may occur during the lyophilization stage and to solve the aggregation problem of trastuzumab.
  • Trastuzumab is a humanized monoclonal antibody used to treat breast cancer that is HER2 receptor positive and in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.
  • trasstuzumab was approved for medical use in the United States in September 1998, and in the European Union in August 2000.
  • Trastuzumab is marketed under the brand name Herceptin® as a sterile, white to pale yellow, preservative-free lyophilized powder for intravenous (IV) administration in two types of vials: a) 150 mg Trastuzumab for concentrate for solution for infusion and b) 440 mg Trastuzumab powder for concentrate for solution for infusion.
  • Each vial of Herceptin® contains Trastuzumab, L-histidine HCI, L-histidine, a,a-trehalose dihydrate and polysorbate 20.
  • BWFI Bacteriostatic Water for Injection
  • trastuzumab The powder for intravenous (IV) administration form of trastuzumab is known in the prior art. However, it is difficult to develop the drug due to some disadvantage properties of active agent.
  • the disadvantage of trastuzumab formulation is the low stability of the product during the lyophilization stage.
  • Aggregation can be dependent upon the concentration, buffer ionic strength, and temperature.
  • Aggregates may be formed when subjected to different environmental conditions such as medium type, temperature, pH and salt concentration during upstream, downstream and storage processes.
  • Patent document numbered EP 2 459 167 B1 discloses a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPIN®), Pertuzumab or T-DM1 , or a mixture of such antibody molecules for subcutaneous injection.
  • a pharmaceutically active anti-HER2 antibody such as e.g. Trastuzumab (HERCEPIN®), Pertuzumab or T-DM1 , or a mixture of such antibody molecules for subcutaneous injection.
  • the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a coformulation.
  • a composition comprising trastuzumab is provided in the lyophilized powder for injection which having good stability, providing bioavailability and which can be easily processed which are stable during the shelflife.
  • the main object of the present invention is to provide a lyophilized powder pharmaceutical composition of trastuzumab which eliminates all aforesaid problems and brings additional advantages to the relevant prior art.
  • Another object of the present invention is to provide a lyophilized powder pharmaceutical composition that solves the aggregation problem formed during long term storage.
  • Another object of the present invention is to provide a lyophilized powder pharmaceutical composition comprising trastuzumab which is characterized by desired stability.
  • Another object of the present invention is to provide a lyophilized powder pharmaceutical composition comprising at least one amino acid as a stabilizer to improve stability.
  • Another object of the present invention is to provide a lyophilized powder pharmaceutical composition comprising at least one saccharide as a stabilizer to improve stability.
  • Another object of the present invention is to provide a lyophilized powder pharmaceutical composition comprising a combination of amino acids and saccharides and/or a mixture of two or more saccharides.
  • Another object of the present invention is to provide an optimized, economical and industry viability composition of trastuzumab.
  • the present invention relates to a lyophilized powder pharmaceutical composition, the composition comprising:
  • composition further comprises at least one or more stabilizers selected from the group comprising dextran 40, a combination of dextran 40 and sucrose, arginine or mixtures thereof.
  • an "anti- HER2 antibody” is a monoclonal antibody targeting HER2, inducing an immune- mediated response that causes internalization and recycling of HER2.
  • said buffering agent is selected from the group comprising histidine, phosphate, tris, acetate and citrate or mixtures thereof.
  • said buffering agent is L-histidine HCI.
  • the L-histidine HCI is present in an amount of 3.36 mg/vial to about 9.9 mg/vial by weight in the total composition.
  • the buffering agent provides a pH of 6.
  • said composition comprises one or more stabilizers which prevent denaturation and/or aggregation problems that may occur during the lyophilization stage of the antibody, thereby forming the stable formulation.
  • Such stabilizers comprise at least one saccharide or a combination of saccharides, amino acids or a combination of amino acids and saccharides.
  • saccharide comprises the general composition (CH2O) n and derivatives thereof, including monosaccharides, disaccharides, trisaccharides, polysaccharides, sugar alcohols, reducing sugars, nonreducing sugars.
  • said saccharide is selected from the group comprising a,a-trehalose, melibiose, sucrose, mannitol, dextran 40 or mixtures thereof.
  • said amino acid is selected from the group comprising L-histidine, arginine, glycine, proline, asparagine or mixtures thereof.
  • said stabilizers are a,a-trehalose dihydrate, and L-histidine wherein the composition further comprises at least one or more stabilizers selected from the group comprising dextran 40, a combination of dextran 40 and sucrose, arginine or mixtures thereof.
  • said composition comprises a,a-trehalose, L- histidine and dextran 40 as stabilizers.
  • Dextran 40 is an excellent fast lyophilizable amorphous bulking agent. It has been observed that adding dextran 40 a further stabilizer to the composition in addition to a,a-trehalose and L-histidine surprisingly overcome the stability problems that may occur during the lyophilization stage.
  • dextrans affects the glass transition temperature (Tg) of freeze- dried products.
  • Tg glass transition temperature
  • said composition comprises a,a-trehalose dihydrate, L-histidine and a mixture of dextran 40 and sucrose as stabilizers.
  • said composition comprises a,a-trehalose dihydrate, L-histidine and arginine as stabilizers.
  • arginine as a further stabilizer to the composition in addition to a,a-trehalose and L-histidine surprisingly increases the stability of the antibody against protein aggregation. Also, using arginine as stabilizer makes freeze drying cycles faster and more efficient.
  • the stabilizers are generally added in amount(s) which protect and/or stabilize the monoclonal antibody at the lowest amount of stabilizer possible, to avoid increasing the viscosity of the final formulation.
  • the total amount of stabilizer is from about 1 to 500 mg/vial by weight in the total composition.
  • said nonionic surfactant is selected from the group comprising polysorbate 20, polysorbate 80, polyethylene glycol, poloxamer or mixtures thereof.
  • said composition comprises polysorbate 20 as a nonionic surfactant.
  • the polysorbate 20 is present in an amount of 0,6 mg/vial to about 1 ,8 mg/vial by weight in the total composition.
  • said pharmaceutical composition comprises trastuzumab.
  • trastuzumab is present in an amount of 150 mg/vial to about 440 mg/vial by weight in the total composition.
  • said pharmaceutical composition is reconstituted with sterile water for injection and administered through intravenous.
  • Example 1 The lyophilized powder pharmaceutical composition
  • Example 2 The lyophilized powder pharmaceutical composition
  • Example 3 The lyophilized powder pharmaceutical composition
  • Example 4 The lyophilized powder pharmaceutical composition
  • Example 5 The lyophilized powder pharmaceutical composition
  • Example 6 The lyophilized powder pharmaceutical composition

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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Abstract

This invention relates to stable pharmaceutical compositions of trastuzumab for injection. Such compositions comprising in addition to trastuzumab, at least one stabilizer or a combination of two or more stabilizers, a buffering agent, a nonionic surfactant and water for injection to overcome the stability problems that may occur during the lyophilization stage and to solve the aggregation problem of trastuzumab.

Description

PHARMACEUTICAL COMPOSITIONS OF TRASTUZUMAB
Field of the invention
This invention relates to stable pharmaceutical compositions of trastuzumab for injection. Such compositions comprising in addition to trastuzumab, at least one stabilizer or a combination of two or more stabilizers, a buffering agent, a nonionic surfactant and water for injection to overcome the stability problems that may occur during the lyophilization stage and to solve the aggregation problem of trastuzumab.
Background of the invention
Trastuzumab is a humanized monoclonal antibody used to treat breast cancer that is HER2 receptor positive and in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.
Trastuzumab was approved for medical use in the United States in September 1998, and in the European Union in August 2000.
Trastuzumab is marketed under the brand name Herceptin® as a sterile, white to pale yellow, preservative-free lyophilized powder for intravenous (IV) administration in two types of vials: a) 150 mg Trastuzumab for concentrate for solution for infusion and b) 440 mg Trastuzumab powder for concentrate for solution for infusion. Each vial of Herceptin® contains Trastuzumab, L-histidine HCI, L-histidine, a,a-trehalose dihydrate and polysorbate 20. Reconstitution with Bacteriostatic Water for Injection, (BWFI) USP, containing 1.1%benzyl alcohol as a preservative, yields 21 mL of a multi-dose solution containing 21mg/mL Trastuzumab, at a pH of approximately 6. (U.S. Food and Drug Administration, Herceptin® Labeling-Package Insert, 29.11.2018)
The powder for intravenous (IV) administration form of trastuzumab is known in the prior art. However, it is difficult to develop the drug due to some disadvantage properties of active agent. The disadvantage of trastuzumab formulation is the low stability of the product during the lyophilization stage.
Industrial-scale production of biopharmaceuticals is a challenging task; preserving the product by limiting stresses that may cause degradation, combined with maximising yield and minimizing resources consumed are key elements of bioprocess development. One form of protein degradation is aggregation. In the biopharmaceutical industry, aggregates are classed as impurities and must be cleared to acceptable levels if a protein formulation is to be used therapeutically. Aggregates are thought to pose a risk of unwanted immunogenicity and may affect product potency and reproducibility.
Out of all probable instabilities, protein aggregation of the mAb formulation has been a major problem that has been associated with a change in the protein structure.
Aggregation can be dependent upon the concentration, buffer ionic strength, and temperature.
Aggregates may be formed when subjected to different environmental conditions such as medium type, temperature, pH and salt concentration during upstream, downstream and storage processes.
There are also a number of challenges surrounding the formulation and development of the lyophilized powder, particularly during the lyophilization stage.
Several patent applications have been filed on a powder formulation of trastuzumab with increased stability.
Patent document numbered EP 2 459 167 B1 discloses a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPIN®), Pertuzumab or T-DM1 , or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a coformulation.
In the literature, it has been shown that some specific amino acids and saccharides may have protective properties against aggregation.
The prior art does not provide any teaching, suggestion or motivation to use the combination of amino acids and saccharides and/or the combination of two or more saccharides as stabilizers in a composition to overcome the stability problems that may occur during the lyophilization stage.
In this invention, to overcome these problems mentioned above, a composition comprising trastuzumab is provided in the lyophilized powder for injection which having good stability, providing bioavailability and which can be easily processed which are stable during the shelflife.
Objects and Brief Description of the Invention
The main object of the present invention is to provide a lyophilized powder pharmaceutical composition of trastuzumab which eliminates all aforesaid problems and brings additional advantages to the relevant prior art.
Another object of the present invention is to provide a lyophilized powder pharmaceutical composition that solves the aggregation problem formed during long term storage.
Another object of the present invention is to provide a lyophilized powder pharmaceutical composition comprising trastuzumab which is characterized by desired stability.
Another object of the present invention is to provide a lyophilized powder pharmaceutical composition comprising at least one amino acid as a stabilizer to improve stability.
Another object of the present invention is to provide a lyophilized powder pharmaceutical composition comprising at least one saccharide as a stabilizer to improve stability.
Another object of the present invention is to provide a lyophilized powder pharmaceutical composition comprising a combination of amino acids and saccharides and/or a mixture of two or more saccharides.
Another object of the present invention is to provide an optimized, economical and industry viability composition of trastuzumab.
Detailed description of the Invention
In accordance with the objects outlined above, detailed features of the present invention are given herein.
The present invention relates to a lyophilized powder pharmaceutical composition, the composition comprising:
- an anti-HER2 antibody,
- a buffering agent,
- at least one stabilizer or a combination two or more stabilizers, - a nonionic surfactant,
- water for injection, wherein said stabilizers are a,a-trehalose dihydrate and L-histidine, wherein the composition further comprises at least one or more stabilizers selected from the group comprising dextran 40, a combination of dextran 40 and sucrose, arginine or mixtures thereof.
An "anti- HER2 antibody" is a monoclonal antibody targeting HER2, inducing an immune- mediated response that causes internalization and recycling of HER2.
According to an embodiment, said buffering agent is selected from the group comprising histidine, phosphate, tris, acetate and citrate or mixtures thereof.
According to one embodiment of the invention, said buffering agent is L-histidine HCI.
According to preferred embodiment of the invention, wherein the L-histidine HCI is present in an amount of 3.36 mg/vial to about 9.9 mg/vial by weight in the total composition.
According to preferred embodiment of the invention, wherein the buffering agent provides a pH of 6.
According to one embodiment of the invention, said composition comprises one or more stabilizers which prevent denaturation and/or aggregation problems that may occur during the lyophilization stage of the antibody, thereby forming the stable formulation.
Examples of such stabilizers comprise at least one saccharide or a combination of saccharides, amino acids or a combination of amino acids and saccharides.
As used herein the term "saccharide" comprises the general composition (CH2O)n and derivatives thereof, including monosaccharides, disaccharides, trisaccharides, polysaccharides, sugar alcohols, reducing sugars, nonreducing sugars.
According to one embodiment of the invention, said saccharide is selected from the group comprising a,a-trehalose, melibiose, sucrose, mannitol, dextran 40 or mixtures thereof.
According to one embodiment of the invention, said amino acid is selected from the group comprising L-histidine, arginine, glycine, proline, asparagine or mixtures thereof.
According to one embodiment of the invention, said stabilizers are a,a-trehalose dihydrate, and L-histidine wherein the composition further comprises at least one or more stabilizers selected from the group comprising dextran 40, a combination of dextran 40 and sucrose, arginine or mixtures thereof.
According to one embodiment of the invention, said composition comprises a,a-trehalose, L- histidine and dextran 40 as stabilizers.
Dextran 40 is an excellent fast lyophilizable amorphous bulking agent. It has been observed that adding dextran 40 a further stabilizer to the composition in addition to a,a-trehalose and L-histidine surprisingly overcome the stability problems that may occur during the lyophilization stage.
Combined or single use of dextrans affects the glass transition temperature (Tg) of freeze- dried products. The use of dextran 40 in combination with disaccharides increases Tg during lyophilization and provides improved storage stability.
According to one embodiment of the invention, said composition comprises a,a-trehalose dihydrate, L-histidine and a mixture of dextran 40 and sucrose as stabilizers.
According to one embodiment of the invention, said composition comprises a,a-trehalose dihydrate, L-histidine and arginine as stabilizers.
It has been also observed that adding arginine as a further stabilizer to the composition in addition to a,a-trehalose and L-histidine surprisingly increases the stability of the antibody against protein aggregation. Also, using arginine as stabilizer makes freeze drying cycles faster and more efficient.
The stabilizers are generally added in amount(s) which protect and/or stabilize the monoclonal antibody at the lowest amount of stabilizer possible, to avoid increasing the viscosity of the final formulation.
According to preferred embodiment of the invention, the total amount of stabilizer is from about 1 to 500 mg/vial by weight in the total composition.
According to one embodiment of the invention, said nonionic surfactant is selected from the group comprising polysorbate 20, polysorbate 80, polyethylene glycol, poloxamer or mixtures thereof.
According to the preferred embodiment of the invention, said composition comprises polysorbate 20 as a nonionic surfactant. According to preferred embodiment of the invention, wherein the polysorbate 20 is present in an amount of 0,6 mg/vial to about 1 ,8 mg/vial by weight in the total composition.
According to one embodiment of the invention, said pharmaceutical composition comprises trastuzumab. According to one embodiment of the invention, wherein trastuzumab is present in an amount of 150 mg/vial to about 440 mg/vial by weight in the total composition.
According to preferred embodiment of the invention, said pharmaceutical composition is reconstituted with sterile water for injection and administered through intravenous.
The following non-limiting examples further illustrate the invention. Example 1 : The lyophilized powder pharmaceutical composition
Figure imgf000007_0001
Example 2: The lyophilized powder pharmaceutical composition
Figure imgf000007_0002
Example 3: The lyophilized powder pharmaceutical composition
Figure imgf000008_0001
Example 4: The lyophilized powder pharmaceutical composition
Figure imgf000008_0002
Example 5: The lyophilized powder pharmaceutical composition
Figure imgf000008_0003
Example 6: The lyophilized powder pharmaceutical composition
Figure imgf000009_0001

Claims

1. A lyophilized powder pharmaceutical composition, the composition comprising:
- an anti-HER2 antibody,
- a buffering agent,
- at least one stabilizer or a combination of two or more stabilizers,
- a nonionic surfactant,
- water for injection, wherein said stabilizers are a,a-trehalose dihydrate and L-histidine, wherein the composition further comprises at least one or more stabilizers selected from the group comprising dextran 40, a combination of dextran 40 and sucrose, arginine or mixtures thereof.
2. The lyophilized powder pharmaceutical composition according to claim 1, wherein the buffering agent is selected from the group comprising histidine, phosphate, tris, acetate and citrate or mixtures thereof.
3. The lyophilized powder pharmaceutical composition according to claim 2, wherein the buffering agent is L-histidine HCI.
4. The lyophilized powder pharmaceutical composition according to claim 3, wherein the L-histidine HCI is present in an amount of 3.36 mg/vial to about 9.9 mg/vial by weight in the total composition.
5. The lyophilized powder pharmaceutical composition according to claim 1, wherein the buffering agent provides a pH of 6.
6. The lyophilized powder pharmaceutical composition according to claim 1, wherein the total amount of stabilizer is 1-500 mg/vial by weight in the total composition.
7. The lyophilized powder pharmaceutical composition according to claim 1, wherein the nonionic surfactant is a polysorbate selected from the group consisting of polysorbate 20, polysorbate 80, polyethylene glycol, poloxamer or mixtures thereof.
8. The lyophilized powder pharmaceutical composition according to claim 7, wherein the nonionic surfactant is a polysorbate 20. The lyophilized powder pharmaceutical composition according to claim 8, wherein the polysorbate 20 is present in an amount of 0,6 mg/vial to about 1 ,8 mg/vial by weight in the total composition. The lyophilized powder pharmaceutical composition according to claim 1 , wherein said anti-HER2 antibody is trastuzumab. The lyophilized powder pharmaceutical composition according to claim 10, wherein trastuzumab is present in an amount of 150 mg/vial to about 440 mg/vial by weight in the total composition. The lyophilized powder pharmaceutical composition according to any one of the preceding claims, comprising;
- trastuzumab,
- L-histidine HCI,
- L-histidine,
- a,a-trehalose dihydrate
- dextran 40,
- polysorbate 20,
- water for injection. The lyophilized powder pharmaceutical composition according to any one of the preceding claims, comprising;
- trastuzumab,
- L-histidine HCI,
- L-histidine,
- a,a-trehalose dihydrate,
- dextran 40 and sucrose,
- polysorbate 20,
- water for injection. The lyophilized powder pharmaceutical composition according to any one of the preceding claims, comprising;
- trastuzumab,
- L-histidine HCI,
- L-histidine,
- a,a-trehalose dihydrate - arginine,
- polysorbate 20,
- water for injection.
15. The lyophilized powder pharmaceutical composition according to claim 1 , wherein the composition is administered through intravenous.
PCT/TR2022/050040 2022-01-19 2022-01-19 Pharmaceutical compositions of trastuzumab WO2023140807A1 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190046641A1 (en) * 2015-11-30 2019-02-14 Medimmune, Llc Optimized ratios of amino acids and sugars as amorphous stabilizing compounds in pharmaceutical compositions containing high concentrations of protein-based therapeutic agents
US20200061190A1 (en) * 2012-12-21 2020-02-27 Glenmark Pharmaceuticals S.A. Antibody formulation
US20200352857A1 (en) * 2017-04-28 2020-11-12 Amgen Inc. Excipients to reduce the viscosity of antibody formulations and formulation compositions

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200061190A1 (en) * 2012-12-21 2020-02-27 Glenmark Pharmaceuticals S.A. Antibody formulation
US20190046641A1 (en) * 2015-11-30 2019-02-14 Medimmune, Llc Optimized ratios of amino acids and sugars as amorphous stabilizing compounds in pharmaceutical compositions containing high concentrations of protein-based therapeutic agents
US20200352857A1 (en) * 2017-04-28 2020-11-12 Amgen Inc. Excipients to reduce the viscosity of antibody formulations and formulation compositions

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