WO2007149334A2 - Vegf antagonist formulations suitable for intravitreal administration - Google Patents
Vegf antagonist formulations suitable for intravitreal administration Download PDFInfo
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- WO2007149334A2 WO2007149334A2 PCT/US2007/014085 US2007014085W WO2007149334A2 WO 2007149334 A2 WO2007149334 A2 WO 2007149334A2 US 2007014085 W US2007014085 W US 2007014085W WO 2007149334 A2 WO2007149334 A2 WO 2007149334A2
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- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
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- A61K38/1793—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
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- 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
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- 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
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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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
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- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- C07—ORGANIC CHEMISTRY
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4705—Regulators; Modulating activity stimulating, promoting or activating activity
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K2319/00—Fusion polypeptide
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Definitions
- the present invention is directed to pharmaceutical formulations suitable for intravitreal administration comprising agents capable of inhibiting vascular endothelial growth factor (VEGF), and to methods for making and using such formulations.
- VEGF vascular endothelial growth factor
- the invention includes liquid pharmaceutical formulations having increased stability, as well as formulations that may be lyophilize and reconstituted for intravitreal administration.
- VEGF Vascular endothelial growth factor
- VEGF trap A soluble VEGF-specific fusion protein antagonist, termed a "VEGF trap" has been described (Kim et al. (2002) Proc. Natl. Acad. Sci. USA 99:11399-404; Holash et al. (2002)
- Ophthalmic formulations are known, see for example, U.S. 7,033,604 and 6,777,429.
- An ophthalmic formulation of a VEGF antibody is described in US 6,676,941.
- Lyophilization freeze drying under controlled conditions
- the lyophilized protein is substantially resistant to degradation, aggregation, oxidation, and other degenerative processes while in the freeze-dried state (see, for example, U.S. 6,436,897).
- Stable formulations of a VEGF-specific fusion protein antagonist are provided.
- Pharmaceutically acceptable formulations are provided that comprise a VEGF "trap" antagonist with a pharmaceutically acceptable carrier.
- liquid and lyophilized formulations are provided.
- a stable liquid ophthalmic formulation of a VEGF-specific fusion protein antagonist comprising a fusion protein that comprises a receptor component consisting essentially of an immunoglobulin-like (Ig) domain 2 of a first VEGF receptor and Ig domain 3 of a second VEGF receptor, and a multimerizing component (also termed a "VEGF trap").
- the first VEGF receptor is FIfI and the second VEGF receptor is FIkI or Flt4.
- the fusion protein has the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4.
- the VEGF antagonist is a dimer comprising two fusion proteins of SEQ ID NO:4.
- a stable liquid ophthalmic formulation comprises i-100 mg/ml VEG F-specific fusion protein antagonist, 0.01-5% of one or more organic co-solvent(s), 30-150 mM of one or more tonicity agent(s), 5-40 mM of a buffering agent, and optionally, 1.0- 7.5% of a stabilizing agent, pH between about 5.8-7.0.
- the organic co-solvent may be polysorbate, for example, polysorbate 20 or polysorbate 80, polyethylene glycol (PEG), for example, PEG 3350, or propylene glycol, or a combination thereof;
- the tonicity agent may be, for example, sodium chloride or potassium chloride;
- the stabilizing agent may be sucrose, sorbitol, glycerol, trehalose, or mannitol;
- the buffering agent may be, for example, phosphate buffer.
- the phosphate buffer is a sodium phosphate buffer.
- the organic co-solvent is polysorbate and/or PEG, the stabilizing agent is sucrose, the buffering agent is phosphate buffer, and the tonicity agent is sodium chloride.
- the stable liquid ophthalmic formulation comprises about 40-50 mg/ml of the VEGF antagonist (SEQ ID NO:4), about 10 mM phosphate buffer, 0.01-3% polysorbate and/or PEG, 40-135 mM sodium chloride, and optionally 5.0% sucrose, pH about 6.2-6.3.
- the stable liquid ophthalmic formulation comprises about 50 mg/ml of the VEGF antagonist (SEQ ID NO:4), 10 mM sodium phosphate buffer, 50 mM sodium chloride, 0.1% polysorbate, and 5% sucrose, pH about 6.2-6.3.
- the stable liquid ophthalmic formulation comprises about 50 mg/ml of the VEGF antagonist (SEQ ID NO:4), 10 mM sodium phosphate buffer, 50 mM sodium chloride, 3% PEG, and 5% sucrose, pH about 6.2-6.3.
- the stable liquid ophthalmic formulation comprises about 40 mg/ml of the VEGF antagonist (SEQ ID NO:4), 10 mM sodium phosphate buffer, 40 mM sodium chloride, 0.03% polysorbate, and 5% sucrose, pH about 6.2-6.3.
- the stable liquid ophthalmic formulation comprises about 40 mg/ml of the VEGF antagonist (SEQ ID NO:4), 10 mM sodium phosphate buffer, 135 mM sodium chloride, and 0.03% polysorbate, pH about 6.2-6.3.
- a stable liquid ophthalmic formulation comprises 1- 100 mg/ml VEGF-specific fusion protein antagonist; 0.01-5% of one or more organic co- solvents); 5-40 mM of a buffering agent; and optionally 30-150 mM of one or more tonicity agent(s) and/or 1.0-7.5% of a stabilizing agent; having a pH between about 5.8-7.0.
- the VEGF antagonist (SEQ ID NO:4) is present at a concentration of about 10 to about 80 mg/ml.
- the VEGF antagonist (SEQ ID NO:4) is present at a concentration of about 10, about 20, about 30, about 40, about 50, about 60, about 70, or about 80 mg/ml. In a preferred embodiment, the VEGF antagonist (SEQ ID NO:4) is present at a concentration of about 40 mg/ml.
- the stabilizing agent is selected from one or more of sucrose, sorbitol, glycerol, trehalose, and mannitol.
- the organic co-solvent is selected from one or more of polysorbate, for example, polysorbate 20 or polysorbate 80, polyethylene glycol (PEG), for example, PEG 3350, and propylene glycol.
- polysorbate for example, polysorbate 20 or polysorbate 80
- PEG polyethylene glycol
- propylene glycol for example, PEG 3350, and propylene glycol.
- the buffer is a phosphate buffer, for example, sodium phosphate.
- the tonicity agent is a salt, for example, sodium chloride.
- the stable liquid ophthalmic formulation comprises 10 mM sodium phosphate buffer, about 0.03 to about 0.1% polysorbate and/or about 3% PEG or propylene glycol, about 40 mM sodium chloride, and about 5% sucrose.
- the stable liquid ophthalmic formulation comprises 10 mM sodium phosphate buffer, about 0.03% polysorbate, about 40 mM sodium chloride, and about 5% sucrose.
- the pH of the formulation is about 6.2 to about 6.3.
- the pH is achieved by mixing mono- and dibasic sodium phosphate to the desired pH without acid/base titration.
- the stable liquid ophthalmic formulation consists essentially of a VEGF antagonist (SEQ ID NO:4) at 40 mg/ml, 10 mM sodium phosphate buffer, polysorbate at 0.03%, sodium chloride at 40 mM, and sucrose at 5%, pH 6.2-6.3.
- SEQ ID NO:4 VEGF antagonist
- a stable liquid ophthalmic formulation comprises about 10 to about 80 mg/ml VEGF antagonist, about 10 mM sodium phosphate buffer, about
- polysorbate 0.03% polysorbate, and about 135 mM sodium chloride, pH of 6.2 to 6.3.
- the VEGF antagonist (SEQ ID NO:4) is present at a concentration of about 10 to about 80 mg/ml. In various embodiments, the VEGF antagonist
- SEQ ID NO:4 is present at a concentration of about 10, about 20, about 30, about 40, about
- the VEGF antagonist is any compound that has a therapeutically active property.
- the VEGF antagonist is any compound that has a therapeutically active property.
- the VEGF antagonist is any compound that has a therapeutically active property.
- the VEGF antagonist is any compound that has a therapeutically active property.
- SEQ ID NO:4 is present at a concentration of about 40 mg/ml.
- the stable liquid ophthalmic formulation comprises 40 mg/ml of
- the stable liquid ophthalmic formulation consists essentially of 40 mg/ml of VEGF antagonist (SEQ ID NO:4), 10 mM sodium phosphate buffer, 0.03% polysorbate, and 135 mM sodium chloride at pH 6.2-6.3.
- a lyophilizable formulation of a VEGF antagonist is provided, wherein upon lyophilization followed by reconstitution, a stable liquid ophthalmic formulation as described herein is obtained.
- a lyophilizable formulation of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist comprising 5-50 mg/ml of the VEGF antagonist, 5-25 mM buffer, such as phosphate buffer, 0.01 to 0.15% of one or more of an organic co-solvent, such as polysorbate, propylene glycol and/or PEG, and optionally 1-10% of a stabilizing agent such as sucrose, sorbitol, trehalose, glycerol, or mannitol, pH about 5.8-7.0.
- the VEGF antagonist (SEQ ID NO:4) is present at about 5, about 10, about 20, about 30, or about 40 mg/ml.
- the lyophilizable ophthalmic formulation of the invention comprises 20 mg/ml of the VEGF antagonist, 10 mM sodium phosphate buffer, 0.03% polysorbate, 0.1 % PEG, and 2.5% sucrose, pH about 6.2-6.3.
- the lyophilizable formulation further comprises sodium chloride.
- the sodium chloride is present at a concentration of about 20 mM. In another specific embodiment, the sodium chloride is present at a concentration of about 67.5 mM.
- the lyophilizable ophthalmic formulation of the invention comprises 20 mg/ml of the VEGF antagonist, 5 mM sodium phosphate buffer, 0.015% polysorbate, 20 mM sodium chloride, and 2.5% sucrose, pH about 6.2-6.3.
- the lyophilizable ophthalmic formulation comprises 5 mg/ml, 10 mg/ml, or 40 mg/ml VEGF antagonist, 5 mM sodium phosphate buffer, 0.015% polysorbate, 20 mM sodium chloride, and 2.5% sucrose, at pH 6.2-6.3.
- the lyophilizable ophthalmic formulation consists essentially of 5 mg/ml, 10 mg/ml, or 40 mg/ml VEGF antagonist (SEQ ID NO:4), 5 mM sodium phosphate buffer, 0.015% polysorbate, 20 mM sodium chloride, and 2.5% sucrose, at pH 6.2-6.3.
- the lyophilizable ophthalmic formulation comprises 20 mg/ml of the VEGF antagonist, 5 mM sodium phosphate buffer, 0.015% polysorbate, and 67.5 mM sodium chloride, pH about 6.2-6.3.
- the lyophilizable ophthalmic formulation consists essentially of 20 mg/ml of the VEGF antagonist (SEQ ID NO:4), 5 mM sodium phosphate buffer, 0.015% polysorbate, and 67.5 mM sodium chloride, pH 6.2-6.3.
- the lyophilizable ophthalmic formulation comprises 5 mg/ml, 10 mg/ml, or 40 mg/ml VEGF antagonist, 5 mM sodium phosphate buffer, 0.015% polysorbate, and 67.5 mM sodium chloride, pH about 6.2-6.3.
- the lyophilizable ophthalmic formulation consists essentially of 5 mg/ml, 10 mg/ml, or 40 mg/ml VEGF antagonist (SEQ ID NO:4), 5 mM sodium phosphate buffer, 0.015% polysorbate, and 67.5 mM sodium chloride, pH about 6.2-6.3.
- the reconstituted formulation is about 2 times the concentration of the pre- lyophilized formulation, e.g., a 20 mg fusion protein/ml pre-lyophilized formulation is reconstituted to a final formulation of 40 mg fusion protein/ml.
- the lyophilized formulation is reconstituted with sterile water suitable for injection.
- the reconstitution liquid is bacteriostatic water.
- the invention features a method of producing a lyophilized formulation of a VEGF-specific fusion protein antagonist, comprising subjecting the lyophilizable formulation of the invention to lyophilization to generate a lyophilized formulation.
- the iyophilized formulation may be lyophilized by any method known in the art for lyophilizing a liquid.
- the invention features a method of producing a reconstituted lyophilized formulation of a VEGF antagonist, comprising reconstituting the lyophilized formulation of the invention to a reconstituted formulation.
- the reconstituted formulation is twice the concentration of the pre-lyophilized formulation, e.g., the method of the invention comprises: (a) producing a pre-lyophilized formulation of a VEGF-specific fusion protein antagonist, (b) subjecting the pre-lyophilized formulation of step (a) to lyophilization; and (c) reconstituting the lyophilized formulation of step (b).
- the invention further features ophthalmic formulations provided in a pre-filled syringe or vial, particularly suitable for intravitreal administration.
- lyophilization freeze-drying under controlled conditions
- the lyophilized protein is substantially resistant to degradation, aggregation, oxidation, and other degenerative processes while in the freeze-dried state.
- the lyophilized protein may be reconstituted with water optionally containing a bacteriostatic preservative (e.g., benzyl alcohol) prior to administration.
- a bacteriostatic preservative e.g., benzyl alcohol
- carrier includes a diluent, adjuvant, excipient, or vehicle with which a composition is administered.
- Carriers can include sterile liquids, such as, for example, water and oils, including oils of petroleum, animal, vegetable or synthetic origin, such as, for example, peanut oil, soybean oil, mineral oil, sesame oil and the like.
- excipient includes a non-therapeutic agent added to a pharmaceutical composition to provide a desired consistency or stabilizing effect.
- suitable pharmaceutical excipients include, for example, starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol mo ⁇ ostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like.
- lyophilized or “freeze-dried” includes a state of a substance that has been subjected to a drying procedure such as lyophilization, where at least 90% of moisture has been removed.
- a VEGF antagonist is a compound capable of blocking or inhibiting the biological action of vascular endothelial growth factor (VEGF), and includes fusion proteins capable of trapping VEGF.
- the VEGF antagonist is the fusion protein of SEQ ID NO:2 or 4; more preferably, SEQ ID NO:4.
- the VEGF antagonist is expressed in a mammalian cell line such as a CHO cell and may be modified post- translationally.
- the fusion protein comprises amino acids 27-457 of SEQ ID NO:4 and is glycosylated at Asn residues 62, 94, 149, 222 and 308.
- the VEGF antagonist is a dimer composed of two fusion proteins of SEQ ID NQ:4.
- the VEGF antagonist of the methods and formulations of the invention can be prepared by any suitable method known in the art, or that comes to be known.
- the VEGF antagonist is preferably substantially free of protein contaminants at the time it is used to prepare the pharmaceutically acceptable formulation.
- substantially free of protein contaminants is meant, preferably, that at least 90 % of the weight of protein of the VEGF-specific fusion protein antagonist preparation used for making a formulation is VEGF fusion protein antagonist protein, more preferably at least 95%, most preferably at least 99%.
- the fusion protein is preferably substantially free of aggregates.
- Substantially free of aggregates means that at least 90% of the weight of fusion protein is not present in an aggregate at the time the fusion protein is used to prepare the pharmaceutically effective formulation.
- the phosphates employed are sodium phosphates and a desired buffering pH is achieved by mixing appropriate amounts of mono- and dibasic sodium phosphate.
- the invention provides a stable pharmaceutically acceptable formulation comprising a VEGF antagonist, wherein the formulation is a liquid formulation suitable for ophthalmic use.
- the liquid formulation comprises a pharmaceutically effective amount of the VEGF antagonist.
- the formulation can also comprise one or more pharmaceutically acceptable carriers, buffers, tonicity agents, stabilizers, and/or excipients.
- An example of a pharmaceutically acceptable liquid formulation comprises a VEGF antagonist in a pharmaceutically effective amount, a buffer, an organic co-solvent such as polysorbate, a tonicity agent such as NaCi 1 and optionally, a stabilizer such as sucrose or trehalose.
- Stability is determined in a number of ways at specified time points, including determination of pH, visual inspection of color and appearance, determination of total protein content by methods known in the art, e.g., UV spectroscopy, and purity is determined by, for example, SDS-PAGE, size-exclusion HPLC, bioassay determination of activity, isoelectric focusing, and isoaspartate quantification.
- a bioassay useful for determining VEGF antagonist activity a BAF/3 VEGFR1/EPOR cell line is used to determine VEGF165 binding by the VEGF antagonist of the invention.
- Liquid formulations can be stored in an oxygen-deprived environment.
- Oxygen-deprived environments can be generated by storing the formulations under an inert gas such as, for example, nitrogen or argon.
- Liquid formulations are preferably stored at about 5°C.
- an ophthalmically acceptable formulation comprising a VEGF antagonist
- the formulation is a lyophilizable formulation.
- Lyophilizable formulations can be reconstituted into solutions, suspensions, emulsions, or any other suitable form for administration or use. Lyophilizable formulations are typically first prepared as liquids, then frozen and lyophilized. The total liquid volume before lyophilization can be less, equal to, or more than, the final reconstituted volume of the lyophilized formulation. The lyophilization process is well known to those of ordinary skill in the art, and typically includes sublimation of water from a frozen formulation under controlled conditions. [0051] Lyophilized formulations can be stored at a wide range of temperatures.
- Lyophilized formulations may be stored below 25°C, for example, refrigerated at 2-8°C, or at room temperature (e.g., approximately 25°C).
- lyophilized formulations are stored below about 25°C, more preferably, at about 4-20 0 C; below about 4°C; below about -20°C; about - 4O 0 C; about -70 0 C, or about -80 0 C.
- Stability of the lyophilized formulation may be determined in a number of ways known to the art, for example, by visual appearance of the cake and/or by moisture content.
- Lyophilized formulations are typically reconstituted for use by addition of an aqueous solution to dissolve the lyophilized formulation.
- aqueous solutions can be used to reconstitute a lyophilized formulation.
- lyophilized formulations are reconstituted using water.
- Lyophilized formulations are preferably reconstituted with a solution consisting essentially of water (e.g., USP WFI, or water for injection) or bacteriostatic water (e.g., USP WFI with 0.9% benzyl alcohol).
- solutions comprising buffers and/or excipients and/or one or more pharmaceutically acceptable carries can also be used.
- Freeze-dried or lyophilized formulations are typically prepared from liquids, that is, from solutions, suspensions, emulsions, and the like.
- the liquid that is to undergo freeze-drying or lyophilization preferably comprises all components desired in a final reconstituted liquid formulation.
- the freeze-dried or lyophilized formulation will render a desired liquid formulation upon reconstitution.
- Example 1 Stability of 50 mg/ml VEGF Trap Liquid Formulation Stored at 5° C in 3 ml Glass Vials.
- Example 2 Stability of 50 mg/ml VEGF Trap Liquid Formulation Stored at 5° C in 3 ml Glass Vials.
- Example 3 Stability of 40 mg/ml VEGF Trap Liquid Formulation Stored at 5° C in 3 ml Glass Vials.
- a liquid formulation containing 40 mg/ml VEGF Trap (SEQ ID NO:4), 10 mM phosphate, 40 mM NaCI, 0.03% poiysorbate 20, 5% sucrose, and pH 6.3, was stored at 5 0 C in 3 ml glass vials and samples tested at 0.5, 1, 2, 3, and 4 months. Stability results are shown in Table 3. Turbidity, percent recovered protein and purity was determined as described above. Table 3. Stability of 40 mg/ml VEGF Trap Protein (VGFT-SS207)
- Example 4 Stability of 40 mg/ml VEGF Trap Liquid Formulation Stored at 5° C in Pre-filled Glass Syringe.
- Example 5 Stability of 40 mg/ml VEGF Trap Liquid Formulation Stored at 5° C in 3 ml Glass Vials.
- Example 6 Stability of 40 mg/ml VEGF Trap Liquid Formulation Stored at 5 0 C in 1 ml Pre- filled Glass Syringe.
- Example 7 Stability of Lyophilized 20 mg/ml VEGF Trap Formulation Stored at 5° C in 3 ml Glass Vials and Reconstituted to 40 mg/ml.
- VEGF trap SEQ ID NO:4
- 5 mM phosphate 20 mM NaCI
- 0.015% polysorbate 20 0.015% polysorbate 20
- pH 6.3 0.015% polysorbate 20
- Samples were stored at 5°C and tested at 1, and 2 months.
- Example 8 Stability of Lyophilized 20 mg/ml VEGF Trap Formulation Stored at 5° C in 3 ml Glass Vials.
- VEGF trap SEQ ID NO:4
- 5 mM phosphate 5 mM phosphate
- 67.5 mM NaCI 0.015% polysorbate 20
- pH 6.3 pH 6.3
- Samples were stored at 5 0 C and tested at 1 , 2, and 3 months.
Abstract
Description
Claims
Priority Applications (14)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020087029933A KR101406811B1 (en) | 2006-06-16 | 2007-06-14 | Vegf antagonist formulations suitable for intravitreal administration |
AU2007261536A AU2007261536B2 (en) | 2006-06-16 | 2007-06-14 | VEGF antagonist formulations suitable for intravitreal administration |
EP20178021.0A EP3753548A1 (en) | 2006-06-16 | 2007-06-14 | Vegf antagonist formulations suitable for intravitreal administration |
PL15169936T PL2944306T3 (en) | 2006-06-16 | 2007-06-14 | Vegf antagonist formulations suitable for intravitreal administration |
MX2008016124A MX2008016124A (en) | 2006-06-16 | 2007-06-14 | Vegf antagonist formulations suitable for intravitreal administration. |
DK11157965.2T DK2364691T3 (en) | 2006-06-16 | 2007-06-14 | VEGF antagonist formulations that can be used for intravitreal administration |
EP07809593A EP2029103A2 (en) | 2006-06-16 | 2007-06-14 | Vegf antagonist formulations suitable for intravitreal administration |
BRPI0713749A BRPI0713749B8 (en) | 2006-06-16 | 2007-06-14 | liquid and non-liquid ophthalmic formulations of a vascular endothelial growth factor antagonist; and, pre-filled syringe suitable for intravitreal administration |
EP15169936.0A EP2944306B1 (en) | 2006-06-16 | 2007-06-14 | Vegf antagonist formulations suitable for intravitreal administration |
JP2009515517A JP5216002B2 (en) | 2006-06-16 | 2007-06-14 | VEGF antagonist preparation suitable for intravitreal administration |
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IL195788A IL195788A (en) | 2006-06-16 | 2008-12-08 | Ophthalmic formulation of vascular endothelial growth factor antagonist, a method of producing the same and syringe suitable for intravitreal administration comprising the same |
CY20211100247T CY1124265T1 (en) | 2006-06-16 | 2021-03-22 | VEGF ANTAGONIST PREPARATIONS SUITABLE FOR INTRAVENOUS ADMINISTRATION |
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US8795669B2 (en) | 2011-07-28 | 2014-08-05 | Regeneron Pharmaceuticals, Inc. | Stabilized formulations containing anti-PCSK9 antibodies |
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US9550837B2 (en) | 2008-12-15 | 2017-01-24 | Regeneron Pharmaceuticals, Inc. | Therapeutic uses of anti-PCSK9 antibodies |
US9561155B2 (en) | 2011-01-28 | 2017-02-07 | Sanofi Biotechnology | Method of reducing cholesterol levels using a human anti-PCSK9 antibody |
US9675692B2 (en) | 2012-05-31 | 2017-06-13 | Regeneron Pharmaceuticals, Inc. | Stabilized formulations containing anti-DLL4 antibodies |
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US9724411B2 (en) | 2008-12-15 | 2017-08-08 | Regeneron Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia and reducing LDL-C using antibodies to PCSK9 |
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WO2018011404A1 (en) * | 2016-07-15 | 2018-01-18 | Philogen S.P.A | Antibody compositions |
WO2018094316A1 (en) | 2016-11-21 | 2018-05-24 | Just Biotherapeutics, Inc. | Aflibercept formulations and uses thereof |
US10076571B2 (en) | 2011-09-16 | 2018-09-18 | Regeneron Pharmaceuticals, Inc. | Methods for reducing lipoprotein(a) levels by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
US10111953B2 (en) | 2013-05-30 | 2018-10-30 | Regeneron Pharmaceuticals, Inc. | Methods for reducing remnant cholesterol and other lipoprotein fractions by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
WO2018199408A1 (en) | 2017-04-26 | 2018-11-01 | Sam Chun Dang Pharm. Co., Ltd. | Ophthalmic pharmaceutical composition |
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US20190117767A1 (en) * | 2014-11-25 | 2019-04-25 | Regeneron Pharmaceuticals, Inc. | Methods and formulations for treating vascular eye diseases |
WO2019099965A1 (en) | 2017-11-20 | 2019-05-23 | Just Biotherapeutics, Inc. | Aflibercept formulations containing a lysine salt as tonicifying agent and uses thereof |
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US10428157B2 (en) | 2013-11-12 | 2019-10-01 | Sanofi Biotechnology | Dosing regimens for use with PCSK9 inhibitors |
WO2019217927A1 (en) * | 2018-05-10 | 2019-11-14 | Regeneron Pharmaceuticals, Inc. | High concentration vegf receptor fusion protein containing formulations |
US10494442B2 (en) | 2013-06-07 | 2019-12-03 | Sanofi Biotechnology | Methods for inhibiting atherosclerosis by administering an inhibitor of PCSK9 |
US10501523B2 (en) | 2014-07-18 | 2019-12-10 | Sanofi | IL-8 level based method of predicting the outcome of colon cancer treatment |
US20200022917A1 (en) * | 2015-12-16 | 2020-01-23 | Regeneron Pharmaceuticals, Inc. | Compositions and methods of manufacturing protein microparticles |
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US10772956B2 (en) | 2015-08-18 | 2020-09-15 | Regeneron Pharmaceuticals, Inc. | Methods for reducing or eliminating the need for lipoprotein apheresis in patients with hyperlipidemia by administering alirocumab |
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US11273171B2 (en) | 2013-07-12 | 2022-03-15 | Iveric Bio, Inc. | Methods for treating or preventing ophthalmological conditions |
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US20130323242A1 (en) * | 2012-06-01 | 2013-12-05 | Ophthotech Corp. | Compositions comprising an anti-pdgf aptamer and a vegf antagonist |
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US10093978B2 (en) | 2013-08-12 | 2018-10-09 | Genentech, Inc. | Compositions for detecting complement factor H (CFH) and complement factor I (CFI) polymorphisms |
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US10179821B2 (en) | 2014-05-01 | 2019-01-15 | Genentech, Inc. | Anti-factor D antibodies |
US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
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US20180207293A1 (en) * | 2017-01-25 | 2018-07-26 | 2C Tech Corp. | Nanoparticles for sustained ophthalmic drug delivery and methods of use |
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AU2018385394A1 (en) | 2017-12-13 | 2020-07-23 | Regeneron Pharmaceuticals, Inc. | Devices and systems for chromatography column bed support management and related methods |
WO2019195386A1 (en) * | 2018-04-05 | 2019-10-10 | Tarveda Therapeutics, Inc. | Pharmaceutical compositions with reduced tert-butanol levels |
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WO2020087003A1 (en) | 2018-10-26 | 2020-04-30 | Amgen Inc. | Formulations comprising a tris buffer and a protein |
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WO2021050687A1 (en) | 2019-09-10 | 2021-03-18 | Coherus Biosciences, Inc. | Stable aqueous formulations of aflibercept |
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JP2023526013A (en) | 2020-05-11 | 2023-06-20 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | Viral clearance by low pH retention |
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EP4262757A1 (en) | 2020-12-17 | 2023-10-25 | Regeneron Pharmaceuticals, Inc. | Fabrication of protein-encapsulating microgels |
WO2023153535A1 (en) * | 2022-02-09 | 2023-08-17 | 삼천당제약주식회사 | Syringe containing ophthalmic formulation |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6436897B2 (en) | 1998-06-01 | 2002-08-20 | Celtrix Pharmaceuticals, Inc. | Pharmaceutical formulations for IGF/IGFBP |
US6676941B2 (en) | 1999-04-28 | 2004-01-13 | Board Of Regents, The University Of Texas System | Antibody conjugate formulations for selectively inhibiting VEGF |
US6777429B1 (en) | 1999-07-23 | 2004-08-17 | Novartis Ag | Ophthalmic composition |
WO2005020972A2 (en) | 2003-08-27 | 2005-03-10 | (Osi) Eyetech, Inc. | Combination therapy for the treatment of ocular neovascular disorders |
US7033604B2 (en) | 2001-07-06 | 2006-04-25 | Sucampo Ag | Composition for topical administration |
WO2006047325A1 (en) | 2004-10-21 | 2006-05-04 | Genentech, Inc. | Method for treating intraocular neovascular diseases |
WO2006104852A2 (en) | 2005-03-25 | 2006-10-05 | Regeneron Pharmaceuticals, Inc. | Vegf antagonist formulations |
Family Cites Families (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1046492A (en) | 1907-11-14 | 1912-12-10 | Walter Chisholm Ranson | Flushing apparatus. |
AU2309692A (en) | 1991-07-03 | 1993-02-11 | Cryolife, Inc. | Method for stabilization of biomaterials |
AU670793B2 (en) | 1992-04-30 | 1996-08-01 | Alpha Therapeutic Corporation | Improved solubilization and stabilization of factor VIII complex |
US6177401B1 (en) | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
GB9410534D0 (en) | 1994-05-26 | 1994-07-13 | Lynxvale Ltd | Improvements in or relating to growth factor inhibitors |
US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
ES2434840T3 (en) | 1995-07-27 | 2013-12-17 | Genentech, Inc. | Formulation of stable isotonic lyophilized protein |
JPH09154588A (en) | 1995-10-07 | 1997-06-17 | Toagosei Co Ltd | Vegf-binding polypeptide |
US6100071A (en) | 1996-05-07 | 2000-08-08 | Genentech, Inc. | Receptors as novel inhibitors of vascular endothelial growth factor activity and processes for their production |
US5763401A (en) | 1996-07-12 | 1998-06-09 | Bayer Corporation | Stabilized albumin-free recombinant factor VIII preparation having a low sugar content |
US7312196B2 (en) | 1997-01-08 | 2007-12-25 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
JPH10273450A (en) * | 1997-03-27 | 1998-10-13 | Toagosei Co Ltd | Therapeutic agent for intraocular neovascular disease |
WO1998045331A2 (en) | 1997-04-07 | 1998-10-15 | Genentech, Inc. | Anti-vegf antibodies |
US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
JPH1180024A (en) | 1997-09-12 | 1999-03-23 | Toagosei Co Ltd | Corneal vascular rebirth inhibitor |
US6472179B2 (en) | 1998-09-25 | 2002-10-29 | Regeneron Pharmaceuticals, Inc. | Receptor based antagonists and methods of making and using |
HU228898B1 (en) | 1999-04-16 | 2013-06-28 | Genentech Inc | Vascular endothelial cell growth factor variants and uses thereof |
US7087411B2 (en) | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
RS50073B (en) | 1999-06-08 | 2009-01-22 | Regeneron Pharmaceuticals I.N.C., | Modified chimeric polypeptides with improved pharmacokinetic properties |
US6833349B2 (en) | 1999-06-08 | 2004-12-21 | Regeneron Pharmaceuticals, Inc. | Methods of treating inflammatory skin diseases |
US7396664B2 (en) | 1999-06-08 | 2008-07-08 | Regeneron Pharmaceuticals, Inc. | VEGF-binding fusion proteins and nucleic acids encoding the same |
US7070959B1 (en) | 1999-06-08 | 2006-07-04 | Regeneron Pharmaceuticals, Inc. | Modified chimeric polypeptides with improved pharmacokinetic properties |
US7001892B1 (en) | 1999-06-11 | 2006-02-21 | Purdue Research Foundation | Pharmaceutical materials and methods for their preparation and use |
CA2423227C (en) | 2000-10-12 | 2011-11-29 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
JP4317010B2 (en) | 2001-07-25 | 2009-08-19 | ピーディーエル バイオファーマ,インコーポレイティド | Stable lyophilized pharmaceutical formulation of IgG antibody |
CN1292655C (en) | 2001-11-08 | 2007-01-03 | 蛋白质设计实验室股份有限公司 | Stable liquid pharmaceutical formulation of IgG antibodies |
GEP20063755B (en) * | 2001-11-09 | 2006-02-27 | Eyetech Pharmaceuticals | Use of VEGF Inhibiting Agents for Treating Ocular Neovascular Diseases |
AU2003219958B2 (en) | 2002-02-27 | 2006-01-05 | Immunex Corporation | Polypeptide formulation |
ATE354592T1 (en) | 2003-03-28 | 2007-03-15 | Regeneron Pharma | VEGF ANTAGONISTS FOR TREATING DIABETES |
KR101208291B1 (en) | 2003-04-04 | 2012-12-05 | 노파르티스 아게 | High concentration antibody and protein formulations |
US20040266688A1 (en) | 2003-05-14 | 2004-12-30 | Nayak Nihar R | Methods for modulating endometrium |
CA2519835A1 (en) | 2003-05-28 | 2004-12-09 | Regeneron Pharmaceuticals, Inc. | Method of treating corneal transplant rejection |
WO2004110490A2 (en) | 2003-06-06 | 2004-12-23 | Regeneron Pharmaceuticals, Inc. | Use of vegf inhibitors for tumor regression |
AR046510A1 (en) * | 2003-07-25 | 2005-12-14 | Regeneron Pharma | COMPOSITION OF A VEGF ANTAGONIST AND AN ANTI-PROLIFERATIVE AGENT |
WO2005016369A1 (en) | 2003-08-06 | 2005-02-24 | Regeneron Pharmaceuticals, Inc. | Use of a vegf antagonist in combination with radiation therapy |
WO2005072772A1 (en) | 2004-01-30 | 2005-08-11 | Suomen Punainen Risti Veripalvelu | Pharmaceutical compositions |
WO2005087808A2 (en) | 2004-03-05 | 2005-09-22 | Ludwig Institute For Cancer Research | Growth factor binding constructs materials and methods |
WO2005102303A2 (en) | 2004-04-21 | 2005-11-03 | Advanced Ocular Systems Limited | Antiprostaglandins for the treatment of ocular pathologies |
CN100361710C (en) | 2004-06-07 | 2008-01-16 | 成都康弘生物科技有限公司 | Construction and application of oncolytic adenovirus recombinant of tumor cell specifically expressing immunoregulation factor GM-CSF |
CA2569108C (en) | 2004-06-08 | 2012-08-21 | Chengdu Kanghong Biotechnologies Co. Ltd | Angiogenesis-inhibiting chimeric protein and the use |
CN1304427C (en) | 2004-06-08 | 2007-03-14 | 成都康弘生物科技有限公司 | Angiogenesis inhibiting fusion protein and its use |
WO2005123104A2 (en) | 2004-06-10 | 2005-12-29 | Regeneron Pharmaceuticals, Inc. | Use of vegf inhibitors for the treatment of human cancer |
JP2008503481A (en) | 2004-06-18 | 2008-02-07 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | Methods of administration and use of VEGF inhibitors for the treatment of malignant pleural effusion |
CN1997386B (en) | 2004-07-30 | 2012-05-30 | 瑞泽恩制药公司 | Methods of treating type I diabetes by blocking VEGF-mediated activity |
US7303748B2 (en) | 2005-02-02 | 2007-12-04 | Regeneron Pharmaceuticals, Inc. | Method of treating eye injury with local administration of a VEGF inhibitor |
KR20080031684A (en) | 2005-06-14 | 2008-04-10 | 암젠 인코포레이티드 | Self-buffering protein formulations |
CN100567325C (en) | 2006-03-31 | 2009-12-09 | 成都康弘生物科技有限公司 | Vegf receptor fusion rotein and the application in the medicine of preparation treatment disease of eye thereof |
CN100502945C (en) | 2006-03-31 | 2009-06-24 | 成都康弘生物科技有限公司 | Application of fusion protein of VEGF receptor for treating disease of eye |
US8216575B2 (en) | 2006-03-31 | 2012-07-10 | Chengdu Kanghong Biotechnologies Co., Ltd. | Inhibition of neovascularization with a soluble chimeric protein comprising VEGF FLT-1 and KDR domains |
LT2944306T (en) | 2006-06-16 | 2021-02-25 | Regeneron Pharmaceuticals, Inc. | Vegf antagonist formulations suitable for intravitreal administration |
CN102233132B (en) | 2010-04-28 | 2013-10-23 | 成都康弘生物科技有限公司 | Application of VEGF acceptor fusion proteins in preparation of drugs for inhibiting growth of ocular surface neovascularization |
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CN107115294B (en) | 2012-01-19 | 2019-10-18 | 北京康弘生物医药有限公司 | A kind of eye drops containing VEGF antagonist |
JOP20200175A1 (en) | 2012-07-03 | 2017-06-16 | Novartis Ag | Syringe |
RU2634406C1 (en) | 2014-01-25 | 2017-10-26 | Чэнду Канхун Байотекнолоджиз Ко., Лтд. | Fused protein, inhibiting angiogenesis or growth of vessels, and its application |
US20160144025A1 (en) | 2014-11-25 | 2016-05-26 | Regeneron Pharmaceuticals, Inc. | Methods and formulations for treating vascular eye diseases |
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Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6436897B2 (en) | 1998-06-01 | 2002-08-20 | Celtrix Pharmaceuticals, Inc. | Pharmaceutical formulations for IGF/IGFBP |
US6676941B2 (en) | 1999-04-28 | 2004-01-13 | Board Of Regents, The University Of Texas System | Antibody conjugate formulations for selectively inhibiting VEGF |
US6777429B1 (en) | 1999-07-23 | 2004-08-17 | Novartis Ag | Ophthalmic composition |
US7033604B2 (en) | 2001-07-06 | 2006-04-25 | Sucampo Ag | Composition for topical administration |
WO2005020972A2 (en) | 2003-08-27 | 2005-03-10 | (Osi) Eyetech, Inc. | Combination therapy for the treatment of ocular neovascular disorders |
WO2006047325A1 (en) | 2004-10-21 | 2006-05-04 | Genentech, Inc. | Method for treating intraocular neovascular diseases |
WO2006104852A2 (en) | 2005-03-25 | 2006-10-05 | Regeneron Pharmaceuticals, Inc. | Vegf antagonist formulations |
Non-Patent Citations (3)
Title |
---|
GERBER ET AL., CANCER RES., vol. 60, 2000, pages 6253 - 6258 |
HOLASH ET AL., PROC. NATL. ACAD. SCI. USA, vol. 99, 2002, pages 11393 - 8 |
KIM ET AL., PROC. NATL. ACAD. SCI. USA, vol. 99, 2002, pages 11399 - 404 |
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