JP5376573B2 - Vegfアンタゴニスト製剤 - Google Patents
Vegfアンタゴニスト製剤 Download PDFInfo
- Publication number
- JP5376573B2 JP5376573B2 JP2008503191A JP2008503191A JP5376573B2 JP 5376573 B2 JP5376573 B2 JP 5376573B2 JP 2008503191 A JP2008503191 A JP 2008503191A JP 2008503191 A JP2008503191 A JP 2008503191A JP 5376573 B2 JP5376573 B2 JP 5376573B2
- Authority
- JP
- Japan
- Prior art keywords
- formulation
- vegf
- fusion protein
- lyophilized
- sucrose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7012—Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/179—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- 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
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- 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
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2318/00—Antibody mimetics or scaffolds
- C07K2318/20—Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics
-
- C—CHEMISTRY; METALLURGY
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Toxicology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Description
本発明は、血管内皮増殖因子(VEGF)を阻害することが可能な物質を含む薬学的製剤、およびそのような製剤を作製し使用するための方法を対象とする。本発明は、増大した安定性を有する薬学的製剤を含む。
血管内皮増殖因子(VEGF)発現は、腫瘍血管新生の重要な媒介物質としてのその役割と一致して、ヒト癌においてほぼ遍在する。VEGF機能の遮断は、分子またはそのVEGFR-2受容体への結合によって、複数の異なる異種移植モデルにおいて移植された腫瘍細胞の増殖を阻害する(例えばGerber et al. (2000) Cancer Res. 60:6253-6258を参照されたい)。可溶性VEGF特異的融合タンパク質アンタゴニストは、「VEGFトラップ」と称して記載されている(Kim et al. (2002) Proc. Natl. Acad. Sci. USA 99:11399-404; Holash et al. (2002) Proc. Natl. Acad. Sci. USA 99:11393-8)。
VEGF特異的融合タンパク質アンタゴニストの安定な製剤が、本明細書において提供される。本発明の薬学的に許容される製剤は、VEGF「トラップ」アンタゴニストを薬学的に許容される担体と共に含む。特定の態様において、液体製剤およびフリーズドライ製剤、または凍結乾燥製剤が提供される。
本発明は、特定の方法および記載した実験条件に限定されず、そのような方法および条件は変化してもよい。また、本発明の範囲は添付の特許請求の範囲によってのみ限定されるため、本明細書で使用される専門用語は、単に特定の態様を説明することを目的とし、指示しない限り限定することを意図したものではないことが理解されるべきである。
タンパク質を含む製剤の安全な取り扱いおよび投与は、薬学的に製剤化する人にとって大きな挑戦を意味する。タンパク質は、安定性の問題を示す固有の化学的および物理的特性を備えている:タンパク質毎に様々な分解経路が存在し、それは化学的および物理的不安定性の両方を意味する。化学的不安定性は、脱アミノ化、凝集、ペプチド主鎖のクリッピング、およびメチオニン残基の酸化を含む。物理的不安定性は、例えば凝集を含む多くの現象を包含する。
「担体」という用語は、それを用いて組成物を投与する、希釈剤、アジュバント、付形剤、または賦形剤を含む。担体は、例えば水、および例えばピーナッツオイル、大豆油、鉱油、ゴマ油などの石油、動物起源、植物起源、もしくは合成起源の油を含む油のような、滅菌した液体を含むことができる。
VEGFアンタゴニストは、血管内皮増殖因子(VEGF)の生物作用をブロックするかまたは阻害することが可能な化合物であり、かつVEGFをトラップすることが可能な融合タンパク質を含む。好ましい態様において、VEGFアンタゴニストはSEQ ID NO:2または4、より好ましくはSEQ ID NO:4の融合タンパク質である。特定の態様において、VEGFアンタゴニストはCHO細胞のような哺乳動物細胞株において発現し、かつ翻訳後に修飾され得る。特定の態様において、融合タンパク質はSEQ ID NO:4のアミノ酸27〜457を含み、かつAsn残基62、94、149、222、および308でグリコシル化される。
本発明の一つの局面において、VEGF特異的融合タンパク質アンタゴニストを含む薬学的に許容される製剤が提供され、製剤はフリーズドライまたは凍結乾燥製剤である。凍結乾燥製剤は、溶液、懸濁液、乳濁液、または投与もしくは使用に適した任意の他の形状へと再組成することができる。凍結乾燥製剤は典型的に、まず液体として調製し、次いで凍結して凍結乾燥する。凍結乾燥前の総液体容量は、凍結乾燥製剤の最終的な再組成容量より少ないか、それに等しいか、またはそれを上回ることが可能である。凍結乾燥プロセスは当業者に周知であり、典型的に、管理された条件下で凍結した製剤から水を昇華することを含む。
一つの局面において、本発明は、VEGF特異的融合タンパク質アンタゴニストを含む安定な薬学的に許容される製剤を提供し、製剤は液体製剤である。好ましくは、液体製剤は薬学的有効量の融合タンパク質を含む。製剤は1つまたは複数の薬学的に許容される担体、緩衝液、充填剤、安定剤、保存剤、および/または付形剤もまた含むことができる。薬学的に許容される液体製剤の例には、薬学的有効量のVEGF特異的融合タンパク質アンタゴニスト、緩衝液、共溶媒、および1つまたは複数の安定剤が含まれる。
本発明の方法を記載する前に、本発明は、記載する特定の方法および実験条件に限定されるものではなく、方法および実験は変更できることが理解されるべきである。本発明の範囲は添付の特許請求の範囲にのみ限定されることから、本明細書で使用される専門用語は、単に特定の態様を説明することを目的としており、限定することを意図しないこともまた理解されるべきである。
10 mM リン酸塩、50 mM NaCl、0.1%ポリソルベート20、20%スクロース、および50 mg/ml VEGFトラップ(SEQ ID NO:4)を含む、pH 6.25の液体製剤を5℃で保管し、試料は3、6、9、12、18、および24ヶ月で試験した。安定性をSE-HPLCによって測定した。表1に示した結果は、12および24ヶ月で、それぞれ98.6%および98.3%のVEGFトラップタンパク質が無傷で(分解されずに)残っていることを示す。濁度はOD405 nmで測定し;サイズ排除HPLCにより、回収したタンパク質の割合を測定した。
10 mM リン酸塩、50 mM NaCl、0.1%ポリソルベート20、20%スクロース、および75 mg/ml VEGFトラップ(SEQ ID NO:4)を含む、pH 6.25の液体製剤を5℃で保管し、試料は0、1、2.3、3、9、12、および15ヶ月で試験した。安定性の結果を表3に示す。
10 mM リン酸塩、50 mM NaCl、0.1%ポリソルベート20、20%スクロース、および100 mg/ml VEGFトラップ(SEQ ID NO:4)を含む、pH 6.25の液体製剤を5℃で保管し、試料は0、1、2.3、3、9、12、および15ヶ月で試験した。安定性の結果を表5に示す。
一つの態様において、本発明は、5 mMリン酸塩、5 mMクエン酸塩、100 mM NaCl、0.1%ポリソルベート20、20%スクロース、25 mg/mlのVEGFトラップタンパク質を含む、pH6.0の安定な液体VEGF結合融合タンパク質(VEGFトラップ)製剤を提供する。製剤は、皮下に送達するか、または希釈して、静脈内注入により送達するかのいずれかが可能である。本製剤の高い重量オスモル濃度のため、製剤を3倍に希釈して、静脈内投与のための等浸透圧溶液を達成する。安定性の研究は、2〜8℃で3年間保管した後、約1%を下回る分解が検出されたことを示した。
再組成した凍結乾燥製剤の安定性は、6ヵ月の期間にわたって測定された。凍結乾燥前の製剤は、10 mMヒスチジン、1.5%PEG 3350、2.5%スクロース、0.75%グリシン、および50 mg/mlVEGFトラップタンパク質を含んだ。凍結乾燥後、再組成した製剤は、20 mMヒスチジン、3%PEG 3350、5%スクロース、1.5%グリシン、および100 mg/ml VEGFトラップタンパク質(SEQ ID NO:4)を含んだ。結果を表8に示す。活性は、マウスBaf/3 VEGFR1/EpoR細胞株に対するヒトVEGFの生物学的効果を阻害するVEGFトラップの能力を直接測定する、細胞に基づくバイオアッセイにおいて測定した。したがって、本バイオアッセイは、タンパク質の生物活性を直接測定する。結果は、相対効力の割合として表す(試験試料IC50/参照VEGF IC50標準×100)。VEGFトラップへのVEGFの結合親和性は、VEGFおよび様々な濃度のVEGFトラップを含む平衡混合物中の遊離VEGFを特異的に測定する高感度ELISAを用いて測定する。結果は、相対結合の割合として表す(試験試料のIC50/参照のIC50×100)。測定したpHは、6.3〜6.5の範囲であった。全ての溶液は、視覚的に透明であった。回収したVEGFトラップの濃度は、紫外分光光度計によりmg/mlとしてA280 nmで測定した。天然の立体構造における回収したVEGFトラップの割合(主要ピーク純度)を、SE-HPLCによって測定した。
Claims (2)
- pH6.0で、5 mMリン酸緩衝液、5 mMクエン酸緩衝液、100 mM NaCl、20%スクロース、0.1%ポリソルベート20および25 mg/mlのSEQ ID NO:4の27〜457位のアミノ酸配列からなる融合タンパク質である血管内皮増殖因子(VEGF)特異的アンタゴニストを含み、2〜8℃の保存において、該融合タンパク質が少なくとも75%の生物活性を保持する、安定な液体製剤:
ここで、該融合タンパク質の生物活性は、マウスBaf/3 VEGFR1/EpoR細胞株に対するヒトVEGFの生物学的効果を阻害する該融合タンパク質の能力を測定することにより決定される。 - 5℃の保存において、該融合タンパク質が少なくとも75%の生物活性を保持する、請求項1記載の安定な液体製剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US66512505P | 2005-03-25 | 2005-03-25 | |
US60/665,125 | 2005-03-25 | ||
PCT/US2006/010600 WO2006104852A2 (en) | 2005-03-25 | 2006-03-22 | Vegf antagonist formulations |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012282406A Division JP5752671B2 (ja) | 2005-03-25 | 2012-12-26 | Vegfアンタゴニスト製剤 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2008535819A JP2008535819A (ja) | 2008-09-04 |
JP2008535819A5 JP2008535819A5 (ja) | 2013-02-21 |
JP5376573B2 true JP5376573B2 (ja) | 2013-12-25 |
Family
ID=36678320
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008503191A Active JP5376573B2 (ja) | 2005-03-25 | 2006-03-22 | Vegfアンタゴニスト製剤 |
JP2012282406A Active JP5752671B2 (ja) | 2005-03-25 | 2012-12-26 | Vegfアンタゴニスト製剤 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012282406A Active JP5752671B2 (ja) | 2005-03-25 | 2012-12-26 | Vegfアンタゴニスト製剤 |
Country Status (20)
Country | Link |
---|---|
US (16) | US20060217311A1 (ja) |
EP (3) | EP1861116B1 (ja) |
JP (2) | JP5376573B2 (ja) |
KR (1) | KR101327270B1 (ja) |
CN (2) | CN101141975B (ja) |
AU (1) | AU2006229930C1 (ja) |
CA (3) | CA2995971A1 (ja) |
CY (2) | CY1116980T1 (ja) |
DK (2) | DK2586459T3 (ja) |
ES (2) | ES2548238T3 (ja) |
HK (1) | HK1116050A1 (ja) |
HU (2) | HUE027096T2 (ja) |
IL (2) | IL185606A (ja) |
LT (1) | LT2586459T (ja) |
NZ (1) | NZ560713A (ja) |
PL (2) | PL1861116T3 (ja) |
PT (2) | PT1861116E (ja) |
SI (2) | SI1861116T1 (ja) |
WO (1) | WO2006104852A2 (ja) |
ZA (1) | ZA200708845B (ja) |
Families Citing this family (48)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7655758B2 (en) | 2004-08-17 | 2010-02-02 | Regeneron Pharmaceuticals, Inc. | Stable liquid IL-1 antagonist formulations |
US7572893B2 (en) * | 2004-08-17 | 2009-08-11 | Regeneron Pharmaceuticals, Inc. | IL-1 antagonist formulations |
US20060217311A1 (en) | 2005-03-25 | 2006-09-28 | Daniel Dix | VEGF antagonist formulations |
CA2654510C (en) | 2006-06-16 | 2015-03-17 | Regeneron Pharmaceuticals, Inc. | Vegf antagonist formulations suitable for intravitreal administration |
WO2009058564A2 (en) | 2007-11-01 | 2009-05-07 | Maxygen, Inc. | Immunosuppressive polypeptides and nucleic acids |
JP5954990B2 (ja) * | 2008-11-03 | 2016-07-20 | モレキュラー・パートナーズ・アーゲーMolecular Partners Ag | Vegf−aレセプター相互作用を阻害する結合タンパク質 |
MX366337B (es) | 2010-10-06 | 2019-07-05 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-receptor de interleucina-4 (il-4r). |
CN102552875B (zh) * | 2010-12-09 | 2015-05-20 | 上海国健生物技术研究院 | 一种双功能vegf受体融合蛋白制剂 |
SG191334A1 (en) | 2011-01-13 | 2013-08-30 | Regeneron Pharma | Use of a vegf antagonist to treat angiogenic eye disorders |
US10864158B2 (en) * | 2011-04-14 | 2020-12-15 | The Regents Of The University Of California | Multilayer thin film drug delivery device and methods of making and using the same |
JO3283B1 (ar) | 2011-04-26 | 2018-09-16 | Sanofi Sa | تركيب يتضمن أفليبيرسيبت, حمض فولينيك, 5- فلورويوراسيل (5- Fu) وإرينوسيتان (FOLFIRI) |
DK2790681T4 (da) | 2011-11-18 | 2023-05-01 | Regeneron Pharma | Fremgangsmåde til fremstilling af en farmaceutisk formulering med langvarig frigivelse omfattende polymercoatede proteinmikropartikler ved anvendelse af spraytørring |
NZ627859A (en) | 2012-01-23 | 2015-09-25 | Regeneron Pharma | Stabilized formulations containing anti-ang2 antibodies |
NZ730271A (en) * | 2012-03-16 | 2022-09-30 | Regeneron Pharma | Non-human animals expressing ph-sensitive immunoglobulin sequences |
AR092325A1 (es) * | 2012-05-31 | 2015-04-15 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-dll4 y kit |
WO2014006113A1 (en) | 2012-07-03 | 2014-01-09 | Sanofi | Method of treating cancer by effective amounts of aflibercept |
WO2014020160A1 (en) * | 2012-08-02 | 2014-02-06 | Sanofi | Article of manufacture comprising aflibercept or ziv-aflibercept |
UA115789C2 (uk) | 2012-09-05 | 2017-12-26 | Трейкон Фармасутікалз, Інк. | Композиція антитіла до cd105 та її застосування |
CN103110105A (zh) * | 2012-11-14 | 2013-05-22 | 江苏江山制药有限公司 | 食品添加剂无糖维生素c钠盐颗粒的生产方法 |
US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
TR201909951T4 (tr) | 2014-07-18 | 2019-07-22 | Sanofi Sa | Kanser olduğundan şüphelenilen bir hastanın aflibersept ile tedavisinin sonucunun öngörülmesine yönelik yöntem. |
CN105435222B (zh) | 2014-09-25 | 2018-05-29 | 信达生物制药(苏州)有限公司 | 重组融合蛋白制剂 |
CN104940926B (zh) * | 2014-09-25 | 2017-09-22 | 信达生物制药(苏州)有限公司 | 重组融合蛋白制剂 |
JP6781508B2 (ja) * | 2014-11-18 | 2020-11-04 | 塩野義製薬株式会社 | 安定化されたペプチド組成物 |
WO2016120753A1 (en) | 2015-01-28 | 2016-08-04 | Pfizer Inc. | Stable aqueous anti- vascular endothelial growth factor (vegf) antibody formulation |
KR101808234B1 (ko) | 2015-06-23 | 2017-12-12 | (주)알테오젠 | IgG Fc 도메인을 가지는 융합 단백질의 안정한 액상 제제 |
SI3384049T1 (sl) | 2015-12-03 | 2023-10-30 | Regeneron Pharmaceuticals, Inc. | Postopki povezovanja genetskih različic s kliničnim izidom pri bolnikih s starostno degeneracijo makule, zdravljenih s proti-VEGF |
AU2016381964B2 (en) | 2015-12-30 | 2024-02-15 | Kodiak Sciences Inc. | Antibodies and conjugates thereof |
AU2017213103B2 (en) | 2016-01-26 | 2022-08-11 | Formycon Ag | Liquid formulation of a VEGF antagonist |
KR101685532B1 (ko) * | 2016-04-26 | 2016-12-13 | 한국프라임제약주식회사 | 혈관내피성장인자 수용체 융합단백질 |
IL310367A (en) | 2016-10-07 | 2024-03-01 | Regeneron Pharma | A stable protein at room temperature that has been lyophilized |
WO2018094316A1 (en) | 2016-11-21 | 2018-05-24 | Just Biotherapeutics, Inc. | Aflibercept formulations and uses thereof |
USD849856S1 (en) | 2017-06-28 | 2019-05-28 | Jumpsport, Inc. | Standing platform |
WO2019019998A1 (zh) * | 2017-07-25 | 2019-01-31 | 江苏恒瑞医药股份有限公司 | 一种il-15蛋白复合物药物组合物及其用途 |
WO2019020777A1 (en) | 2017-07-26 | 2019-01-31 | Formycon Ag | LIQUID FORMULATION OF A VEGF ANTAGONIST |
EP3713591A1 (en) | 2017-11-20 | 2020-09-30 | Just-Evotec Biologics, Inc. | Aflibercept formulations containing a lysine salt as tonicifying agent and uses thereof |
KR102494021B1 (ko) * | 2017-12-22 | 2023-02-06 | 삼성바이오에피스 주식회사 | Vegf 길항제를 포함하는 액상 조성물 |
KR20200112893A (ko) | 2018-01-26 | 2020-10-05 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 항-vegf 제제를 사용한 혈관신생 장애의 치료 방법 및 조성물 |
US11426446B2 (en) | 2018-03-08 | 2022-08-30 | Coherus Biosciences, Inc. | Stable aqueous formulations of aflibercept |
US11667702B2 (en) | 2018-03-08 | 2023-06-06 | Coherus Biosciences, Inc. | Stable aqueous formulations of aflibercept |
CN108671229B (zh) * | 2018-05-08 | 2022-03-25 | 华博生物医药技术(上海)有限公司 | 一种重组人血管内皮生长因子受体-抗体融合蛋白的药物组合制剂 |
JOP20200275A1 (ar) * | 2018-05-10 | 2020-11-02 | Regeneron Pharma | صيغ تحتوي على بروتين اندماج لمستقبلvegf مرتفعة التركيز |
US11519020B2 (en) | 2018-05-25 | 2022-12-06 | Regeneron Pharmaceuticals, Inc. | Methods of associating genetic variants with a clinical outcome in patients suffering from age-related macular degeneration treated with anti-VEGF |
WO2021050687A1 (en) | 2019-09-10 | 2021-03-18 | Coherus Biosciences, Inc. | Stable aqueous formulations of aflibercept |
JP2022553640A (ja) | 2019-10-10 | 2022-12-26 | コディアック サイエンシーズ インコーポレイテッド | 眼障害を処置する方法 |
JP2023502501A (ja) | 2019-11-25 | 2023-01-24 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 眼内血管新生のための長時間作用型vegf阻害剤 |
PE20221770A1 (es) | 2019-12-06 | 2022-11-11 | Regeneron Pharma | Composiciones de proteina anti-vegf y metodos para producir la misma |
KR102337471B1 (ko) * | 2019-12-23 | 2021-12-09 | 한국프라임제약주식회사 | 혈관내피성장인자 수용체 융합단백질을 포함하는 약제학적 제형 |
Family Cites Families (61)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2309692A (en) | 1991-07-03 | 1993-02-11 | Cryolife, Inc. | Method for stabilization of biomaterials |
WO1993022336A1 (en) * | 1992-04-30 | 1993-11-11 | 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 |
US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
PT1516628E (pt) * | 1995-07-27 | 2013-09-24 | Genentech Inc | Formulação de proteína liofilizada isotónica estável |
JPH09154588A (ja) * | 1995-10-07 | 1997-06-17 | Toagosei Co Ltd | Vegf結合性ポリペプチド |
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 (ja) | 1997-03-27 | 1998-10-13 | Toagosei Co Ltd | 眼内血管新生性疾患治療薬 |
ES2273415T3 (es) | 1997-04-07 | 2007-05-01 | Genentech, Inc. | Anticuerpos anti-vegf. |
US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
JPH1180024A (ja) | 1997-09-12 | 1999-03-23 | Toagosei Co Ltd | 角膜血管新生阻害剤 |
US6436897B2 (en) * | 1998-06-01 | 2002-08-20 | Celtrix Pharmaceuticals, Inc. | Pharmaceutical formulations for IGF/IGFBP |
US6472179B2 (en) * | 1998-09-25 | 2002-10-29 | Regeneron Pharmaceuticals, Inc. | Receptor based antagonists and methods of making and using |
ES2265931T3 (es) | 1999-04-16 | 2007-03-01 | Genentech, Inc. | Variantes del factor de crecimiento celular endotelial vascular (vegf) y sus usos. |
BR0010017A (pt) | 1999-04-28 | 2002-06-11 | Univ Texas | Composições e processos para o tratamento de câncer por inibição seletiva de vegf |
US7070959B1 (en) | 1999-06-08 | 2006-07-04 | Regeneron Pharmaceuticals, Inc. | Modified chimeric polypeptides with improved pharmacokinetic properties |
US6833349B2 (en) | 1999-06-08 | 2004-12-21 | Regeneron Pharmaceuticals, Inc. | Methods of treating inflammatory skin diseases |
NZ515913A (en) | 1999-06-08 | 2004-01-30 | Regeneron Pharma | Modified chimeric polypeptides with improved pharmacokinetic properties |
US7396664B2 (en) * | 1999-06-08 | 2008-07-08 | Regeneron Pharmaceuticals, Inc. | VEGF-binding fusion proteins and nucleic acids encoding the same |
US7087411B2 (en) | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
US7001892B1 (en) * | 1999-06-11 | 2006-02-21 | Purdue Research Foundation | Pharmaceutical materials and methods for their preparation and use |
WO2002030463A2 (en) * | 2000-10-12 | 2002-04-18 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
ATE454137T1 (de) * | 2001-07-25 | 2010-01-15 | Facet Biotech Corp | Stabile lyophilisierte pharmazeutische formulierung des igg-antikörpers daclizumab |
KR100913714B1 (ko) | 2001-11-08 | 2009-08-24 | 패시트 바이오테크 코포레이션 | Igg 항체의 안정한 액상 약학 제형물 |
WO2003072060A2 (en) | 2002-02-27 | 2003-09-04 | Immunex Corporation | Polypeptide formulation |
EP1608685B1 (en) * | 2003-03-28 | 2007-02-21 | Regeneron Pharmaceuticals, Inc. | Vegf antagonists for the treatment of diabetes |
EP1610820B2 (en) * | 2003-04-04 | 2013-08-21 | Genentech, Inc. | High concentration antibody and protein formulations |
US20040266688A1 (en) | 2003-05-14 | 2004-12-30 | Nayak Nihar R | Methods for modulating endometrium |
EP1626989A2 (en) | 2003-05-28 | 2006-02-22 | Regeneron Pharmaceuticals, Inc. | Method of treating corneal transplant rejection by using vegf antagonists |
CA2519875C (en) | 2003-06-06 | 2014-01-14 | Regeneron Pharmaceuticals, Inc. | Method of tumor regression with vegf inhibitors |
ITMI20031261A1 (it) | 2003-06-20 | 2004-12-21 | Messersi Packaging Srl | Macchina reggiatrice con gruppo perfezionato di movimentazione della reggia. |
AR046510A1 (es) | 2003-07-25 | 2005-12-14 | Regeneron Pharma | Composicion de un antagonista de vegf y un agente anti-proliferativo |
WO2005016369A1 (en) | 2003-08-06 | 2005-02-24 | Regeneron Pharmaceuticals, Inc. | Use of a vegf antagonist in combination with radiation therapy |
DK1660057T3 (da) | 2003-08-27 | 2012-08-20 | Ophthotech Corp | Kombinationsterapi til behandling af neovaskulære øjenlidelser |
WO2005072772A1 (en) * | 2004-01-30 | 2005-08-11 | Suomen Punainen Risti Veripalvelu | Pharmaceutical compositions |
DE602005027673D1 (de) | 2004-03-05 | 2011-06-09 | Vegenics Pty Ltd | Materialien und verfahren für wachstumsfaktorbindende konstrukte |
EP1740168A2 (en) | 2004-04-21 | 2007-01-10 | Advanced Ocular Systems Limited | Antiprostaglandins for the treatment of ocular pathologies |
CN100361710C (zh) | 2004-06-07 | 2008-01-16 | 成都康弘生物科技有限公司 | 肿瘤细胞专一表达免疫调节因子gm-csf的溶瘤性腺病毒重组体的构建及其应用 |
CN1304427C (zh) | 2004-06-08 | 2007-03-14 | 成都康弘生物科技有限公司 | 抑制血管新生的融合蛋白质及其用途 |
WO2005121176A1 (fr) | 2004-06-08 | 2005-12-22 | Chengdu Kanghong Biotechnologies Co. Ltd | Proteine chimerique inhibitrice d'angiogenese et utilisation associee |
EP1753442A2 (en) | 2004-06-10 | 2007-02-21 | Regeneron Pharmaceuticals, Inc. | Method of administering and using vegf inhibitors for the treatment of human cancer |
AU2005265071A1 (en) | 2004-06-18 | 2006-01-26 | Memorial Sloan-Kettering Cancer Center | VEGF inhibitors for the treatment of malignant pleural effusion |
CN1997386B (zh) | 2004-07-30 | 2012-05-30 | 瑞泽恩制药公司 | 通过阻断vegf介导的活性来治疗i型糖尿病的方法 |
NZ596663A (en) | 2004-10-21 | 2013-07-26 | Genentech Inc | Use of vegf antagonists in intraocular neovascular disease treatment |
WO2006088650A2 (en) * | 2005-02-02 | 2006-08-24 | Regeneron Pharmaceuticals, Inc. | Method of treating eye injury with local administration of a vegf inhibitor |
US20060217311A1 (en) | 2005-03-25 | 2006-09-28 | Daniel Dix | VEGF antagonist formulations |
SG162788A1 (en) | 2005-06-14 | 2010-07-29 | Amgen Inc | Self-buffering protein formulations |
CN100502945C (zh) | 2006-03-31 | 2009-06-24 | 成都康弘生物科技有限公司 | Vegf受体融合蛋白在治疗眼睛疾病中的应用 |
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 |
CN100567325C (zh) | 2006-03-31 | 2009-12-09 | 成都康弘生物科技有限公司 | Vegf受体融合蛋白及其在制备治疗眼睛疾病的药物中的应用 |
CA2654510C (en) | 2006-06-16 | 2015-03-17 | Regeneron Pharmaceuticals, Inc. | Vegf antagonist formulations suitable for intravitreal administration |
CN102233132B (zh) | 2010-04-28 | 2013-10-23 | 成都康弘生物科技有限公司 | Vegf受体融合蛋白在制备抑制眼表新生血管生长的药物中的应用 |
CN102380096B (zh) | 2010-08-31 | 2014-04-30 | 成都康弘生物科技有限公司 | 一种含有抑制血管增生的融合蛋白的药物组合物及用途 |
CN103212075B (zh) | 2012-01-19 | 2017-06-27 | 成都康弘生物科技有限公司 | 一种含有vegf拮抗剂的滴眼液 |
JOP20200175A1 (ar) | 2012-07-03 | 2017-06-16 | Novartis Ag | حقنة |
RU2634406C1 (ru) | 2014-01-25 | 2017-10-26 | Чэнду Канхун Байотекнолоджиз Ко., Лтд. | Слитый белок, ингибирующий ангиогенез или рост сосудов, и его применение |
US20160144025A1 (en) | 2014-11-25 | 2016-05-26 | Regeneron Pharmaceuticals, Inc. | Methods and formulations for treating vascular eye diseases |
-
2006
- 2006-03-22 US US11/387,256 patent/US20060217311A1/en not_active Abandoned
- 2006-03-22 CA CA2995971A patent/CA2995971A1/en active Pending
- 2006-03-22 WO PCT/US2006/010600 patent/WO2006104852A2/en active Application Filing
- 2006-03-22 AU AU2006229930A patent/AU2006229930C1/en active Active
- 2006-03-22 LT LTEP13152402.7T patent/LT2586459T/lt unknown
- 2006-03-22 PT PT67485946T patent/PT1861116E/pt unknown
- 2006-03-22 ES ES06748594.6T patent/ES2548238T3/es active Active
- 2006-03-22 SI SI200631996T patent/SI1861116T1/sl unknown
- 2006-03-22 SI SI200632195T patent/SI2586459T1/sl unknown
- 2006-03-22 CA CA2598711A patent/CA2598711C/en active Active
- 2006-03-22 EP EP06748594.6A patent/EP1861116B1/en active Active
- 2006-03-22 CN CN2006800085696A patent/CN101141975B/zh active Active
- 2006-03-22 EP EP17159239.7A patent/EP3195874A1/en not_active Ceased
- 2006-03-22 PL PL06748594T patent/PL1861116T3/pl unknown
- 2006-03-22 HU HUE06748594A patent/HUE027096T2/en unknown
- 2006-03-22 PT PT131524027T patent/PT2586459T/pt unknown
- 2006-03-22 ES ES13152402.7T patent/ES2633574T3/es active Active
- 2006-03-22 DK DK13152402.7T patent/DK2586459T3/en active
- 2006-03-22 EP EP13152402.7A patent/EP2586459B1/en active Active
- 2006-03-22 CN CN201210090068.4A patent/CN102614134B/zh active Active
- 2006-03-22 JP JP2008503191A patent/JP5376573B2/ja active Active
- 2006-03-22 PL PL13152402T patent/PL2586459T3/pl unknown
- 2006-03-22 CA CA3142945A patent/CA3142945A1/en active Pending
- 2006-03-22 DK DK06748594.6T patent/DK1861116T3/en active
- 2006-03-22 ZA ZA200708845A patent/ZA200708845B/xx unknown
- 2006-03-22 NZ NZ560713A patent/NZ560713A/en unknown
- 2006-03-22 HU HUE13152402A patent/HUE034109T2/en unknown
- 2006-03-22 KR KR1020077024202A patent/KR101327270B1/ko active IP Right Grant
-
2007
- 2007-08-30 IL IL185606A patent/IL185606A/en active IP Right Grant
-
2008
- 2008-05-16 HK HK08105425.6A patent/HK1116050A1/xx unknown
-
2010
- 2010-07-13 US US12/835,065 patent/US8110546B2/en active Active
-
2012
- 2012-01-04 US US13/343,214 patent/US8404638B2/en active Active
- 2012-03-23 US US13/428,510 patent/US8710004B2/en active Active
- 2012-12-26 JP JP2012282406A patent/JP5752671B2/ja active Active
-
2013
- 2013-06-04 US US13/909,745 patent/US8921316B2/en active Active
- 2013-06-27 IL IL227215A patent/IL227215A/en active IP Right Grant
-
2014
- 2014-11-21 US US14/550,385 patent/US9416167B2/en active Active
-
2015
- 2015-11-26 CY CY20151101068T patent/CY1116980T1/el unknown
-
2016
- 2016-03-08 US US15/064,343 patent/US9511140B2/en active Active
- 2016-05-10 US US15/150,840 patent/US9636400B2/en active Active
- 2016-11-03 US US15/342,989 patent/US20170073407A1/en not_active Abandoned
-
2017
- 2017-08-02 CY CY20171100827T patent/CY1119243T1/el unknown
- 2017-08-31 US US15/692,893 patent/US10406226B2/en active Active
-
2019
- 2019-08-08 US US16/535,610 patent/US10857231B2/en active Active
-
2020
- 2020-11-17 US US16/950,584 patent/US11806398B2/en active Active
-
2021
- 2021-05-04 US US17/307,240 patent/US20210252147A1/en not_active Abandoned
- 2021-05-05 US US17/308,801 patent/US20210252105A1/en active Pending
- 2021-05-06 US US17/313,627 patent/US20210393778A1/en active Pending
- 2021-05-07 US US17/314,992 patent/US20210393530A1/en active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5376573B2 (ja) | Vegfアンタゴニスト製剤 | |
US8802107B2 (en) | VEGF antagonist formulations for intravitreal administration |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090319 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110908 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20111205 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20111212 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120307 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120905 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121226 |
|
A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20121226 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130125 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20130218 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130306 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130530 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130606 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130918 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130919 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5376573 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R153 | Grant of patent term extension |
Free format text: JAPANESE INTERMEDIATE CODE: R153 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |