WO2003007988A1 - Flüssige formulierung enthaltend cetuximab und einen polyoxyethylensorbitanfettsäureester - Google Patents
Flüssige formulierung enthaltend cetuximab und einen polyoxyethylensorbitanfettsäureester Download PDFInfo
- Publication number
- WO2003007988A1 WO2003007988A1 PCT/EP2002/006696 EP0206696W WO03007988A1 WO 2003007988 A1 WO2003007988 A1 WO 2003007988A1 EP 0206696 W EP0206696 W EP 0206696W WO 03007988 A1 WO03007988 A1 WO 03007988A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cetuximab
- solution
- polyoxyethylene
- liquid pharmaceutical
- pharmaceutical formulation
- Prior art date
Links
Classifications
-
- 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
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
Definitions
- the present invention relates to a stable liquid pharmaceutical formulation comprising the chimeric monoclonal antibody C225 (cetuximab ®) against the receptor of epidermal growth factor
- Cetuximab ® is a promising antibody that binds to the EGF receptor. Cetuximab ® and C225 is recombined different species from the DNA, and was first described by Naramura et al. (Cancer Immunol Immunotherapy 37, 343-349, 1993). With regard to the production of Cetuximab ® referenced called scientific literature.
- Cetuximab ® is administered parenterally as a solution for therapeutic use.
- a particular problem with antibody solutions is their tendency to aggregate and form protein multimers. In the case of reducible multimers, this may be due to unintended intermolecular disulfide bridge formation through an interaction between approaching moieties. Also suitable are hydrophobic interactions and the associated formation of non-reducible multimers. Furthermore, there are deamidation reactions, which subsequently lead to protein degradation reactions. As a result of the mentioned tendency to aggregation, product precipitations occur during storage of antibody solutions, so that a reproducible removal from the container containing the solution is called into question. In addition, parenteral administration of particle-containing solution can lead to embolisms. As a result, a reproducible
- a common method for stabilizing monoclonal antibodies is the freeze-drying of solutions containing antibodies as well as excipients.
- lyophilization is very time and energy consuming and therefore expensive.
- the lyophilisate must first be reconstituted before administration.
- EP 0 073 371 describes intravenously administrable compositions containing immunoglobulins which have a pH of from 3.5 to 5.0 for stabilization. However, such low pH values lead to undesirable incompatibility reactions at the injection site.
- US 6,171,586 B1 discloses the use of an acetate buffer pH 4.48 to 5.5, a surfactant and a polyol in a liquid formulation of antibodies, excluding NaCl for isotonization. Due to the low pH value as well as the lack of isotonization, incompatibility reactions at the injection site can also occur.
- EP 0 280 358, EP 0 170 983 and US Pat. No. 5,945,098 may be mentioned at this point.
- EP 0 280 358 describes the addition of dextran to a
- Antibody solution for stabilization against certain hormones achieving stability over nine months.
- EP 0 170 983 describes the stabilization of a thermolabile monoclonal antibody by heating together with hydrolyzed
- Ovalbumin whereby the antibody after 7 days of storage at 45 ° C was still stable.
- the addition of proteins of other species to administrable formulations intended for parenteral administration is undesirable because of the problems involved, in particular their possible antigenicity.
- US 5,945,098 discloses the use of glycine, polysorbate 80 and polyethylene glycol to stabilize a liquid formulation of immunoglobulin G.
- cetuximab ® suitable for parenteral administration, fluid formulation that is well tolerated and when stored at room temperature over a year is at least stable.
- the formulation should have a simple structure and contain no toxicologically harmful excipients.
- cetuximab ® contains a phosphate buffer in the range of approximately pH 6 to approximately pH 8 and a polyoxyethylene sorbitan fatty acid ester.
- the subject of the present invention is therefore a stable liquid pharmaceutical composition containing a phosphate buffer in the range of pH 6 to pH 8 and a polyoxyethylene sorbitan fatty acid ester.
- the pH is in the range of 6.5 to 7.5, more preferably a pH of about 7.2.
- Suitable phosphate buffers are solutions of mono- and / or di-
- phosphate buffer can in the formulation of the invention in a
- Concentration range from 2 mM to 100 mM. Preferred is a concentration range of 5 mM to 20 mM, more preferably about 10 mM.
- Cetuximab ® can in the formulation of the invention in a
- 2 mg / ml to 10 mg / ml, more preferably about 5 mg / ml are included.
- polyethylene sorbitan fatty acid esters are also known under the trademark Tween.
- Polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monopalmitate, and polyoxyethylene (20) sorbitan monostearate are particularly useful in the formulation of this invention.
- Polyoxyethylene (20) sorbitan monolaurate and polyoxyethylene (20) sorbitan monooleate are preferred, of which polyoxyethylene (20) sorbitan monooleate is particularly preferred.
- Polyethylene sorbitan fatty acid esters may be included in the formulation in a concentration of 0.001% to 1.0%. Preferably, 0.005% to 0.1%, more preferably about 0.01% are included.
- the formulation according to the invention additionally contains a
- Isotonizing agent preferably a physiologically acceptable salt, such as sodium chloride or potassium chloride, or a physiological compatible polyol, such as glucose or glycerol, in a concentration required for isotonization.
- the invention is therefore a liquid formulation comprising Cetuximab ®, a phosphate buffer in the range of approximately pH 6 to approximately pH 8, a polyoxyethylene sorbitan fatty acid ester and an isotonizing agent in a concentration necessary for establishing isotonicity.
- the formulation contains sodium chloride as an isotonizing agent.
- the liquid formulation of approximately 5mg / ml Cetuximab ® contains about 10 mM
- Phosphate buffer with a pH of about 7.2, about 145 mM sodium chloride and about 0.01% polyoxyethylene (20) sorbitan monooleate Phosphate buffer with a pH of about 7.2, about 145 mM sodium chloride and about 0.01% polyoxyethylene (20) sorbitan monooleate.
- the formulation of the invention can be prepared by a cetuximab ® solution containing the ingredients listed are added. Conveniently, this is a solution with a defined concentration of cetuximab ®, as it is obtained in its preparation, mixed with defined volumes of stock solutions containing the said further ingredients in defined concentration and and optionally diluted with water to the pre-calculated concentration. Alternatively, the ingredients of the cetuximab ® containing feed solution may also be added as solids. Is cetuximab ® as a solid, for example as a lyophilisate, the formulation of the invention can be prepared by cetuximab ® one or more of the further first in water or an
- one or more of the ingredients contained in the inventive formulation are already during or added at the end of the manufacturing process of cetuximab ®.
- this can be done by using Cetuximab ®, several or all further ingredients containing aqueous solution is dissolved in the last step of carried out after its preparation purification directly in a one.
- the respective further ingredient (s) need only be added in a lesser amount and / or not at all to prepare the formulation. It is particularly preferred if, in the last step of the purification carried out after its preparation, the particular ingredient is dissolved directly in an aqueous solution containing all further ingredients, so that the formulation according to the invention is obtained directly.
- the preparation was carried out by mixing defined volumes of the respective ingredients in a defined concentration containing aqueous
- Solution A drug solution containing:
- Solution B (buffer / salt solution): corresponds to solution A, but contains no active ingredient.
- Solution C polyoxyethylene sorbitan fatty acid ester solution: corresponds to solution B, but additionally contains 1% by weight of polyoxyethylene (20) sorbitan monooleate.
- the prepared solution was filtered with a sterile filter before filling.
- the vials were filled with a pipette with 2 ml solution each.
- Example 2 (comparative formulation) Aqueous solution containing:
- Example 3 To prepare the comparative formulation, 10 ml each of the solutions A and B described in Example 1 were combined with each other.
- the preparation was carried out by mixing defined volumes of the respective ingredients in a defined concentration containing aqueous solutions.
- the following solutions were used:
- Solution B polyoxyethylene sorbitan fatty acid ester glucose solution
- Example 1 and for comparison purposes vials containing solution according to Example 2 stored at 40 ° C and 75% relative humidity. Prior to storage and after defined storage periods, 3 vials were assessed visually by direct irradiation with a cold light source and the absorption of the solutions at 350 and 550 nm was determined, which represents a measure of the turbidity. Furthermore, 3 vials were each removed and analyzed for the content of cetuximab ® and decomposition products by HPLC-gel filtration examined.
- phosphate buffer pH 7.2 was used as a flow agent.
Abstract
Description
Claims
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002453342A CA2453342A1 (en) | 2001-07-13 | 2002-06-18 | Liquid formulation comprising cetuximab and a fatty acid ester of polyoxyethylene sorbitan |
KR10-2004-7000530A KR20040018458A (ko) | 2001-07-13 | 2002-06-18 | Cetuximab 및 폴리옥시에틸렌 소르비탄 지방산에스테르를 포함하는 액형 제제 |
HU0401046A HUP0401046A3 (en) | 2001-07-13 | 2002-06-18 | Liquid formulation comprising cetuximab and a fatty acid ester of polyoxyethylene sorbitan |
JP2003513593A JP2004536129A (ja) | 2001-07-13 | 2002-06-18 | セツキシマブおよびポリオキシエチレンソルビタン脂肪酸エステルを含む液体製剤 |
SK86-2004A SK862004A3 (en) | 2001-07-13 | 2002-06-18 | Liquid formulation comprising cetuximab and a fatty acid ester of polyoxyethylene sorbitan |
MXPA04000340A MXPA04000340A (es) | 2001-07-13 | 2002-06-18 | FORMULACION LIQUIDA QUE COMPRENDE CETUXIMAB Y eSTER DE aCIDO GRASO DE POLIOXIETILEN SORBITaN. |
US10/483,404 US20040170632A1 (en) | 2001-07-13 | 2002-06-18 | Liquid formulation comprising cetuximab and a fatty acid ester of polyoxyethylene sorbitan |
PL02364599A PL364599A1 (en) | 2001-07-13 | 2002-06-18 | Liquid formulation comprising cetuximab and a fatty acid ester of polyoxyethylene sorbitan |
BR0211060-1A BR0211060A (pt) | 2001-07-13 | 2002-06-18 | Formulação lìquida compreendendo cetuximab e um éster de ácido graxo de polioxietileno sorbitano |
EP02751038A EP1406658A1 (de) | 2001-07-13 | 2002-06-18 | Flüssige formulierung enthaltend cetuximab und einen polyoxyethylensorbitan-fettsäureester |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10133394A DE10133394A1 (de) | 2001-07-13 | 2001-07-13 | Flüssige Formulierung enthaltend Cetuximab |
DE10133394.3 | 2001-07-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2003007988A1 true WO2003007988A1 (de) | 2003-01-30 |
Family
ID=7691220
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2002/006696 WO2003007988A1 (de) | 2001-07-13 | 2002-06-18 | Flüssige formulierung enthaltend cetuximab und einen polyoxyethylensorbitanfettsäureester |
Country Status (18)
Country | Link |
---|---|
US (1) | US20040170632A1 (de) |
EP (1) | EP1406658A1 (de) |
JP (1) | JP2004536129A (de) |
KR (1) | KR20040018458A (de) |
CN (1) | CN1231264C (de) |
AR (1) | AR039358A1 (de) |
BR (1) | BR0211060A (de) |
CA (1) | CA2453342A1 (de) |
CZ (1) | CZ2004189A3 (de) |
DE (1) | DE10133394A1 (de) |
HU (1) | HUP0401046A3 (de) |
MX (1) | MXPA04000340A (de) |
PE (1) | PE20030433A1 (de) |
PL (1) | PL364599A1 (de) |
RU (1) | RU2004102395A (de) |
SK (1) | SK862004A3 (de) |
WO (1) | WO2003007988A1 (de) |
ZA (1) | ZA200401161B (de) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005051355A1 (de) * | 2003-11-29 | 2005-06-09 | Merck Patent Gmbh | Feste formen von anti-egfr-antikörpern |
WO2005077414A1 (de) * | 2004-02-12 | 2005-08-25 | Merck Patent Gmbh | Hochkonzentrierte, flüssige formulierungen von anti-egfr-antikörpern |
JP2006517233A (ja) * | 2003-02-10 | 2006-07-20 | エラン ファーマシューティカルズ,インコーポレイテッド | 免疫グロブリン製剤およびその調製の方法 |
WO2007128557A1 (en) | 2006-05-03 | 2007-11-15 | Bayer Schering Pharma Aktiengesellschaft | Combination of an anti edb fibronectin domain antibody l19-sip and an anti-egfr antibody |
JP2008519757A (ja) * | 2004-11-12 | 2008-06-12 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 抗egfr抗体の固形物 |
CN1886158B (zh) * | 2003-11-26 | 2011-09-07 | 默克专利有限公司 | 包含抗egf受体抗体的药物制剂 |
US8263631B2 (en) | 2006-02-09 | 2012-09-11 | Daiichi Sankyo Company, Limited | Anti-cancer pharmaceutical compositions and methods for treating patients with cancer |
US11738068B2 (en) | 2018-06-25 | 2023-08-29 | Jcr Pharmaceuticals Co., Ltd. | Protein-containing aqueous liquid formulation |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005113018A2 (en) * | 2004-04-27 | 2005-12-01 | Wellstat Biologics Corporation | Cancer treatment using viruses and camptothecins |
ES2362898T3 (es) * | 2005-02-28 | 2011-07-14 | EISAI R&D MANAGEMENT CO., LTD. | Nuevo uso combinado de un compuesto de sulfonamina en el tratamiento de cáncer. |
WO2008045373A2 (en) * | 2006-10-06 | 2008-04-17 | Amgen Inc. | Stable antibody formulations |
AU2007309616B2 (en) * | 2006-10-20 | 2011-10-06 | Amgen Inc. | Stable polypeptide formulations |
CN107773755B (zh) * | 2016-08-31 | 2021-06-22 | 上海津曼特生物科技有限公司 | 抗表皮生长因子受体单克隆抗体的注射液制剂 |
CA3063324A1 (en) | 2017-05-16 | 2018-11-22 | Bhami's Research Laboratory, Pvt. Ltd. | High concentration protein formulations with reduced viscosity |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996040210A1 (en) * | 1995-06-07 | 1996-12-19 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth of tumors |
WO1997004801A1 (en) * | 1995-07-27 | 1997-02-13 | Genentech, Inc. | Stabile isotonic lyophilized protein formulation |
US5945098A (en) * | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU4128089A (en) * | 1988-09-15 | 1990-03-22 | Rorer International (Overseas) Inc. | Monoclonal antibodies specific to human epidermal growth factor receptor and therapeutic methods employing same |
US7060808B1 (en) * | 1995-06-07 | 2006-06-13 | Imclone Systems Incorporated | Humanized anti-EGF receptor monoclonal antibody |
-
2001
- 2001-07-13 DE DE10133394A patent/DE10133394A1/de not_active Withdrawn
-
2002
- 2002-06-18 MX MXPA04000340A patent/MXPA04000340A/es unknown
- 2002-06-18 CN CNB028141059A patent/CN1231264C/zh not_active Expired - Fee Related
- 2002-06-18 US US10/483,404 patent/US20040170632A1/en not_active Abandoned
- 2002-06-18 HU HU0401046A patent/HUP0401046A3/hu unknown
- 2002-06-18 SK SK86-2004A patent/SK862004A3/sk not_active Application Discontinuation
- 2002-06-18 CA CA002453342A patent/CA2453342A1/en not_active Abandoned
- 2002-06-18 CZ CZ2004189A patent/CZ2004189A3/cs unknown
- 2002-06-18 BR BR0211060-1A patent/BR0211060A/pt not_active IP Right Cessation
- 2002-06-18 EP EP02751038A patent/EP1406658A1/de not_active Withdrawn
- 2002-06-18 RU RU2004102395/15A patent/RU2004102395A/ru not_active Application Discontinuation
- 2002-06-18 JP JP2003513593A patent/JP2004536129A/ja not_active Withdrawn
- 2002-06-18 PL PL02364599A patent/PL364599A1/xx unknown
- 2002-06-18 KR KR10-2004-7000530A patent/KR20040018458A/ko not_active Application Discontinuation
- 2002-06-18 WO PCT/EP2002/006696 patent/WO2003007988A1/de not_active Application Discontinuation
- 2002-07-11 PE PE2002000618A patent/PE20030433A1/es not_active Application Discontinuation
- 2002-07-12 AR ARP020102605A patent/AR039358A1/es unknown
-
2004
- 2004-02-12 ZA ZA200401161A patent/ZA200401161B/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5945098A (en) * | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
WO1996040210A1 (en) * | 1995-06-07 | 1996-12-19 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth of tumors |
WO1997004801A1 (en) * | 1995-07-27 | 1997-02-13 | Genentech, Inc. | Stabile isotonic lyophilized protein formulation |
Non-Patent Citations (5)
Title |
---|
"PHARMACEUTICAL RESEARCH, NEW YORK, NY, US", PHARMACEUTICAL RESEARCH, NEW YORK, NY, US, vol. 11, no. 10, SUPPL, 1 October 1994 (1994-10-01), pages S73, XP002083453, ISSN: 0724-8741 * |
CLELAND ET AL: "The development of stable protein formulations: A close look at protein aggregation, deamidation and oxidation", CRITICAL REVIEWS IN THERAPEUTIC DRUG CARRIER SYSTEMS, XX, XX, vol. 10, no. 4, 1993, pages 307 - 377, XP002083452, ISSN: 0743-4863 * |
KIBBE: "Handbook of Pharmaceutical excipients", 2000, AMERICAN PHARMACEUTICAL ASSOCIATION, WASHINGTON DC, XP002214330 * |
ROTE LISTE SERVICE GMBH: "Rote Liste 2001", 2001, ECV. EDITIO CANTOR VERLAG FÜR MEDIZIN UND NATURWISSENSCHAFTEN GMBH, FRANKFURT, XP002214329 * |
SHIN D M ET AL: "Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer.", CLINICAL CANCER RESEARCH: AN OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH. UNITED STATES MAY 2001, vol. 7, no. 5, May 2001 (2001-05-01), pages 1204 - 1213, XP002214328, ISSN: 1078-0432 * |
Cited By (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4728948B2 (ja) * | 2003-02-10 | 2011-07-20 | エラン ファーマシューティカルズ,インコーポレイテッド | 免疫グロブリン製剤およびその調製の方法 |
US8900577B2 (en) | 2003-02-10 | 2014-12-02 | Biogen Idec Ma Inc. | Immunoglobulin formulation and method of preparation thereof |
JP2006517233A (ja) * | 2003-02-10 | 2006-07-20 | エラン ファーマシューティカルズ,インコーポレイテッド | 免疫グロブリン製剤およびその調製の方法 |
US8815236B2 (en) | 2003-02-10 | 2014-08-26 | Biogen Idec Ma Inc. | Method for treating multiple sclerosis and crohn's disease |
JP2014028831A (ja) * | 2003-02-10 | 2014-02-13 | Elan Pharmaceuticals Inc | 免疫グロブリン製剤およびその調製の方法 |
US8349321B2 (en) | 2003-02-10 | 2013-01-08 | Elan Pharmaceuticals, Inc. | Immunoglobulin formulation and method of preparation thereof |
JP2011088913A (ja) * | 2003-02-10 | 2011-05-06 | Elan Pharmaceuticals Inc | 免疫グロブリン製剤およびその調製の方法 |
CN1886158B (zh) * | 2003-11-26 | 2011-09-07 | 默克专利有限公司 | 包含抗egf受体抗体的药物制剂 |
EP1974723A2 (de) | 2003-11-29 | 2008-10-01 | Merck Patent GmbH | Feste Formen von anti-EGFR-Antikörpern |
EP1974723A3 (de) * | 2003-11-29 | 2010-06-09 | Merck Patent GmbH | Feste Formen von anti-EGFR-Antikörpern |
AU2004292742B9 (en) * | 2003-11-29 | 2011-11-24 | Merck Patent Gmbh | Solid forms of anti-EGFR-antibodies |
WO2005051355A1 (de) * | 2003-11-29 | 2005-06-09 | Merck Patent Gmbh | Feste formen von anti-egfr-antikörpern |
AU2004292742B2 (en) * | 2003-11-29 | 2011-08-25 | Merck Patent Gmbh | Solid forms of anti-EGFR-antibodies |
AU2005211890B2 (en) * | 2004-02-12 | 2011-07-28 | Merck Patent Gmbh | Highly concentrated liquid formulations of anti-EGFR antibodies |
JP2007522157A (ja) * | 2004-02-12 | 2007-08-09 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 抗egfr抗体の高濃縮液体製剤 |
WO2005077414A1 (de) * | 2004-02-12 | 2005-08-25 | Merck Patent Gmbh | Hochkonzentrierte, flüssige formulierungen von anti-egfr-antikörpern |
JP2008519757A (ja) * | 2004-11-12 | 2008-06-12 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 抗egfr抗体の固形物 |
US8263631B2 (en) | 2006-02-09 | 2012-09-11 | Daiichi Sankyo Company, Limited | Anti-cancer pharmaceutical compositions and methods for treating patients with cancer |
WO2007128557A1 (en) | 2006-05-03 | 2007-11-15 | Bayer Schering Pharma Aktiengesellschaft | Combination of an anti edb fibronectin domain antibody l19-sip and an anti-egfr antibody |
US11738068B2 (en) | 2018-06-25 | 2023-08-29 | Jcr Pharmaceuticals Co., Ltd. | Protein-containing aqueous liquid formulation |
Also Published As
Publication number | Publication date |
---|---|
HUP0401046A2 (en) | 2006-04-28 |
PE20030433A1 (es) | 2003-05-24 |
RU2004102395A (ru) | 2005-05-27 |
KR20040018458A (ko) | 2004-03-03 |
CA2453342A1 (en) | 2003-01-30 |
DE10133394A1 (de) | 2003-01-30 |
EP1406658A1 (de) | 2004-04-14 |
MXPA04000340A (es) | 2004-05-04 |
CN1231264C (zh) | 2005-12-14 |
US20040170632A1 (en) | 2004-09-02 |
HUP0401046A3 (en) | 2006-11-28 |
CN1527724A (zh) | 2004-09-08 |
SK862004A3 (en) | 2004-07-07 |
CZ2004189A3 (cs) | 2004-05-12 |
ZA200401161B (en) | 2004-10-22 |
PL364599A1 (en) | 2004-12-13 |
AR039358A1 (es) | 2005-02-16 |
JP2004536129A (ja) | 2004-12-02 |
BR0211060A (pt) | 2004-07-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1687031B1 (de) | Pharmazeutische zubereitung enthaltend einen antikörper gegen den rezeptor für einen epidermalen wachstumsfaktor (egf-rezeptor) | |
EP1455824B1 (de) | Lyophilisierte zubereitung enthaltend antikörper gegen den egf-rezeptor | |
AT407707B (de) | Hochkonzentriertes immunglobulin-präparat und verfahren zu seiner herstellung | |
DE69334134T2 (de) | Wässrige Formulierung enthaltend Menschliches Wachstumshormon | |
DE3240177C2 (de) | ||
DE68907124T3 (de) | Verfahren zum Stabilisieren von menschlichen Albuminlösungen und so erhaltene Lösung. | |
EP1406658A1 (de) | Flüssige formulierung enthaltend cetuximab und einen polyoxyethylensorbitan-fettsäureester | |
DE3438830A1 (de) | Nifedipin enthaltende darreichungsform und verfahren zu ihrer herstellung | |
CH642852A5 (de) | Material, das zur markierung mit einem radionuklid geeignet ist, verfahren zu dessen herstellung und dessen verwendung. | |
DE69827357T2 (de) | Menschliches Wachstumshormon enthaltende pharmazeutische Zusammensetzung | |
DE2827027B2 (de) | Gefriergetrocknetes natives T -globulin-Präparat zur intravenösen Verabreichung | |
DE19535571A1 (de) | Pharmazeutische Kombinationspräparate und deren Verwendung zur Behandlung von Hämodialysepatienten | |
DE10204792A1 (de) | Lyophilisierte Zubereitung enthaltend Immuncytokine | |
DE3115080A1 (de) | Arzneimittel fuer die orale verabreichung und verfahren zu seiner herstellung | |
DE60101979T2 (de) | Lösung enthaltend N-[O-(p-pivaloyloxybenzenesulfonylamino)benzoyl]glyzin Mononatriumsalz Tetrahydrat und diese Lösung enthaltendes Arzneimittel | |
EP3099330B1 (de) | Stabile alkoholische lösung von alprostadil | |
DE60005188T2 (de) | Grf-haltige lyophilisierte arzneizusammensetzungen | |
DE2401453A1 (de) | Pharmazeutische zusammensetzung zur behandlung von hautproliferationserkrankungen | |
EP0108248B1 (de) | Lösungsvermittlerfreie, wässrige Nitroglycerinlösung | |
DE2518509B2 (de) | Pharmazeutisches Mittel für Antitumoraktivität, enthaltend Abrin | |
DE2721034C2 (de) | ||
DE19957371A1 (de) | Mitomycin C-Lösung | |
EP2293817B1 (de) | Stabilisierte flüssigformulierung | |
DE10040707A1 (de) | Kolloidale Pharmakomodulation injizierter Arzneimittel | |
EP2863887A1 (de) | Emulsion zur pharmazeutischen anwendung und verfahren zu deren herstellung |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2002751038 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2003513593 Country of ref document: JP Ref document number: 2453342 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2004/000340 Country of ref document: MX Ref document number: 10483404 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 20028141059 Country of ref document: CN Ref document number: 1020047000530 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: PV2004-189 Country of ref document: CZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 862004 Country of ref document: SK |
|
WWE | Wipo information: entry into national phase |
Ref document number: 172/KOLNP/2004 Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2004/01161 Country of ref document: ZA Ref document number: 200401161 Country of ref document: ZA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2002354848 Country of ref document: AU |
|
WWP | Wipo information: published in national office |
Ref document number: 2002751038 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1-2004-500015 Country of ref document: PH |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: PV2004-189 Country of ref document: CZ |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 2002751038 Country of ref document: EP |