CA2374964C - Process for producing an injectable medicament preparation - Google Patents
Process for producing an injectable medicament preparation Download PDFInfo
- Publication number
- CA2374964C CA2374964C CA2374964A CA2374964A CA2374964C CA 2374964 C CA2374964 C CA 2374964C CA 2374964 A CA2374964 A CA 2374964A CA 2374964 A CA2374964 A CA 2374964A CA 2374964 C CA2374964 C CA 2374964C
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- Prior art keywords
- spacer
- compound
- pharmaceutical composition
- protein
- aliphatic carbon
- 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.)
- Expired - Lifetime
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Classifications
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Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
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- Virology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19926154A DE19926154A1 (de) | 1999-06-09 | 1999-06-09 | Verfahren zur Herstellung einer injizierbaren Arzneimittelzubereitung |
| DE19926154.7 | 1999-06-09 | ||
| PCT/EP2000/005272 WO2000076551A2 (de) | 1999-06-09 | 2000-06-07 | Verfahren zur herstellung einer injizierbaren arzneimittelzubereitung |
Publications (2)
| Publication Number | Publication Date |
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| CA2374964A1 CA2374964A1 (en) | 2000-12-21 |
| CA2374964C true CA2374964C (en) | 2012-05-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2374964A Expired - Lifetime CA2374964C (en) | 1999-06-09 | 2000-06-07 | Process for producing an injectable medicament preparation |
Country Status (13)
| Country | Link |
|---|---|
| US (5) | US7387771B1 (https=) |
| EP (3) | EP2347770B2 (https=) |
| JP (5) | JP5517384B2 (https=) |
| AT (1) | ATE339225T1 (https=) |
| AU (1) | AU779697B2 (https=) |
| CA (1) | CA2374964C (https=) |
| CY (2) | CY1105701T1 (https=) |
| DE (2) | DE19926154A1 (https=) |
| DK (3) | DK1704864T3 (https=) |
| ES (3) | ES2269160T3 (https=) |
| PT (3) | PT1704864E (https=) |
| SI (1) | SI1704864T1 (https=) |
| WO (1) | WO2000076551A2 (https=) |
Families Citing this family (70)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6849714B1 (en) | 1999-05-17 | 2005-02-01 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| CA2363712C (en) | 1999-05-17 | 2011-05-10 | Conjuchem Inc. | Long lasting insulinotropic peptides |
| US7601691B2 (en) | 1999-05-17 | 2009-10-13 | Conjuchem Biotechnologies Inc. | Anti-obesity agents |
| US7144854B1 (en) | 1999-09-10 | 2006-12-05 | Conjuchem, Inc. | Long lasting anti-angiogenic peptides |
| JP4216480B2 (ja) | 1999-05-17 | 2009-01-28 | コンジュケム バイオテクノロジーズ インコーポレイテッド | ウイルス感染の長期持続性融合ペプチドインヒビター |
| US6514500B1 (en) | 1999-10-15 | 2003-02-04 | Conjuchem, Inc. | Long lasting synthetic glucagon like peptide {GLP-!} |
| US6887470B1 (en) | 1999-09-10 | 2005-05-03 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| DE19926154A1 (de) | 1999-06-09 | 2000-12-14 | Ktb Tumorforschungs Gmbh | Verfahren zur Herstellung einer injizierbaren Arzneimittelzubereitung |
| DE19926475A1 (de) | 1999-06-10 | 2000-12-14 | Ktb Tumorforschungs Gmbh | Träger-Pharmaka-Konjugate |
| WO2001017568A2 (en) * | 1999-09-07 | 2001-03-15 | Conjuchem, Inc. | Bioconjugation in vivo to pulmonary or blood components |
| EP1889639A3 (en) * | 1999-09-07 | 2008-04-09 | ConjuChem Biotechnologies Inc. | Methods and compositions containing succinimide or maleimide derivatives of antineoplastic agents, for producing long lasting antineoplastic agents |
| US6706892B1 (en) | 1999-09-07 | 2004-03-16 | Conjuchem, Inc. | Pulmonary delivery for bioconjugation |
| US7090851B1 (en) | 1999-09-10 | 2006-08-15 | Conjuchem Inc. | Long lasting fusion peptide inhibitors of viral infection |
| US6961567B1 (en) * | 2000-12-07 | 2005-11-01 | Palm, Inc. | Generic activation and registration framework for wireless devices |
| US7555571B1 (en) * | 2001-01-05 | 2009-06-30 | Palm, Inc. | Activation of mobile computing device on a cellular network |
| CN1491233A (zh) | 2001-02-02 | 2004-04-21 | 康久化学公司 | 长效生长激素释放因子衍生物 |
| ATE396202T1 (de) | 2001-02-16 | 2008-06-15 | Conjuchem Biotechnologies Inc | Lang wirkendes glucagon-ähnliches peptid-2 für die behandlung von gastrointestinalen krankheiten und störungen |
| US8812398B2 (en) * | 2001-05-08 | 2014-08-19 | Qualcomm Incorporated | Key for a wireless-enabled device |
| US7741453B2 (en) | 2001-05-31 | 2010-06-22 | Conjuchem Biotechnologies, Inc. | Long lasting fusion peptide inhibitors for HIV infection |
| US8435529B2 (en) | 2002-06-14 | 2013-05-07 | Immunomedics, Inc. | Combining radioimmunotherapy and antibody-drug conjugates for improved cancer therapy |
| US7591994B2 (en) | 2002-12-13 | 2009-09-22 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
| US8877901B2 (en) | 2002-12-13 | 2014-11-04 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
| US9770517B2 (en) | 2002-03-01 | 2017-09-26 | Immunomedics, Inc. | Anti-Trop-2 antibody-drug conjugates and uses thereof |
| EP1572242B1 (en) | 2002-12-13 | 2014-04-16 | Immunomedics, Inc. | Immunoconjugates with an intracellularly-cleavable linkage |
| DE10310082A1 (de) | 2003-03-07 | 2004-09-16 | Ktb Tumorforschungsgesellschaft Mbh | Protein-bindende Doxorubicin-Peptid-Derivate |
| GB0321613D0 (en) * | 2003-09-15 | 2003-10-15 | Drug Discovery Lab As | Compounds |
| DK2100904T3 (da) | 2004-04-23 | 2010-11-08 | Conjuchem Biotechnologies Inc | Fast fase til anvendelse i en fremgangsmåde til rensning af albuminkonjugater |
| DE102005002991A1 (de) * | 2005-01-21 | 2006-07-27 | Rösner Research GmbH & Co.KG | Verfahren zur Herstellung von Albumin-Konjugaten mit Gyrasehemmern |
| US9707302B2 (en) | 2013-07-23 | 2017-07-18 | Immunomedics, Inc. | Combining anti-HLA-DR or anti-Trop-2 antibodies with microtubule inhibitors, PARP inhibitors, bruton kinase inhibitors or phosphoinositide 3-kinase inhibitors significantly improves therapeutic outcome in cancer |
| US10058621B2 (en) | 2015-06-25 | 2018-08-28 | Immunomedics, Inc. | Combination therapy with anti-HLA-DR antibodies and kinase inhibitors in hematopoietic cancers |
| US8039432B2 (en) * | 2005-11-09 | 2011-10-18 | Conjuchem, Llc | Method of treatment of diabetes and/or obesity with reduced nausea side effect |
| DE102006024528A1 (de) * | 2006-05-23 | 2007-11-29 | Albupharm Heidelberg Gmbh & Co. Kg | Neue, an der Tumorphysiologie orientierte Formulierung eines Zytostatikums, insbesondere von cis-Platin |
| DE102007002726A1 (de) * | 2007-01-18 | 2008-07-31 | Bayer Schering Pharma Aktiengesellschaft | Neue Kaskaden-Polymer-Komplexe, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Mittel |
| ES2704199T3 (es) | 2007-02-16 | 2019-03-14 | Vergell Medical S A | Profármacos de doble acción |
| EP3912643B8 (en) | 2009-02-13 | 2023-08-23 | Immunomedics, Inc. | Immunoconjugates with an intracellularly-cleavable linkage |
| EP2289558A1 (en) * | 2009-08-25 | 2011-03-02 | KTB Tumorforschungsgesellschaft mbH | Bisphosphonate-prodrugs |
| EP2359802B1 (en) * | 2010-02-12 | 2014-06-18 | Evonik Degussa GmbH | Cosmetic composition containing polyglycerol partial ester |
| EP2382993A1 (en) | 2010-04-19 | 2011-11-02 | KTB Tumorforschungsgesellschaft mbH | Combination of drugs with protein-binding prodrugs |
| US9382329B2 (en) | 2012-08-14 | 2016-07-05 | Ibc Pharmaceuticals, Inc. | Disease therapy by inducing immune response to Trop-2 expressing cells |
| US9931417B2 (en) | 2012-12-13 | 2018-04-03 | Immunomedics, Inc. | Antibody-SN-38 immunoconjugates with a CL2A linker |
| US12310958B2 (en) | 2012-12-13 | 2025-05-27 | Immunomedics, Inc. | Antibody-drug conjugates and uses thereof |
| SI2900277T1 (sl) | 2012-12-13 | 2022-05-31 | Immunomedics, Inc. | Odmerki imunokonjugatov protiteles in SN-38 za boljšo učinkovitost in zmanjšano toksičnost |
| US10413539B2 (en) | 2012-12-13 | 2019-09-17 | Immunomedics, Inc. | Therapy for metastatic urothelial cancer with the antibody-drug conjugate, sacituzumab govitecan (IMMU-132) |
| US10206918B2 (en) | 2012-12-13 | 2019-02-19 | Immunomedics, Inc. | Efficacy of anti-HLA-DR antiboddy drug conjugate IMMU-140 (hL243-CL2A-SN-38) in HLA-DR positive cancers |
| US10744129B2 (en) | 2012-12-13 | 2020-08-18 | Immunomedics, Inc. | Therapy of small-cell lung cancer (SCLC) with a topoisomerase-I inhibiting antibody-drug conjugate (ADC) targeting Trop-2 |
| EP3915369A1 (en) | 2012-12-13 | 2021-12-01 | CytRx Corporation | Anthracycline formulations |
| WO2015012904A2 (en) | 2012-12-13 | 2015-01-29 | Immunomedics, Inc. | Antibody-sn-38 immunoconjugates with a cl2a linker |
| US20240139324A1 (en) | 2012-12-13 | 2024-05-02 | Immunomedics, Inc. | Dosages of immunoconjugates of antibodies and sn-38 for improved efficacy and decreased toxicity |
| US9492566B2 (en) | 2012-12-13 | 2016-11-15 | Immunomedics, Inc. | Antibody-drug conjugates and uses thereof |
| US10137196B2 (en) | 2012-12-13 | 2018-11-27 | Immunomedics, Inc. | Dosages of immunoconjugates of antibodies and SN-38 for improved efficacy and decreased toxicity |
| RU2015129800A (ru) | 2012-12-21 | 2017-01-30 | Биоэллаенс К. В. | Гидрофильные саморазрушающиеся линкеры и их конъюгаты |
| CN113842392A (zh) * | 2013-06-05 | 2021-12-28 | 西特克斯公司 | 用于治疗癌症的细胞毒素剂 |
| US11253606B2 (en) | 2013-07-23 | 2022-02-22 | Immunomedics, Inc. | Combining anti-HLA-DR or anti-Trop-2 antibodies with microtubule inhibitors, PARP inhibitors, Bruton kinase inhibitors or phosphoinositide 3-kinase inhibitors significantly improves therapeutic outcome in cancer |
| SG11201610620UA (en) | 2014-06-20 | 2017-01-27 | Bioalliance Cv | Anti-folate receptor aplha (fra) antibody-drug conjugates and methods of using thereof |
| EP3049399A4 (en) | 2014-11-20 | 2017-10-25 | Pharosgen | Prodrugs activated by caspase |
| WO2016172427A1 (en) | 2015-04-22 | 2016-10-27 | Immunomedics, Inc. | Isolation, detection, diagnosis and/or characterization of circulating trop-2-positive cancer cells |
| US11384104B2 (en) * | 2015-06-19 | 2022-07-12 | Centurion Biopharma Corporation | Delivery systems for controlled drug release |
| US10195175B2 (en) | 2015-06-25 | 2019-02-05 | Immunomedics, Inc. | Synergistic effect of anti-Trop-2 antibody-drug conjugate in combination therapy for triple-negative breast cancer when used with microtubule inhibitors or PARP inhibitors |
| MX377528B (es) | 2015-12-09 | 2025-03-10 | Univ Wien Med | Compuestos de platino funcionalizados con monomaleimida para la terapia del cáncer. |
| SG11201805557SA (en) | 2016-01-08 | 2018-07-30 | Bioalliance Cv | Tetravalent anti-psgl-1 antibodies and uses thereof |
| CN115969970A (zh) | 2016-02-10 | 2023-04-18 | 免疫医疗公司 | Abcg2抑制剂与sacituzumab govitecan的组合 |
| KR20180112060A (ko) | 2016-02-23 | 2018-10-11 | 타베다 세라퓨틱스, 인코포레이티드 | Hsp90 표적화된 접합체 및 이의 입자 및 제형 |
| JP7379795B2 (ja) | 2016-04-27 | 2023-11-15 | イミューノメディクス、インコーポレイテッド | チェックポイント阻害薬に再発／耐性を示す腫瘍を治療するための抗Ｔｒｏｐ－２－ＳＮ－３８抗体薬物複合体の効果 |
| US10918734B2 (en) | 2017-03-27 | 2021-02-16 | Immunomedics, Inc. | Treatment of high Trop-2 expressing triple negative breast cancer (TNBC) with sacituzumab govitecan (IMMU-132) overcomes homologous recombination repair (HRR) rescue mediated by Rad51 |
| WO2018187074A1 (en) | 2017-04-03 | 2018-10-11 | Immunomedics, Inc. | Subcutaneous administration of antibody-drug conjugates for cancer therapy |
| EP3668538A4 (en) | 2017-08-15 | 2021-06-16 | NantCell, Inc. | HANK-CETUXIMAB COMBINATIONS AND PROCEDURES |
| JP2021014409A (ja) * | 2017-11-21 | 2021-02-12 | 京都薬品工業株式会社 | タンパク質結合性薬物 |
| CN111712511B (zh) | 2017-11-30 | 2024-07-16 | 拉德克斯公司 | 澳瑞他汀e衍生物的白蛋白结合产物 |
| IL305268A (en) | 2017-11-30 | 2023-10-01 | Centurion Biopharma Corp | Maytansinoid-based drug delivery systems |
| WO2020081174A1 (en) | 2018-10-16 | 2020-04-23 | Nant Holdings Ip, Llc | Alpha emitter compositions and methods |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4251445A (en) | 1978-03-24 | 1981-02-17 | Weltman Joel K | N-succinimidyl haloacetyl aminobenzoates as coupling agents |
| DE3060377D1 (en) | 1979-08-29 | 1982-07-01 | Nihon Mediphysics Co Ltd | 2-oxopropionaldehyde bis(thiosemicarbazone)derivatives and their production and use |
| US4894226A (en) * | 1986-11-14 | 1990-01-16 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polyproline conjugation |
| US5612034A (en) * | 1990-10-03 | 1997-03-18 | Redcell, Inc. | Super-globuling for in vivo extended lifetimes |
| US5827819A (en) * | 1990-11-01 | 1998-10-27 | Oregon Health Sciences University | Covalent polar lipid conjugates with neurologically active compounds for targeting |
| EP0493745A1 (en) * | 1990-12-21 | 1992-07-08 | Dojindo Laboratories | Fluorescent compound, complex, reagent, and specific binding assay employing said reagent |
| DE4122210C2 (de) | 1991-07-04 | 1999-04-01 | Deutsches Krebsforsch | Konjugate aus tumoraktiver Verbindung und Serumalbumin sowie Verfahren zu deren Herstellung und ihre Verwendung |
| US5622929A (en) | 1992-01-23 | 1997-04-22 | Bristol-Myers Squibb Company | Thioether conjugates |
| HUT77263A (hu) | 1994-09-13 | 1998-03-02 | Theratech Inc. | Kémiai anyagok bejuttatása egy specifikus sejttípus sejtjeinek belsejébe |
| IT1282625B1 (it) * | 1996-02-14 | 1998-03-31 | Zambon Spa | Composizione farmaceutica atta ad inibire la formazione di metastasi tumorali |
| US5840733A (en) * | 1996-07-01 | 1998-11-24 | Redcell, Canada, Inc. | Methods and compositions for producing novel conjugates of thrombin inhibitors and endogenous carriers resulting in anti-thrombins with extended lifetimes |
| DE19636889A1 (de) | 1996-09-11 | 1998-03-12 | Felix Dr Kratz | Antineoplastisch wirkende Transferrin- und Albuminkonjugate zytostatischer Verbindungen aus der Gruppe der Anthrazykline, Alkylantien, Antimetabolite und Cisplatin-Analoga und diese enthaltende Arzneimittel |
| US5879897A (en) | 1996-09-23 | 1999-03-09 | Wake Forest University | Methods and compositions for the diagnosis of extraesophageal gastric reflux |
| DE69830305T2 (de) * | 1997-02-20 | 2006-02-02 | Dime, David S., Toronto | Ortsspezifische arzneimittel verabreichung |
| AU9063398A (en) | 1997-09-12 | 1999-04-05 | Exiqon A/S | Oligonucleotide analogues |
| JP2002512640A (ja) * | 1998-03-23 | 2002-04-23 | コンジュケム，インコーポレーテッド | 持続性治療薬の局所送達 |
| DE19923168A1 (de) | 1999-05-20 | 2000-11-23 | Roche Diagnostics Gmbh | Neue Fluoreszenzfarbstoffe und ihre Verwendung als Fluoreszenzmarker |
| DE19926154A1 (de) * | 1999-06-09 | 2000-12-14 | Ktb Tumorforschungs Gmbh | Verfahren zur Herstellung einer injizierbaren Arzneimittelzubereitung |
| DE19926475A1 (de) * | 1999-06-10 | 2000-12-14 | Ktb Tumorforschungs Gmbh | Träger-Pharmaka-Konjugate |
| US20060233701A1 (en) | 2005-03-30 | 2006-10-19 | Thomas Parias | Method and apparatus to improve the industrial production of hydrogen-carbon monoxide |
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