KR20140097205A - 흑색종을 치료하는 치료 조합물 및 방법 - Google Patents
흑색종을 치료하는 치료 조합물 및 방법 Download PDFInfo
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- KR20140097205A KR20140097205A KR1020147013878A KR20147013878A KR20140097205A KR 20140097205 A KR20140097205 A KR 20140097205A KR 1020147013878 A KR1020147013878 A KR 1020147013878A KR 20147013878 A KR20147013878 A KR 20147013878A KR 20140097205 A KR20140097205 A KR 20140097205A
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
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- 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
- C07K16/2869—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against hormone receptors
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- 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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3053—Skin, nerves, brain
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
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PCT/US2012/061533 WO2013063001A1 (en) | 2011-10-28 | 2012-10-24 | Therapeutic combinations and methods of treating melanoma |
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KR20170058432A (ko) * | 2014-10-10 | 2017-05-26 | 화이자 인코포레이티드 | 상승 효과적 아우리스타틴 조합 |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2843595C (en) | 2011-08-01 | 2022-10-18 | Genentech, Inc. | Methods of treating cancer using pd-1 axis binding antagonists and mek inhibitors |
US9216170B2 (en) | 2012-03-19 | 2015-12-22 | Hoffmann-La Roche Inc. | Combination therapy for proliferative disorders |
WO2016011160A1 (en) | 2014-07-15 | 2016-01-21 | Genentech, Inc. | Compositions for treating cancer using pd-1 axis binding antagonists and mek inhibitors |
CN108025035B (zh) * | 2015-08-03 | 2023-06-13 | Enb治疗公司 | 用于治疗与etbr激活相关的癌症的组合物和方法 |
FR3053042B1 (fr) | 2016-06-24 | 2018-08-10 | Commissariat A L'energie Atomique Et Aux Energies Alternatives | Anticorps dirige contre le sous-type b des recepteurs aux endothelines et ses utilisations |
WO2018134254A1 (en) | 2017-01-17 | 2018-07-26 | Heparegenix Gmbh | Protein kinase inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death |
WO2024209089A1 (en) | 2023-04-07 | 2024-10-10 | Commissariat A L'energie Atomique Et Aux Energies Alternatives | Use of antibody against the endothelin receptor b for diagnostic and therapeutic applications |
FR3155708A1 (fr) * | 2023-11-27 | 2025-05-30 | Skymab Biotherapeutics | Conjugue anticorps-medicament et ses utilisations |
FR3155709A1 (fr) * | 2023-11-27 | 2025-05-30 | Skymab Biotherapeutics | Conjugue anticorps-medicament et ses utilisations |
Family Cites Families (149)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US633410A (en) | 1898-09-22 | 1899-09-19 | George A Ames | Ice-cutter. |
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
US3896111A (en) | 1973-02-20 | 1975-07-22 | Research Corp | Ansa macrolides |
US4151042A (en) | 1977-03-31 | 1979-04-24 | Takeda Chemical Industries, Ltd. | Method for producing maytansinol and its derivatives |
US4137230A (en) | 1977-11-14 | 1979-01-30 | Takeda Chemical Industries, Ltd. | Method for the production of maytansinoids |
US4307016A (en) | 1978-03-24 | 1981-12-22 | Takeda Chemical Industries, Ltd. | Demethyl maytansinoids |
US4265814A (en) | 1978-03-24 | 1981-05-05 | Takeda Chemical Industries | Matansinol 3-n-hexadecanoate |
JPS5562090A (en) | 1978-10-27 | 1980-05-10 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
JPS5566585A (en) | 1978-11-14 | 1980-05-20 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
JPS55164687A (en) | 1979-06-11 | 1980-12-22 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
US4256746A (en) | 1978-11-14 | 1981-03-17 | Takeda Chemical Industries | Dechloromaytansinoids, their pharmaceutical compositions and method of use |
JPS55102583A (en) | 1979-01-31 | 1980-08-05 | Takeda Chem Ind Ltd | 20-acyloxy-20-demethylmaytansinoid compound |
JPS55162791A (en) | 1979-06-05 | 1980-12-18 | Takeda Chem Ind Ltd | Antibiotic c-15003pnd and its preparation |
JPS55164685A (en) | 1979-06-08 | 1980-12-22 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
JPS55164686A (en) | 1979-06-11 | 1980-12-22 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
US4309428A (en) | 1979-07-30 | 1982-01-05 | Takeda Chemical Industries, Ltd. | Maytansinoids |
JPS5645483A (en) | 1979-09-19 | 1981-04-25 | Takeda Chem Ind Ltd | C-15003phm and its preparation |
JPS5645485A (en) | 1979-09-21 | 1981-04-25 | Takeda Chem Ind Ltd | Production of c-15003pnd |
EP0028683A1 (en) | 1979-09-21 | 1981-05-20 | Takeda Chemical Industries, Ltd. | Antibiotic C-15003 PHO and production thereof |
WO1981001145A1 (en) | 1979-10-18 | 1981-04-30 | Univ Illinois | Hydrolytic enzyme-activatible pro-drugs |
WO1982001188A1 (en) | 1980-10-08 | 1982-04-15 | Takeda Chemical Industries Ltd | 4,5-deoxymaytansinoide compounds and process for preparing same |
US4450254A (en) | 1980-11-03 | 1984-05-22 | Standard Oil Company | Impact improvement of high nitrile resins |
US4313946A (en) | 1981-01-27 | 1982-02-02 | The United States Of America As Represented By The Secretary Of Agriculture | Chemotherapeutically active maytansinoids from Trewia nudiflora |
US4315929A (en) | 1981-01-27 | 1982-02-16 | The United States Of America As Represented By The Secretary Of Agriculture | Method of controlling the European corn borer with trewiasine |
JPS57192389A (en) | 1981-05-20 | 1982-11-26 | Takeda Chem Ind Ltd | Novel maytansinoid |
US4485045A (en) | 1981-07-06 | 1984-11-27 | Research Corporation | Synthetic phosphatidyl cholines useful in forming liposomes |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4544545A (en) | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
US4970198A (en) | 1985-10-17 | 1990-11-13 | American Cyanamid Company | Antitumor antibiotics (LL-E33288 complex) |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
US5079233A (en) | 1987-01-30 | 1992-01-07 | American Cyanamid Company | N-acyl derivatives of the LL-E33288 antitumor antibiotics, composition and methods for using the same |
AU600575B2 (en) | 1987-03-18 | 1990-08-16 | Sb2, Inc. | Altered antibodies |
US4975278A (en) | 1988-02-26 | 1990-12-04 | Bristol-Myers Company | Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells |
US5606040A (en) | 1987-10-30 | 1997-02-25 | American Cyanamid Company | Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group |
US5770701A (en) | 1987-10-30 | 1998-06-23 | American Cyanamid Company | Process for preparing targeted forms of methyltrithio antitumor agents |
US5053394A (en) | 1988-09-21 | 1991-10-01 | American Cyanamid Company | Targeted forms of methyltrithio antitumor agents |
FI903489A0 (fi) | 1988-11-11 | 1990-07-10 | Medical Res Council | Ligander med en enda sektion, receptorer innehaollande naemnda ligander, foerfaranden foer deras framstaellning samt anvaendning av liganderna och receptorerna. |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
CA2026147C (en) | 1989-10-25 | 2006-02-07 | Ravi J. Chari | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5959177A (en) | 1989-10-27 | 1999-09-28 | The Scripps Research Institute | Transgenic plants expressing assembled secretory antibodies |
US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
CA2095633C (en) | 1990-12-03 | 2003-02-04 | Lisa J. Garrard | Enrichment method for variant proteins with altered binding properties |
US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
ATE255131T1 (de) | 1991-06-14 | 2003-12-15 | Genentech Inc | Humanisierter heregulin antikörper |
GB9114948D0 (en) | 1991-07-11 | 1991-08-28 | Pfizer Ltd | Process for preparing sertraline intermediates |
JP3050424B2 (ja) * | 1991-07-12 | 2000-06-12 | 塩野義製薬株式会社 | ヒトエンドセリンリセプター |
WO1993006217A1 (en) | 1991-09-19 | 1993-04-01 | Genentech, Inc. | EXPRESSION IN E. COLI OF ANTIBODY FRAGMENTS HAVING AT LEAST A CYSTEINE PRESENT AS A FREE THIOL, USE FOR THE PRODUCTION OF BIFUNCTIONAL F(ab')2 ANTIBODIES |
US5362852A (en) | 1991-09-27 | 1994-11-08 | Pfizer Inc. | Modified peptide derivatives conjugated at 2-hydroxyethylamine moieties |
FI941572A7 (fi) | 1991-10-07 | 1994-05-27 | Oncologix Inc | Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenete lmä |
WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
DE69333807T2 (de) | 1992-02-06 | 2006-02-02 | Chiron Corp., Emeryville | Marker für krebs und biosynthetisches bindeprotein dafür |
ZA932522B (en) | 1992-04-10 | 1993-12-20 | Res Dev Foundation | Immunotoxins directed against c-erbB-2(HER/neu) related surface antigens |
ES2152483T3 (es) | 1992-11-13 | 2001-02-01 | Idec Pharma Corp | Aplicacion terapeutica en anticuerpos quimericos y radiomarcados contra el antigeno de diferenciacion restringida de los linfocitos b humanos para el tratamiento del linfoma de celulas b. |
US5635483A (en) | 1992-12-03 | 1997-06-03 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Tumor inhibiting tetrapeptide bearing modified phenethyl amides |
US5780588A (en) | 1993-01-26 | 1998-07-14 | Arizona Board Of Regents | Elucidation and synthesis of selected pentapeptides |
WO1994029351A2 (en) | 1993-06-16 | 1994-12-22 | Celltech Limited | Antibodies |
US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
US5789199A (en) | 1994-11-03 | 1998-08-04 | Genentech, Inc. | Process for bacterial production of polypeptides |
US6214388B1 (en) | 1994-11-09 | 2001-04-10 | The Regents Of The University Of California | Immunoliposomes that optimize internalization into target cells |
US5663149A (en) | 1994-12-13 | 1997-09-02 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory pentapeptide heterocyclic and halophenyl amides |
US5840523A (en) | 1995-03-01 | 1998-11-24 | Genetech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
US5712374A (en) | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
GB9603256D0 (en) | 1996-02-16 | 1996-04-17 | Wellcome Found | Antibodies |
US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
PT994903E (pt) | 1997-06-24 | 2005-10-31 | Genentech Inc | Metodos e composicoes para glicoproteinas galactosiladas |
US6040498A (en) | 1998-08-11 | 2000-03-21 | North Caroline State University | Genetically engineered duckweed |
DE69840412D1 (de) | 1997-10-31 | 2009-02-12 | Genentech Inc | Methoden und zusammensetzungen bestehend aus glykoprotein-glykoformen |
US6610833B1 (en) | 1997-11-24 | 2003-08-26 | The Institute For Human Genetics And Biochemistry | Monoclonal human natural antibodies |
WO1999029888A1 (en) | 1997-12-05 | 1999-06-17 | The Scripps Research Institute | Humanization of murine antibody |
US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
ES2292236T3 (es) | 1998-04-02 | 2008-03-01 | Genentech, Inc. | Variantes de anticuerpos y sus fragmentos. |
DE69942021D1 (de) | 1998-04-20 | 2010-04-01 | Glycart Biotechnology Ag | Glykosylierungs-engineering von antikörpern zur verbesserung der antikörperabhängigen zellvermittelten zytotoxizität |
US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
NZ539776A (en) | 1999-01-15 | 2006-12-22 | Genentech Inc | Polypeptide variants with altered effector function |
DK2270150T4 (da) | 1999-04-09 | 2019-08-26 | Kyowa Hakko Kirin Co Ltd | Fremgangsmåde til at kontrollere aktiviteten af immunologisk funktionelt molekyle. |
US7566452B1 (en) * | 1999-05-04 | 2009-07-28 | New York University | Cancer treatment with endothelin receptor antagonists |
ATE303445T1 (de) | 1999-10-04 | 2005-09-15 | Medicago Inc | Verfahren zur regulation der transkription von fremden genen in gegenwart von stickstoff |
US7125978B1 (en) | 1999-10-04 | 2006-10-24 | Medicago Inc. | Promoter for regulating expression of foreign genes |
EP1229125A4 (en) | 1999-10-19 | 2005-06-01 | Kyowa Hakko Kogyo Kk | PROCESS FOR PREPARING A POLYPEPTIDE |
EP1240319A1 (en) | 1999-12-15 | 2002-09-18 | Genentech, Inc. | Shotgun scanning, a combinatorial method for mapping functional protein epitopes |
CA2395660A1 (en) | 1999-12-29 | 2001-07-12 | Immunogen, Inc. | Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use |
US7097840B2 (en) | 2000-03-16 | 2006-08-29 | Genentech, Inc. | Methods of treatment using anti-ErbB antibody-maytansinoid conjugates |
CA2403425C (en) | 2000-04-11 | 2013-08-27 | Genentech, Inc. | Multivalent antibodies and uses therefor |
US6946292B2 (en) | 2000-10-06 | 2005-09-20 | Kyowa Hakko Kogyo Co., Ltd. | Cells producing antibody compositions with increased antibody dependent cytotoxic activity |
EP3690043A1 (en) | 2000-10-06 | 2020-08-05 | Kyowa Kirin Co., Ltd. | Antibody composition-producing cell |
US7064191B2 (en) | 2000-10-06 | 2006-06-20 | Kyowa Hakko Kogyo Co., Ltd. | Process for purifying antibody |
US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
ES2295228T3 (es) | 2000-11-30 | 2008-04-16 | Medarex, Inc. | Roedores transcromosomicos transgenicos para la preparacion de anticuerpos humanos. |
US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
US6441163B1 (en) | 2001-05-31 | 2002-08-27 | Immunogen, Inc. | Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents |
HUP0700103A3 (en) | 2001-08-03 | 2012-09-28 | Glycart Biotechnology Ag | Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity |
HUP0600342A3 (en) | 2001-10-25 | 2011-03-28 | Genentech Inc | Glycoprotein compositions |
US20040093621A1 (en) | 2001-12-25 | 2004-05-13 | Kyowa Hakko Kogyo Co., Ltd | Antibody composition which specifically binds to CD20 |
WO2003084569A1 (fr) | 2002-04-09 | 2003-10-16 | Kyowa Hakko Kogyo Co., Ltd. | Medicament contenant une composition anticorps |
AU2003236015A1 (en) | 2002-04-09 | 2003-10-20 | Kyowa Hakko Kirin Co., Ltd. | Process for producing antibody composition |
JPWO2003085119A1 (ja) | 2002-04-09 | 2005-08-11 | 協和醗酵工業株式会社 | 抗体組成物のFcγ受容体IIIaに対する結合活性を高める方法 |
AU2003236019A1 (en) | 2002-04-09 | 2003-10-20 | Kyowa Hakko Kirin Co., Ltd. | Drug containing antibody composition appropriate for patient suffering from Fc Gamma RIIIa polymorphism |
EA200401325A1 (ru) | 2002-04-09 | 2005-04-28 | Киова Хакко Когио Ко., Лтд. | Клетки с модифицированным геномом |
ATE503829T1 (de) | 2002-04-09 | 2011-04-15 | Kyowa Hakko Kirin Co Ltd | Zelle mit erniedrigter oder deletierter aktivität eines am gdp-fucosetransport beteiligten proteins |
JP4753578B2 (ja) | 2002-06-03 | 2011-08-24 | ジェネンテック, インコーポレイテッド | 合成抗体ファージライブラリー |
ATE499116T1 (de) | 2002-08-16 | 2011-03-15 | Immunogen Inc | Vernetzer mit hoher reaktivität und löslichkeit und ihre verwendung bei der herstellung von konjugaten für die gezielte abgabe von kleinmolekularen arzneimitteln |
EP1391213A1 (en) | 2002-08-21 | 2004-02-25 | Boehringer Ingelheim International GmbH | Compositions and methods for treating cancer using maytansinoid CD44 antibody immunoconjugates and chemotherapeutic agents |
US7361740B2 (en) | 2002-10-15 | 2008-04-22 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
AR042485A1 (es) | 2002-12-16 | 2005-06-22 | Genentech Inc | Anticuerpo humanizado que se une al cd20 humano |
AU2004205631A1 (en) | 2003-01-16 | 2004-08-05 | Genentech, Inc. | Synthetic antibody phage libraries |
US20060104968A1 (en) | 2003-03-05 | 2006-05-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases |
US7871607B2 (en) | 2003-03-05 | 2011-01-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases |
US7755007B2 (en) | 2003-04-17 | 2010-07-13 | K&H Manufacturing, Inc | Heated pet mat |
US8088387B2 (en) | 2003-10-10 | 2012-01-03 | Immunogen Inc. | Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates |
US7276497B2 (en) | 2003-05-20 | 2007-10-02 | Immunogen Inc. | Cytotoxic agents comprising new maytansinoids |
WO2005035586A1 (ja) | 2003-10-08 | 2005-04-21 | Kyowa Hakko Kogyo Co., Ltd. | 融合蛋白質組成物 |
AU2004280065A1 (en) | 2003-10-09 | 2005-04-21 | Kyowa Hakko Kirin Co., Ltd. | Process for producing antibody composition by using RNA inhibiting the function of alpha1,6-fucosyltransferase |
NO347530B1 (no) | 2003-11-05 | 2023-12-11 | Roche Glycart Ag | Et humanisert type II anti-CD20 antistoff og vertscelle som produserer et humanisert type II anti-CD20 antistoff samt en fremgangsmåte for fremstilling og en farmasøytisk sammensetning. |
BRPI0416028B8 (pt) | 2003-11-06 | 2021-05-25 | Seattle Genetics Inc | composto, conjugados do composto, composição farmacêutica e usos do conjugado |
JPWO2005053742A1 (ja) | 2003-12-04 | 2007-06-28 | 協和醗酵工業株式会社 | 抗体組成物を含有する医薬 |
US7004206B2 (en) | 2004-01-29 | 2006-02-28 | Viken James P | Automatic fluid exchanger |
AU2005216251B2 (en) | 2004-02-23 | 2011-03-10 | Genentech, Inc. | Heterocyclic self-immolative linkers and conjugates |
ZA200608130B (en) | 2004-03-31 | 2008-12-31 | Genentech Inc | Humanized anti-TGF-beta antibodies |
US7785903B2 (en) | 2004-04-09 | 2010-08-31 | Genentech, Inc. | Variable domain library and uses |
ES2403055T3 (es) | 2004-04-13 | 2013-05-13 | F. Hoffmann-La Roche Ag | Anticuerpos anti-P-selectina |
EP1753463A2 (en) | 2004-06-01 | 2007-02-21 | Genentech, Inc. | Antibody drug conjugates and methods |
TWI380996B (zh) | 2004-09-17 | 2013-01-01 | Hoffmann La Roche | 抗ox40l抗體 |
RU2412947C2 (ru) | 2004-09-23 | 2011-02-27 | Дженентек, Инк. | Антитела, сконструированные на основе цистеинов, и их конъюгаты |
JO3000B1 (ar) | 2004-10-20 | 2016-09-05 | Genentech Inc | مركبات أجسام مضادة . |
US20070020657A1 (en) * | 2005-05-20 | 2007-01-25 | Grebe Stefan K | Methods for detecting circulating tumor cells |
US8871720B2 (en) | 2005-07-07 | 2014-10-28 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine carboxy modifications at the C-terminus |
WO2007008603A1 (en) | 2005-07-07 | 2007-01-18 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine side-chain modifications at the c-terminus |
RS51782B (en) * | 2005-10-07 | 2011-12-31 | Exelixis Inc. | AZETIDINS AS MAK INHIBITORS FOR THE TREATMENT OF PROLIFERATIVE DISEASES |
US8679490B2 (en) | 2005-11-07 | 2014-03-25 | Genentech, Inc. | Binding polypeptides with diversified and consensus VH/VL hypervariable sequences |
US20070237764A1 (en) | 2005-12-02 | 2007-10-11 | Genentech, Inc. | Binding polypeptides with restricted diversity sequences |
EP2016101A2 (en) | 2006-05-09 | 2009-01-21 | Genentech, Inc. | Binding polypeptides with optimized scaffolds |
DK2059533T3 (da) | 2006-08-30 | 2013-02-25 | Genentech Inc | Multispecifikke antistoffer |
US20080226635A1 (en) | 2006-12-22 | 2008-09-18 | Hans Koll | Antibodies against insulin-like growth factor I receptor and uses thereof |
CN100592373C (zh) | 2007-05-25 | 2010-02-24 | 群康科技(深圳)有限公司 | 液晶显示面板驱动装置及其驱动方法 |
EP2235064B1 (en) | 2008-01-07 | 2015-11-25 | Amgen Inc. | Method for making antibody fc-heterodimeric molecules using electrostatic steering effects |
JP2011527703A (ja) * | 2008-07-11 | 2011-11-04 | ノバルティス アーゲー | (a)ホスホイノシタイド3−キナーゼ阻害剤および(b)Ras/Raf/Mek経路のモジュレーターの配合物 |
MA33974B1 (fr) * | 2009-10-12 | 2013-02-01 | Hoffmann La Roche | Combinaisons d'un inhibiteur de pi3k et d'un inhibiteur de mek |
RU2595389C2 (ru) * | 2010-02-23 | 2016-08-27 | Дженентек, Инк. | Композиции и способы для диагностики и лечения опухолей |
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2012
- 2012-10-24 JP JP2014538892A patent/JP6251682B2/ja not_active Expired - Fee Related
- 2012-10-24 WO PCT/US2012/061533 patent/WO2013063001A1/en active Application Filing
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- 2012-10-24 EA EA201490879A patent/EA201490879A1/ru unknown
- 2012-10-24 EP EP12842985.9A patent/EP2776051A4/en not_active Withdrawn
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- 2012-10-24 CN CN201280065175.XA patent/CN104039340B/zh not_active Expired - Fee Related
- 2012-10-24 KR KR1020147013878A patent/KR20140097205A/ko not_active Withdrawn
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- 2012-10-24 CA CA2850034A patent/CA2850034A1/en not_active Abandoned
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2014
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- 2014-04-22 IL IL232135A patent/IL232135A0/en unknown
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20170058432A (ko) * | 2014-10-10 | 2017-05-26 | 화이자 인코포레이티드 | 상승 효과적 아우리스타틴 조합 |
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EA201490879A1 (ru) | 2014-08-29 |
MX2014004991A (es) | 2014-05-22 |
CO7151543A2 (es) | 2014-12-29 |
CL2014001092A1 (es) | 2014-07-25 |
CN104039340B (zh) | 2017-04-05 |
JP2014532648A (ja) | 2014-12-08 |
PH12014500925A1 (en) | 2014-06-09 |
TW201325613A (zh) | 2013-07-01 |
AR088509A1 (es) | 2014-06-11 |
JP2018027948A (ja) | 2018-02-22 |
WO2013063001A1 (en) | 2013-05-02 |
SG11201401815XA (en) | 2014-05-29 |
CN104039340A (zh) | 2014-09-10 |
JP6251682B2 (ja) | 2017-12-20 |
IL232135A0 (en) | 2014-05-28 |
PE20142312A1 (es) | 2015-01-25 |
EP2776051A4 (en) | 2015-06-17 |
IN2014CN03062A (enrdf_load_stackoverflow) | 2015-07-31 |
EP2776051A1 (en) | 2014-09-17 |
CA2850034A1 (en) | 2013-05-02 |
AU2012328980A1 (en) | 2014-04-24 |
BR112014009953A2 (pt) | 2017-12-05 |
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