HRP20160045T1 - Metoda lijeäśenja raka pomoä†u antagonista dll4 i kemoterapijskog sredstva - Google Patents
Metoda lijeäśenja raka pomoä†u antagonista dll4 i kemoterapijskog sredstva Download PDFInfo
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- HRP20160045T1 HRP20160045T1 HRP20160045TT HRP20160045T HRP20160045T1 HR P20160045 T1 HRP20160045 T1 HR P20160045T1 HR P20160045T T HRP20160045T T HR P20160045TT HR P20160045 T HRP20160045 T HR P20160045T HR P20160045 T1 HRP20160045 T1 HR P20160045T1
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- 239000002246 antineoplastic agent Substances 0.000 title claims 17
- 229940127089 cytotoxic agent Drugs 0.000 title claims 17
- 206010028980 Neoplasm Diseases 0.000 title claims 14
- 201000011510 cancer Diseases 0.000 title claims 11
- 239000005557 antagonist Substances 0.000 title 1
- 239000012634 fragment Substances 0.000 claims 22
- 239000000427 antigen Substances 0.000 claims 21
- 102000036639 antigens Human genes 0.000 claims 21
- 108091007433 antigens Proteins 0.000 claims 21
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 claims 10
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 claims 10
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 claims 10
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 claims 10
- 239000012829 chemotherapy agent Substances 0.000 claims 7
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 6
- 150000003230 pyrimidines Chemical class 0.000 claims 6
- 229960004316 cisplatin Drugs 0.000 claims 5
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims 5
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims 4
- 229960002949 fluorouracil Drugs 0.000 claims 4
- 229910052697 platinum Inorganic materials 0.000 claims 3
- 238000011518 platinum-based chemotherapy Methods 0.000 claims 3
- 230000001225 therapeutic effect Effects 0.000 claims 3
- 206010005003 Bladder cancer Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 230000036210 malignancy Effects 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 2
- 230000004614 tumor growth Effects 0.000 claims 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims 2
- 206010005949 Bone cancer Diseases 0.000 claims 1
- 208000018084 Bone neoplasm Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 206010039491 Sarcoma Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims 1
- 229960004117 capecitabine Drugs 0.000 claims 1
- 229960004562 carboplatin Drugs 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 229960005277 gemcitabine Drugs 0.000 claims 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims 1
- 229950010897 iproplatin Drugs 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 230000003211 malignant effect Effects 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229960001756 oxaliplatin Drugs 0.000 claims 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 206010046766 uterine cancer Diseases 0.000 claims 1
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- A61K33/243—Platinum; Compounds thereof
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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
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- 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
- A61K31/28—Compounds containing heavy metals
- A61K31/282—Platinum compounds
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
- A61K31/435—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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
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- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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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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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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- C07K2317/00—Immunoglobulins specific features
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- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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Claims (14)
1. Izolirano ljudsko antitijelo ili njegov fragment koji veže antigen koji se konkretno vezuje za ljudski ligand 4 tipa delta (hDll4) za primjenu u liječenju raka ili smanjenju ili zaustavljanju rasta tumora u ispitanika primjenom u kombinaciji s kemoterapijskim sredstvom, naznačen time, što se ljudsko antitijelo ili njegov fragment koji veže antigen sastoji od varijabilne regije teškog lanca (HCVR) koja sadrži sekvence teškog lanca CDR1, CDR2 i CDR3 sa SEQ ID NO:22, odnosno 24, odnosno 26 te varijabilne regije lakog lanca (LCVR) koja sadrži sekvence lakog lanca CDR1, CDR2 i CDR3 sa SEQ ID NO:30, odnosno 32, odnosno 34, kemoterapijsko sredstvo je kemoterapijsko sredstvo na bazi platine ili analog pirimidina, a rak ili tumor je solidni malignitet.
2. Ljudsko antitijelo ili fragment koji veže antigen za primjenu prema zahtjevu 1, naznačen time, što se antitijelo ili fragment koji veže antigen sastoji od HCVR sekvence sa SEQ ID NO:20 ili SEQ ID NO:116 ili LCVR sekvence sa SEQ ID NO:28 ili SEQ ID NO:118.
3. Ljudsko antitijelo ili fragment koji veže antigen za primjenu prema zahtjevu 1, naznačen time, što se spomenuto antitijelo ili fragment koji veže antigen sastoji od kombinacije HCVR/LCVR sa SEQ ID NO:20/28 ili 116/118.
4. Ljudsko antitijelo ili fragment koji veže antigen za primjenu prema bilo kojem od zahtjeva 1-3, naznačen time, što:
kemoterapijsko sredstvo na bazi platine je cisplatin, karboplatin, iproplatin ili oksaliplatin ili njihova farmaceutski prihvatljiva sol;
analog pirimidina je gemcitabin, 5-FU ili kapecitabin ili njihova farmaceutski prihvatljiva sol.
5. Ljudsko antitijelo ili fragment koji veže antigen za primjenu prema zahtjevu 4, naznačen time, što je kemoterapijsko sredstvo cisplatin ili 5-FU.
6. Primjena ljudskog antitijela ili fragmenta koji veže antigen koji se sastoji od varijabilne regije teškog lanca (HCVR) koja sadrži sekvence teškog lanca CDR1, CDR2 i CDR3 sa SEQ ID NO:22, odnosno 24, odnosno 26 te varijabilne regije lakog lanca (LCVR) koja sadrži sekvence lakog lanca CDR1, CDR2 i CDR3 sa SEQ ID NO:30, odnosno 32, odnosno 34, u proizvodnji lijeka za liječenje raka ili smanjenje ili zaustavljanju rasta tumora u ispitanika primjenom u kombinaciji s kemoterapijskim sredstvom, naznačena time, što je kemoterapijsko sredstvo kemoterapijsko sredstvo na bazi platine ili analog pirimidina, a rak ili tumor je solidni malignitet.
7. Ljudsko antitijelo ili fragment koji veže antigen za primjenu prema bilo kojem od zahtjeva 1-5 ili za primjenu prema zahtjevu 6, naznačen time, što je rak odabran iz raka jajnika, raka maternice, raka dojke, raka pluća, raka jetre, raka debelog crijeva, raka mokraćnog mjehura, raka bubrega, raka prostate, raka gušterače, raka želuca, raka kostiju, raka kože i malignog sarkoma mekih tkiva.
8. Ljudsko antitijelo ili fragment koji veže antigen za primjenu prema zahtjevu 7, naznačen time, što je rak odabran iz raka pluća, raka debelog crijeva ili raka mokraćnog mjehura.
9. Ljudsko antitijelo ili fragment koji veže antigen za primjenu prema bilo kojem od zahtjeva 1-5 i 7-8 ili za primjenu prema bilo kojem od zahtjeva 6-8, naznačen time, što su antitijelo ili fragment koji veže antigen i kemoterapijsko sredstvo namijenjeni za istovremenu ili uzastopnu primjenu.
10. Ljudsko antitijelo ili fragment koji veže antigen za primjenu prema bilo kojem od zahtjeva 1-5 i 7-8 ili za primjenu prema bilo kojem od zahtjeva 6-8, naznačen time, što se spomenuto ljudsko antitijelo ili fragment koji veže antigen daje ljudskom ispitaniku u kombinaciji sa spomenutim kemoterapijskim sredstvom.
11. Farmaceutski pripravak koji sadrži antitijelo ili njegov fragment koji veže antigen koji se sastoji od varijabilne regije teškog lanca (HCVR) koja sadrži sekvence teškog lanca CDR1, CDR2 i CDR3 sa SEQ ID NO:22, odnosno 24, odnosno 26 te varijabilne regije lakog lanca (LCVR) koja sadrži sekvence lakog lanca CDR1, CDR2 i CDR3 sa SEQ ID NO:30, odnosno 32, odnosno 34, kemoterapijsko sredstvo odabrano iz kemoterapijskog sredstva na bazi platine ili analoga pirimidina, pri čemu je kemoterapijsko sredstvo opcionalno cisplatin ili 5-FU, i farmaceutski prihvatljivi nosač.
12. Komplet koji se sastoji od spremnika koji sadrži antitijelo ili njegov fragment koji veže antigen koji se sastoji od varijabilne regije teškog lanca (HCVR) koja sadrži sekvence teškog lanca CDR1, CDR2 i CDR3 sa SEQ ID NO:22, odnosno 24, odnosno 26 te varijabilne regije lakog lanca (LCVR) koja sadrži sekvence lakog lanca CDR1, CDR2 i CDR3 sa SEQ ID NO:30, odnosno 32, odnosno 34 te još jednog ili više spremnika koji sadrže najmanje jedno kemoterapijsko sredstvo odabrano iz kemoterapijskog sredstva na bazi platine ili analoga pirimidina, pri čemu je kemoterapijsko sredstvo opcionalno cisplatin ili 5-FU.
13. Antitijelo ili fragment koji veže antigen za primjenu u terapijskoj metodi smanjenja količine kemoterapijskog sredstva potrebne za postizanje željenog terapijskog učinka u ispitanika s rakom ili tumorom, koja se sastoji od davanja spomenutog antitijela ili fragmenta koji veže antitijelo ispitaniku u kombinaciji s kemoterapijskim sredstvom;
naznačen time, što se antitijelo ili fragment koji veže antigen sastoji od varijabilne regije teškog lanca (HCVR) koja sadrži sekvence teškog lanca CDR1, CDR2 i CDR3 sa SEQ ID NO:22, odnosno 24, odnosno 26 te varijabilne regije lakog lanca (LCVR) koja sadrži sekvence lakog lanca CDR1, CDR2 i CDR3 sa SEQ ID NO:30, odnosno 32, odnosno 34;
naznačen time, što je kemoterapijsko sredstvo kemoterapijsko sredstvo na bazi platine ili analog pirimidina, pri čemu je kemoterapijsko sredstvo opcionalno cisplatin ili 5-FU;
i naznačen time, što je količina kemoterapijskog sredstva smanjena u usporedbi s količinom potrebnom za jednaki terapijski učinak u odsustvu antitijela ili fragmenta koji veže antigen.
14. Antitijelo ili fragment koji veže antigen za primjenu prema zahtjevu 13, naznačen time, što je količina kemoterapijskog sredstva potrebna za postizanje željenog terapijskog učinka smanjena za najmanje 20 % ili 30 % do 50 %.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22046509P | 2009-06-25 | 2009-06-25 | |
| US30188110P | 2010-02-05 | 2010-02-05 | |
| PCT/US2010/039999 WO2010151770A1 (en) | 2009-06-25 | 2010-06-25 | Method of treating cancer with dll4 antagonist and chemotherapeutic agent |
| EP10728555.3A EP2445528B1 (en) | 2009-06-25 | 2010-06-25 | Method of treating cancer with dll4 antagonist and chemotherapeutic agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20160045T1 true HRP20160045T1 (hr) | 2016-02-12 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20160045TT HRP20160045T1 (hr) | 2009-06-25 | 2016-01-14 | Metoda lijeäśenja raka pomoä†u antagonista dll4 i kemoterapijskog sredstva |
Country Status (28)
| Country | Link |
|---|---|
| US (3) | US8518887B2 (hr) |
| EP (1) | EP2445528B1 (hr) |
| JP (2) | JP6038650B2 (hr) |
| KR (1) | KR101750723B1 (hr) |
| CN (1) | CN102481365A (hr) |
| AR (1) | AR077241A1 (hr) |
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| RU2448979C2 (ru) * | 2006-12-14 | 2012-04-27 | Ридженерон Фармасьютикалз, Инк. | Антитела человека к дельта-подобному лиганду-4 человека |
| TWI513465B (zh) | 2009-06-25 | 2015-12-21 | Regeneron Pharma | 以ｄｌｌ４拮抗劑與化學治療劑治療癌症之方法 |
| DK2488204T3 (en) | 2009-10-16 | 2016-06-06 | Oncomed Pharm Inc | Therapeutic combination and use of DLL4 antagonist antibodies and blood pressure lowering agents |
| WO2012092539A2 (en) * | 2010-12-31 | 2012-07-05 | Takeda Pharmaceutical Company Limited | Antibodies to dll4 and uses thereof |
| HRP20230078T1 (hr) | 2011-09-23 | 2023-05-12 | Mereo Biopharma 5, Inc. | Sredstva za vezivanje vegf/dll4 i njihova uporaba |
| GB2523211B (en) | 2012-01-27 | 2020-03-18 | Univ Jefferson | MCT protein inhibitor-related prognostic and therapeutic methods |
| US20150240240A1 (en) * | 2012-09-13 | 2015-08-27 | Thomas Jefferson University | Msf reprograms myofibroblasts toward lactate production and fuel anaerboic tumor growth |
| US9599620B2 (en) * | 2012-10-31 | 2017-03-21 | Oncomed Pharmaceuticals, Inc. | Methods and monitoring of treatment with a DLL4 antagonist |
| AR093445A1 (es) * | 2012-11-14 | 2015-06-10 | Regeneron Pharma | Metodos para tratar el cancer de ovario con antagonistas de dll4 |
| WO2014172627A1 (en) | 2013-04-19 | 2014-10-23 | Thomas Jefferson University | Caveolin-1 related methods for treating glioblastoma with temozolomide |
| US20170143787A1 (en) * | 2014-02-19 | 2017-05-25 | Pertinax Therapeutics Inc. | Chemokine receptor antagonist and its combinational therapy |
| ES2808153T3 (es) | 2014-10-31 | 2021-02-25 | Mereo Biopharma 5 Inc | Terapia de combinación para tratamiento de enfermedad |
| JP2018528970A (ja) * | 2015-09-16 | 2018-10-04 | サントル、ナショナール、ド、ラ、ルシェルシュ、シアンティフィク、（セーエヌエルエス） | 悪性腫瘍を治療および／または腫瘍再発を予防するためのゲル化組成物 |
| WO2017053705A1 (en) | 2015-09-23 | 2017-03-30 | Oncomed Pharmaceuticals, Inc. | Methods and compositions for treatment of cancer |
| CN110339350A (zh) | 2019-07-25 | 2019-10-18 | 广州中科蓝华生物科技有限公司 | 一种抗肿瘤的联合用药物组合物及其应用 |
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| US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| JP4124480B2 (ja) | 1991-06-14 | 2008-07-23 | ジェネンテック・インコーポレーテッド | 免疫グロブリン変異体 |
| GEP20063752B (en) | 2000-10-13 | 2006-02-27 | Biogen Inc | Humanized Anti-LT-Beta-R Antibodies |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US7138370B2 (en) | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
| US20040101920A1 (en) | 2002-11-01 | 2004-05-27 | Czeslaw Radziejewski | Modification assisted profiling (MAP) methodology |
| EP1656391B1 (en) | 2003-08-13 | 2010-10-13 | Pfizer Products Inc. | Modified human igf-1r antibodies |
| US20060134121A1 (en) | 2004-10-29 | 2006-06-22 | Gavin Thurston | DII4 antagonists, assays, and therapeutic methods thereof |
| US20070213266A1 (en) | 2005-09-01 | 2007-09-13 | Vasgene Therapeutics, Inc. | Methods for using and identifying modulators of Delta-like 4 |
| US8329408B2 (en) * | 2005-10-31 | 2012-12-11 | Bayer Healthcare Llc | Methods for prognosis and monitoring cancer therapy |
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| KR20090027227A (ko) | 2006-06-06 | 2009-03-16 | 제넨테크, 인크. | 항-ｄｌｌ4 항체 및 이의 사용 방법 |
| CL2007001624A1 (es) | 2006-06-06 | 2008-01-18 | Genentech Inc | Uso de un anticuerpo que se une a dll4 para el tratamiento de tumor, cancer o trastorno de proliferacion celular. |
| PT2066694E (pt) | 2006-09-29 | 2016-01-27 | Oncomed Pharm Inc | Composições e métodos de diagnóstico e tratamento do cancro |
| RU2448979C2 (ru) * | 2006-12-14 | 2012-04-27 | Ридженерон Фармасьютикалз, Инк. | Антитела человека к дельта-подобному лиганду-4 человека |
| US20100119526A1 (en) * | 2007-01-26 | 2010-05-13 | Bioinvent International Ab | DLL4 Signaling Inhibitors and Uses Thereof |
| EP1958632A1 (en) * | 2007-02-14 | 2008-08-20 | Dan Stoicescu | Use of condensed pyrimidine derivatives for the treatment of autoimmune and inflammatory diseases |
| AU2009294415B2 (en) * | 2008-09-19 | 2015-09-24 | Medimmune Llc | Antibodies directed to DLL4 and uses thereof |
| EP2356146A1 (en) * | 2008-11-07 | 2011-08-17 | Fabrus Llc | Anti-dll4 antibodies and uses thereof |
| TWI513465B (zh) | 2009-06-25 | 2015-12-21 | Regeneron Pharma | 以ｄｌｌ４拮抗劑與化學治療劑治療癌症之方法 |
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