HRP20170130T1 - Načini liječenja dijabetesa antagonistima gena dll4 - Google Patents
Načini liječenja dijabetesa antagonistima gena dll4 Download PDFInfo
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- HRP20170130T1 HRP20170130T1 HRP20170130TT HRP20170130T HRP20170130T1 HR P20170130 T1 HRP20170130 T1 HR P20170130T1 HR P20170130T T HRP20170130T T HR P20170130TT HR P20170130 T HRP20170130 T HR P20170130T HR P20170130 T1 HRP20170130 T1 HR P20170130T1
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- Prior art keywords
- dll4
- antagonist
- seq
- antibody
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- 239000005557 antagonist Substances 0.000 title claims 20
- 206010012601 diabetes mellitus Diseases 0.000 title claims 4
- 108700041286 delta Proteins 0.000 claims 24
- 101150109170 dll4 gene Proteins 0.000 claims 20
- 239000012634 fragment Substances 0.000 claims 8
- 239000003814 drug Substances 0.000 claims 5
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 claims 4
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 claims 4
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 claims 4
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 claims 4
- 102000005650 Notch Receptors Human genes 0.000 claims 4
- 108010070047 Notch Receptors Proteins 0.000 claims 4
- 239000008280 blood Substances 0.000 claims 4
- 210000004369 blood Anatomy 0.000 claims 4
- 108020001507 fusion proteins Proteins 0.000 claims 4
- 102000037865 fusion proteins Human genes 0.000 claims 4
- 230000003993 interaction Effects 0.000 claims 4
- 230000019491 signal transduction Effects 0.000 claims 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 3
- 239000008103 glucose Substances 0.000 claims 3
- 229940124597 therapeutic agent Drugs 0.000 claims 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims 1
- 108010036949 Cyclosporine Proteins 0.000 claims 1
- 102000004877 Insulin Human genes 0.000 claims 1
- 108090001061 Insulin Proteins 0.000 claims 1
- 108010002352 Interleukin-1 Proteins 0.000 claims 1
- 108090001005 Interleukin-6 Proteins 0.000 claims 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims 1
- 239000000730 antalgic agent Substances 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 229960001265 ciclosporin Drugs 0.000 claims 1
- 229930182912 cyclosporin Natural products 0.000 claims 1
- 230000010030 glucose lowering effect Effects 0.000 claims 1
- 229940125721 immunosuppressive agent Drugs 0.000 claims 1
- 239000003018 immunosuppressive agent Substances 0.000 claims 1
- 229940125396 insulin Drugs 0.000 claims 1
- 229960000485 methotrexate Drugs 0.000 claims 1
- 229940005483 opioid analgesics Drugs 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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Claims (9)
1. Antagonist liganda sličnog delti 4 (Dll4) za primjenu u sprječavanju, liječenju ili olakšavanju dijabetesa melitusa tip 1 u bolesnika, naznačen time, što antagonist blokira interakciju između Dll4 i Notch receptora, što sprječava, liječi ili olakšava dijabetes i naznačen time, što je antagonist Dll4 antitijelo ili njegov fragment koji konkretno vezuje hDll4 i blokira Dll4-Notch signalne puteve, ili fuzijski protein koji se sastoji od izvanstanične domene Dll4 koja je spojena s Fc domenom humanog IgG-a.
2. Antagonist liganda sličnog delti 4 (Dll4) za primjenu u snižavanje razine glukoze u krvi povezane s dijabetesom melitusom tip 1 u bolesnika kojem je to neophodno, naznačen time, što antagonist blokira interakciju između Dll4 i Notch receptora, što snižava razinu glukoze u krvi i naznačen time, što je antagonist Dll4 antitijelo ili njegov fragment koji konkretno vezuje hDll4 i blokira Dll4-Notch signalne puteve, ili fuzijski protein koji se sastoji od izvanstanične domene Dll4 koja je spojena s Fc domenom humanog IgG-a.
3. Antagonist Dll4 za primjenu prema bilo kojem od prethodnih zahtjeva, naznačen time, što se antitijelo ili njegov fragment sastoji od varijabilne regije teškog lanca (HCVR) koja sadrži sekvence teškog lanca CDR1, CDR2 i CDR3 od SEQ ID NO:22, odnosno 24, odnosno 26, i varijabilne regije lakog lanca (LCVR) koja sadrži sekvence lakog lanca CDR1, CDR2 i CDR3 od SEQ ID NO:30, odnosno 32, odnosno 34.
4. Antagonist Dll4 za primjenu prema zahtjevu 3, naznačen time, što se antitijelo ili njegov fragment sastoji od (a) HCVR sekvence od SEQ ID NO: 20 ili 116 i LCVR sekvence od SEQ ID NO:28 ili 118, ili (b) kombinacije HCVR/LCVR od SEQ ID NO: 20/28 ili 116/118.
5. Antagonist Dll4 za primjenu prema bilo kojem od prethodnih zahtjeva u kombinaciji s najmanje još jednim dodatnim terapeutskim sredstvom odabranim iz sredstva za sniženje glukoze u krvi, imunosupresiva, protuupalnog sredstva i analgetskog sredstva, pri čemu opcionalno:
(i) dodatno terapeutsko sredstvo je najmanje jedno sredstvo odabrano iz grupe koja se sastoji od inzulina ili njegovih analoga, glukokortikosteroida, ciklosporina, metotreksata, nesteroidnih protuupalnih lijekova (NSAID), antagonista TNF-α, antagonista IL-1, antagonista IL-6 i opioida; i/ili
(ii) antagonista Dll4 i najmanje jedno dodatno terapeutsko sredstvo su namijenjeni za istovremenu ili uzastopnu primjenu.
6. Primjena antagonista liganda sličnog delti 4 (Dll4) u proizvodnji lijeka za sprječavanje, liječenje ili olakšavanje dijabetesa melitusa tip 1 u bolesnika, naznačena time, što antagonist blokira interakciju između Dll4 i Notch receptora i naznačena time, što je antagonist Dll4 antitijelo ili njegov fragment koji konkretno vezuje hDll4 i blokira Dll4-Notch signalne puteve, ili fuzijski protein koji se sastoji od izvanstanične domene Dll4 koja je spojena s Fc domenom humanog IgG-a.
7. Primjena antagonista liganda sličnog delti 4 (Dll4) u proizvodnji lijeka za snižavanje razine glukoze u krvi povezane s dijabetesom melitusom tip 1 u bolesnika, naznačena time, što antagonist blokira interakciju između Dll4 i Notch receptora, i naznačena time, što je antagonist Dll4 antitijelo ili njegov fragment koji konkretno vezuje hDll4 i blokira Dll4-Notch signalne puteve, ili fuzijski protein koji se sastoji od izvanstanične domene Dll4 koja je spojena s Fc domenom humanog IgG-a.
8. Primjena prema zahtjevu 6 ili 7, naznačena time, što se antitijelo ili njegov fragment sastoji od varijabilne regije teškog lanca (HCVR) koja sadrži sekvence teškog lanca CDR1, CDR2 i CDR3 od SEQ ID NO:22, odnosno 24, odnosno 26, i varijabilne regije lakog lanca (LCVR) koja sadrži sekvence lakog lanca CDR1, CDR2 i CDR3 od SEQ ID NO:30, odnosno 32, odnosno 34.
9. Primjena prema zahtjevu 8, naznačena time, što se antitijelo ili njegov fragment sastoji od (a) HCVR sekvence od SEQ ID NO: 20 ili 116 i LCVR sekvence od SEQ ID NO:28 ili 118, ili (b) HCVR/LCVR kombinacije od SEQ ID NO: 20/28 ili 116/118.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US29980110P | 2010-01-29 | 2010-01-29 | |
US36168710P | 2010-07-06 | 2010-07-06 | |
US38869710P | 2010-10-01 | 2010-10-01 | |
EP11701735.0A EP2528945B1 (en) | 2010-01-29 | 2011-01-28 | Methods of treating diabetes with dll4 antagonists |
PCT/US2011/022817 WO2011094467A2 (en) | 2010-01-29 | 2011-01-28 | Methods of treating diabetes with dll4 antagonists |
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Publication Number | Publication Date |
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HRP20170130T1 true HRP20170130T1 (hr) | 2017-03-24 |
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HRP20170130TT HRP20170130T1 (hr) | 2010-01-29 | 2017-01-26 | Načini liječenja dijabetesa antagonistima gena dll4 |
HRP20170249TT HRP20170249T1 (hr) | 2010-01-29 | 2017-02-16 | Načini liječenja autoimunih bolesti antagonistima gena dll4 |
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HRP20170249TT HRP20170249T1 (hr) | 2010-01-29 | 2017-02-16 | Načini liječenja autoimunih bolesti antagonistima gena dll4 |
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EP (2) | EP2528946B1 (hr) |
JP (2) | JP5997613B2 (hr) |
KR (2) | KR101832118B1 (hr) |
CN (2) | CN102884081A (hr) |
AR (1) | AR080026A1 (hr) |
AU (2) | AU2011210773B2 (hr) |
BR (2) | BR112012018766A2 (hr) |
CA (2) | CA2787615C (hr) |
CY (2) | CY1118223T1 (hr) |
DK (2) | DK2528945T3 (hr) |
ES (2) | ES2605430T3 (hr) |
HR (2) | HRP20170130T1 (hr) |
HU (2) | HUE032985T2 (hr) |
IL (2) | IL220887A (hr) |
JO (2) | JO3183B1 (hr) |
LT (2) | LT2528945T (hr) |
MX (2) | MX343553B (hr) |
MY (2) | MY156538A (hr) |
PL (2) | PL2528946T3 (hr) |
PT (2) | PT2528945T (hr) |
RS (2) | RS55595B1 (hr) |
RU (2) | RU2587620C2 (hr) |
SG (4) | SG10201500416RA (hr) |
SI (2) | SI2528945T1 (hr) |
SM (2) | SMT201600412B (hr) |
TW (2) | TWI564019B (hr) |
UY (1) | UY33206A (hr) |
WO (2) | WO2011094465A1 (hr) |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
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NO347649B1 (no) | 2006-12-14 | 2024-02-12 | Regeneron Pharma | Humant antistoff eller antistoff fragment som spesifikt binder human deltaliknende ligand 4 (hDII4), nukleinsyremolekyl som koder for slike og vektor og vert-vektorsystemer, samt fremgangsmåte for fremstilling, sammensetning og anvendelse. |
EP3029070A1 (en) | 2009-08-29 | 2016-06-08 | AbbVie Inc. | Therapeutic dll4 binding proteins |
ES2895226T3 (es) | 2009-10-16 | 2022-02-18 | Mereo Biopharma 5 Inc | Combinación terapéutica y uso de anticuerpos antagonistas de DLL4 y agentes antihipertensivos |
JO3183B1 (ar) | 2010-01-29 | 2018-03-08 | Regeneron Pharma | طرق لمعالجة أمراض المناعة الذاتية مضادات dll4 |
MY160628A (en) | 2010-03-02 | 2017-03-15 | Abbvie Inc | Therapeutic DLL4 Binding Proteins |
BR112014007035B1 (pt) | 2011-09-23 | 2021-05-04 | Oncomed Pharmaceuticals, Inc | anticorpos biespecíficos que se ligam a vegf/dll4, composição farmacêutica e célula procariótica, fúngica ou de levedura que compreende os mesmos, moléculas de polinucleotídeo, vetor, usos terapêuticos e método para a produção de um anticorpo |
KR101535341B1 (ko) * | 2012-07-02 | 2015-07-13 | 한화케미칼 주식회사 | Dll4에 특이적으로 결합하는 신규한 단일클론항체 및 이의 용도 |
KR20210111353A (ko) | 2012-11-01 | 2021-09-10 | 애브비 인코포레이티드 | 항-vegf/dll4 이원 가변 도메인 면역글로불린 및 이의 용도 |
TW201438736A (zh) * | 2012-11-14 | 2014-10-16 | Regeneron Pharma | 以dll4拮抗劑治療卵巢癌之方法 |
EP3020731B1 (en) | 2013-07-09 | 2019-06-12 | ABLBio | Novel dual-targeted protein specifically binding to dll4 and vegf, and use thereof |
CN111239415B (zh) * | 2013-10-17 | 2024-03-26 | 综合医院公司 | 鉴定响应于用于自身免疫性疾病的治疗的受试者的方法以及用于治疗该疾病的组合物 |
WO2015154795A1 (en) * | 2014-04-08 | 2015-10-15 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Combination therapy for the treatment of autoimmune diseases |
DK3212233T3 (da) | 2014-10-31 | 2020-07-27 | Oncomed Pharm Inc | Kombinationsterapi til behandling af sygdom |
AU2016326609B2 (en) | 2015-09-23 | 2023-03-09 | Mereo Biopharma 5, Inc. | Methods and compositions for treatment of cancer |
EP3886856A4 (en) * | 2018-11-29 | 2022-01-19 | Zucco Sassi Yonezawa Siviglia, Debora | METHOD FOR TREATING OR PREVENTING SEIZURES ASSOCIATED WITH AN EPILEPTIC DISORDER |
US11446262B2 (en) | 2018-11-29 | 2022-09-20 | Debora Zucco Sassi Yonezawa Siviglia | Neuroquiescence—a treatment for neurodevelopmental and neurodegenerative bioelectrical dysregulation and demyelination |
WO2022210802A1 (ja) * | 2021-03-30 | 2022-10-06 | 国立大学法人熊本大学 | 筋萎縮症治療剤 |
WO2023159166A1 (en) * | 2022-02-18 | 2023-08-24 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Single-domain antibodies (nanobodies) targeting the notch ligand dll4 and methods of their use |
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US6927044B2 (en) | 1998-09-25 | 2005-08-09 | Regeneron Pharmaceuticals, Inc. | IL-1 receptor based cytokine traps |
US7138370B2 (en) | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
BR0311161A (pt) * | 2002-05-21 | 2005-03-29 | Cv Therapeutics Inc | Método de tratamento de diabetes |
WO2005103081A2 (en) | 2004-04-20 | 2005-11-03 | Genmab A/S | Human monoclonal antibodies against cd20 |
US20060134121A1 (en) | 2004-10-29 | 2006-06-22 | Gavin Thurston | DII4 antagonists, assays, and therapeutic methods thereof |
AU2006326417B2 (en) * | 2005-12-16 | 2012-05-24 | Regeneron Pharmaceuticals, Inc. | Therapeutic methods for inhibiting tumor growth with Dll4 antagonists |
CN102585002A (zh) | 2006-06-02 | 2012-07-18 | 瑞泽恩制药公司 | 人il-6受体的高亲和力抗体 |
KR20090027227A (ko) * | 2006-06-06 | 2009-03-16 | 제넨테크, 인크. | 항-dll4 항체 및 이의 사용 방법 |
WO2007143689A2 (en) | 2006-06-06 | 2007-12-13 | Genentech, Inc. | Compositions and methods for modulating vascular development |
WO2008019144A2 (en) | 2006-08-07 | 2008-02-14 | Regeneron Pharmaceuticals, Inc. | Threapeutic methods for treating vascular eye disorders with dll4 antagonists |
MX2009003229A (es) | 2006-09-29 | 2009-06-18 | Oncomed Pharm Inc | Composiciones y metodos para diagnosticar y tratar cancer. |
NO347649B1 (no) * | 2006-12-14 | 2024-02-12 | Regeneron Pharma | Humant antistoff eller antistoff fragment som spesifikt binder human deltaliknende ligand 4 (hDII4), nukleinsyremolekyl som koder for slike og vektor og vert-vektorsystemer, samt fremgangsmåte for fremstilling, sammensetning og anvendelse. |
EP3029070A1 (en) | 2009-08-29 | 2016-06-08 | AbbVie Inc. | Therapeutic dll4 binding proteins |
JO3183B1 (ar) * | 2010-01-29 | 2018-03-08 | Regeneron Pharma | طرق لمعالجة أمراض المناعة الذاتية مضادات dll4 |
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