HRP20192313T1 - Novo anti-netrin-1 protutijelo - Google Patents
Novo anti-netrin-1 protutijelo Download PDFInfo
- Publication number
- HRP20192313T1 HRP20192313T1 HRP20192313TT HRP20192313T HRP20192313T1 HR P20192313 T1 HRP20192313 T1 HR P20192313T1 HR P20192313T T HRP20192313T T HR P20192313TT HR P20192313 T HRP20192313 T HR P20192313T HR P20192313 T1 HRP20192313 T1 HR P20192313T1
- Authority
- HR
- Croatia
- Prior art keywords
- seq
- sequence
- netrin
- polypeptide
- variant
- Prior art date
Links
- 229920001184 polypeptide Polymers 0.000 claims 13
- 102000004196 processed proteins & peptides Human genes 0.000 claims 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims 13
- 108010074223 Netrin-1 Proteins 0.000 claims 10
- 102000009065 Netrin-1 Human genes 0.000 claims 10
- 239000002299 complementary DNA Substances 0.000 claims 7
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 125000003275 alpha amino acid group Chemical group 0.000 claims 5
- 201000011510 cancer Diseases 0.000 claims 5
- 210000004881 tumor cell Anatomy 0.000 claims 5
- 108010030865 Netrin Receptors Proteins 0.000 claims 4
- 102000005951 Netrin Receptors Human genes 0.000 claims 4
- 150000001413 amino acids Chemical class 0.000 claims 4
- 239000012634 fragment Substances 0.000 claims 4
- 230000007850 degeneration Effects 0.000 claims 3
- 230000002068 genetic effect Effects 0.000 claims 3
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims 2
- 101150032479 UNC-5 gene Proteins 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 229940044683 chemotherapy drug Drugs 0.000 claims 2
- 229960002949 fluorouracil Drugs 0.000 claims 2
- 108010014066 DCC Receptor Proteins 0.000 claims 1
- 102000016896 DCC Receptor Human genes 0.000 claims 1
- 101000672311 Homo sapiens Netrin receptor UNC5A Proteins 0.000 claims 1
- 101000672316 Homo sapiens Netrin receptor UNC5B Proteins 0.000 claims 1
- 102100040288 Netrin receptor UNC5A Human genes 0.000 claims 1
- 102100040289 Netrin receptor UNC5B Human genes 0.000 claims 1
- 229930012538 Paclitaxel Natural products 0.000 claims 1
- 230000006907 apoptotic process Effects 0.000 claims 1
- 230000030833 cell death Effects 0.000 claims 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims 1
- 229960004316 cisplatin Drugs 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 229960004679 doxorubicin Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 229960001592 paclitaxel Drugs 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 210000002536 stromal cell Anatomy 0.000 claims 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 1
Classifications
-
- 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
-
- 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
- A61K39/39533—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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- 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
-
- C—CHEMISTRY; METALLURGY
- 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]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Claims (20)
1. Izolirani ili pročišćeni polipeptid:
- koji se sastoji od sekvence SEQ ID NO: 3, ili varijante polipeptida koja je najmanje 85% identična cijeloj duljini SEQ ID NO: 3, ili varijante koja se sastoji od ulomka od najmanje 20 uzastopnih aminokiselina SEQ ID NO: 3, ili
- kodiran pomoću cDNK sekvence SEQ ID NO: 4, ili njezine varijante zbog degeneracije genetskog koda, ili varijante cDNK koja je najmanje 85% identična cijeloj duljini SEQ ID NO: 4.
2. Polipeptid prema zahtjevu 1, naznačen time što je sekvenca prikazana u SEQ ID NO: 35, ili varijanta polipeptida koja je najmanje 85% identična cijeloj duljini SEQ ID NO: 35.
3. Polipeptid prema zahtjevu 1, naznačen time što je kodiran pomoću cDNK sekvence SEQ ID NO: 36 ili njezine varijante zbog degeneracije genetičkog koda, ili varijante cDNK koja je najmanje 85% identična cijeloj duljini SEQ ID NO: 36.
4. Polipeptid prema zahtjevu 1, naznačen time što se sastoji od polipeptida koji je najmanje 90, 95, 96, 97, 98 ili 99 % identičan cijeloj duljini SEQ ID NO: 3, ili polipeptida koji se sastoji od ulomka od najmanje 25 ili 30 uzastopnih aminokiselina SEQ ID NO: 3.
5. cDNK sekvenca SEQ ID NO: 4 ili 36, ili njezine varijante zbog degeneracije genetičkog koda, ili varijanta cDNK koja je najmanje 85% identična cijeloj duljini SEQ ID NO: 4 ili 36.
6. cDNK prema zahtjevu 5, naznačena time što je najmanje 90, 95, 96, 97, 98 ili 99 % identična cijeloj duljini SEQ ID NO: 4 ili 36.
7. Upotreba polipeptida prema bilo kojem od zahtjeva 1 do 4 naznačena time što je za pripremu monoklonskog protutijela.
8. Monoklonsko protutijelo koje veže netrin-1 koje:
(i) specifično se veže za polipeptid sa aminokiselinskom sekvencom SEQ ID NO: 3 ili 35 ili varijantu polipeptida koja je najmanje 85 % identična SEQ ID NO: 3 ili 35, ili varijantu polipeptida koja se sastoji od ulomka od najmanje 20 uzastopnih aminokiselina SEQ ID NO: 3 ; ili
(2i) sadrži CDR1-H sekvence SEQ ID NO: 5, CDR2-H sekvence SEQ ID NO: 6, CDR3-H sekvence SEQ ID NO: 7, i CDR1-L sekvence SEQ ID NO: 8, CDR2-L sekvence YAS i CDR3-L sekvence SEQ ID NO: 9; ili
(3i) sadrži CDR1-H sekvence SEQ ID NO: 28, CDR2-H sekvence SEQ ID NO: 29, CDR3-H sekvence SEQ ID NO: 30, i CDR1-L sekvence SEQ ID NO: 31, CDR2-L sekvence SEQ ID NO: 32 i CDR3-L sekvence SEQ ID NO: 9,
pri čemu navedeno protutijelo ima svojstvo vezanja za netrin-1 i izazivanja stanične smrti ili apoptoze tumorske stanice preko UNC5 receptora ili DCC receptora.
9. Monoklonsko protutijelo koje veže netrin-1 prema zahtjevu 8, naznačeno time što se protutijelo definirano pod (i) specifično veže za polipeptid koji je najmanje 90, 95, 96, 97, 98 ili 99 % identičan sa SEQ ID NO: 3.
10. Monoklonsko protutijelo koje veže netrin-1 prema bilo kojem od zahtjeva 8 do 9, naznačeno time što predstavlja njegov ulomak za vezivanje epitopa.
11. Monoklonsko protutijelo koje veže netrin-1 prema bilo kojem od zahtjeva 8 do 10, naznačeno time što sadrži aminokiselinsku sekvencu SEQ ID NO: 10, 11, 12 ili 13, poželjno obje sekvence SEQ ID NO: 10 i 11, ili SEQ ID NO: 12 i 13.
12. Monoklonsko protutijelo koje veže netrin-1 prema bilo kojem od zahtjeva 8 do 11, naznačeno time što sadrži aminokiselinsku sekvencu odabranu iz skupine SEQ ID NO: 14 do 19 i/ili iz skupine SEQ ID NO: 20 do 27, poželjno sadrži aminokiselinsku sekvencu odabranu iz skupine SEQ ID NO: 14 do 19 i aminokiselinsku sekvencu odabranu iz skupine SEQ ID NO: 20 do 27.
13. Monoklonsko protutijelo koje veže netrin-1 prema zahtjevu 12, naznačeno time što sadrži par aminokiselinskih sekvenci odabranih od parova SEQ ID NO: 14 i 20; 15 i 21; 16 i 22; 17 i 23; 17 i 24; 16 i 25; 17 i 26; 17 i 22; 18 i 25; i 16 i 21.
14. Monoklonsko protutijelo koje veže netrin-1 prema zahtjevu 13, naznačeno time što nadalje sadrži humanu kapa konstantnu domenu u lakom lancu, i humanu IgG1 konstantnu domenu u teškom lancu.
15. Farmaceutski pripravak naznačen time što sadrži protutijelo prema bilo kojem od zahtjeva 8 do 14, i farmaceutski prihvatljiv nosač, nosač ili razrjeđivač.
16. Pripravak prema zahtjevu 15, naznačen time što je za uporabu za liječenje subjekta od raka, pri čemu navedeni rak ima tumorske stanice koje eksprimiraju netrin-1 receptor.
17. Pripravak prema zahtjevu 15, naznačen time što je za uporabu za liječenje subjekta od raka, naznačen time što navedeni rak ima tumorske stanice koje eksprimiraju netrin-1 receptor i netrin-1 ili tumorske stanice koje eksprimiraju netrin-1 receptor unutar stromalnih stanica koje eksprimiraju netrin-1.
18. Pripravak za uporabu prema zahtjevu 16 ili 17, naznačen time što je rak onaj gdje tumorske stanice eksprimiraju ili prekomjerno eksprimiraju netrin-1 receptor, naročito klase UNC5, posebno UNC5B i/ili UNC5A, i/ili DCC.
19. Pripravak za uporabu prema zahtjevu 16, naznačen time što se pripravak koja sadrži monoklonsko protutijelo koristi u kombinaciji s kemoterapeutskim lijekom kod pacijenta.
20. Pripravak za uporabu prema zahtjevu 19, naznačen time što je navedeni kemoterapeutski lijek doksorubicin, 5-fluorouracil (5FU), paklitaksel, ili cisplatin.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14305034.2A EP2893939A1 (en) | 2014-01-10 | 2014-01-10 | Anti-netrin-1 antibody |
| PCT/EP2015/050306 WO2015104360A1 (en) | 2014-01-10 | 2015-01-09 | Novel anti-netrin-1 antibody |
| EP15700118.1A EP3092003B1 (en) | 2014-01-10 | 2015-01-09 | Novel anti-netrin-1 antibody |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20192313T1 true HRP20192313T1 (hr) | 2020-03-20 |
Family
ID=49958401
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20192313TT HRP20192313T1 (hr) | 2014-01-10 | 2019-12-23 | Novo anti-netrin-1 protutijelo |
Country Status (28)
| Country | Link |
|---|---|
| US (2) | US10494427B2 (hr) |
| EP (2) | EP2893939A1 (hr) |
| JP (1) | JP6586095B2 (hr) |
| KR (1) | KR102360967B1 (hr) |
| CN (1) | CN105979966B (hr) |
| AR (1) | AR099068A1 (hr) |
| AU (1) | AU2015205575B2 (hr) |
| BR (1) | BR112016015811B1 (hr) |
| CA (1) | CA2936308C (hr) |
| CL (1) | CL2016001753A1 (hr) |
| DK (1) | DK3092003T3 (hr) |
| EA (1) | EA034676B1 (hr) |
| ES (1) | ES2770620T3 (hr) |
| HR (1) | HRP20192313T1 (hr) |
| HU (1) | HUE048088T2 (hr) |
| IL (1) | IL246603B (hr) |
| LT (1) | LT3092003T (hr) |
| MX (1) | MX2016009029A (hr) |
| NZ (1) | NZ721975A (hr) |
| PH (1) | PH12016501339B1 (hr) |
| PL (1) | PL3092003T3 (hr) |
| PT (1) | PT3092003T (hr) |
| RS (1) | RS59818B1 (hr) |
| SG (1) | SG11201605562VA (hr) |
| SI (1) | SI3092003T1 (hr) |
| TW (1) | TWI699211B (hr) |
| WO (1) | WO2015104360A1 (hr) |
| ZA (1) | ZA201604640B (hr) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2893939A1 (en) * | 2014-01-10 | 2015-07-15 | Netris Pharma | Anti-netrin-1 antibody |
| AR106543A1 (es) | 2015-11-02 | 2018-01-24 | Netris Pharma | Terapia de combinación de agente neutralizante de ntn1 con fármacos que inhiben el control epigenético |
| CN110291105B (zh) * | 2017-01-05 | 2024-03-01 | 奈特里斯药物公司 | 导蛋白-1干扰药物和免疫检查点抑制剂药物的组合治疗 |
| AU2020357889A1 (en) * | 2019-10-04 | 2022-03-24 | Albert Einstein College Of Medicine | KIR3DL3 is an inhibitory receptor of the immune system and uses thereof |
| IL310300A (en) | 2021-07-27 | 2024-03-01 | Netris Pharma | Netrin-1 detection, accompanying testing and radiation-based therapy |
| EP4245772A1 (en) | 2022-03-18 | 2023-09-20 | Netris Pharma | Anti-netrin-1 antibody to treat liver inflammation |
| EP4249509A1 (en) | 2022-03-22 | 2023-09-27 | Netris Pharma | Anti-netrin-1 antibody against arthritis-associated pain |
| WO2023186968A1 (en) | 2022-03-29 | 2023-10-05 | Netris Pharma | Novel mcl-1 inhibitor and combination of mcl-1 and a bh3 mimetic, such as a bcl-2 inhibitor |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
| US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
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| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
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| DE69233482T2 (de) | 1991-05-17 | 2006-01-12 | Merck & Co., Inc. | Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
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| AU2001293870A1 (en) | 2000-10-16 | 2002-04-29 | Bayer Aktiengesellschaft | Regulation of human netrin binding membrane receptor unc5h-1 |
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| WO2006019904A1 (en) | 2004-07-14 | 2006-02-23 | University Of Utha Research Foundation | Netrin-related compositions and uses |
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| EP2329838A3 (fr) | 2004-11-22 | 2013-02-13 | Centre National de la Recherche Scientifique | Nétrine 4 mutée, ses fragments et leur utilisation comme médicaments |
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| PL1989546T3 (pl) | 2006-02-28 | 2017-03-31 | Centre National De La Recherche Scientifique (Cnrs) | Poszukiwanie związków o działaniu przeciwnowotworowym z zastosowaniem aktywności netryny-1 |
| EP2050764A1 (en) | 2007-10-15 | 2009-04-22 | sanofi-aventis | Novel polyvalent bispecific antibody format and uses thereof |
| WO2009141440A1 (en) | 2008-05-21 | 2009-11-26 | Centre National De La Recherche Scientifique (Cnrs) | Netrin-1 overexpression as a biological marker and a survival factor for aggressive neuroblastoma |
| JP5147062B2 (ja) | 2008-07-17 | 2013-02-20 | Ｎｅｃトーキン株式会社 | 巻線部品 |
| AR074369A1 (es) | 2008-11-20 | 2011-01-12 | Genentech Inc | Anticuerpos anti-unc 5b (receptor de netrina) y metodos de uso |
| EP2208738A1 (en) | 2009-01-09 | 2010-07-21 | Centre National pour la Recherche Scientifique (CNRS) | Method for the selection of endothelial cells death inducers via netrin-1 and its applications |
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| CN103339507A (zh) | 2010-08-26 | 2013-10-02 | 霍夫曼-拉罗奇有限公司 | DCC第五纤连蛋白III型域的重组Fc融合蛋白 |
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| EP2893939A1 (en) * | 2014-01-10 | 2015-07-15 | Netris Pharma | Anti-netrin-1 antibody |
-
2014
- 2014-01-10 EP EP14305034.2A patent/EP2893939A1/en not_active Withdrawn
-
2015
- 2015-01-09 PT PT157001181T patent/PT3092003T/pt unknown
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