HRP20100385T1 - Humanizirani anti-cmet antagonisti - Google Patents
Humanizirani anti-cmet antagonisti Download PDFInfo
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- HRP20100385T1 HRP20100385T1 HR20100385T HRP20100385T HRP20100385T1 HR P20100385 T1 HRP20100385 T1 HR P20100385T1 HR 20100385 T HR20100385 T HR 20100385T HR P20100385 T HRP20100385 T HR P20100385T HR P20100385 T1 HRP20100385 T1 HR P20100385T1
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- 239000005557 antagonist Substances 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract 4
- 238000000034 method Methods 0.000 claims abstract 2
- 241001529936 Murinae Species 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 229920001184 polypeptide Polymers 0.000 claims 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims 4
- 102000005962 receptors Human genes 0.000 claims 3
- 108020003175 receptors Proteins 0.000 claims 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 claims 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 claims 2
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 claims 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 206010038389 Renal cancer Diseases 0.000 claims 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 2
- 206010043515 Throat cancer Diseases 0.000 claims 2
- 230000004913 activation Effects 0.000 claims 2
- 230000004663 cell proliferation Effects 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 206010017758 gastric cancer Diseases 0.000 claims 2
- 102000057308 human HGF Human genes 0.000 claims 2
- 201000010982 kidney cancer Diseases 0.000 claims 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 201000002528 pancreatic cancer Diseases 0.000 claims 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 2
- 230000002062 proliferating effect Effects 0.000 claims 2
- 201000011549 stomach cancer Diseases 0.000 claims 2
- 238000006467 substitution reaction Methods 0.000 claims 2
- 102220582564 4-hydroxy-2-oxoglutarate aldolase, mitochondrial_N78A_mutation Human genes 0.000 claims 1
- 102220492945 Nuclear RNA export factor 1_R71A_mutation Human genes 0.000 claims 1
- 102220506801 Vitelline membrane outer layer protein 1 homolog_N73T_mutation Human genes 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- 210000004754 hybrid cell Anatomy 0.000 claims 1
- 230000035772 mutation Effects 0.000 claims 1
- 238000003127 radioimmunoassay Methods 0.000 claims 1
- 230000009897 systematic effect Effects 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
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- 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
- 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
- C07K16/005—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies constructed by phage libraries
-
- 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
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- 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
-
- 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
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- 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
- C07K2317/90—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Abstract
Humanizirani oblik murinskog anti-c-met antitijela, naznačen time, da obuhvaća: (a) najmanje jednu HVR sekvencu odabranu iz skupine koja se sastoji od: (i) HVR-L1 koja sadrži sekvencu A1-A17, pri čemu A1-A17 je KSSQSLLYTSSQKNYLA, (ii) HVR-L2 koja sadrži sekvencu B1-B7, pri čemu B1-B7 je WASTRES, (iii) HVR-L3 koja sadrži sekvencu C1-C9, pri čemu C1-C9 je QQYYAYPWT, (iv) HVR-H1 koja sadrži sekvencu D1-D10, pri čemu D1-D10 je GYTFTSYWLH, i (v) HVR-H2 koja sadrži sekvencu E1-E18, pri čemu E1-E18 je GMIDPSNSOTRFNPNFKD; i (b) varijantu HVR-H3 koja sadrži sekvencu TYRSYVTPLDY, SYRSYVTPLDY, TYSSYVTPLDY, SYSSYVTPLDY, TYSSYVTSLDY ili TYSSYVTALDYpri čemu je monovalentni afinitet spomenutog antitijela prema humanom c-met-u veći nego monovalentni afinitet murinskog antitijela koji sadrži varijablu sekvence slabog lanca prikazanu kao SEQ ID NO:9 i varijablu sekvence jakog lanca prikazanu kao SEQ ID NO:10 i pri čemu spomenuto antitijelo inhibira staničnu proliferaciju ovisnu o c-met bolje nego referentno antitijelo koje sadrži kimerno anti-c-met antitijelo koje obuhvaća varijablu sekvence slabog i jakog lanca prikazanu kao SEQ ID NO:9 odnosno 10. Patent sadrži još 46 patentnih zahtjeva.
Claims (47)
1. Humanizirani oblik murinskog anti-c-met antitijela, naznačen time, da obuhvaća:
(a) najmanje jednu HVR sekvencu odabranu iz skupine koja se sastoji od:
(i) HVR-L1 koja sadrži sekvencu A1-A17, pri čemu A1-A17 je KSSQSLLYTSSQKNYLA,
(ii) HVR-L2 koja sadrži sekvencu B1-B7, pri čemu B1-B7 je WASTRES,
(iii) HVR-L3 koja sadrži sekvencu C1-C9, pri čemu C1-C9 je QQYYAYPWT,
(iv) HVR-H1 koja sadrži sekvencu D1-D10, pri čemu D1-D10 je GYTFTSYWLH, i
(v) HVR-H2 koja sadrži sekvencu E1-E18, pri čemu E1-E18 je GMIDPSNSOTRFNPNFKD; i
(b) varijantu HVR-H3 koja sadrži sekvencu TYRSYVTPLDY, SYRSYVTPLDY, TYSSYVTPLDY, SYSSYVTPLDY, TYSSYVTSLDY ili TYSSYVTALDY
pri čemu je monovalentni afinitet spomenutog antitijela prema humanom c-met-u veći nego monovalentni afinitet murinskog antitijela koji sadrži varijablu sekvence slabog lanca prikazanu kao SEQ ID NO:9 i varijablu sekvence jakog lanca prikazanu kao SEQ ID NO:10 i pri čemu spomenuto antitijelo inhibira staničnu proliferaciju ovisnu o c-met bolje nego referentno antitijelo koje sadrži kimerno anti-c-met antitijelo koje obuhvaća varijablu sekvence slabog i jakog lanca prikazanu kao SEQ ID NO:9 odnosno 10.
2. Antitijelo prema zahtjevu 1, naznačeno time, da barem jedan dio sustavnog okvira sekvence je humana sekvenca podudarnog okvira.
3. Antitijelo prema zahtjevu 1, naznačeno time, da obuhvaća varijantu HVR-L2 koja ima sekvencu prikazanu kao SEQ ID NO:72.
4. Antitijelo prema zahtjevu 1, naznačeno time, da obuhvaća varijantu HVR-H2 koja ima sekvencu prikazanu kao SEQ ID NO:98.
5. Antitijelo prema zahtjevu 1, naznačeno time, da obuhvaća HVR-L1 koja ima sekvencu prikazanu kao SEQ ID NO:1.
6. Antitijelo prema zahtjevu 1, naznačeno time, da obuhvaća HVR-L3 koja ima sekvencu prikazanu kao SEQ ID NO:3.
7. Antitijelo prema zahtjevu 1, naznačeno time, da varijanta HVR-H1 sadrži sekvencu TYRSYVTPLDY, TYSSYVTPLDY, TYSSYVTSLDY ili TYSSYVTALDY.
8. Antitijelo prema zahtjevu 1, naznačeno time, da monovalentni afinitet antitijela prema humanom c-met je barem 3-obujma veći nego monovalentni afinitet murinskog antitijela koji sadrži varijablu sekvence slabog lanca i jakog lanca prikazanu kao SEQ ID NO:9 i 10 u Slici 7.
9. Humanizirano antitijelo prema zahtjevu 1, naznačeno time, da je murinsko antitijelo proizvedeno od hibridne stanične linije deponirane pod American Type Culture Collection Accession Number ATCC s oznakom HB-11895 (hibridom 5D5.11.6).
10. Antitijelo prema zahtjevu 1, naznačeno time, da je afinitet vezanja izražen kao Kd vrijednost.
11. Antitijelo prema zahtjevu 1, 8 ili 9, naznačeno time, da je afinitet vezanja izmjeren od strane Biacore ili radioimuno-testiranjem.
12. Antitijelo prema zahtjevu 1, naznačeno time, da obuhvaća humanu κ podskupinu 1 sekvence podudarnog okvira.
13. Antitijelo prema zahtjevu 1, naznačeno time, da obuhvaća humanu podskupinu III jakog lanca sekvence podudarnog okvira.
14. Antitijelo prema zahtjevu 13, naznačeno time, da sustavni okvir sekvence sadrži supstituciju na poziciji 71, 73 i/ili 78.
15. Antitijelo prema zahtjevu 14, naznačeno time, da spomenuta supstitucija je R71A, N73T i/ili N78A.
16. Antitijelo prema zahtjevu 1, naznačeno time, da humanizirano antitijelo inhibira vezanje humanog hepatocitnog faktora rasta (hepatocyte growth factor - HGF) na njegov receptor bolje nego referentno antitijelo koje sadrži kimerno anti-c-met antitijelo koje obuhvaća varijablu sekvence slabog lanca i jakog lanca prikazanu kao SEQ ID NO:9 odnosno 10.
17. Antitijelo prema zahtjevu 16, naznačeno time, da antitijelo inhibira vezanje s vrijednosti IC50 koja je manja od polovice one od kimernog antitijela.
18. Antitijelo prema zahtjevu 17, naznačeno time, da je IC50 određena preko raspona koncentracije antitijela od oko 0,01 nM do oko 1000 nM.
19. Antitijelo prema zahtjevu 1, naznačeno time, da humanizirano antitijelo inhibira aktivaciju receptora humanog hepatocitnog faktora rasta (HGF) bolje nego referentno antitijelo koje sadrži kimerno anti-c-met antitijelo koje obuhvaća varijablu sekvence slabog lanca i jakog lanca prikazanu kao SEQ ID NO:9 odnosno 10.
20. Antitijelo prema zahtjevu 19, naznačeno time, da antitijelo inhibira aktivaciju receptora s vrijednosti IC50 koja je manja od polovice one od kimernog antitijela.
21. Antitijelo prema zahtjevu 20, naznačeno time, da IC50 je određena preko raspona koncentracije antitijela od oko 0,1 nM do oko 100 nM.
22. Antitijelo prema zahtjevu 1, naznačeno time, da humanizirano antitijelo inhibira staničnu proliferaciju s vrijednosti IC50 koja je manja od polovice one od kimernog antitijela.
23. Antitijelo prema zahtjevu 22, naznačeno time, da IC50 je određena preko raspona koncentracije antitijela od oko 0,01 nM do oko 100 nM.
24. Antitijelo prema bilo kojem prethodnom zahtjevu, naznačeno time, da oba humanizirano antitijelo i kimerno antitijelo su monovalentni.
25. Antitijelo prema prethodnim zahtjevima, naznačeno time, da oba humanizirano antitijelo i kimerno antitijelo sadrže jednostruko Fab područje povezano na Fc područje.
26. Antitijelo prema zahtjevu 1, naznačeno time, da obuhvaća varijablu domene jakog lanca koja sadrži HVR1-HC, HVR2-HC i HVR3-HC sekvence prikazane kao SEQ ID NO:191, 192 odnosno 193.
27. Antitijelo prema zahtjevu 26, naznačeno time, da varijabla domene sadrži FR1-HC, FR2-HC, FR3-HC i FR4-HC sekvence prikazane kao SEQ ID NO:187 odnosno do 190.
28. Antitijelo prema zahtjevu 26 ili 27, naznačeno time, da antitijelo obuhvaća CH1 i/ili Fc prikazane kao SEQ ID NO:194 odnosno 195.
29. Antitijelo prema zahtjevu 1, naznačeno time, da obuhvaća varijablu domene slabog lanca koja sadrži HVR1-LC, HVR2-LC i HVR3-LC sekvence prikazane kao SEQ ID NO:183, 184 odnosno 185.
30. Antitijelo prema zahtjevu 29, naznačeno time, da varijabla domene obuhvaća FR1-LC, FR2-LC, FR3-LC i FR4-LC sekvence prikazane kao SEQ ID NO:179 odnosno do 182.
31. Antitijelo prema zahtjevu 29 ili 30, naznačeno time, da antitijelo sadrži CL1 sekvencu prikazanu kao SEQ ID NO:186.
32. Antitijelo, naznačeno time, da sadrži varijablu domene jakog lanca prema bilo kojem zahtjevu 26 do 28 i varijablu domene slabog lanca prema bilo kojem zahtjevu 29 do 31.
33. Antitijelo prema zahtjevu 32, naznačeno time, da sadrži varijablu domene jakog lanca koja obuhvaća HVR1-HC, HVR2-HC i HVR3-HC sekvence prikazane kao SEQ ID NO:191 odnosno do 193, FR1-HC, FR2-HC, FR3-HC i FR4-HC sekvence prikazane kao SEQ ID NO: 187 odnosno do 190, te CH1 i Fc prikazane kao SEQ ID NO:194 odnosno 195, zatim varijablu domene slabog lanca koja obuhvaća HVR1-LC, HVR2-LC i HVR3-LC sekvence prikazane kao SEQ ID NO:183 odnosno do 185, FR1-LC, FR2-LC, FR3-LC i FR4-LC sekvence prikazane kao SEQ ID NO: 179 odnosno do 182, te CL1 sekvencu prikazanu kao SEQ ID NO:186.
34. Antitijelo prema zahtjevu 32 ili 33, naznačeno time, da je antitijelo monovalentno i da sadrži Fc područje.
35. Antitijelo prema zahtjevu 34, naznačeno time, da Fc područje obuhvaća prvi i drugi polipeptid, pri čemu prvi i drugi polipeptid svaki sadrži jednu ili više mutacija u odnosu na divlji tip humanog Fc.
36. Antitijelo prema zahtjevu 35, naznačeno time, da prvi polipeptid sadrži Fc sekvencu prikazanu kao SEQ ID NO:195, a drugi polipeptid sadrži sekvencu prikazanu kao SEQ ID NO:196.
37. Antitijelo prema bilo kojem prethodnom zahtjevu, naznačeno time, da se koristi u postupku liječenja.
38. Antitijelo prema bilo kojem prethodnom zahtjevu, naznačeno time, da se koristi u postupku liječenja raka.
39. Antitijelo prema zahtjevu 38, naznačeno time, da rak je rak grla, rak mozga, rak bubrega, rak želuca, kolorektalni rak i/ili rak pankreasa.
40. Antitijelo prema bilo kojem zahtjevu 1 do 36, naznačeno time, da se koristi u postupku liječenja proliferativnih poremećaja.
41. Uporaba antitijela prema bilo kojem zahtjevu 1 do 36, naznačena time, da se primjenjuje u proizvodnji lijeka za liječenje raka.
42. Uporaba prema zahtjevu 41, naznačena time, da rak je rak grla, rak mozga, rak bubrega, rak želuca, kolorektalni rak i/ili rak pankreasa.
43. Uporaba antitijela prema bilo kojem zahtjevu 1 do 36, naznačena time, da se primjenjuje u proizvodnji lijeka za liječenje proliferativnih poremećaja.
44. Nukleinska kiselina, naznačena time, da kodira antitijelo prema bilo kojem zahtjevu 1 do 36.
45. Stanica domaćina, naznačena time, da obuhvaća nukleinsku kiselinu prema zahtjevu 44.
46. Sastav, naznačen time, da sadrži antitijelo prema bilo kojem zahtjevu 1 do 36.
47. Sastav prema zahtjevu 46, naznačen time, da sastav sadrži nosač.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59899104P | 2004-08-05 | 2004-08-05 | |
| PCT/US2005/027626 WO2006015371A2 (en) | 2004-08-05 | 2005-08-04 | Humanized anti-cmet antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20100385T1 true HRP20100385T1 (hr) | 2010-10-31 |
Family
ID=35787927
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20100385T HRP20100385T1 (hr) | 2004-08-05 | 2010-07-13 | Humanizirani anti-cmet antagonisti |
Country Status (27)
| Country | Link |
|---|---|
| US (6) | US7476724B2 (hr) |
| EP (1) | EP1773885B1 (hr) |
| JP (2) | JP5068651B2 (hr) |
| KR (1) | KR101397851B1 (hr) |
| CN (3) | CN102942631B (hr) |
| AT (1) | ATE465181T1 (hr) |
| AU (1) | AU2005267720B2 (hr) |
| BR (1) | BRPI0513666A (hr) |
| CA (1) | CA2575402A1 (hr) |
| CY (1) | CY1111622T1 (hr) |
| DE (1) | DE602005020799D1 (hr) |
| DK (1) | DK1773885T3 (hr) |
| ES (1) | ES2344793T3 (hr) |
| HK (2) | HK1100779A1 (hr) |
| HR (1) | HRP20100385T1 (hr) |
| IL (3) | IL180588A (hr) |
| ME (1) | ME01803B (hr) |
| MX (1) | MX2007001470A (hr) |
| NO (1) | NO20071188L (hr) |
| NZ (1) | NZ552485A (hr) |
| PL (1) | PL1773885T3 (hr) |
| PT (1) | PT1773885E (hr) |
| RS (1) | RS51326B (hr) |
| RU (1) | RU2398777C2 (hr) |
| SI (1) | SI1773885T1 (hr) |
| WO (1) | WO2006015371A2 (hr) |
| ZA (1) | ZA200701656B (hr) |
Families Citing this family (206)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100056762A1 (en) * | 2001-05-11 | 2010-03-04 | Old Lloyd J | Specific binding proteins and uses thereof |
| SG149815A1 (en) | 2003-11-06 | 2009-02-27 | Seattle Genetics Inc | Monomethylvaline compounds capable of conjugation to ligands |
| PT1773885E (pt) * | 2004-08-05 | 2010-07-21 | Genentech Inc | Antagonistas anti-cmet humanizados |
| WO2006132670A2 (en) * | 2004-11-12 | 2006-12-14 | Seattle Genetics, Inc. | Auristatins having an aminobenzoic acid unit at the n terminus |
| EP2322622A3 (en) * | 2005-03-25 | 2012-03-07 | National Research Council of Canada | Method for isolation of soluble polypeptides |
| WO2007008848A2 (en) | 2005-07-07 | 2007-01-18 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine carboxy modifications at the c-terminus |
| CA2614436C (en) | 2005-07-07 | 2016-05-17 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine side-chain modifications at the c-terminus |
| US7750116B1 (en) | 2006-02-18 | 2010-07-06 | Seattle Genetics, Inc. | Antibody drug conjugate metabolites |
| CN101611318B (zh) | 2006-09-07 | 2015-03-04 | 奥塔哥创新有限公司 | 生物标记物 |
| MY188368A (en) | 2006-09-08 | 2021-12-06 | Abbott Lab | Interleukin-13 binding proteins |
| US7883705B2 (en) * | 2007-02-14 | 2011-02-08 | Kyowa Hakko Kirin Co., Ltd. | Anti FGF23 antibody and a pharmaceutical composition comprising the same |
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