DK1648998T3 - Specifikke bindingsmidler til hepatocytvækstfaktor - Google Patents
Specifikke bindingsmidler til hepatocytvækstfaktor Download PDFInfo
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- DK1648998T3 DK1648998T3 DK04776560.7T DK04776560T DK1648998T3 DK 1648998 T3 DK1648998 T3 DK 1648998T3 DK 04776560 T DK04776560 T DK 04776560T DK 1648998 T3 DK1648998 T3 DK 1648998T3
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Classifications
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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
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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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- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
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- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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- C07—ORGANIC CHEMISTRY
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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
- C07K2317/73—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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- 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
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Claims (88)
1. Isoleret antistof, der kan binde mindst et polypeptid valgt blandt • SEQ ID NO: 164; • SEQ ID NO: 165; •SEQ ID NO: 123, • aminosyrer 495-556 af human HGF; • aminosyrer 507-585 af human HGF; og • aminosyrer 506-728 af human HGF, hvor antistoffet kan neutralisere binding af HGF til c-Met.
2. Isoleret antistof ifølge krav 1, hvor antistoffet kan binde et humant/muse kimært HGF-polypeptid, hvor det kimære polypeptid omfatter et muse HGF-molekyle med aminosyrer 506-728 af human HGF i stedet for den homologe musesekvens, og hvor antistoffet ikke binder signifikant til muse HGF.
3. Isoleret antistof ifølge krav 2, hvor det kimære polypeptid omfatter et muse HGF-molekyle med aminosyrer 507-585 af human HGF i stedet for den homologe musesekvens.
4. Isoleret antistof, hvor antistoffet kan binde hepatocytvækstfaktor (HGF), hvor antistoffet kan neutralisere binding af HGF til c-Met, og antistoffet er valgt blandt: et antistof omfattende en let kæde, der omfatter SEQ ID NO: 60, 70 og 80, og en tung kæde, der omfatter SEQ ID NO: 90, 100 og 110; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 61,71 og 81, og en tung kæde, der omfatter SEQ ID NO: 91, 101 og 111; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 62, 72 og 82, og en tung kæde, der omfatter SEQ ID NO: 92, 102 og 112; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 63, 73 og 83, og en tung kæde, der omfatter SEQ ID NO: 93, 103 og 113; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 64, 74 og 84, og en tung kæde, der omfatter SEQ ID NO: 94, 104 og 114; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 65, 75 og 85, og en tung kæde, der omfatter SEQ ID NO: 95, 105 og 115; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 66, 76 og 86, og en tung kæde, der omfatter SEQ ID NO: 96, 106 og 116; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 67, 77 og 87, og en tung kæde, der omfatter SEQ ID NO: 97, 107 og 117; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 68, 78 og 88, og en tung kæde, der omfatter SEQ ID NO: 98, 108 og 118; og et antistof omfattende en let kæde, der omfatter SEQ ID NO: 69, 79 og 89, og en tung kæde, der omfatter SEQ ID NO: 99, 109 og 119.
5. Antistof ifølge krav 4, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 60, 70 og 80, og en tung kæde, der omfatter SEQ ID NO: 90, 100 og 110.
6. Antistof ifølge krav 4, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 61,71 og 81, og en tung kæde, der omfatter SEQ ID NO: 91, 101 og 111.
7. Antistof ifølge krav 4, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 62, 72 og 82, og en tung kæde, der omfatter SEQ ID NO: 92, 102 og 112.
8. Antistof ifølge krav 4, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 63, 73 og 83, og en tung kæde, der omfatter SEQ ID NO: 93, 103 og 113.
9. Antistof ifølge krav 4, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 64, 74 og 84, og en tung kæde, der omfatter SEQ ID NO: 94, 104 og 114.
10. Antistof ifølge krav 4, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 65, 75 og 85, og en tung kæde, der omfatter SEQ ID NO: 95, 105 og 115.
11. Antistof ifølge krav 4, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 66, 76 og 86, og en tung kæde, der omfatter SEQ ID NO: 96, 106 og 116.
12. Antistof ifølge krav 4, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 67, 77 og 87, og en tung kæde, der omfatter SEQ ID NO: 97, 107 og 117.
13. Antistof ifølge krav 4, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 68, 78 og 88, og en tung kæde, der omfatter SEQ ID NO: 98, 108 og 118.
14. Antistof ifølge krav 4, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 69, 79 og 89, og en tung kæde, der omfatter SEQ ID NO: 99, 109 og 119.
15. Antistof ifølge krav 4, hvor antistoffet er valgt blandt: et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 24 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 25 fra rest 20 til rest 141; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 26 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekven-sen af SEQ ID NO: 27 fra rest 20 til rest 137; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 28 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 29 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 30 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 31 fra rest 20 til rest 148; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 32 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 33 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 34 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 35 fra rest 20 til rest 144; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 36 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 37 fra rest 20 til rest 142; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 38 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 39 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 40 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 41 fra rest 20 til rest 140; og et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 42 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 43 fra rest 20 til rest 139.
16. Antistof ifølge krav 15, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 24 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 25 fra rest 20 til rest 141.
17. Antistof ifølge krav 15, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 26 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 27 fra rest 20 til rest 137.
18. Antistof ifølge krav 15, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 28 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 29 fra rest 20 til rest 139.
19. Antistof ifølge krav 15, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 30 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 31 fra rest 20 til rest 148.
20. Antistof ifølge krav 15, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 32 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 33 fra rest 20 til rest 139.
21. Antistof ifølge krav 15, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 34 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 35 fra rest 20 til rest 144.
22. Antistof ifølge krav 15, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 36 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 37 fra rest 20 til rest 142.
23. Antistof ifølge krav 15, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 38 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 39 fra rest 20 til rest 139.
24. Antistof ifølge krav 15, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 40 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 41 fra rest 20 til rest 140.
25. Antistof ifølge krav 15, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 42 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 43 fra rest 20 til rest 139.
26. Antistof ifølge krav 23, hvor den lette kæde endvidere omfatter aminosyresekvensen af SEQ ID NO: 44, og den tunge kæde endvidere omfatter aminosyresekvensen af SEQ ID NO: 46.
27. Isoleret antistof, der kan neutralisere binding af HGF til c-Met, og som konkurrerer om binding til HGF med mindst et antistof valgt blandt: et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 24 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 25 fra rest 20 til rest 141; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 26 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 27 fra rest 20 til rest 137; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 28 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 29 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 30 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 31 fra rest 20 til rest 148; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 32 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 33 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 34 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 35 fra rest 20 til rest 144; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 36 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 37 fra rest 20 til rest 142; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 38 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 39 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 40 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 41 fra rest 20 til rest 140; og et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 42 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 43 fra rest 20 til rest 139.
28. Antistof ifølge krav 27, hvor antistoffet konkurrerer om binding til HGF med et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 36 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekven- sen af SEQ ID NO: 37 fra rest 20 til rest 142.
29. Antistof ifølge krav 27, hvor antistoffet konkurrerer om binding til HGF med et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 38 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 39 fra rest 20 til rest 139.
30. Antistof ifølge et hvilket om helst af krav 1 til 29, som er et enkeltkædet antistof.
31. Antistof ifølge krav 30, hvor det enkeltkædede antistof er et enkeltkædet Fv-antistof.
32. Antistof ifølge et hvilket som helst af krav 1 til 29, som er et Fab-antistof.
33. Antistof ifølge et hvilket som helst af krav 1 til 29, som er et Fab’-antistof.
34. Antistof ifølge et hvilket som helst af krav 1 til 29, som er et F(ab’)2-antistof.
35. Antistof ifølge et hvilket som helst af krav 1 til 29, som er et fuldt humant an tistof.
36. Antistof ifølge et hvilket som helst af krav 1-3 eller 27-29, som er et humaniseret antistof.
37. Sammensætning, der omfatter et antistof ifølge et hvilket som helst af krav 1 til 36 og en farmaceutisk acceptabel bærer.
38. Sammensætning ifølge krav 37 og mindst et middel til anvendelse ved en fremgangsmåde til behandling af cancer hos en patient, og hvor det mindst ene middel er valgt blandt: et medlem af geldanamycinfamilien af anisamycinantibio- tika; en antagonist af Grb 2Src homologi 2; en Gab1 modulator, dominant-negativ Src; en von-Hippel-Landau inhibitor; et ikke-steroidt antiinflammatorisk lægemiddel (NSAID); en COX-2 inhibitor; Celebrex™ (celecoxib); Vioxx™ (rofecoxib); en vaskulær endotelial vækstfaktor (VEGF); en VEGF modulator; en fi-broblastvækstfaktor (FGF)-modulator; en epidermal vækstfaktor (EGF)-modula-tor; en keratinocytvækstfaktor (KGF); et KGF-relateret molekyle; en KGF modulator; en matrixmetalloproteinase (MMP)-modulator; IL-2; Proluekin; Flerceptin; Rituxan; Zevalin; Erbitux; epratuzumab; et antistof til OPGL; en inhibitor til Ang-2; et antistof til VEGF-2; avastin; et antineoplastisk middel; et antimitotisk middel; en antimetabolit; og et alkylsulphonat.
39. Sammensætning ifølge krav 37 og mindst et middel til anvendelse ved en fremgangsmåde til behandling af en massiv tumor hos en patient, og hvor det mindst ene middel er valgt blandt: et medlem af geldanamycinfamilien af anisa-mycinantibiotika; en antagonist af Grb2 Src homologi 2; en Gab1 modulator, dominant-negativ Src; en von-Hippel-Landau inhibitor; et ikke-steroidt antiinflammatorisk lægemiddel (NSAID); en COX-2 inhibitor; Celebrex™ (celecoxib); Vioxx™ (rofecoxib); en vaskulær endotelial vækstfaktor (VEGF); en VEGF modulator; en fibroblastvækstfaktor (FGF)-modulator; en epidermal vækstfaktor (EGF)-modulator; en keratinocytvækstfaktor (KGF); et KGF-relateret molekyle; en KGF modulator; en matrixmetalloproteinase (MMP)-modulator; IL-2; Proluekin; Herceptin; Rituxan; Zevalin; Erbitux; epratuzumab; et antistof til OPGL; en inhibitor til Ang-2; et antistof til VEGF-2; avastin; et antineoplastisk middel; et antimitotisk middel; en antimetabolit; og et alkylsulphonat.
40. Sammensætning ifølge krav 37 til anvendelse ved en fremgangsmåde til behandling af cancer hos en patient.
41. Sammensætning ifølge krav 37 til anvendelse ved en fremgangsmåde til behandling af en massiv tumor hos en patient.
42. Antistof ifølge et hvilket som helst af krav 1 til 36 og mindst et kemoterapimiddel til anvendelse ved en fremgangsmåde til behandling af cancer hos en patient.
43. Antistof ifølge krav 42, hvor fremgangsmåden omfatter indgift af antistoffet før anvendelsen af kemoterapibehandlingen.
44. Antistof ifølge krav 42, hvor fremgangsmåden omfatter indgift af antistoffet samtidig med anvendelsen af kemoterapibehandlingen.
45. Antistof ifølge krav 42, hvor fremgangsmåden omfatter indgift af antistoffet efter anvendelsen af kemoterapibehandlingen.
46. Antistof ifølge et hvilket som helst af krav 1 til 36 og stråleterapi til anvendelse ved en fremgangsmåde til behandling af cancer hos en patient.
47. Antistof ifølge krav 46, hvor fremgangsmåden omfatter indgift af antistoffet før anvendelsen af strålebehandlingen.
48. Antistof ifølge krav 46, hvor fremgangsmåden omfatter indgift af antistoffet samtidig med anvendelsen af strålebehandlingen.
49. Antistof ifølge krav 46, hvor fremgangsmåden omfatter indgift af antistoffet efter anvendelsen af strålebehandlingen.
50. Fremgangsmåde til detektering af niveauet af hepatocytvækstfaktor (HGF) i en prøve, omfattende at bringe prøven i kontakt med antistoffet ifølge et hvilket som helst af krav 1 til 36.
51. Polypeptid, der består af en aminosyresekvens valgt blandt •SEQ ID NO: 164; •SEQ ID NO: 165; •SEQ ID NO: 123: • aminosyrer 495-556 af human HGF; og • aminosyrer 507-585 af human HGF.
52. Fremgangsmåde til opnåelse af et antistof ifølge et hvilket som helst af krav 1 til 36, der kan binde hepatocytvækstfaktor (HGF), omfattende at indgive mindst et polypeptid, der består af en aminosyresekvens valgt blandt •SEQ ID NO: 164; •SEQ ID NO: 165; •SEQ ID NO: 123; • aminosyrer 495-556 af human HGF; og • aminosyrer 507-585 af human HGF til et ikke-humant dyr og at opnå et antistof, der kan binde HGF fra dyret.
53. Værtscelle, der omfatter et første polynucleotid, der indkoder en let kæde, og et andet polynucleotid, der indkoder en tung kæde, hvor den lette kæde og den tunge kæde danner et antistof, som kan binde hepatocytvækstfaktor (HGF), og antistoffet er valgt blandt: et antistof omfattende en let kæde, der omfatter SEQ ID NO: 60, 70 og 80, og en tung kæde, der omfatter SEQ ID NO: 90, 100 og 110; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 61,71 og 81, og en tung kæde, der omfatter SEQ ID NO: 91, 101 og 111; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 62, 72 og 82, og en tung kæde, der omfatter SEQ ID NO: 92, 102 og 112; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 63, 73 og 83, og en tung kæde, der omfatter SEQ ID NO: 93, 103 og 113; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 64, 74 og 84, og en tung kæde, der omfatter SEQ ID NO: 94, 104 og 114; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 65, 75 og 85, og en tung kæde, der omfatter SEQ ID NO: 95, 105 og 115; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 66, 76 og 86, og en tung kæde, der omfatter SEQ ID NO: 96, 106 og 116; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 67, 77 og 87, og en tung kæde, der omfatter SEQ ID NO: 97, 107 og 117; et antistof omfattende en let kæde, der omfatter SEQ ID NO: 68, 78 og 88, og en tung kæde, der omfatter SEQ ID NO: 98, 108 og 118; og et antistof omfattende en let kæde, der omfatter SEQ ID NO: 69, 79 og 89, og en tung kæde, der omfatter SEQ ID NO: 99, 109 og 119.
54. Værtscelle ifølge krav 53, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 60, 70 og 80, og en tung kæde, der omfatter SEQ ID NO: 90, 100 og 110.
55. Værtscelle ifølge krav 53, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 61, 71 og 81, og en tung kæde, der omfatter SEQ ID NO: 91, 101 og 111.
56. Værtscelle ifølge krav 53, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 62, 72 og 82, og en tung kæde, der omfatter SEQ ID NO: 92, 102 og 112.
57. Værtscelle ifølge krav 53, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 63, 73 og 83, og en tung kæde, der omfatter SEQ ID NO: 93, 103 og 113.
58. Værtscelle ifølge krav 53, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 64, 74 og 84, og en tung kæde, der omfatter SEQ ID NO: 94, 104 og 114.
59. Værtscelle ifølge krav 53, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 65, 75 og 85, og en tung kæde, der omfatter SEQ ID NO: 95, 105 og 115.
60. Værtscelle ifølge krav 53, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 66, 76 og 86, og en tung kæde, der omfatter SEQ ID NO: 96, 106 og 116.
61. Værtscelle ifølge krav 53, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 67, 77 og 87, og en tung kæde, der omfatter SEQ ID NO: 97, 107 og 117.
62. Værtscelle ifølge krav 53, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 68, 78 og 88, og en tung kæde, der omfatter SEQ ID NO: 98, 108 og 118.
63. Værtscelle ifølge krav 53, hvor antistoffet omfatter en let kæde, der omfatter SEQ ID NO: 69, 79 og 89, og en tung kæde, der omfatter SEQ ID NO: 99, 109 og 119.
64. Værtscelle ifølge krav 53, hvor antistoffet er valgt blandt: et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 24 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 25 fra rest 20 til rest 141; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 26 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 27 fra rest 20 til rest 137; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 28 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 29 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 30 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 31 fra rest 20 til rest 148; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 32 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 33 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 34 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 35 fra rest 20 til rest 144; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 36 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 37 fra rest 20 til rest 142; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 38 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 39 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 40 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 41 fra rest 20 til rest 140; og et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 42 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 43 fra rest 20 til rest 139.
65. Værtscelle ifølge krav 64, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 24 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 25 fra rest 20 til rest 141.
66. Værtscelle ifølge krav 64, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 26 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 27 fra rest 20 til rest 137.
67. Værtscelle ifølge krav 64, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 28 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 29 fra rest 20 til rest 139.
68. Værtscelle ifølge krav 64, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 30 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 31 fra rest 20 til rest 148.
69. Værtscelle ifølge krav 64, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 32 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 33 fra rest 20 til rest 139.
70. Værtscelle ifølge krav 64, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 34 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 35 fra rest 20 til rest 144.
71. Værtscelle ifølge krav 64, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 36 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 37 fra rest 20 til rest 142.
72. Værtscelle ifølge krav 64, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 38 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 39 fra rest 20 til rest 139.
73. Værtscelle ifølge krav 64, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 40 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 41 fra rest 20 til rest 140.
74. Værtscelle ifølge krav 64, hvor antistoffet omfatter en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 42 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 43 fra rest 20 til rest 139.
75. Værtscelle ifølge krav 72, hvor den lette kæde endvidere omfatter aminosyresekvensen af SEQ ID NO: 44, og den tunge kæde endvidere omfatter aminosyresekvensen af SEQ ID NO: 46.
76. Værtscelle, der omfatter et første polynucleotid, der indkoder en let kæde, og et andet polynucleotid, der indkoder en tung kæde, hvor den lette kæde og den tunge kæde danner et antistof, der kan binde et humant/muse kimært HGF-polpeptid, hvor det kimære polypeptid omfatter et muse HGF-molekyle med aminosyrer 506-728 af human HGF i stedet for den homologe musesekvens, hvor antistoffet ikke binder signifikant til muse HGF, og hvor antistoffet kan neutralisere binding af HGF til c-Met.
77. Værtscelle ifølge krav 76, hvor det kimære polypeptid omfatter et muse HGF-molekyle med aminosyrer 507-585 af human HGF i stedet for den homologe musesekvens.
78. Værtscelle, der omfatter et første polynucleotid, der indkoder en let kæde, og et andet polynucleotid, der indkoder en tung kæde, hvor den lette kæde og den tunge kæde danner et antistof, der kan neutralisere binding af FIGF til c-Met, og som konkurrerer om binding til HGF med mindst et antistof valgt blandt: et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 24 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 25 fra rest 20 til rest 141; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 26 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 27 fra rest 20 til rest 137; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 28 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 29 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 30 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 31 fra rest 20 til rest 148; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 32 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 33 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 34 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekven- sen af SEQ ID NO: 35 fra rest 20 til rest 144; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 36 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 37 fra rest 20 til rest 142; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 38 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 39 fra rest 20 til rest 139; et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 40 fra rest 23 til rest 129, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 41 fra rest 20 til rest 140; og et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 42 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 43 fra rest 20 til rest 139.
79. Værtscelle ifølge krav 78, hvor antistoffet konkurrerer om binding til HGF med et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 36 fra rest 21 til rest 133, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 37 fra rest 20 til rest 142.
80. Værtscelle ifølge krav 78, hvor antistoffet konkurrerer om binding til HGF med et antistof omfattende en let kæde, der omfatter aminosyresekvensen af SEQ ID NO: 38 fra rest 21 til rest 128, og en tung kæde, der omfatter aminosyresekvensen af SEQ ID NO: 39 fra rest 20 til rest 139.
81. Værtscelle ifølge et hvilket som helst af krav 53 til 80, hvor det første poly-nucleotid og det andet polynucleotid er funktionsmæssigt koblet således, at de indkoder et enkeltkædet antistof.
82. Værtscelle ifølge krav 81, hvor det enkeltkædede antistof er et enkeltkædet Fv-antistof.
83. Værtscelle ifølge et hvilket som helst af krav 53 til 80, der indkoder et Fab-antistof.
84. Værtscelle ifølge et hvilket som helst af krav 53 til 80, der indkoder et Fab’-antistof.
85. Værtscelle ifølge et hvilket som helst af krav 53 til 80, der indkoder et F(ab’)2-antistof.
86. Værtscelle ifølge et hvilket som helst af krav 53 til 80, der indkoder et fuldt humant antistof.
87. Værtscelle ifølge et hvilket som helst af krav 76-80, der er et humaniseret antistof.
88. Fremgangsmåde til fremstilling af et antistof, der kan binde hepato-cytvækstfaktor (HGF), omfattende at udtrykke et første polynucleotid og et andet polynucleotid i en isoleret værtscelle, hvor det første polynucleotid indkoder en let kæde, og det andet polynucleotid indkoder en tung kæde, hvor den lette kæde og den tunge kæde danner et antistof ifølge et hvilket som helst af krav 1 til 36.
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PCT/US2004/018936 WO2005017107A2 (en) | 2003-07-18 | 2004-07-16 | Specific binding agents to hepatocyte growth factor |
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