ES2592511T3 - Composiciones del dominio de fibronectina estabilizados, métodos y usos - Google Patents

Composiciones del dominio de fibronectina estabilizados, métodos y usos Download PDF

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ES2592511T3
ES2592511T3 ES11775616.3T ES11775616T ES2592511T3 ES 2592511 T3 ES2592511 T3 ES 2592511T3 ES 11775616 T ES11775616 T ES 11775616T ES 2592511 T3 ES2592511 T3 ES 2592511T3
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seq
amino acid
acid sequence
methods
fibronectin domain
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Steven Jacobs
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Janssen Biotech Inc
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    • C12N15/1034—Isolating an individual clone by screening libraries
    • C12N15/1044—Preparation or screening of libraries displayed on scaffold proteins
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    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • 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
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2318/00—Antibody mimetics or scaffolds
    • C07K2318/20—Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Un polipéptido que comprende una molécula de base de armazón que comprende dominios en bucle topológicamente similares a dominios del dominio del tercer fibronectino, el polipéptido tiene una secuencia de amino ácido basada en una secuencia de consenso del demonio del tercer fibronectino poseyendo: i. La secuencia de amino ácido de SEQ ID NO: 16, en la cual residuos específicos de SEQ ID NO: 16 son reemplazados y mejorada la estabilidad térmica y la estabilidad química de la molécula de base de armazón, en la cual la molécula con base de armazón comprende uno o más sustituciones selectas de un grupo consistente en N46V, E14P, L17A y E86I; o ii. La secuencia de amino ácido seleccionada de un grupo que consiste en SEQ ID NOs: 142, 143 y 147-151

Description

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Tabla 2
5
15
Secuencia
Descripción 1st Suma de puntuación 2nd Suma de puntuación Score suma (cadena) Score sum (molécula)
Tenascina
Alt. Scaff. 6.01 5.85 11.86 11.86
Tencon
Alt. Scaff. 5.83 7.37 13.20 13.20
adalimumab
Vh Humanizado mAb 9.45 8.06 17.50 45.42
VI
15.29 12.63 27.92
cetuximab
Vh Quimérico mAb 17.63 16.89 34.52 64.44
VI
14.45 14.47 29.92
Rituximab
Vh Quimérico mAb 16.57 14.38 30.96 61.65
VI
16.63 14.06 30.69
basiliximab
Vh Quimérico mAb 16.48 13.40 29.89 59.98
VI
16.05 13.05 29.09
Tabla 3. Bucles
Bucle
Residuos de SEC ID NO:16 Secuencia de aminoacido
A-B
13-16 TEDS
B-C
22-28 TAPDAAF
C-D
38-43 SEKVGE
D-E
51-54 GSER
E-F
60-64 GLKPG
F-G
75-81 KGGHRSN
Tabla 4. Caffolds union a IgG
35
45
55
Clon No.
B:C Bucle Residuos 22-28(Sec ID Nº) F:G Bucle Residuos 75-81 (Sec ID Nº) Mutaciones Scaffold
1
SYGFNN (21) QIGPIIP (46)
2
TYEGES (22) QIGPIIP (46)
3
TYESES (23) QIGPIIP (46)
4
TNWMDS (24) SIRTIDS (47)
5
KSVFIM (25) PKFHSPL (48)
6
YSSYAT (26) WKTTIWF (49)
7
RFHPFP (27) RKNWKTR (50)
8
MMCMPL (28) RLFRIYQ (51)
9
YCRVRD (29) WLSRSYD (52)
10
SYGFNN (21) WLSRSYD (52)
11
MDCFMG (30) WLSRSCD (53)
12
TYRFNS (31) WMGPYCD (54)
13
ASRRSL (32) RRRRYSF (55)
14
TIESES (33) HIVPMVP (56)
15
TL*MQS (34) QIEPIIR (57)
16
IYDSES (35) PSAANNP (58)
17
VRLRYVQ (59)
18
QVGPLIP (60)
19
RIGPILP (61)
20
QIGPLLP (62)
21
RIGPLLP (63)
18
Continuación
5
10
15
20
25
30
35
40
45
50
55
60
65
Clon No.
B:C Bucle Residuos 22-28(Sec ID Nº) F:G Bucle Residuos 75-81 (Sec ID Nº) Mutaciones Scaffold
22
QVGPLLP (64)
23
RIGPMLP (65)
24
QIGPVLP (66)
25
RIGPVLP (67)
26
QIGPMMP (68)
27
QVGPLVP (69)
28
QIGPMLP (70) R18P
29
QVGPILP (71)
30
QVGPLLP (64)
31
QVGPMLP (72)
32
QIGPIVP (73) 133V
33
MIGPLLP (74)
34
QIGPLFP (75)
35
QIGPVLP (66) T59A
36
QIGPMVP (76)
37
QIGPIVP (77)
38
RIEPILP (78) V74G
39
VAGSVWP (79)
40
REGATLY (80)
41
KQIPPIL (81) S38G
42
LSLSSVL (82)
43
HMLLPLP (83) V74A
44
MIGPLIP (84)
45
TIGPHIP (85)
46
EIGPCLP (86)
47
EIGPVLP (87)
48
KIGPCLP (88) Y35H
49
MIGPVLP (89)
50
QIGPILP (90) S52P
51
QIGPILP (90) Q36R
52
QIGPILP (90)
53
EVGPILP (91)
54
QVGPLLP (92) A23T
55
QIGPVMP (93)
56
QIGPCVP (94)
57
QIGPLVP (95)
58
RGLVMPM (96) V74A
59
MIGPILP (97)
19
Continuación
15
25
35
45
55
Clon No..
B:C Bucle Residuos 22-28(Sec ID Nº) F:G Bucle Residuos 75-81 (Sec ID Nº) Mutaciones Scaffold
60
QIGPILP (90) E37G
61
QIGPILP (90) T68A
62
QIGPILP (90) T22I
63
QIGPILP (90) S52F
64
QIGPILP (90) Y56H
65
QIGPILP (90) A44V
66
QIGPILP (90) P24S
67
RIGPILP (61)
68
CIGPMVP (98)
69
FIGPVLP (99)
70
HIGPILP (100)
71
HIGPIMP (101)
72
HIGPYLP (102)
73
HVGPILP (103)
74
IIGPLLP (104)
75
LIGPLLP (105)
76
MVGPLLP (106)
77
NIGPYLP (107)
78
NIGPYLP (108)
79
QIGPHLP (109)
80
QIGPIIP (46)
82
QIGPILG (110)
83
QIGPILS (111)
83
QIGPILT (112)
84
QIGPIMP (113)
85
QIGPIPI (114)
86
QIGPLLN (115)
87
QIGPLLP (62)
88
QIGPVFP (116)
89
QIGPVLS (117)
90
QIGPWLP (118)
92
QVGPILP (71)
93
QVGPILR (118)
94
QVGPIMN (119)
95
QVGPIMP (120)
96
QVGPIVP (121)
97
QVGPLLS (122)
98
QVGPVLP (123)
20
Continuación
5
10
15
20
25
30
35
Clon No..
B:C Bucle Residuos 22-28(Sec ID Nº) F:G Bucle Residuos 75-81 (Sec ID Nº) Mutaciones Scaffold
99
QVGPVLT (124)
100
RIGPIMP (125)
101
RIGPIVP (126)
102
RIGPMFP (127)
103
RIGPMIP (128)
104
RIGPMVP (129)
105
RIGPVIP (130)
106
RVGPILP (131)
107
RVGPLLP (132)
108
TVGPHIP (133)
109
DRKRFI (36) PSWRSNW (134)
110
EFWRGS (37) QIGPLLP (62)
111
GLLDPL (38) ALRATLE (135)
112
GLVLPE (39) KYGYLTP (136)
113
MASDGL (40) RIGPMLP (137)
114
NKTETN (41) NPFCSRF (138)
115
QAERKV (42) QIGPLLP (62)
116
QAERKV (42) RIGPLLP (63)
117
SQVCTL (43) YYLHQWC (139)
118
YFDKDS (44) QIGPLLP (62)
119
YFECEP (45) HIVPLLR (140)
40
Secuencias:
SEC ID NO. 1:
45
imagen17
SEC ID NO. 2:
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SEC ID NO. 3:
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SEC IDE NO. 4
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21
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Claims (1)

  1. imagen1
    imagen2
ES11775616.3T 2010-04-30 2011-04-29 Composiciones del dominio de fibronectina estabilizados, métodos y usos Active ES2592511T3 (es)

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US329980P 2010-04-30
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