ES2603061T3 - Interrupción de la percepción de quórum en bacterias mediada por anticuerpos - Google Patents

Interrupción de la percepción de quórum en bacterias mediada por anticuerpos Download PDF

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ES2603061T3
ES2603061T3 ES14180831.1T ES14180831T ES2603061T3 ES 2603061 T3 ES2603061 T3 ES 2603061T3 ES 14180831 T ES14180831 T ES 14180831T ES 2603061 T3 ES2603061 T3 ES 2603061T3
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seq
amino acid
kynp
hapten
cyclic peptide
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Kim D. Janda
Gunnar F. Kaufmann
Junguk Park
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Scripps Research Institute
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/12—Cyclic peptides with only normal peptide bonds in the ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • 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
    • A61K39/02—Bacterial antigens
    • A61K39/085—Staphylococcus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
    • C07K16/1271—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Micrococcaceae (F), e.g. Staphylococcus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/64—Cyclic peptides containing only normal peptide links
    • 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
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • 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

Abstract

Una entidad molecular inmunogénica que comprende al menos un hapteno ligado a un vehículo macromolecular, en donde el hapteno comprende un péptido cíclico que comprende un anillo macrocíclico, en donde el péptido cíclico comprende la secuencia de aminoácidos seleccionada del grupo que consiste RIPT(Xa+2)TGFF (SEQ ID NO: 110), GVNP(Xa+2)GGWF (SEQ ID NO: 96), KAKT(Xa+2)TVLY (SEQ ID NO: 97), KTKT(Xa+2)TVLY (SEQ ID NO: 98), GANP(Xa+2)OLYY (SEQ ID NO: 99), GANP(Xa+2)ALYY (SEQ ID NO: 100), GYST(Xa+2)SYYF (SEQ ID NO: 101), GYRT(Xa+2)NTYF (SEQ ID NO: 102), YNP(Xa+2)VGYF (SEQ ID NO: 103), GGKV(Xa+2)SAYF (SEQ ID NO: 104), SVKP(Xa+2)TGFA (SEQ ID NO: 105), DSV(Xa+2)ASYF (SEQ ID NO: 106), KYNP(Xa+2)SNYL (SEQ ID NO: 107), KYNP(Xa+2)ASYL (SEQ ID NO: 108), KYNP(Xa+2)ANYL (SEQ ID NO: 109), DI(Xa+2)NAYF (SEQ ID NO: 111), DM(Xa+2)NGYF (SEQ ID NO: 112), KYNP(Xa+2)LGFL (SEQ ID NO: 113), KYYP(Xa+2)FGYF (SEQ ID NO: 114), GARP(Xa+2)GGFF (SEQ ID NO: 115), GAKP(Xa+2)GGFF (SEQ ID NO: 116), YSP(Xa+2)TNFF (SEQ ID NO: 117), YSP(Xa+2)TNF (SEQ ID NO: 118), QN(Xa+2)PNIFGQWM (SEQ ID NO: 119), en donde el último residuo de aminoácido de cada secuencia es X1, que es un residuo de aminoácido que está unido covalentemente a un grupo R a través del respectivo grupo carbonilo; Xa+2 es cualquier aminoácido, del cual el respectivo átomo de carbono está unido covalentemente a R; en donde R comprende -CH2O-, -CH2CH2O-, -CH2CH(CH3)O-, -CH2-fenil-O-, -CH2S, -CH2CH2S- ó -(CH2)nNH-, en donde n va de 1 a aproximadamente 4; y en donde el residuo de aminoácido N-terminal del péptido cíclico está unida al vehículo macromolecular; y en donde el vehículo macromolecular tiene un tamaño suficiente, en conjunción con el hapteno unido al mismo, para activar la aparición de una respuesta inmune por parte de un organismo expuesto a la entidad molecular inmunogénica.

Description

imagen1
imagen2
imagen3
imagen4
imagen5
imagen6
imagen7
imagen8
imagen9
imagen10
imagen11
imagen12
imagen13
imagen14
imagen15
imagen16
imagen17
imagen18
imagen19
imagen20
AP4-24H11
imagen21 imagen22
AP4-29E10-1
imagen23 imagen24
AP4-29E10-2
imagen25 imagen26
AP1-15B4-∆
imagen27 imagen28
AP4-24H11-∆
imagen29 imagen30
AP4-29E10-1-∆
imagen31 imagen32
AP4-29E10-2-∆
imagen33 imagen34
Secuencias de ácidos nucleicos que codifican las cadenas variables pesadas y ligeras de anticuerpos monoclonales de ratón Secuencias de aminoácidos de anticuerpos scFv humanos
Anticuerpo
Cadena pesada variable Cadena ligera variable
AP1-15B4
imagen35 imagen36
AP4-24H11
imagen37 imagen38
AP4-29E10-1
imagen39 imagen40
AP4-29E10-2
imagen41 imagen42
AP1-15B4-∆
imagen43 imagen44
AP4-24H11-∆
imagen45 imagen46
AP4-29E10-1-∆
imagen47 imagen48
AP4-29E10-2-∆
imagen49 imagen50
imagen51
imagen52
imagen53
Secuencias de nucleótidos que codifican las cadenas variables pesadas y ligeras de anticuerpos scFv humanos
Anticuerp o
Cadena pesada variable Cadena ligera variable
AP1-2
imagen54 imagen55
AP1-6
imagen56 imagen57
AP1-8
imagen58 imagen59
AP1-11
imagen60 imagen61
AP1-15
imagen62 imagen63
AP1-16
imagen64 imagen65
AP1-19
imagen66 imagen67
AP3-1
imagen68 imagen69
AP3-2
imagen70 imagen71
AP3-3
imagen72 imagen73
AP3-5
imagen74 imagen75
AP3-6
imagen76 imagen77
AP3-8
imagen78 imagen79
AP3-10
imagen80 imagen81
AP3-13
imagen82 imagen83
AP3-20
imagen84 imagen85
AP4-8
imagen86 imagen87
AP4-14
imagen88 imagen89
AP4-20
imagen90 imagen91
Ácidos nucleicos que codifican las scFvs humanas
Anticuerpo
Cadena variable pesada
AP1-2
imagen92
AP1-6
imagen93
AP1-8
imagen94
AP1-11
imagen95
AP1-15
imagen96
AP1-16
imagen97
AP1-19
imagen98
AP3-1
imagen99
AP3-2
imagen100
AP3-3
imagen101
AP3-5
imagen102
AP3-6
imagen103
AP3-8
imagen104
AP3-10
imagen105
AP3-13
imagen106
AP3-20
imagen107
AP4-8
imagen108
AP4-14
imagen109
imagen110
imagen111
imagen112
imagen113
imagen114
imagen115
imagen116
imagen117
imagen118
imagen119
–
imagen120
imagen121
imagen122
imagen123
imagen124
imagen125
-
imagen126
imagen127
imagen128
imagen129
imagen130
~
~
imagen131
-
-
-
imagen132
imagen133
imagen134
-
imagen135
imagen136
29B8
> 625 µM > 625 µM > 625 µM > 625 µM
29D5
> 625 µM > 625 µM > 625 µM > 625 µM
30C9
156 µM > 625 µM > 625 µM > 625 µM
30H8
> 625 µM > 625 µM > 625 µM > 625 µM
30H11
156 µM 156 µM 4,9-2,5 µM > 625 µM
AP4 Sups
AIP1 wt AIP2 wt AIP3 wt AIP4 wt
9G2
> 25 µM > 25 µM > 25 µM ~ 700 nM
12A2
> 25 µM > 25 µM > 25 µM > 25 µM
13G5
> 25 µM > 25 µM > 25 µM > 25 µM
15B3
> 25 µM > 25 µM > 25 µM > 25 µM
15C3
> 25 µM > 25 µM > 25 µM > 25 µM
15E8
> 25 µM > 25 µM > 25 µM > 25 µM
16D1
> 25 µM > 25 µM > 25 µM > 25 µM
17G2
> 25 µM > 25 µM > 25 µM > 25 µM
18D3
> 25 µM > 25 µM > 25 µM > 25 µM
18G10
> 25 µM > 25 µM > 25 µM > 25 µM
22B8
> 25 µM > 25 µM > 25 µM > 25 µM
22D9
> 25 µM > 25 µM > 25 µM > 25 µM
22F2
> 25 µM > 25 µM > 25 µM > 25 µM
22G7
> 25 µM > 25 µM > 25 µM > 25 µM
23C4
> 25 µM > 25 µM > 25 µM > 25 µM
23E6
~ 6 µM > 25 µM > 25 µM ~ 390 nM
24H11
~ 5 µM > 25 µM > 25 µM ~ 98 nM
26E8
> 25 µM > 25 µM > 25 µM > 25 µM
27E9
> 25 µM > 25 µM > 25 µM > 25 µM
29E10
~ 3 µM > 25 µM > 25 µM ~ 24 nM
Todos los hibridomas competitivos fueron re-evaluados, mostrándose el promedio. El AP4-29E10 fue evaluado 5 veces distintas, mostrando una variabilidad que oscila entre 2 nM y 110 nM, pero centrada principalmente alrededor de 24 nM.
Las secuencias de aminoácidos y de nucleótidos correspondientes a anticuerpos monoclonales seleccionados fueron determinadas, y se muestran en las Tablas presentadas a continuación.
Secuencias de aminoácidos de las cadenas variables pesadas y ligeras de anticuerpos monoclonales de ratón
Anticuerpo
Cadena pesada variable Cadena ligera variable
AP1-15B4
imagen137 imagen138
AP4-24H11
imagen21 imagen22
AP4-29E10-1
imagen23 imagen24
AP4-29E10-2
imagen25 imagen26
AP1-15B4-∆
imagen27 imagen28
AP4-24H11-∆
imagen29 imagen30
AP4-29E10-1-∆
imagen31 imagen32
AP4-29E10-2-∆
imagen33 imagen34
Secuencias de ácidos nucleicos que codifican las cadenas variables pesadas y ligeras de anticuerpos monoclonales de ratón
Anticuerpo
Cadena pesada variable Cadena ligera variable
AP1-15B4
imagen35 imagen36
AP4-24H11
imagen37 imagen38
AP4-29E10-1
imagen39 imagen40
AP4-29E10-2
imagen41 imagen42
AP1-15B4-∆
imagen43 imagen44
AP4-24H11-∆
imagen45 imagen46
AP4-29E10-1-∆
imagen47 imagen48
AP4-29E10-2-∆
imagen49 imagen50
imagen139
imagen140
imagen141
imagen142
AP3-10
imagen143
AP3-13
imagen144
AP3-20
imagen145
AP4-8
imagen146
AP4-14
imagen147
AP4-20
imagen148
Secuencias de nucleótidos que codifican las cadenas variables pesadas y ligeras de anticuerpos scFv humanos
Anticuerpo
Cadena pesada variable Cadena ligera variable
AP1-2
imagen149 imagen150
AP1-6
imagen151 imagen152
AP1-8
imagen153 imagen154
AP1-11
imagen155 imagen156
AP1-15
imagen157 imagen158
AP1-16
imagen159 imagen160
AP1-19
imagen161 imagen162
AP3-1
imagen163 imagen164
AP3-2
imagen165 imagen166
AP3-3
imagen167 imagen168
AP3-5
imagen169 imagen170
AP3-6
imagen171 imagen172
AP3-8
imagen173 imagen174
AP3-10
imagen175 imagen176
AP3-13
imagen177 imagen178
AP3-20
imagen179 imagen180
AP4-8
imagen181 imagen182
AP4-14
imagen183 imagen184
AP4-20
imagen185 imagen186
Ácidos nucleicos que codifican las scFvs humanas
Anticuerpo
Cadena variable pesada
AP1-2
imagen92
AP1-6
imagen93
AP1-8
imagen94
AP1-11
imagen95
AP1-15
imagen96
AP1-16
imagen97
AP1-19
imagen98
AP3-1
imagen99
AP3-2
imagen100
AP3-3
imagen101
AP3-5
imagen102
AP3-6
imagen103
AP3-8
imagen104
AP3-10
imagen105
AP3-13
imagen106
AP3-20
imagen107
imagen187
imagen188
imagen189
imagen190
imagen191
-
imagen192

Claims (1)

  1. imagen1
ES14180831.1T 2007-10-25 2008-10-24 Interrupción de la percepción de quórum en bacterias mediada por anticuerpos Active ES2603061T3 (es)

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CN (2) CN101835484B (es)
AU (1) AU2008317331B2 (es)
CA (2) CA2703133C (es)
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EP2211889B1 (en) 2014-08-20
US20170043020A1 (en) 2017-02-16
JP2011500814A (ja) 2011-01-06
EP2211889A4 (en) 2012-01-11
CN101835484B (zh) 2014-07-16
CA2703133C (en) 2017-09-19
JP2014221774A (ja) 2014-11-27
CN104211775A (zh) 2014-12-17
JP2018021021A (ja) 2018-02-08
CA2703133A1 (en) 2009-04-30
KR101557173B1 (ko) 2015-10-05
EP2211889A2 (en) 2010-08-04
WO2009055054A2 (en) 2009-04-30
EP2842565A1 (en) 2015-03-04
US20100291093A1 (en) 2010-11-18
CA2975568A1 (en) 2009-04-30
CN101835484A (zh) 2010-09-15
AU2008317331A1 (en) 2009-04-30
US9394371B2 (en) 2016-07-19
WO2009055054A3 (en) 2009-09-03
AU2008317331B2 (en) 2013-08-29
JP6183910B2 (ja) 2017-08-23
JP5581490B2 (ja) 2014-09-03
KR20100102100A (ko) 2010-09-20
EP2842565B1 (en) 2016-08-24

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