ES2548518T3 - Conjugado molecular - Google Patents
Conjugado molecular Download PDFInfo
- Publication number
- ES2548518T3 ES2548518T3 ES06838327.2T ES06838327T ES2548518T3 ES 2548518 T3 ES2548518 T3 ES 2548518T3 ES 06838327 T ES06838327 T ES 06838327T ES 2548518 T3 ES2548518 T3 ES 2548518T3
- Authority
- ES
- Spain
- Prior art keywords
- molecule
- conjugate
- thiol
- group
- antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 238000000034 method Methods 0.000 claims abstract description 88
- 125000003396 thiol group Chemical class [H]S* 0.000 claims abstract description 47
- 239000002253 acid Substances 0.000 claims abstract description 20
- 230000007935 neutral effect Effects 0.000 claims abstract description 19
- 125000003172 aldehyde group Chemical group 0.000 claims abstract description 16
- -1 linker compound Chemical class 0.000 claims abstract description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 7
- 230000003647 oxidation Effects 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims description 50
- 102000004190 Enzymes Human genes 0.000 claims description 27
- 108090000790 Enzymes Proteins 0.000 claims description 27
- 230000009870 specific binding Effects 0.000 claims description 17
- 239000002105 nanoparticle Substances 0.000 claims description 11
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 150000003573 thiols Chemical class 0.000 description 94
- 238000010186 staining Methods 0.000 description 76
- 238000001514 detection method Methods 0.000 description 63
- 125000005647 linker group Chemical group 0.000 description 44
- 239000000523 sample Substances 0.000 description 40
- 229940088598 enzyme Drugs 0.000 description 34
- 239000000243 solution Substances 0.000 description 27
- 210000001519 tissue Anatomy 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 23
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 23
- 238000011534 incubation Methods 0.000 description 23
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 20
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- 238000005859 coupling reaction Methods 0.000 description 16
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- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
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- 239000012634 fragment Substances 0.000 description 11
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- 150000001412 amines Chemical class 0.000 description 10
- 239000000499 gel Substances 0.000 description 10
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 10
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 10
- 150000003923 2,5-pyrrolediones Chemical group 0.000 description 9
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- 108010085238 Actins Proteins 0.000 description 8
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 description 8
- 125000003277 amino group Chemical group 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
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- 150000001875 compounds Chemical class 0.000 description 8
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- 238000003756 stirring Methods 0.000 description 8
- 229910052717 sulfur Inorganic materials 0.000 description 8
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 7
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- 239000011780 sodium chloride Substances 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 7
- 239000011592 zinc chloride Substances 0.000 description 7
- 235000005074 zinc chloride Nutrition 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
- 108091034120 Epstein–Barr virus-encoded small RNA Proteins 0.000 description 6
- 239000004365 Protease Substances 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 229960002685 biotin Drugs 0.000 description 6
- 239000011616 biotin Substances 0.000 description 6
- 150000001718 carbodiimides Chemical class 0.000 description 6
- 230000018044 dehydration Effects 0.000 description 6
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- 239000003599 detergent Substances 0.000 description 6
- 230000007717 exclusion Effects 0.000 description 6
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 6
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
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- 229910052760 oxygen Inorganic materials 0.000 description 6
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 6
- 239000011535 reaction buffer Substances 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- PIFIISOIFYMVLS-UHFFFAOYSA-N 6-acetylsulfanylhexanoic acid Chemical compound CC(=O)SCCCCCC(O)=O PIFIISOIFYMVLS-UHFFFAOYSA-N 0.000 description 5
- 241000283707 Capra Species 0.000 description 5
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- 125000002252 acyl group Chemical group 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 229910052681 coesite Inorganic materials 0.000 description 5
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- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 229910021645 metal ion Inorganic materials 0.000 description 5
- CRMPEIJSRPNMRH-UHFFFAOYSA-N n-(1-hydrazinyl-1-oxo-4-sulfanylbutan-2-yl)acetamide Chemical compound CC(=O)NC(CCS)C(=O)NN CRMPEIJSRPNMRH-UHFFFAOYSA-N 0.000 description 5
- 125000004043 oxo group Chemical group O=* 0.000 description 5
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 5
- 235000012239 silicon dioxide Nutrition 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
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- IHVODYOQUSEYJJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]amino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)C(CC1)CCC1CN1C(=O)C=CC1=O IHVODYOQUSEYJJ-UHFFFAOYSA-N 0.000 description 4
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- 108010001336 Horseradish Peroxidase Proteins 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- WLDHEUZGFKACJH-UHFFFAOYSA-K amaranth Chemical compound [Na+].[Na+].[Na+].C12=CC=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(O)=C1N=NC1=CC=C(S([O-])(=O)=O)C2=CC=CC=C12 WLDHEUZGFKACJH-UHFFFAOYSA-K 0.000 description 4
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Classifications
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
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- A61K47/68—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
- A61K47/6815—Enzymes
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- C12Y—ENZYMES
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Landscapes
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Applications Claiming Priority (3)
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US73979405P | 2005-11-23 | 2005-11-23 | |
US739794P | 2005-11-23 | ||
PCT/US2006/045302 WO2007062177A2 (en) | 2005-11-23 | 2006-11-21 | Molecular conjugate |
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ES2548518T3 true ES2548518T3 (es) | 2015-10-19 |
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ES06838327.2T Active ES2548518T3 (es) | 2005-11-23 | 2006-11-21 | Conjugado molecular |
ES16001225T Active ES2804129T3 (es) | 2005-11-23 | 2006-11-21 | Conjugado anticuerpo-enzima |
ES15001958.6T Active ES2677555T3 (es) | 2005-11-23 | 2006-11-21 | Conjugado molecular |
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ES16001225T Active ES2804129T3 (es) | 2005-11-23 | 2006-11-21 | Conjugado anticuerpo-enzima |
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EP1877101B1 (en) | 2005-04-28 | 2016-11-16 | Ventana Medical Systems, Inc. | Enzymes conjugated to antibodies via a peg heterobifuctional linker |
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JP5199880B2 (ja) | 2005-11-23 | 2013-05-15 | ベンタナ・メデイカル・システムズ・インコーポレーテツド | 分子コンジュゲート |
US8492129B2 (en) * | 2005-12-12 | 2013-07-23 | Innova Biosciences, Ltd. | Production of conjugates |
CA3069091C (en) * | 2006-11-01 | 2021-09-14 | Ventana Medical Systems, Inc. | Haptens, hapten conjugates, compositions thereof and method for their preparation and use |
US7682789B2 (en) * | 2007-05-04 | 2010-03-23 | Ventana Medical Systems, Inc. | Method for quantifying biomolecules conjugated to a nanoparticle |
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US9193763B2 (en) | 2007-08-17 | 2015-11-24 | Purdue Research Foundation | PSMA binding ligand-linker conjugates and methods for using |
WO2009055387A1 (en) * | 2007-10-22 | 2009-04-30 | Thermo Fisher Scientific | Polymerized conjugates for biological applications |
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MY151184A (en) | 2008-07-23 | 2014-04-30 | Hanmi Science Co Ltd | A polypeptide complex comprising non-peptidyl polymer having three functional ends |
WO2010078376A2 (en) | 2008-12-30 | 2010-07-08 | Ventana Medical Systems, Inc. | Fc-specific polymer-conjugated antibodies and their diagnostic use |
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US9951324B2 (en) | 2010-02-25 | 2018-04-24 | Purdue Research Foundation | PSMA binding ligand-linker conjugates and methods for using |
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NO2872646T3 (US20100136652A1-20100603-C00009.png) | 2012-07-12 | 2018-01-27 | ||
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2006
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- 2006-11-21 CN CN201410234039.XA patent/CN104090095B/zh active Active
- 2006-11-21 WO PCT/US2006/045302 patent/WO2007062177A2/en active Application Filing
- 2006-11-21 EP EP15001958.6A patent/EP2963011B1/en active Active
- 2006-11-21 EP EP06838327.2A patent/EP1951316B1/en active Active
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- 2006-11-21 ES ES16001225T patent/ES2804129T3/es active Active
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- 2006-11-21 DK DK06838327.2T patent/DK1951316T3/en active
- 2006-11-21 US US11/603,425 patent/US20070117153A1/en not_active Abandoned
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2009
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Also Published As
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EP3095467B1 (en) | 2020-05-06 |
US20140205995A1 (en) | 2014-07-24 |
CN101535244B (zh) | 2014-07-23 |
ES2804129T3 (es) | 2021-02-03 |
EP1951316B1 (en) | 2015-08-19 |
EP2963011A1 (en) | 2016-01-06 |
WO2007062177A3 (en) | 2009-05-28 |
US20160195540A1 (en) | 2016-07-07 |
CN104090095B (zh) | 2016-06-01 |
CA2631005C (en) | 2017-02-28 |
AU2006318438B2 (en) | 2011-09-22 |
US20100136652A1 (en) | 2010-06-03 |
AU2006318438A1 (en) | 2007-05-31 |
CN101535244A (zh) | 2009-09-16 |
CA2631005A1 (en) | 2007-05-31 |
US9310373B2 (en) | 2016-04-12 |
WO2007062177A2 (en) | 2007-05-31 |
CN104090095A (zh) | 2014-10-08 |
JP2009521405A (ja) | 2009-06-04 |
EP1951316A2 (en) | 2008-08-06 |
ES2677555T3 (es) | 2018-08-03 |
HK1121054A1 (en) | 2009-04-17 |
JP5199880B2 (ja) | 2013-05-15 |
DK1951316T3 (en) | 2015-08-31 |
DK2963011T3 (en) | 2018-08-06 |
EP2963011B1 (en) | 2018-05-09 |
HK1198485A1 (en) | 2015-05-08 |
EP3095467A1 (en) | 2016-11-23 |
US8686122B2 (en) | 2014-04-01 |
US20070117153A1 (en) | 2007-05-24 |
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