WO1990012871A1 - Anticorps monoclonal sv17-6e10 specifique de la proteine amyloide cerebrovasculaire - Google Patents

Anticorps monoclonal sv17-6e10 specifique de la proteine amyloide cerebrovasculaire Download PDF

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Publication number
WO1990012871A1
WO1990012871A1 PCT/US1990/002003 US9002003W WO9012871A1 WO 1990012871 A1 WO1990012871 A1 WO 1990012871A1 US 9002003 W US9002003 W US 9002003W WO 9012871 A1 WO9012871 A1 WO 9012871A1
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WIPO (PCT)
Prior art keywords
monoclonal antibody
cells
antibody
mouse
alzheimer
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PCT/US1990/002003
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English (en)
Inventor
Kwang S. Kim
Henryk M. Wisniewski
Guang Y. Wen
Cheng-Mo James Chen
Victor J. Sapienza
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Research Foundation For Mental Hygiene, Inc.
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Publication of WO1990012871A1 publication Critical patent/WO1990012871A1/fr

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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
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals

Definitions

  • the present invention relates to neurological disorders, and, more particularly, to antibodies that are specific for peptides associated therewith.
  • Alzheimer's disease is characterized by three major pathological markers. They are neuritic plaques, neurofibrillary tangles and cerebrovascular a ⁇ vyloidosis. Glenner, et al., Biochem. Biophys . Res.
  • Plaque and cerebrovascular amyloid are primarily made up of a 40- to 42- a ino acid residue peptide, called the B-peptide.
  • Down's Syndrome is a disability charactei ized by the inheritance of an extra copy of chromosome 21 c in each cell. Older persons afflicted with Down's Syndrome display dementia that resembles Alzheimer's disease. The cerebral tissues of these individuals exhibit the same neuropathological findings of Alzheimer's disease, i.e., amyloid-containing neuritic plaques, neurofibrillary tangles and cerebrovascular amyloidosis. The amyloid deposits of Down's Syndrome contain the same peptide as the amyloid deposits found in the brains of Alzheimer's disease victims. See, Glenner et al., Biochem. Biophys. Res. Comm., 12.2:1131 (1984).
  • 35 u disease using body fluids such as spinal fluid, serum or urine.
  • the invention provides a monoclonal antibody, designated SV17-6E10, and antigen - binding fragments thereof which are 5 specifically reactive with a peptide whose concentration level is elevated in individuals having Alzheimer's disease or Down's syndrome as compared to individuals of substantially the same age who are not so-afflicted and which does not react with other monoclonal antibody, designated SV17-6E10, and antigen - binding fragments thereof which are 5 specifically reactive with a peptide whose concentration level is elevated in individuals having Alzheimer's disease or Down's syndrome as compared to individuals of substantially the same age who are not so-afflicted and which does not react with other
  • the monoclonal antibodies of the invention are of subclass IgG, .
  • Papain-digestion produced antigen-binding fragments e.g. Fab
  • the monoclonal antibody is produced by a hybridoma formed by fusion of cells from a myeloma line, usually of mouse origin, and antibody-producing cells, also usually of mouse origin, ' previously immunized with a peptide whose concentration level is ⁇ elevated in individuals having Alzheimer's disease or Down's syndrome as compared to individuals of substantially the same age who are not so-afflicted and which do not react with other peptides of human origin, such as one which forms a portion of a
  • a mouse NSO myeloma line is used, particularly with antibody-producing cells from a mouse previously immunized with a peptide comprising the sequence , Q comprising asp - ala - glu - phe - arg - his - a ⁇ p - ser - gly - tyr - glu - val - his - his - gin - lys - leu.
  • the invention provides a hybridoma cell line capable of producing the monoclonal antibodies described above.
  • the invention provides a composition for quantitatively determining a peptide whose concentration level characteristic of Alzheimer's disease or Down's syndrome in an individual.
  • the composition comprises a monoclonal antibody or antigen - binding fragment thereof in accordance with the invention and a detectable moiety which is directly or indirectly associated therewith.
  • the monoclonal antibody is conjugated to an enzyme and the detectable moiety comprises a chromogenic redox substrate for the enzyme.
  • the monoclonal antibody is conjugated to one partner of a specific binding pair and the other partner of the specific binding pair is conjugated to a detectable moiety or a substance capable of rendering the moiety detectable.
  • the monoclonal antibody or antigen - binding fragment thereof additionally serves as an antigen of the specific binding pair.
  • the partner for the monoclonal or fragment is an anti-immunoglobulin antibody, usually anti - IgG and usually from a species other than that of its partner, which is labeled, such as with a fluorophore like fluorescein isothiocyanate.
  • one partner of the specific binding pair is selected from biotin and its binding analogs and the other partner is selected from avidin and its binding analogs.
  • the detectable moiety is a chromophore, fluorophore or luminophore and the substance capable of rendering it detectable is an energy donor or catalyst therefor.
  • the invention provides an immunoassay method.
  • the method comprises contacting a sample, from the individual suspected of having Alzheimer's disease or Down's syndrome, with the composition of the invention and quantitatively observing any detectable response.
  • Monoclonal antibody SV17-6E10 is very unique in that no monoclonal antibody reactive to this peptide (17 amino acid residue) has previously been reported. Monoclonal antibody SV17-6E10 has been used, as exemplified below, in immunoassays for characterizing the amyloid peptide and precursor amyloid peptides in connection with biogenesis of B-amyloid peptide plaques found in Alzheimer's
  • Fig. 1(a) shows amyloid plaques stained with SV17-6E10 monoclonal antibody
  • Fig. 1(b) shows a serial section stained with SCVAP-2F9 monoclonal antibody.
  • SV17 17-residue synthetic cerebrovascular amyloid peptide (SV17), having the sequence asp - ala - glu - phe -
  • mice BALB/CJ female mice (Jackson Laboratories,
  • mice 20 Bar Harbor, ME were immunized via the back foot pads with Ribi adjuvant (200 ul) (Ribi Immunochem Research, Inc., Hamilton, MT) containing SV17-KLH antigen (25-50 ug) . At 21 days after the initial injection, these mice were immunized
  • mice 25 intraperit ' oneally with SV17-KLH antigen (25-50 ug) in Ribi adjuvant (200 ul) four times at about four week intervals.
  • mice received intraperitoneal booster injections of SV17 (200 ug) n without adjuvant.
  • Immune spleen cells were harvested as described in Galfre, et al., Methods Enzymol., 2:73 (1981). A mouse with the highest titer after SV17-KLH antigen immunization was selected for hybrid clone production.
  • the immune spleen cells were incubated with the NSO myeloma cells and fused at a ratio of 5:1 in the presence of polyethyleneglycol 1500
  • Dulbecco minimum essential medium containing 15% fetal bovine serum, 10 -4 M hypoxanthme, 1.6 x
  • Hybrid cell growth was detected by the ELISA technique using the synthetic peptide antigen (1 ug/ml) coated on the wells. Supernatant fluid in several wells were found to contain SV17 - specific antibody.
  • Example 2 Monoclonal Antibody SV17-6E10 Immunocytochemistry Reagent
  • Monoclonal antibody SV17-6E10 was used in the experiments reported by this example as an immunocytochemistry reagent. Paraffin -embedded, formalin - fixed Alzheimer and normal control cortex sections (6 urn) were stained using the avidin-biotin complex technique (Bethesda Research Laboratories, Bethesda, MD) . Amyloid present in neuritic plaques and cortical and meningeal vessels in brain sections of Alzheimer's pat-ients were stained and those of non-a flicted controls were not. No staining of Alzheimer neurofibrillary tangles or axons/neuroEilaments either in tissue sections or in isolated neurons were observed with monoclonal antibody SV17-6E10.
  • the immunoreactivity of monoclonal antibody SV17-6E10 was then compared with that of SVCAP-2F9 (or SVCAP-4G8) on the amyloid plaques. Comparison of their immunoreactivities with amyloid plaques using serial sections (6 urn thickness) revealed that there were two types of amyloid plaques present. Regardless of high concentration of SV17-6E10 used, one group of plaques was lightly stained while the other group of plaques was darkly stained (Fig. la). When SCVAP-2F9 or SCVAP-4G8 monoclonal antibody was used, these two groups of plaques all reacted with equal staining intensity (Fig. lb).
  • Monoclonal antibody SV17-6E10 was raised against the amino acid residue 1-17 of the synthetic amyloid B-protein while SCVAP-2F9 and SCVAP-4G8 are monoclonal antibodies ⁇ specific to an epitope in the 17-24 amino acid segment of the synthetic amyloid B-protein. Judging from these observations, the amount of the peptide with amino acids 1-17 was not equally present in these plaques. However, the amount of B amyloid 5 protein having amino acids 17-24 was approximately the same in all the plaques as evidenced by equal staining density. The availability of SV17-6E10 and SCVAP-2F9 or SCVAP-4G8 makes it possible to reveal for the first time that the plaques are composed of
  • the immunohistochemical staining procedure used was as follows.
  • the deparaffinized sections (6
  • ]_ urn thickness were washed in 0.05M Tris-based buffer (TBS) (pH 7.6) and 0.15M NaCl (TBS) for 5-10 minutes and immersed in undiluted 99% formic acid (Sigma Chemical Co., St. Louis, MO) for 3-4 hours. They were then washed with tap water (3-4 times) and then
  • DAB diaminobenzidine tetrahydrochloride
  • Fab Fragments Of Monoclonal Antibody SV17-6E10 Fab fragments of monoclonal antibody SV17-6E10 were prepared and tested as follows. Immunoglobulin IgG purified by protein A column was
  • the Fab fragments were dialyzed against PBS and used for immunostaining of brain sections.
  • B-amyloid protein was detected using the double antibody sandwich procedure described in Kim, et al., J. Clin. Microbiol., 1£:331 (1983).
  • amino acid residue 11 is gluta ine here.
  • SV17-6E10 : 4G8HRP refers to the 0 reagent wherein SV17-6E10 is used as the capture antibody and 4G8HRP is the detection antibody.
  • SCVAP-4G8 is the capture antibody and SV17-6E10HRP is the detecting antibody. The results are reported in

Abstract

Un anticorps monoclonal SV17-6E10 et un fragment de liaison spécifique de celui-ci sont capables de réagir spécifiquement avec un peptide dont la concentration est élevée chez des individus qui souffrent du syndrome de Down ou de la maladie d'Alzheimer, par rapport à des individus ayant essentiellement le même âge mais qui ne sont pas atteints de ces maladies. Cet anticorps monoclonal et son fragment de liaison spécifique ne réagissent pas avec d'autres peptides d'origine humaine. Une lignée de cellules d'hybridomes est capable de produire cet anticorps monoclonal, une composition réactive contient l'anticorps monoclonal ou ses fragments de liaison spécifique et un procédé d'immunodosage permet de les utiliser.
PCT/US1990/002003 1989-04-14 1990-04-13 Anticorps monoclonal sv17-6e10 specifique de la proteine amyloide cerebrovasculaire WO1990012871A1 (fr)

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Cited By (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5593846A (en) * 1992-07-10 1997-01-14 Athena Neurosciences Methods for the detection of soluble β-amyloid peptide
US5714471A (en) * 1995-01-06 1998-02-03 Sibia Neurosciences, Inc. Peptide and peptide analog protease inhibitors
US5744368A (en) * 1993-11-04 1998-04-28 Research Foundation Of State University Of New York Methods for the detection of soluble amyloid β-protein (βAP) or soluble transthyretin (TTR)
US5837672A (en) * 1992-07-10 1998-11-17 Athena Neurosciences, Inc. Methods and compositions for the detection of soluble β-amyloid peptide
US5863902A (en) * 1995-01-06 1999-01-26 Sibia Neurosciences, Inc. Methods of treating neurodegenerative disorders using protease inhibitors
US6114133A (en) * 1994-11-14 2000-09-05 Elan Pharmaceuticals, Inc. Methods for aiding in the diagnosis of Alzheimer's disease by measuring amyloid-β peptide (x-≧41)
US6245964B1 (en) 1993-10-27 2001-06-12 Elan Pharmaceuticals, Inc. Transgenic rodent comprising APP-Swedish
US6710226B1 (en) 1997-12-02 2004-03-23 Neuralab Limited Transgenic mouse assay to determine the effect of Aβ antibodies and Aβ Fragments on alzheimer's disease characteristics
US6743427B1 (en) 1997-12-02 2004-06-01 Neuralab Limited Prevention and treatment of amyloidogenic disease
US6750324B1 (en) 1997-12-02 2004-06-15 Neuralab Limited Humanized and chimeric N-terminal amyloid beta-antibodies
US6787637B1 (en) 1999-05-28 2004-09-07 Neuralab Limited N-Terminal amyloid-β antibodies
US6787143B1 (en) 1997-12-02 2004-09-07 Neuralab Limited Prevention and treatment of amyloidogenic disease
US6808712B2 (en) 1997-12-02 2004-10-26 Neuralab Limited Prevention and treatment of amyloidogenic disease
US6815175B2 (en) 2001-03-16 2004-11-09 Cornell Research Foundation, Inc. Anti-amyloid peptide antibody based diagnosis and treatment of a neurological disease or disorder
US6875434B1 (en) 1997-12-02 2005-04-05 Neuralab Limited Methods of treatment of Alzheimer's disease
US6923964B1 (en) 1997-12-02 2005-08-02 Neuralab Limited Active immunization of AScr for prion disorders
WO2006095041A1 (fr) * 2005-03-09 2006-09-14 Consejo Superior De Investigaciones Científicas Methode de diagnostic in vitro de la maladie d'alzheimer au moyen d'un anticorps monoclonal
WO2008104580A1 (fr) 2007-03-01 2008-09-04 Probiodrug Ag Nouvelle utilisation d'inhibiteurs de la glutaminyl cyclase
US7427392B1 (en) 1994-11-14 2008-09-23 Elan Pharmaceuticals, Inc. Methods for aiding in the diagnosis of alzheimer's disease by measuring amyloid-β peptide (x-≧41) and tau
US7700751B2 (en) 2000-12-06 2010-04-20 Janssen Alzheimer Immunotherapy Humanized antibodies that recognize β-amyloid peptide
US7732162B2 (en) 2003-05-05 2010-06-08 Probiodrug Ag Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases
EP2224000A1 (fr) * 2007-10-29 2010-09-01 Kyoto University Anticorps et son utilisation
US7790856B2 (en) 1998-04-07 2010-09-07 Janssen Alzheimer Immunotherapy Humanized antibodies that recognize beta amyloid peptide
US7871615B2 (en) 2003-05-30 2011-01-18 Janssen Alzheimer Immunotherapy Humanized antibodies that recognize beta amyloid peptide
US7893214B2 (en) 1997-12-02 2011-02-22 Janssen Alzheimer Immunotherapy Humanized antibodies that recognize beta amyloid peptide
WO2011029920A1 (fr) 2009-09-11 2011-03-17 Probiodrug Ag Dérivés hétérocycliques en tant qu'inhibiteurs de glutaminyle cyclase
US7977316B2 (en) 1999-06-01 2011-07-12 Elan Pharmaceuticals, Inc. Prevention and treatment of amyloidogenic diseases
US7993627B2 (en) 1992-07-10 2011-08-09 Elan Pharmaceuticals, Inc. Methods for determining whether a compound alters the amount of at least one αβ (X-41) peptide and the amount of either total αβ or at least one αβ (X-40) peptide produced by a non-human mammal
US8003097B2 (en) 2007-04-18 2011-08-23 Janssen Alzheimer Immunotherapy Treatment of cerebral amyloid angiopathy
WO2011107530A2 (fr) 2010-03-03 2011-09-09 Probiodrug Ag Nouveaux inhibiteurs
WO2011110613A1 (fr) 2010-03-10 2011-09-15 Probiodrug Ag Inhibiteurs hétérocycliques de la glutaminyl cyclase (qc, ec 2.3.2.5)
WO2011131748A2 (fr) 2010-04-21 2011-10-27 Probiodrug Ag Nouveaux inhibiteurs
US8105594B2 (en) 1998-05-21 2012-01-31 Alan Solomon Methods for amyloid removal using anti-amyloid antibodies
US8128928B2 (en) 2002-03-12 2012-03-06 Wyeth Llc Humanized antibodies that recognize beta amyloid peptide
WO2012123563A1 (fr) 2011-03-16 2012-09-20 Probiodrug Ag Dérivés de benzimidazole en tant qu'inhibiteurs de la glutaminyl cyclase
US8613920B2 (en) 2007-07-27 2013-12-24 Janssen Alzheimer Immunotherapy Treatment of amyloidogenic diseases
US8784810B2 (en) 2006-04-18 2014-07-22 Janssen Alzheimer Immunotherapy Treatment of amyloidogenic diseases
US8916165B2 (en) 2004-12-15 2014-12-23 Janssen Alzheimer Immunotherapy Humanized Aβ antibodies for use in improving cognition
EP2865670A1 (fr) 2007-04-18 2015-04-29 Probiodrug AG Dérivés de thio-urée utilisés comme inhibiteurs de la glutaminyl cyclase
US9067981B1 (en) 2008-10-30 2015-06-30 Janssen Sciences Ireland Uc Hybrid amyloid-beta antibodies
US9146244B2 (en) 2007-06-12 2015-09-29 Ac Immune S.A. Polynucleotides encoding an anti-beta-amyloid monoclonal antibody
US9175094B2 (en) 2007-06-12 2015-11-03 Ac Immune S.A. Monoclonal antibody
US9221900B2 (en) 2010-07-30 2015-12-29 Ac Immune S.A. Methods for identifying safe and functional humanized antibodies
US9255932B2 (en) 2011-04-12 2016-02-09 Aracion Biotech, S.L. Antibody, kit and method for determining amyloid peptides
US9403902B2 (en) 2007-10-05 2016-08-02 Ac Immune S.A. Methods of treating ocular disease associated with amyloid-beta-related pathology using an anti-amyloid-beta antibody
US9644025B2 (en) 2007-10-17 2017-05-09 Wyeth Llc Immunotherapy regimes dependent on ApoE status
EP3461819A1 (fr) 2017-09-29 2019-04-03 Probiodrug AG Inhibiteurs de la glutaminyl-cyclase

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4666829A (en) * 1985-05-15 1987-05-19 University Of California Polypeptide marker for Alzheimer's disease and its use for diagnosis

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4666829A (en) * 1985-05-15 1987-05-19 University Of California Polypeptide marker for Alzheimer's disease and its use for diagnosis

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
GLENNER et al., "Alzheimer's disease and Down's Syndrome: sharing of a unique cerebrovascular amyloid fibril protein", BIOCHEM. BIOPHYS. RES. COMM. 122, pages 1131-1135, Published 16 August 1984. *
GLENNER et al., "Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein", BIOCHEM. BIOPHYS. RES. COMM. 120: No. 3, pages 885-890, Published 16 May 1984. *
GODING, "Monoclonal antibodies: Principles and Practice", Published 1983 by ACADEMIC PRESS INC. (London), see pages 56-97 and pages 209-249. *
KANG et al., "The precursor of Altheimer's disease amyloid A4 protein resembles a cell-surface receptor", NATURE, Vol. 325: pages 733-736, Published 19 February 1989. *
ROBAKIS et al., "Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neurity plaque amyloid peptides", PROC. NATL. ACAD. SCI., Vol. 84, pages 4190-4194, Published June 1987. *
SELKOE et al., "Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease", SCIENCE 235: pages 873-877, Published 20 February 1987. *
WONG et al., "Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related", PROC. NATL. ACAD. SCI. USA 82: pages 8729-8732. Published December 1985. *

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US5837672A (en) * 1992-07-10 1998-11-17 Athena Neurosciences, Inc. Methods and compositions for the detection of soluble β-amyloid peptide
US6284221B1 (en) 1992-07-10 2001-09-04 Elan Pharmaceuticals, Inc. Method for identifying β-amyloid peptide production inhibitors
US7993627B2 (en) 1992-07-10 2011-08-09 Elan Pharmaceuticals, Inc. Methods for determining whether a compound alters the amount of at least one αβ (X-41) peptide and the amount of either total αβ or at least one αβ (X-40) peptide produced by a non-human mammal
US5766846A (en) * 1992-07-10 1998-06-16 Athena Neurosciences Methods of screening for compounds which inhibit soluble β-amyloid peptide production
US5593846A (en) * 1992-07-10 1997-01-14 Athena Neurosciences Methods for the detection of soluble β-amyloid peptide
US7179953B2 (en) 1993-10-27 2007-02-20 Elan Pharmaceuticals, Inc. Monitoring APP cleavage in transgenic rodents comprising an APP-Swedish mutation
US6245964B1 (en) 1993-10-27 2001-06-12 Elan Pharmaceuticals, Inc. Transgenic rodent comprising APP-Swedish
US7608749B2 (en) 1993-10-27 2009-10-27 Elan Pharmaceuticals, Inc. Monitoring APP cleavage in transgenic rodents comprising an APP Swedish mutation
US6586656B2 (en) 1993-10-27 2003-07-01 Elan Pharmaceuticals, Inc. Transgenic rodents harboring APP allele having Swedish mutation
US5744368A (en) * 1993-11-04 1998-04-28 Research Foundation Of State University Of New York Methods for the detection of soluble amyloid β-protein (βAP) or soluble transthyretin (TTR)
US7700309B2 (en) 1994-11-14 2010-04-20 Elan Pharmaceuticals, Inc. Methods for aiding in the diagnosis of alzheimer's disease by measuring amyloid-β peptide (X->41) and tau
US7811769B2 (en) 1994-11-14 2010-10-12 Elan Pharmaceuticals, Inc. Methods for aiding in the diagnosis of Alzheimer's disease by measuring amyloid-β peptide (x-≧41) and tau
US7427392B1 (en) 1994-11-14 2008-09-23 Elan Pharmaceuticals, Inc. Methods for aiding in the diagnosis of alzheimer's disease by measuring amyloid-β peptide (x-≧41) and tau
US6114133A (en) * 1994-11-14 2000-09-05 Elan Pharmaceuticals, Inc. Methods for aiding in the diagnosis of Alzheimer's disease by measuring amyloid-β peptide (x-≧41)
US5863902A (en) * 1995-01-06 1999-01-26 Sibia Neurosciences, Inc. Methods of treating neurodegenerative disorders using protease inhibitors
US6153171A (en) * 1995-01-06 2000-11-28 Sibia Neurosciences, Inc. Methods for identifying compounds effective for treating neurodegenerative disorders and for monitoring the therapeutic intervention therefor
US6051684A (en) * 1995-01-06 2000-04-18 Sibia Neurosciences Inc. Methods of treating neurodegenerative disorders using protease inhibitors
US6017887A (en) * 1995-01-06 2000-01-25 Sibia Neurosciences, Inc. Peptide, peptide analog and amino acid analog protease inhibitors
US6015879A (en) * 1995-01-06 2000-01-18 Sibia Neurosciences, Inc. Peptide and peptide analog protease inhibitors
US5969100A (en) * 1995-01-06 1999-10-19 Sibia Neurosciences, Inc. Peptide, peptide analog and amino acid analog protease inhibitors
US5962419A (en) * 1995-01-06 1999-10-05 Sibia Neurosciences, Inc. Peptide and peptide analog protease inhibitors
US5872101A (en) * 1995-01-06 1999-02-16 Sibia Neurosciences, Inc. Methods of treating neurodegenerative disorders using protease inhibitors
US5804560A (en) * 1995-01-06 1998-09-08 Sibia Neurosciences, Inc. Peptide and peptide analog protease inhibitors
US5714471A (en) * 1995-01-06 1998-02-03 Sibia Neurosciences, Inc. Peptide and peptide analog protease inhibitors
US6787143B1 (en) 1997-12-02 2004-09-07 Neuralab Limited Prevention and treatment of amyloidogenic disease
US8642044B2 (en) 1997-12-02 2014-02-04 Janssen Alzheimer Immunotherapy Prevention and treatment of amyloidogenic disease
US6787140B1 (en) 1997-12-02 2004-09-07 Neuralab Limited Prevention and treatment of amyloidogenic disease
US6787139B1 (en) 1997-12-02 2004-09-07 Neuralab Limited Prevention and treatment of amyloidogenic disease
US6808712B2 (en) 1997-12-02 2004-10-26 Neuralab Limited Prevention and treatment of amyloidogenic disease
US6710226B1 (en) 1997-12-02 2004-03-23 Neuralab Limited Transgenic mouse assay to determine the effect of Aβ antibodies and Aβ Fragments on alzheimer's disease characteristics
US6818218B2 (en) 1997-12-02 2004-11-16 Neuralab Limited Prevention and treatment of amyloidogenic disease
US6875434B1 (en) 1997-12-02 2005-04-05 Neuralab Limited Methods of treatment of Alzheimer's disease
US6890535B1 (en) 1997-12-02 2005-05-10 Neuralab Limited Pharmaceutical compositions and methods for treatment of amyloid diseases
US6923964B1 (en) 1997-12-02 2005-08-02 Neuralab Limited Active immunization of AScr for prion disorders
US6936246B1 (en) 1997-12-02 2005-08-30 Neuralab Limited Passive immunization of ASCR for prion disorders
US6982084B2 (en) 1997-12-02 2006-01-03 Neuralab Limited Prevention and treatment of amyloidogenic disease
US9051363B2 (en) 1997-12-02 2015-06-09 Janssen Sciences Ireland Uc Humanized antibodies that recognize beta amyloid peptide
US6787523B1 (en) 1997-12-02 2004-09-07 Neuralab Limited Prevention and treatment of amyloidogenic disease
US6787144B1 (en) 1997-12-02 2004-09-07 Neuralab Limited Prevention and treatment of amyloidogenic disease
US8034348B2 (en) 1997-12-02 2011-10-11 Janssen Alzheimer Immunotherapy Prevention and treatment of amyloidogenic disease
US6787138B1 (en) 1997-12-02 2004-09-07 Neuralab Limited Prevention and treatment of amyloidogenic disease
US8034339B2 (en) 1997-12-02 2011-10-11 Janssen Alzheimer Immunotherapy Prevention and treatment of amyloidogenic disease
US7893214B2 (en) 1997-12-02 2011-02-22 Janssen Alzheimer Immunotherapy Humanized antibodies that recognize beta amyloid peptide
US6750324B1 (en) 1997-12-02 2004-06-15 Neuralab Limited Humanized and chimeric N-terminal amyloid beta-antibodies
US8535673B2 (en) 1997-12-02 2013-09-17 Janssen Alzheimer Immunotherapy Prevention and treatment of amyloidogenic disease
US6743427B1 (en) 1997-12-02 2004-06-01 Neuralab Limited Prevention and treatment of amyloidogenic disease
US7790856B2 (en) 1998-04-07 2010-09-07 Janssen Alzheimer Immunotherapy Humanized antibodies that recognize beta amyloid peptide
US8105594B2 (en) 1998-05-21 2012-01-31 Alan Solomon Methods for amyloid removal using anti-amyloid antibodies
US6787637B1 (en) 1999-05-28 2004-09-07 Neuralab Limited N-Terminal amyloid-β antibodies
US8124081B2 (en) 1999-06-01 2012-02-28 Crimagua Limited Prevention and treatment of amyloidogenic diseases
US7977316B2 (en) 1999-06-01 2011-07-12 Elan Pharmaceuticals, Inc. Prevention and treatment of amyloidogenic diseases
US7700751B2 (en) 2000-12-06 2010-04-20 Janssen Alzheimer Immunotherapy Humanized antibodies that recognize β-amyloid peptide
US6815175B2 (en) 2001-03-16 2004-11-09 Cornell Research Foundation, Inc. Anti-amyloid peptide antibody based diagnosis and treatment of a neurological disease or disorder
US8128928B2 (en) 2002-03-12 2012-03-06 Wyeth Llc Humanized antibodies that recognize beta amyloid peptide
US8809010B2 (en) 2003-05-05 2014-08-19 Probiodrug Ag Method for prophylactic treatment of alzheimer's disease using inhibitors of glutaminyl cyclase and glutamate cyclases
US7732162B2 (en) 2003-05-05 2010-06-08 Probiodrug Ag Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases
US7871615B2 (en) 2003-05-30 2011-01-18 Janssen Alzheimer Immunotherapy Humanized antibodies that recognize beta amyloid peptide
US8916165B2 (en) 2004-12-15 2014-12-23 Janssen Alzheimer Immunotherapy Humanized Aβ antibodies for use in improving cognition
WO2006095041A1 (fr) * 2005-03-09 2006-09-14 Consejo Superior De Investigaciones Científicas Methode de diagnostic in vitro de la maladie d'alzheimer au moyen d'un anticorps monoclonal
US7932048B2 (en) 2005-03-09 2011-04-26 Consejo Superior De Investigaciones Cientificas Method for the in vitro diagnosis of alzheimer's disease using a monoclonal antibody
ES2259270A1 (es) * 2005-03-09 2006-09-16 Consejo Superior De Investigaciones Cientificas Metodo de diagnostico in vitro de la enfermedad de alzheimer mediante un anticuerpo monoclonal.
US8784810B2 (en) 2006-04-18 2014-07-22 Janssen Alzheimer Immunotherapy Treatment of amyloidogenic diseases
EP2481408A2 (fr) 2007-03-01 2012-08-01 Probiodrug AG Nouvelle utilisation d'inhibiteurs glutaminyle cyclase
WO2008104580A1 (fr) 2007-03-01 2008-09-04 Probiodrug Ag Nouvelle utilisation d'inhibiteurs de la glutaminyl cyclase
US8003097B2 (en) 2007-04-18 2011-08-23 Janssen Alzheimer Immunotherapy Treatment of cerebral amyloid angiopathy
EP2865670A1 (fr) 2007-04-18 2015-04-29 Probiodrug AG Dérivés de thio-urée utilisés comme inhibiteurs de la glutaminyl cyclase
US9146244B2 (en) 2007-06-12 2015-09-29 Ac Immune S.A. Polynucleotides encoding an anti-beta-amyloid monoclonal antibody
US9585956B2 (en) 2007-06-12 2017-03-07 Ac Immune S.A. Polynucleotides encoding anti-amyloid beta monoclonal antibodies
US9175094B2 (en) 2007-06-12 2015-11-03 Ac Immune S.A. Monoclonal antibody
US8613920B2 (en) 2007-07-27 2013-12-24 Janssen Alzheimer Immunotherapy Treatment of amyloidogenic diseases
US9403902B2 (en) 2007-10-05 2016-08-02 Ac Immune S.A. Methods of treating ocular disease associated with amyloid-beta-related pathology using an anti-amyloid-beta antibody
US9644025B2 (en) 2007-10-17 2017-05-09 Wyeth Llc Immunotherapy regimes dependent on ApoE status
US8445649B2 (en) 2007-10-29 2013-05-21 Tao Health Life Pharma Co., Ltd. Antibody and use thereof
EP2224000A4 (fr) * 2007-10-29 2012-06-27 Tao Health Life Pharma Co Ltd Anticorps et son utilisation
EP2224000A1 (fr) * 2007-10-29 2010-09-01 Kyoto University Anticorps et son utilisation
US9067981B1 (en) 2008-10-30 2015-06-30 Janssen Sciences Ireland Uc Hybrid amyloid-beta antibodies
WO2011029920A1 (fr) 2009-09-11 2011-03-17 Probiodrug Ag Dérivés hétérocycliques en tant qu'inhibiteurs de glutaminyle cyclase
WO2011107530A2 (fr) 2010-03-03 2011-09-09 Probiodrug Ag Nouveaux inhibiteurs
WO2011110613A1 (fr) 2010-03-10 2011-09-15 Probiodrug Ag Inhibiteurs hétérocycliques de la glutaminyl cyclase (qc, ec 2.3.2.5)
WO2011131748A2 (fr) 2010-04-21 2011-10-27 Probiodrug Ag Nouveaux inhibiteurs
US9221900B2 (en) 2010-07-30 2015-12-29 Ac Immune S.A. Methods for identifying safe and functional humanized antibodies
WO2012123563A1 (fr) 2011-03-16 2012-09-20 Probiodrug Ag Dérivés de benzimidazole en tant qu'inhibiteurs de la glutaminyl cyclase
US9255932B2 (en) 2011-04-12 2016-02-09 Aracion Biotech, S.L. Antibody, kit and method for determining amyloid peptides
US9863961B2 (en) 2011-04-12 2018-01-09 Araclon Biotech, S.L. Method for determination of amyloid peptides with anti-amyloid antibody
EP3461819A1 (fr) 2017-09-29 2019-04-03 Probiodrug AG Inhibiteurs de la glutaminyl-cyclase

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