WO1998007850B1 - Agents for pre-symptomatic detection and therapeutic targeting of alzheimer's disease and down syndrome in humans - Google Patents
Agents for pre-symptomatic detection and therapeutic targeting of alzheimer's disease and down syndrome in humansInfo
- Publication number
- WO1998007850B1 WO1998007850B1 PCT/EP1997/004599 EP9704599W WO9807850B1 WO 1998007850 B1 WO1998007850 B1 WO 1998007850B1 EP 9704599 W EP9704599 W EP 9704599W WO 9807850 B1 WO9807850 B1 WO 9807850B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- seq
- humans
- disease
- alzheimer
- proteins
- Prior art date
Links
- 206010001897 Alzheimer's disease Diseases 0.000 title claims abstract 9
- 201000010374 Down syndrome Diseases 0.000 title claims abstract 9
- 238000001514 detection method Methods 0.000 title 1
- 230000001225 therapeutic Effects 0.000 title 1
- 241000282412 Homo Species 0.000 claims abstract 12
- 102000004965 antibodies Human genes 0.000 claims abstract 9
- 108090001123 antibodies Proteins 0.000 claims abstract 9
- 102000004169 proteins and genes Human genes 0.000 claims abstract 9
- 108090000623 proteins and genes Proteins 0.000 claims abstract 9
- 239000002773 nucleotide Substances 0.000 claims abstract 6
- 125000003729 nucleotide group Chemical group 0.000 claims abstract 6
- 238000003745 diagnosis Methods 0.000 claims abstract 3
- 206010044688 Trisomy 21 Diseases 0.000 claims 5
- 125000000539 amino acid group Chemical group 0.000 claims 4
- 230000000694 effects Effects 0.000 claims 4
- 206010042602 Supraventricular extrasystoles Diseases 0.000 claims 3
- 150000001413 amino acids Chemical class 0.000 claims 3
- 210000001124 Body Fluids Anatomy 0.000 claims 2
- 238000002965 ELISA Methods 0.000 claims 2
- 108020004999 Messenger RNA Proteins 0.000 claims 2
- 210000002381 Plasma Anatomy 0.000 claims 2
- 210000003296 Saliva Anatomy 0.000 claims 2
- 210000002966 Serum Anatomy 0.000 claims 2
- 239000010839 body fluid Substances 0.000 claims 2
- 229920002106 messenger RNA Polymers 0.000 claims 2
- 210000004927 Skin cells Anatomy 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 230000000903 blocking Effects 0.000 claims 1
- 210000004027 cells Anatomy 0.000 claims 1
- 239000000284 extract Substances 0.000 claims 1
- 239000012530 fluid Substances 0.000 claims 1
- 239000003550 marker Substances 0.000 claims 1
- 210000001519 tissues Anatomy 0.000 claims 1
- 230000035897 transcription Effects 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract 2
- 108020004707 nucleic acids Proteins 0.000 abstract 2
- 150000007523 nucleic acids Chemical class 0.000 abstract 2
- 229920001276 Ammonium polyphosphate Polymers 0.000 abstract 1
- 210000003917 Chromosomes, Human Anatomy 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
Abstract
Agents and methods for the diagnosis and therapy of Alzheimer's disease and the related condition Down syndrome are disclosed. Such agents include four genes located within the region of human chromosome 21 occupied by the APP gene, which are exclusively expressed in Alzheimer's disease or Down syndrome, respectively, the proteins encoded and expressed by these genes, the nucleic acid molecules influencing their expression, and endogenous antibodies produced in humans with Alzheimer's disease and Down syndrome against the above proteins. Also disclosed are antibodies and nucleotides to detect the presence of the proteins and nucleic acids in humans.
Claims
70
AMENDED CLAIMS
[received by the International Bureau on 16 September 1998 (16.09.98); original claims 1-25 replaced by amended claims 1-10 (2 pages)]
(1) Specific ELISA methods for presymptotnatic diagnosis of Downs syndrome in humans; this involves detecting, in extracts from human skin cells, serum, plasma and saliva, a Downs syndrome specific marker "DSAS", "SEQ ID:N03" or the DSAS- containing protein "PAC" , "SEQ ID.NOIO" .
(2) A specific ELISA method of claim 1 which detects endogenous antibodies produced in humans body fluids against DSAS, SEQ ID:N03 and/or PAC, SEQ ID:NO10. The endogenous antibody is detected in all humans afflicted with Downs syndrome, in humans before any clinical symptoms of Downs symptoms appear and also in mothers carrying Downs syndrome babies .
(3) A method for preventing and treating Downs syndrome in humans that targets dsas, SEQ ID.NOl; pac, SEQ ID:N09; DSAS, SEQ ID.N03; PAC, SEQ ID:NO10; anti-DSAS endogenous antibody or anti- PAC endogenous antibody.
(4) Methods for presymptomatic diagnosis of all forms of Alzheimer's disease and clinically related conditions in humans that involve detecting in human cells, tissue and/or body fluids (serum, plasma, spinal fluid, saliva) rriRNA, "alzaε", SEQ ID.NOll (specifically 204-241) or, mR A "alzasl", SEQ ID.N015 (specifically 55-156) or, mRNA "alzaε2", SEQ ID.N024 (specifically nucleotides 97-132) .
(5) The method of claim 4 which detects the proteins "ALZASp", SEQ ID.N012 expressed by alzas (SEQ ID.NOll) specifically amino acids 68 - 79 which are encoded by alzaε nucleotides 204 - 241 or the protein "ALZAS1", SEQ ID.N016 expressed by alzasl (SEQ ID.N015) specifically amino acid 20-51 which are encoded by alzasl nucleotides 55-156 or "ALZAS2" (SEQ ID.N025) expressed by alzas2 (SEQ ID.N024) especially amino acids 33-44 which are encoded by alzaε2 nucleotides 97-132.
(6) The amino acid sequences of claim 5 wherein these sequences are amino acid residues 68-79 from SEQ ID.NOll; amino acid residues 20-51 from SEQ ID:N016 and amino acid residues 33-44 from SEQ ID.N025.
(7) A method of claim 4 that detects an endogenous antibody produced in humans about to become afflicted or already afflicted with Alzheimer's disease, that is directed against epitopes within the amino acid residues of claim 6.
71
(8) Methods for preventing, controlling and treating Alzheimer's disease and other closely related clinical condition in humans that involve, blocking transcription of mRNA molecules from the group of claim 4 which have the sequence ID numbers SEQ ID.NOll, SEQ ID-N015 and SEQ ID.N024, specifically nucleotides 204-241, 55-156 and 97-132 respectively, or preventing the expression of or activity of the proteins of claims numbers 5 and 6, or preventing the activity of the endogenous antibodies of claim 7.
(9) A method of claim 5 which detects the proteins of the group "hypl(ALZASP) " SEQ ID.N013, "hyp2 (ALZASp) " SEQ ID-.N014 and "hyp(ALZAS2) " SEQ ID:N026 in humans about to be afflicted or afflicted with Alzheimer's disease or associated clinical conditions .
(10) The methods of claim 8 which involves preventing the expression or activity of the proteins of claim 9 , and activity of the anti-endogenous antibody directed against these proteins when they are expressed in humans afflicted with Alzheimer's disease and closely related clinical conditions.
72
STATEMENT UNDER ARTICLE 19
In our view the amended claims have no significant impact on the description or the drawings of the present application; however, changes in the latter which might be deemed necessary by others will be done during the preliminary examination phase of the application. A copy of this letter and the amended claims are being sent simultaneously to the International Preliminary Examining Authority.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE69737754T DE69737754T2 (en) | 1996-08-22 | 1997-08-22 | SUBSTANCES FOR PRESYMPTOMATIC RECOGNITION AND TARGETED THERAPY OF ALZHEIMER DISEASE IN HUMANS. |
| EP97909219A EP0970203B1 (en) | 1996-08-22 | 1997-08-22 | Agents for pre-symptomatic detection and therapeutic targeting of alzheimer's disease in humans |
| JP51043798A JP2001503968A (en) | 1996-08-22 | 1997-08-22 | Drugs for detection and therapeutic targeting of presymptomatic Alzheimer's disease and Down's syndrome in humans |
| AU47002/97A AU4700297A (en) | 1996-08-22 | 1997-08-22 | Agents for pre-symptomatic detection and therapeutic targeting of alzheimer's disease and down syndrome in humans |
| HK00104316A HK1026919A1 (en) | 1996-08-22 | 2000-07-12 | agents for pre-symptomatic detection and therapeutic targeting of alzheimer's disease in humans |
| US12/273,639 US20090192295A1 (en) | 1996-08-22 | 2008-11-19 | Agents for pre-symptomatic detection and therapeutic targeting of alzheimer's disease and down syndrome in humans |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2,183,901 | 1996-08-22 | ||
| CA002183901A CA2183901A1 (en) | 1996-08-22 | 1996-08-22 | Targets for therapy and diagnosis of alzheimer's disease and down syndrome in humans |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/700,922 Continuation US20050064439A1 (en) | 1996-08-22 | 2003-11-03 | Agents for pre-symptomatic detection and therapeutic targeting of alzheimer's disease and down syndrome in humans |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO1998007850A2 WO1998007850A2 (en) | 1998-02-26 |
| WO1998007850A3 WO1998007850A3 (en) | 1998-09-17 |
| WO1998007850B1 true WO1998007850B1 (en) | 1998-11-05 |
Family
ID=4158777
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1997/004599 WO1998007850A2 (en) | 1996-08-22 | 1997-08-22 | Agents for pre-symptomatic detection and therapeutic targeting of alzheimer's disease and down syndrome in humans |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0970203B1 (en) |
| JP (1) | JP2001503968A (en) |
| AU (1) | AU4700297A (en) |
| CA (1) | CA2183901A1 (en) |
| DE (1) | DE69737754T2 (en) |
| HK (1) | HK1026919A1 (en) |
| WO (1) | WO1998007850A2 (en) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2206774A1 (en) * | 1997-06-16 | 1998-12-16 | Rick E. Preddie | "prionins", highly specific markers for noninvasive presymptomatic defection of tse diseases, and targets for therapeutic reagents to prevent and control tse diseases in animals and humans |
| 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 |
| US20080050367A1 (en) | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
| US6787523B1 (en) | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
| TWI239847B (en) | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
| US7790856B2 (en) | 1998-04-07 | 2010-09-07 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
| US20030147882A1 (en) | 1998-05-21 | 2003-08-07 | Alan Solomon | Methods for amyloid removal using anti-amyloid antibodies |
| DE19856261C1 (en) | 1998-12-07 | 2000-03-30 | Hoechst Marion Roussel De Gmbh | Detection of gamma-secretase by detection of A-beta peptide useful for determining gamma-secretase activity and for identifying inhibitors |
| US6787637B1 (en) | 1999-05-28 | 2004-09-07 | Neuralab Limited | N-Terminal amyloid-β antibodies |
| UA81216C2 (en) | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
| GB0012123D0 (en) * | 2000-05-20 | 2000-07-12 | Univ Dundee | Alzheimer's disease assay |
| US7700751B2 (en) | 2000-12-06 | 2010-04-20 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize β-amyloid peptide |
| MY139983A (en) | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
| DE10303974A1 (en) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid β (1-42) oligomers, process for their preparation and their use |
| TWI306458B (en) | 2003-05-30 | 2009-02-21 | Elan Pharma Int Ltd | Humanized antibodies that recognize beta amyloid peptide |
| WO2005063796A1 (en) * | 2003-12-31 | 2005-07-14 | Posco | Inhibitors of amyloid precursor protein processing |
| US7341991B2 (en) | 2003-12-31 | 2008-03-11 | Posco | Inhibitors of amyloid precursor protein processing |
| WO2006066089A1 (en) | 2004-12-15 | 2006-06-22 | Neuralab Limited | Humanized amyloid beta antibodies for use in improving cognition |
| PT1976877E (en) | 2005-11-30 | 2014-04-29 | Abbvie Inc | Monoclonal antibodies against amyloid beta protein and uses thereof |
| EP1954718B1 (en) | 2005-11-30 | 2014-09-03 | AbbVie Inc. | Anti-a globulomer antibodies, antigen-binding moieties thereof, corresponding hybridomas, nucleic acids, vectors, host cells, methods of producing said antibodies, compositions comprising said antibodies, uses of said antibodies and methods of using said antibodies |
| US8784810B2 (en) | 2006-04-18 | 2014-07-22 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| US20100311767A1 (en) | 2007-02-27 | 2010-12-09 | Abbott Gmbh & Co. Kg | Method for the treatment of amyloidoses |
| US8003097B2 (en) | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
| EP2182983B1 (en) | 2007-07-27 | 2014-05-21 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases with humanised anti-abeta antibodies |
| JO3076B1 (en) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | Immunotherapy regimes dependent on apoe status |
| US9067981B1 (en) | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
| JP2013523182A (en) | 2010-04-15 | 2013-06-17 | アボット・ラボラトリーズ | Amyloid beta-binding protein |
| EP2603524A1 (en) | 2010-08-14 | 2013-06-19 | AbbVie Inc. | Amyloid-beta binding proteins |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5877015A (en) * | 1991-01-21 | 1999-03-02 | Imperial College Of Science, Technology Of Medicine | APP770 mutant in alzheimer's disease |
| AU2765992A (en) * | 1991-10-03 | 1993-05-03 | Indiana University Foundation | Method for screening for alzheimer's disease |
| JPH07508410A (en) * | 1992-06-18 | 1995-09-21 | ジェンファーム インターナショナル インコーポレイテッド | Method for producing transgenic non-human animals having yeast artificial chromosomes |
| WO1994013798A1 (en) * | 1992-12-16 | 1994-06-23 | Bergmann Johanna E | Agents for the prevention and treatment of human alzheimer's disease |
| CA2126787A1 (en) * | 1994-06-27 | 1995-12-28 | Rick E. Preddie | Agents for the prevention and treatment of human alzheimer's disease |
-
1996
- 1996-08-22 CA CA002183901A patent/CA2183901A1/en not_active Abandoned
-
1997
- 1997-08-22 JP JP51043798A patent/JP2001503968A/en active Pending
- 1997-08-22 EP EP97909219A patent/EP0970203B1/en not_active Expired - Lifetime
- 1997-08-22 AU AU47002/97A patent/AU4700297A/en not_active Abandoned
- 1997-08-22 DE DE69737754T patent/DE69737754T2/en not_active Expired - Lifetime
- 1997-08-22 WO PCT/EP1997/004599 patent/WO1998007850A2/en active IP Right Grant
-
2000
- 2000-07-12 HK HK00104316A patent/HK1026919A1/en not_active IP Right Cessation
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