Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2003-05-16
2009-02-03
Prouty, Rebecca (Department: 1652)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C435S194000
Reexamination Certificate
active
07485712
ABSTRACT:
The present invention relates to a DNA sequence encoding a novel neuronal protein kinase (NPK) which phosphorylates tau proteins as well as other microtubule associated proteins (MAPs) in positions crucial for the binding to microtubules. The invention further relates to Serine or Theorine residues and epitopes comprising said residues phosphorylated by said NPK on said MAPs, to antibodies specifically binding to said protein kinase, pharmaceutical compositions comprising inhibitors to said protein kinase, in particular for the treatment of Alzheimer's disease and cancer, to diagnostic kits and to in vitro diagnostic methods for the detection of Alzheimer's disease and cancer.
REFERENCES:
Albala et al., “Characterization of the transcripts encoding 2 isoforms of human microtubule-associated protein-2 (MAP-2),”Gene, 136:377-378 (1993).
Anderton, “Expression and processing of pathological proteins in Alzheimer's disease,”Hippocampus, 3:227-237 (1993).
Baas, et al., “Processes induced by tau expression in Sf9-cells have an axon-like microtubule organization,”J.Cell Biol., 115:1333-1344 (1991).
Baumann, et al., “Abnormal Alzheimer-like phosphorylation of tau protein by cyclin-dependent kinases cdk2 and cdk5,”FEBS Lett., 336:417-424 (1993).
Berling, et al., “Phosphorylation of microtubule-associated proteins MAP2a,b and MAP2c at serine 136 by proline-directed kinases in vivo and in vitro,”Eur.J. Cell Biol., 64:120-130 (1994).
Biernat, et al., “The switch of tau protein to an Alzheimer-like state includes the phosphorylation of two serine-proline motifs upstream of the microtubule binding region,”EMBO J., 11:1593-1597 (1992).
Biernat, et al., “Phosphorylation of serine 262 strongly reduces the binding of tau protein to microtubules: Distinction between PHF-like immunoreactivity and microtubule binding,”Neuron, 11:153-163 (1993).
Boyle, et al., “Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin layer cellulose plate,”Methods Enzymol., 201:110-149 (1991).
Bramblett, et al., “Abnormal tau phosphorylation at Ser (396) in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding,”Neuron, 10:1089-1099 (1993).
Brandt, et al., “Functional organization of microtubule-associated protein tau: Identification of regions which affect microtubule growth, nucleation, and bundle formation in vitro,”J.Biol.Chem., 268:3414-3419 (1993).
Brion, et al., “A68 proteins in Alzheimers-disease are composed of several tau isoforms in a phosphorylated state which affects their electrophoretic mobilities,”Biochem.J., 279:831-836 (1991).
Brugg, et al., “Phosphorylation determines the binding of microtubule-associated protein-2 (MAP2) to microtubules in living cells,”J.Cell.Biol., 114:735-743 (1991).
Butler, et al., “Microheterogeneity of microtubule-associated tau-proteins is due to differences in phosphorylation,”J.Neurochem., 47:1517-1522 (1986).
Butner, et al., “Tau-protein binds to microtubules through a flexible array of distributed weak sites,”J.Cell Biol., 115:717-730 (1991).
Casnelli, et al., “Assay of protein kinases using peptides with basic residues for phosphocellulose binding,”Meth.Enzymology, 200:115-120 (1991).
Chapin, et al., “Non-neuronal 210 kD Mn microtubule-associated protein (MAP4) contains a domain homologous to the microtubule-binding domains of neuronal MAP2 and tau,”J.Cell Sci., 98:27-36 (1991).
Chapin, et al., “Microtubule stabilization by assembly-promoting microtubule-associated proteins: A repeat performance,”Cell Mot.Cytoskel, 23:236-243 (1992).
Chen, et al., “Projection domains of MAP2 and tau determine spacings between microtubules in dendrites and axons,”Nature, 360:674-677 (1992).
Cleveland, et al., “Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin,”J.Mol.Biol. 116:207-225 (1977).
Correas, et al., “Microtubule associated protein tau is phosphorylated by protein kinase C on its tubulin binding domain,”J.Biol.Chem., 267:15721-15728 (1992).
Drechsel, et al., “Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau,”Mol.Biol.Cell, 3:1141-1154 (1992).
Drewes, et al., “Mitogen-activated protein (MAP) kinase transforms tau protein into an Alzheimer like state,”EMBO J., 11:2131-2138 (1992).
Drewes, et al., “Dephosphorylation of tau protein and Alzheimer paired helical filaments by calcineurin and phosphatase-2A,”FEBS Lett., 336:425-432 (1993).
Drubin, et al., “Tau protein function in living cells,”J.Cell Biol. 103:2739-2746 (1986).
Ennulat, et al., “Two separate 18-amino acid domains of tau promote the polymerization of tubulin,”J.Biol.Chem. 264:5327-5330 (1989).
Geahlen, et al., “Detection of protein kinase activity in sodium dodedyl sulfate-polyacrylamide gels,”Anal.Biochem., 153:151-158 (1986).
Goedert, et al., “Multiple isoforms of human microtubule-associated protein-tau: Sequences and localization in neurofibrillary tangles of Alzheimer-disease,”Neuron3:519-526 (1989).
Goedert, et al., “Tau proteins of Alzheimer paired helical filaments: Abnormal phosphorylation of all six brain isoforms,”Neuron, 8:159-168 (1992).
Goedert, et al., “Tau protein and the neurofibrillary pathology of Alzheimer's disease,”Trends in Neurosci., 16:460-465 (1993).
Gong, et al., “Alzheimer's disease abnormally phosphorylated tau is dephosphorylated by protein phosphatase-2b (calcineurin),”J.Neurochem., 62:803-806 (1994).
Goode, et al., “Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau,”J.Cell Biol., 124:769-782 (1994).
Greenberg, et al., “Hydrofluoric acid-treated tau-PHF proteins display the same biochemical properties as normal tau,”J.Biol.Chem., 267:264-569 (1992).
Grundke-Igbal, et al., “Abnormal phosphorylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology,”Proc.Nat'l.Acad.Sci.(USA), 83:4913-4917 (1986).
Gustke, et al., “The Alzheimer-like phosphorylation of tau protein reduces microtubule binding and involves Ser-Pro and Thr-Pro motifs,”FEBS Letts., 307:199-205 (1992).
Gustke, et al., “Domains of Tau Protein and Interactions with Microtubules,”Biochemistry, 33:9511-9522 (1994).
Hagestedt, et al., “Tau protein becomes long and stiff upon phosphorylation: Correlation between paracrystalline structure and degree of phosphorylation,”J.Cell Biol. 109:1643-1651 (1989).
Hanger, et al., “Glycogen-synthase kinase-3 induced Alzheimer's disease-like phosphorylation of tau: Generation of paired helical filament epitopes and neuronal localization of the kinase,”Neurosci.Lett. 147:58-62 (1992).
Hanks, et al., “Protein-kinase catalytic domain sequence database: Identification of conserved features of primary structure and classification of family members,”Meth.Enzymol., 200:38-62 (1991).
Hasegawa, et al., “Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain,”J.Biol.Chem., 26:17047-17054 (1992).
Himmler, et al., “Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains,”Mol.Cell Biol., 9:1381-1388 (1989).
Hirokawa, et al., “Microtubule organization and dynamics dependent on microtubule-associated proteins,”Curr.Opinion Cell Biol. 6:74-81 (1994).
Hirs, et al., “Modification of cysteins residues,”Methods Enzymol., 11:325-329 (1967).
Inglis, et al., “Emk, a protein-kinase with homologs in yeast maps to mouse chromosome-19,”Mamm.Genome, 4:401-
Biernat Jacek
Drewes Gerard
Mandelkow Eckhard
Mandelkow Eva-Marie
Marshall & Gerstein & Borun LLP
Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.V.
Prouty Rebecca
LandOfFree
Protein kinase (NPK-110) does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Protein kinase (NPK-110), we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Protein kinase (NPK-110) will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-4123249