Paul V Greengard, 98450 E 63Rd St APT 11J, New York, NY 10065

6429010, Aug 6, 2002

Aug 5, 1998

09/129668

Paul Greengard - New York NY
Barbara Porton - New York NY

The Rockefeller University - New York NY

C12N 1500

4353201, 43525231, 43525233, 43525234, 43525235, 43525411, 4352542, 435325, 435348, 435352, 435358, 435362, 435366, 435368, 435419, 536 235

A new synapsin protein, designated synapsin III, its amino acid sequence, and its human gene have been isolated and characterized. Furthermore, isoforms of synapsin III, e. g. , synapsin IIIa, IIIb and IIIc, and have isolated and characterized, and cDNA encoding these isoforms has also been isolated and characterized. The synapsin III gene is located on human chromosome 22, in the vicinity of a region previously identified as a susceptibility locus for schizophrenia. The information and experimental tools provided by this discovery can be used to generate new therapeutic agents or diagnostic assays for this new protein, its associated mRNA or its associated genomic DNA. Due to its role in neurotransmission and synaptogenesis, isoforms of synapsin III are associated with the symptoms of psychiatric diseases, especially schizophrenia.

6444201, Sep 3, 2002

May 13, 1996

08/644433

Hui-Quan Han - Scotch Plains NJ
Paul Greengard - New York NY
Kenneth S. Kosik - Belmont MA
Adriana Ferreira - Boston MA

The Rockefeller University - New York NY
Brighan and Womens Hospital - Boston MA

A61K 3820

424 852, 514 12

The role of synapsin II in both the reformation and the maintenance of synaptic connections in cultured hippocampal neurons can be the basis of therapy for neurodegenerative disorder, particularly Alzheimer disease, which involve the disruption of synapses. When synapsin II expression in neurons is blocked by antisense synapsin II oligonucleotides, the ability of hippocampal neurons to reform as well as to maintain synapses is severely disrupted. Antisense suppression of synapsin II after axon formation but immediately before synaptogenesis prevents synapse formation. Suppression of synapsin II after synaptogenesis disrupts the majority of existing synapses. Re-expression of synapsin II in synapsin deficient neurons achieved after removing the antisense oligonucleotides leads to the re-establishment of synaptic connections, providing direct evidence that synapsin II is required for the maintenance and/or restoration of synapses. Thus, therapeutic methods based on the reformation and the maintenance of synapses, including delivery of the synapsin cDNAS or proteins into the patients nervous system, use of the synapsin cDNAS to promote the synapse forming ability of cells for grafting, and use of agents that increase the expression of, enhancing the activity of, or mimic the activity of, the endogenous synapsins, can provide treatment of neurodegenerative disorders.

6989362, Jan 24, 2006

Oct 13, 2000

09/687959

James A. Bibb - New York NY, US
Paul Greengard - New York NY, US

The Rockefeller University - New York NY

A61K 31/77
A61K 31/40
A61K 31/407
A61P 25/14
A61P 25/16
C07D 487/02

514 1, 514415, 514 43, 514411, 424 7838, 548484

The present invention discloses that DARPP-32 is substrate for the cyclin dependent kinase Cdk5. The phosphorylation takes place at a specific threonine residue of DARPP-32 (Threonine 75). The Cdk5 catalyzed phosphorylation of DARPP-32 converts this protein into an inhibitor of the cAMP dependent protein kinase (PKA) and furthermore prevents it from being converted to an inhibitor of protein phosphatase 1 (PP1). Methods of identifying agents that modulate the phosphorylation of DARPP-32 by Cdk5 are disclosed. Methods of treating dopamine dysfunction in animal subjects are also provided.

7129073, Oct 31, 2006

Jun 18, 2002

10/175190

Feng Liu - Plainsboro NJ, US
Angus C. Nairn - Guilford CT, US
Paul Greengard - New York NY, US

The Rockefeller University - New York NY

C12N 9/12

435194, 435184

The present invention provides methods and compositions for modulating the activities of metabotropic glutamate receptor intracellular signaling molecules. The present invention provides methods and compositions for modulating the activities of casein kinase I and/or cyclin-dependent kinase 5 in cells or tissues. The present invention provides methods of modulating the function of calcium channels in cells or tissues. The present invention provides methods of treating calcium channel dysfunction. The present invention provides methods of identifying agents that modulate the activities of the metabotropic glutamate receptor intracellular signaling molecules casein kinase I and/or cyclin-dependent kinase 5 for use in such treatments.

7320785, Jan 22, 2008

Aug 12, 2002

10/218137

Paul Greengard - New York NY, US
Per Svenningsson - New York NY, US
Sergey V. Rakhilin - Yorktown NY, US
Natalia Starkova - New York NY, US

The Rockefeller University - New York NY

A61K 49/00
G01N 33/53
G01N 33/567

424 92, 424 91, 435 72, 435 721

The present invention provides methods and compositions for modulating the phosphorylation of DARPP-32 in a serotonergic receptor intracellular signaling pathway. The invention provides methods and compositions for modulating the activities of DARPP-32, casein kinase 1 (CK1), cyclin-dependent kinase 5 (Cdk5), AMPA receptors, protein phosphatase-1 (PP-1), protein phosphatase 2C (PP2C), protein phosphatase 2B (PP2B) and/or protein phosphatase 2A (PP2A) in cells or tissues. The invention provides methods of treating serotonergic intracellular signaling pathway disorders, e. g. , depression. The invention provides methods of treating dopamine-related disorders. The invention provides methods of identifying agents that modulate the activities of serotonergic receptor intracellular signaling molecules, DARPP-32, casein kinase 1, cyclin-dependent kinase 5, AMPA receptors, protein phosphatase-1, protein phosphatase 2C, protein phosphatase 2B and/or protein phosphatase 2A, for use in such treatments. The invention also provides methods of modulating phosphorylation-dependent activation of AMPA receptors for use in such treatments.

7427485, Sep 23, 2008

Sep 3, 2002

10/233448

Paul Greengard - New York NY, US
Gilberto Fisone - Stockholm, SE

The Rockefeller University - New York NY

C12Q 1/48
C12Q 1/42
G01N 33/53

435 71, 435 15, 435 21

The present invention provides a method for identifying an agent to be tested for an ability to treat a psychotic disorder in a patient in need of such treatment. The invention provides a method for screening candidate drugs for anti-psychotic drug activity, preferably atypical anti-psychotic activity, comprising contacting cells or tissues with a candidate drug, determining levels of phosphorylation of the intracellular signaling proteins, DARPP-32, ERK1, ERK2 and CREB, in said cells or tissues and determining the pattern of the levels of phosphorylation of the proteins. The pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB is, in certain embodiments, compared with the pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB in the presence of an atypical anti-psychotic drug.

7910586, Mar 22, 2011

Jan 6, 2003

10/337261

William Netzer - New York NY, US
Paul Greengard - New York NY, US
Huaxi Xu - New York NY, US

The Rockefeller University - New York NY

A01N 43/58
A01N 43/54
A01N 43/40
A01N 43/42
A61K 31/50
A61K 31/435
A61K 31/44
C07D 239/42
C07D 401/04
C07D 471/04
C07D 471/22
C07D 487/04

514247, 514256, 514257, 514277, 514279

The present invention provides methods and compositions for modulating levels of amyloid-β peptide (Aβ) exhibited by cells or tissues. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate Aβ levels. The invention also provides modulation of Aβ levels via selective modulation (e. g. , inhibition) of ATP-dependent γ-secretase activity. The invention also provides methods of preventing, treating or ameliorating the symptoms of a disorder, including but not limited to an Aβ-related disorder, by administering a modulator of γ-secretase, including, but not limited to, a selective inhibitor of ATP-dependent γ-secretase activity or an agent that decreases the formation of active (or optimally active) γ-secretase. The invention also provides the use of inhibitors of ATP-dependent γ-secretase activity to prevent, treat or ameliorate the symptoms of Alzheimer's disease.

8470548, Jun 25, 2013

Dec 22, 2011

13/335402

Per Svenningsson - New York NY, US
Paul Greengard - New York NY, US

Intra-Cellular Therapies, Inc. - New York

G01N 33/53
G01N 33/567
G01N 33/542
C12Q 1/68

435 792, 436501, 436504

The present invention relates to the use of p11 as a drug target as well as a tool for the diagnosis, treatment and development of p11/5-HT receptor related disorders. The invention further relates to p11 knock-out animals as well as p11 transgenic animals and their use as models for the development of novel psychotherapeutic agents, and to methods of diagnosis, prophylaxis and treatment of p11/5-HT receptor related disorders.