Curagen Corporation

Bioxcel Therapeutics, Inc.

Bioxcel Corporation

Genaissance Pharmaceuticals, Inc.

Onkosxcel Therapeutics, LLC

Krishnan Nandabalan

Meijia Yang

Vincent Peter Schulz

Jonathan Marc Rothberg

Frank Yocca

Deepa Saini

Harsh Negi

Sameer Sharma

Theodore Samuel Kalbfleisch

James Robert Knight

Luca Rastelli

Stephen Bryant Liggett

Richard S Judson

J Claiborne Stephens

Vimal Mehta

Ramkesh Meena

Catherine B Stack

Connie M Drysdale

Meija Yang

Vincent Peter Schultz

The present invention discloses a method of treating agitation or the signs of agitation in a subject comprising the sublingual administration of an effective amount of an alpha-2 adrenergic agonist, more particularly Dexmedetomidine, or a pharmaceutically acceptable salt thereof. The method is particularly suitable for the treatment of agitation associated with neurodegenerative and/or neuropsychiatric diseases. The present invention also discloses the sublingual administration of an alpha-2 adrenergic agonist, more particularly Dexmedetomidine or a pharmaceutically acceptable salt thereof at a dose that is effective to treat agitation or the signs of agitation in a subject, but does not cause significant sedation.

Use of sublingual dexmedetomidine for the treatment of agitation

The present invention generally relates to a method of diagnosing, prognosing and treating prostate cancer patients. Particularly, the present invention relates to a method of selecting patients with castration resistant prostate cancer (CrPC) for combination therapy comprising a selective dipeptidyl peptidase inhibitor and a PD-1 axis antagonist. The present invention provides a computational approach to identifying potential patients for CrPC. The present invention also relates to a method of treating castration resistant prostate cancer (CrPC) patients with said combination therapy.

Predictive and diagnostic methods for prostate cancer

The invention discloses a method of treating, preventing or ameliorating tumor or symptoms resulting from defective neurofibromatosis type-2 gene in a subject by administering to the subject a therapeutically effective amount of a ubiquitin-proteasome system inhibitor which inhibits or slows the growth of neurofibromatosis type-2-deficient tumor or associated symptoms. The invention also includes methods of diagnosis and screening of patients for neurofibromatosis type-2 and mesothelioma.

Use of ubiquitin-proteasome system inhibitors for treatment of tumors associated with neurofibromatosis type-2

A method, non-transitory computer readable medium, and pharmaceutical assessment computing device that effectively reformulates and repositions pharmaceutical molecule data. With this technology, therapeutic area data comprising a medical condition and pharmaceutical molecule data corresponding to the medical condition is obtained. The pharmaceutical molecule data comprises pharmaceutical molecule identifiers and usage data parameters with corresponding usage data values for each of the pharmaceutical molecule identifiers. Each of the usage data values is compared to a corresponding usage threshold value. Reformulation opportunities are determined for each of the pharmaceutical molecule identifiers comprising a usage data value that exceeds the corresponding usage threshold value. The reformulation opportunities comprise the usage data parameters and associated usage data values corresponding to the pharmaceutical molecule identifiers which comprise a usage data value that exceeds the corresponding usage threshold value. A pharmaceutical molecule report based on the reformulation opportunities is provided.

Methods for reformulating and repositioning pharmaceutical data and devices thereof

The present invention relates to complexes of the 53BP2 protein with proteins identified as interacting with 53BP2 by a yeast two hybrid assay system. The proteins identified to interact with 53BP2 are &bgr;-tubulin, p62, hnRNP G, and three gene products, 53BP2-IP1, 53BP2-IP2, and 53BP2-IP3 encoded, in part, by the EST R72810 sequence. Thus, the invention provides complexes of 53BP2 and &bgr;-tubulin, p62, hnRNP G, 53BP2-IP1, 53BP2-IP2, and 53BP2-IP3 and derivatives, fragments and analogs thereof. The invention also provides the 53BP2-IP1, 53BP2-IP2 and 53BP2-IP3 genes and proteins and derivatives, fragments and analogs thereof. Methods of screening the complexes for efficacy in treating and/or preventing certain diseases and disorders, particularly cancer, autoimmune disease and neurodegenerative disease are also provided.

53BP2 complexes

Genotypes and haplotypes for thirteen polymorphic sites in the &bgr; -adrenergic receptor (&bgr; AR) gene are disclosed. Compositions and methods for predicting genetic predisposition to disease associated with polymorphic sites in the (&bgr; AR) gene, as well as for predicting response to &bgr;-agonists, are also disclosed.

Association of &bgr;2-adrenergic receptor haplotypes with drug response

The present invention relates to complexes of the HPS protein with proteins identified as interacting with HPS protein by a modified yeast two hybrid assay system. The proteins identified to interact with HPS protein are 14-3-3 protein, Hrs, atrophin-1, DGS-I, nuclear factor NF90, HPIP1 and human HN1 homolog protein. Accordingly, the present invention discloses complexes of HPS protein and 14-3-3 protein, Hrs, atrophin-1, DGS-I, nuclear factor NF90, HPIP1 and human HN1 homolog protein, and derivatives, fragments and analogs thereof. Additionally, the present invention also discloses nucleic acids encoding the HPIP1 and human HN1 homolog protein, or derivatives, fragments and analogs thereof. Methods of screening the complexes or proteins for efficacy in treating and/or preventing certain diseases and disorders, particularly atopic diseases, autoimmune diseases, neurodegenerative disease, cancer, pigmentation disorders, platelet dysfunction and viral diseases, are also disclosed herein.

Isolation and characterization of Hermansky Pudlak Syndrome (HPS) protein complexes and HPS protein-interacting proteins

The present invention relates to complexes of the CDK2 protein with proteins identified as interacting with CDK2 by a modified yeast two hybrid assay system. The proteins identified to interact with CDK2 are cyclin H, cyclin I, ERH, and two gene products, hsReq*-1 and hsReq*-2, which are splice variants of the gene hsReq. Thus, the invention provides complexes of CDK2 and cyclin H, cyclin I, ERH, hsReq*-1, and hsReq*-2, and derivatives, fragments and analogs thereof. The invention also provides nucleic acids encoding the hsReq*-1 and hsReq*-2, and proteins and derivatives, fragments and analogs thereof. Methods of screening the complexes for efficacy in treating and/or preventing certain diseases and disorders, particularly cancer, atherosclerosis and neurodegenerative disease are also provided.

HsReq*1 and hsReq*2proteins and use thereof to detect CDK2

The present invention discloses complexes of the Nlk1 protein with proteins identified as interacting with the Nlk1 protein (Nlk1 protein-IPs) by a modified, improved yeast two hybrid assay system. The proteins which were identified to interact with the Nlk1 protein, and thus form complexes, included: TrkA, protein phosphatase 1&agr;, 14-3-3&egr;, &agr;-tropomyosin, vimentin, p0071, Ini-1, IP-1, IP-2, IP-3, IP-4 and IP-5, as well as derivatives, fragments analogs and homologs thereof. Methodologies of screening these aforementioned complexes for efficacy in treating and/or preventing various diseases and disorders, particularly, neoplasia, neurodegenerative disease, hypertrophic cardiomyopathy, viral infections and metabolic diseases and disorders are also disclosed herein.

NLK1 protein and NLK1 protein complexes

Methods are described for detecting protein-protein interactions, among two populations of proteins, each having a complexity of at least 100. Encoded proteins are fused either to the DNA-binding domain of a transcriptional activator or to the activation domain of a transcriptional activator. Two yeast strains, of the opposite mating type and carrying one type each of the fusion proteins are mated together. Productive interactions between the two halves due to protein-protein interactions lead to the reconstitution of the transcriptional activator, which in turn leads to the activation of a reporter gene containing a binding site for the DNA-binding domain. This analysis can be carried out for two or more populations of proteins. The differences in the genes encoding the proteins involved in the protein-protein interactions are characterized, thus leading to the identification of specific protein-protein interactions, and the genes encoding the interacting proteins, relevant to a particular tissue, stage or disease. Furthermore, inhibitors that interfere with these protein-protein interactions are identified by their ability to inactivate a reporter gene. The screening for such inhibitors can be in a multiplexed format where a set of inhibitors will be screened against a library of interactors. Further, information-processing methods and systems are described. These methods and systems pro vide for identification of the genes coding for detected interacting proteins, for assembling a unified database of protein-protein interaction data, and for processing this unified database to obtain protein interaction domain and protein pathway information.

Identification and comparison of protein&mdash;protein interactions that occur in populations and identification of inhibitors of these interactors

Methods are described for detecting protein-protein interactions, among two populations of proteins, each having a complexity of at least 1,000. For example, proteins are fused either to the DNA-binding domain of a transcriptional activator or to the activation domain of a transcriptional activator. Two yeast strains, of the opposite mating type and carrying one type each of the fusion proteins are mated together. Productive interactions between the two halves due to protein-protein interactions lead to the reconstitution of the transcriptional activator, which in turn leads to the activation of a reporter gene containing a binding site for the DNA-binding domain. This analysis can be carried out for two or more populations of proteins. The differences in the genes encoding the proteins involved in the protein-protein interactions are characterized, thus leading to the identification of specific protein-protein interactions, and the genes encoding the interacting proteins, relevant to a particular tissue, stage or disease. Furthermore, inhibitors that interfere with these protein-protein interactions are identified by their ability to inactivate a reporter gene. The screening for such inhibitors can be in a multiplexed format where a set of inhibitors will be screened against a library of interactors.

Identification and comparison of protein-protein interactions that occur in populations and indentification of inhibitors of these interactors

Disclosed are complexes of the MDM2 protein and a novel MDM2-interacting protein (MDMIP). Also disclosed are nucleic acids encoding the MDMIP polypeptide, as well as derivatives, fragments, analogs and homologs of the MDMIP polypeptide and MDM2-MDMIP complexes.

Nucleic acid encoding the MDM interacting protein

Methods are described for detecting protein--protein interactions, among two populations of proteins, each having a complexity of at least 1,000. For example, proteins are fused either to the DNA-binding domain of a transcriptional activator or to the activation domain of a transcriptional activator. Two yeast strains, of the opposite mating type and carrying one type each of the fusion proteins are mated together. Productive interactions between the two halves due to proten--protein interactions lead to the reconstitution of the transcriptional activator, which in turn leads to the activation of a reporter gene containing a binding site for the DNA-binding domain. This analysis can be carried out for two or more populations of proteins. The differences in the genes encoding the proteins involved in the protein--protein interactions are characterized, thus leading to the identification of specific protein--protein interactions, and the genes encoding the interacting proteins, relevant to a particular tissue, stage or disease. Furthermore, inhibitors that interfere with these protein--protein interactions are identified by their ability to inactivate a reporter gene. The screening for such inhibitors can be in a multiplexed format where a set of inhibitors will be screened against a library of interactors.

Growing community of inventors

Guilford, CT, United States of America

Krishnan Nandabalan