Patents Assigned to Locus Pharmaceuticals, Inc.
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Patent number: 8962623Abstract: A compound of formula (I): wherein all symbols have the same meanings as defined in the specification; a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug thereof, has an Itk inhibitory activity, and is useful as a method for preventing and/or treating atopic dermatitis, and the like.Type: GrantFiled: February 29, 2012Date of Patent: February 24, 2015Assignee: Locus Pharmaceuticals, Inc.Inventors: Rupa S. Shetty, Martha J. Kelly, Bin Liu, Jinming Zou, Kristofer K. Moffett, Younghee Lee, Dora Do-York Wong
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Publication number: 20140187529Abstract: A compound of formula (I): wherein all symbols have the same meanings as defined in the specification; a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug thereof, has an Itk inhibitory activity, and is useful as a method for preventing and/or treating atopic dermatitis, and the like.Type: ApplicationFiled: February 29, 2012Publication date: July 3, 2014Applicant: LOCUS PHARMACEUTICALS, INC.Inventors: Rupa S. Shetty, Martha J. Kelly, Bin Liu, Jinming Zou, Kristopher K. Moffett, Younghee Lee
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Patent number: 8765754Abstract: A compound of formula (I): wherein all symbols have the same meanings as defined in the specification; a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug thereof, has a Btk inhibitory activity, and is useful as a method for preventing and/or treating a rheumatoid arthritis, an autoimmune disease, a B cell lymphoma of cancer, and the like.Type: GrantFiled: April 28, 2010Date of Patent: July 1, 2014Assignee: Locus Pharmaceuticals, Inc.Inventors: Zenon Konteatis, Kristofer Moffett, Younghee Lee, Wenchun Chao, Dora Do-York Wong
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Publication number: 20120232054Abstract: A compound of formula (I): wherein all symbols have the same meanings as defined in the specification; a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug thereof, has a Btk inhibitory activity, and is useful as a method for preventing and/or treating a rheumatoid arthritis, an autoimmune disease, a B cell lymphoma of cancer, and the like.Type: ApplicationFiled: April 28, 2010Publication date: September 13, 2012Applicant: LOCUS PHARMACEUTICALS, INC.Inventors: Kevin J. Moriarty, Dora Do-York Wong, Zenon Konteatis, Kristofer Moffett, Younghee Lee, Wenchun Chao
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Patent number: 7741479Abstract: The present invention is directed to a compound having the formula wherein R1, R2, G, and Q are defined herein. The compounds of the present invention are useful as inhibitors of protein kinases such as MAP kinases, in particular p38 kinases. The present invention is also directed to compositions comprising a compound according to the above formula. The compounds and compositions described herein are useful for treating and preventing an inflammatory condition or disease. The present invention is also directed to a method of treating or preventing a protein kinase-mediated condition.Type: GrantFiled: December 7, 2005Date of Patent: June 22, 2010Assignee: Locus Pharmaceuticals, Inc.Inventors: Enrique Luis Michelotti, Eric Bruce Springman, Duyan Nguyen, Rupa S. Shetty, Younghee Lee, Kristofer Kent Moffett, Jennifer Lee Ludington, Ted Tsutomis Fujimoto, Zenon D. Konteatis, Bin Liu, Frank Hollinger, Bruce D. Dorsey
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Publication number: 20100041642Abstract: Urea containing compounds that inhibit MAP kinases, pharmaceutical compositions including such compounds and methods for using these compounds to treat inflammatory diseases and cancer are described herein.Type: ApplicationFiled: August 15, 2009Publication date: February 18, 2010Applicant: LOCUS PHARMACEUTICALS, INC.Inventors: Duyan NGUYEN, Martha KELLY, Kristofer MOFFETT, Enrique Luis MICHELOTTI, Bin Liu
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Publication number: 20090299647Abstract: A new approach to identifying binding conformations of chemical fragments and biological molecules is presented, in which fragment poses are explored in a systematic fashion. In an embodiment, for each pose, a fast computation is performed of the fragment interaction with the biological molecule using interpolation on a grid. Once the energies of fragment poses are computed, thermodynamical quantities such as binding affinity, binding enthalpy, and binding entropy are computed by direct sum over fragment poses. Using the present invention, it is possible to navigate fragment configuration space to identify separate binding modes. The present invention can be used to scan an entire biological molecule to identify possible binding pockets, or it can be used for localized explorations limited to interesting areas of known binding pockets.Type: ApplicationFiled: June 10, 2009Publication date: December 3, 2009Applicant: Locus Pharmaceuticals, Inc.Inventors: Paolo Carnevali, Gergely Toth, Siavash N. Meshkat
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Patent number: 7612200Abstract: The present invention is directed to a compound having the formula wherein R1, R2, R3, R4, G, and Q are defined herein. The compounds of the present invention are useful as inhibitors of protein kinases. The present invention is also directed to compositions comprising a compound according to the above formula. The present invention is also directed to compounds that stabilize the open conformation of a protein kinase, a crystallized protein kinase in the open conformation, and uses thereof. The compounds and compositions described herein are useful for treating and preventing an inflammatory condition or disease.Type: GrantFiled: December 7, 2005Date of Patent: November 3, 2009Assignee: Locus Pharmaceuticals, Inc.Inventors: Enrique Luis Michelotti, William R. Moore, Jr., Eric Bruce Springman
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Publication number: 20090171642Abstract: Methods and systems for estimating the free energy of molecules from a plurality of fragments are disclosed. A number of poses for each fragment in an unbound state and a sum of the free energy values for each fragment may be determined. A number of acceptable poses for each of a plurality of fragments when bound may also be determined. An entropy loss may be estimated based on at least the number of acceptable poses for each of the plurality of fragments when bound and the number of poses for each fragment in an unbound state. A free energy value may be determined for the plurality of fragments when bound based on the entropy loss.Type: ApplicationFiled: December 27, 2007Publication date: July 2, 2009Applicant: LOCUS PHARMACEUTICALS, INC.Inventors: George Talbot, Matthew Clark
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Publication number: 20090093479Abstract: The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3-R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur.Type: ApplicationFiled: December 17, 2008Publication date: April 9, 2009Applicant: LOCUS PHARMACEUTICALS, INC.Inventors: Martha KELLY, Younghee LEE, Bin LIU, Ted FUJIMOTO, Joel FREUNDLICH, Bruce D. DORSEY, Gary A. FLYNN, Arifa HUSAIN
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Publication number: 20090094012Abstract: Methods and systems for analyzing a macromolecule for potential binding sites are disclosed. Multiple molecular species and a free energy value may be selected. An operation for a molecular fragment of one of the molecular species may be selected from insertion, deletion and movement operations. The selected operation may be performed on a computer representation of an instance of a molecular fragment at one of a plurality of binding sites based on a grand canonical ensemble probability density function associated with the selected operation. Information may be stored pertaining to the plurality of binding sites. The operation selecting, performing and information storing operations may be performed multiple times. Multiple occupation probabilities may be provided based on the stored information. The occupation probabilities may include, for each molecular species, a probability that an instance of a molecular fragment of the molecular species resides at a binding site.Type: ApplicationFiled: October 9, 2007Publication date: April 9, 2009Applicant: LOCUS PHARMACEUTICALS, INC.Inventor: Matthew Clark
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Patent number: 7504401Abstract: The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3-R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur.Type: GrantFiled: August 30, 2004Date of Patent: March 17, 2009Assignee: Locus Pharmaceuticals, Inc.Inventors: Martha Kelly, Bruce D. Dorsey, Gary A. Flynn
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Publication number: 20080280891Abstract: The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3-R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur.Type: ApplicationFiled: June 27, 2007Publication date: November 13, 2008Applicant: Locus Pharmaceuticals, Inc.Inventors: Martha Kelly, Younghee Lee, Bin Liu, Ted Fujimoto, Joel Freundlich, Bruce D. Dorsey, Gary A. Flynn, Arifa Husain, William R. Moore, Jr.
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Patent number: 7415361Abstract: A method implemented in the form of a computer simulation code for evaluating the free energy of binding between polypeptide amino acid residues and one or more molecular fragment types is presented. The basis of the method is a novel weighted Metropolis Monte Carlo approach for sampling the grand canonical ensemble. By making use of the properties of the grand canonical ensemble, the affinity of fragments for binding in the vicinity of each protein residue can be efficiently computed. The binding volume associated to each fragment-residue pair is estimated on the basis of a simple proximity criteria, and a useful affinity mapping of the protein surface can be obtained in this way. The analysis of such data for various fragment types provides valuable information to help identify protein binding sites, as well as to identify key fragments used for building potential drug leads.Type: GrantFiled: August 18, 2004Date of Patent: August 19, 2008Assignee: Locus Pharmaceuticals, Inc.Inventors: Stephan Brunner, David Mosenkis, Frank P. Hollinger, William Chiang
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Publication number: 20070185098Abstract: The present invention is directed to a compound having the formula wherein R1, R2, R3, R4, G, and Q are defined herein. The compounds of the present invention are useful as inhibitors of protein kinases. The present invention is also directed to compositions comprising a compound according to the above formula. The present invention is also directed to compounds that stabilize the open conformation of a protein kinase, a crystallized protein kinase in the open conformation, and uses thereof. The compounds and compositions described herein are useful for treating and preventing an inflammatory condition or disease.Type: ApplicationFiled: January 4, 2007Publication date: August 9, 2007Applicant: Locus Pharmaceuticals, Inc.Inventors: Enrique Michelotti, William Moore, Eric Springman
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Publication number: 20070016374Abstract: A new approach to identifying binding conformations of chemical fragments and biological molecules is presented, in which fragment poses are explored in a systematic fashion. In an embodiment, for each pose, a fast computation is performed of the fragment interaction with the biological molecule using interpolation on a grid. Once the energies of fragment poses are computed, thermodynamical quantities such as binding affinity, binding enthalpy, and binding entropy are computed by direct sum over fragment poses. Using the present invention, it is possible to navigate fragment configuration space to identify separate binding modes. The present invention can be used to scan an entire biological molecule to identify possible binding pockets, or it can be used for localized explorations limited to interesting areas of known binding pockets.Type: ApplicationFiled: July 14, 2005Publication date: January 18, 2007Applicant: Locus Pharmaceuticals, Inc.Inventors: Paolo Carnevali, Gergely Toth, Siavash Meshkat
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Publication number: 20050222776Abstract: A method for characterizing a molecular fragment to collect data related to the fragment that allows its evaluation for drug discovery purposes. Starting with a two-dimensional model of the fragment, an initial three-dimensional model of the fragment is derived. Conformers of the fragment are identified. The conformers are then clustered, and a representative conformer is selected from each cluster. An ab initio or semi-empirical calculation and analysis is performed on one or more of the selected conformers. Each atom in the selected conformer is then assigned a type. The selected conformer is analyzed to determine if it is structurally symmetric. If so, the three-dimensional model of the fragment is adjusted to reflect the symmetry. The size of the fragment is calculated to allow geometric analysis of how the fragment physically fits with the protein and/or other fragments. The solvation energy of the fragment is calculated. The free energy curve for the fragment is calculated.Type: ApplicationFiled: March 31, 2004Publication date: October 6, 2005Applicant: Locus Pharmaceuticals, Inc.Inventors: Jennifer Ludington, Ted Fujimoto, Frank Hollinger
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Publication number: 20050123995Abstract: A method implemented in the form of a computer simulation code for evaluating the free energy of binding between polypeptide amino acid residues and one or more molecular fragment types is presented. The basis of the method is a novel weighted Metropolis Monte Carlo approach for sampling the grand canonical ensemble. By making use of the properties of the grand canonical ensemble, the affinity of fragments for binding in the vicinity of each protein residue can be efficiently computed. The binding volume associated to each fragment-residue pair is estimated on the basis of a simple proximity criteria, and a useful affinity mapping of the protein surface can be obtained in this way. The analysis of such data for various fragment types provides valuable information to help identify protein binding sites, as well as to identify key fragments used for building potential drug leads.Type: ApplicationFiled: August 18, 2004Publication date: June 9, 2005Applicant: Locus Pharmaceuticals, Inc.Inventors: Stephan Brunner, David Mosenkis, Frank Hollinger, William Chiang
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Publication number: 20040220746Abstract: Methods and systems for improving virtual representations of large molecules provide a “prepared” virtual representation of the target protein. The prepared virtual representation of the target protein is useful for further in-silico, or computer processing. Further processing can include, without limitation, designing of small molecules that will potentially bind and/or interact with the target protein. In accordance with the invention, one or more features of the virtual representation of the protein are assessed. One or more of a variety of assessments can be performed including, without limitation, analyzing for completeness (e.g., missing and/or incomplete residues and/or side chains), identifying missing (typically smaller) atoms, determining ionization states (i.e., protonated or not), determining orientation of bonds, and/or identifying atoms that are not part of the protein.Type: ApplicationFiled: March 3, 2004Publication date: November 4, 2004Applicant: Locus Pharmaceuticals, Inc.Inventor: Frank P. Hollinger