Patents Assigned to Heptares Therapeutics Limited
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Patent number: 9670183Abstract: This invention relates to compounds that are agonists of the muscarinic M1 receptor and/or M4 receptor and which are useful in the treatment of muscarinic M1/M4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds include those according to formula (1), or a salt thereof, wherein Q, R1, R2, R3 and R4 are as defined herein.Type: GrantFiled: February 6, 2015Date of Patent: June 6, 2017Assignee: Heptares Therapeutics LimitedInventors: Giles Albert Brown, Julie Elaine Cansfield, Miles Stuart Congreve, Michael Alistair O'Brien, Mark Pickworth, Mark David Rackham, Benjamin Gerald Tehan, Barry John Teobald
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Publication number: 20170145075Abstract: A method for producing a mutant G-protein coupled receptor (GPCR) with increased stability relative to a parent GPCR, the method comprising making one or more mutations in the amino acid sequence that defines a Class 1 parent GPCR, wherein (i) the one or more mutations are located within a window of i plus or minus 5 residues, where i is the position of amino acid residue 3.55 in the parent GPCR, and/or (ii) the one or more mutations are located within a window of i minus 2 to i residues, where i is the position of amino acid residue 5.63 in the parent GPCR, and/or (iii) the one or more mutations are located within a window of i minus 4 to i plus 1 residues, where i is the position of amino acid residue 7.42 in the parent GPCR, to provide one or more mutants of the parent GPCR with increased stability.Type: ApplicationFiled: June 29, 2016Publication date: May 25, 2017Applicant: Heptares Therapeutics LimitedInventors: Nathan Jacob Robertson, Fiona Hamilton Marshall
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Patent number: 9593106Abstract: The present invention provides muscarinic M4 receptor agonists of formula (I) and pharmaceutically acceptable salts thereof, wherein m, n, p, q, R, R2 and R3 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases such as schizophrenia, Alzheimer's disease and various cognitive disorders as well as in the treatment or alleviation of pain.Type: GrantFiled: February 7, 2014Date of Patent: March 14, 2017Assignee: Heptares Therapeutics LimitedInventors: David Livermore, Kathryn White, Miles Congreve, Giles Brown, Michael O'Brien
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Patent number: 9573929Abstract: This invention relates to compounds that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula I, where n is 1 or 2; p is 0, 1 or 2; q is 0, 1 or 2; and R1-R6 are as defined herein.Type: GrantFiled: November 13, 2015Date of Patent: February 21, 2017Assignee: Heptares Therapeutics LimitedInventors: Miles Stuart Congreve, Giles Albert Brown, Julie Elaine Cansfield, Benjamin Gerald Tehan
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Patent number: 9555044Abstract: The disclosures herein relate to novel compounds of formula wherein W, X and Y1, Y2, Y3 and Y4 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of neurological or psychiatric disorders associated with orexin receptors.Type: GrantFiled: January 13, 2016Date of Patent: January 31, 2017Assignee: Heptares Therapeutics LimitedInventors: Miles Stuart Congreve, John Andrew Christopher, Benjamin Gerald Tehan, Sukhbinder Singh Klair, Sarah Joanne Aves
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Publication number: 20160052991Abstract: The invention relates to mutant G-protein coupled receptors with increased conformational stability, and methods of use thereof. In some aspects, polynucleotides encoding the mutant G-protein coupled receptors are provided. In some aspects, host cells comprising the polynucleotides are provided. In some aspects, the invention relates to crystallized forms of the mutant G-protein coupled receptors, and methods of preparing the same.Type: ApplicationFiled: August 26, 2015Publication date: February 25, 2016Applicant: Heptares Therapeutics LimitedInventors: Richard Henderson, Christopher Gordon Tate, Francesca Magnani, Maria Josefa Serrano-Vega, Yoko Shibata, Antony Johannes Warne, Malcolm Peter Weir
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Patent number: 9266857Abstract: This invention relates to compounds (Formula (1)) that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula where R1-R5, X1, X2 and p are as defined herein.Type: GrantFiled: September 18, 2013Date of Patent: February 23, 2016Assignee: Heptares Therapeutics LimitedInventors: Giles Albert Brown, Julie Elaine Cansfield, Miles Stuart Congreve, Mark Pickworth, Benjamin Gerald Tehan
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Patent number: 9260505Abstract: A method of producing a conformational specific binding partner of a GPCR, the method comprising: a) providing a mutant GPCR of a parent GPCR, wherein the mutant GPCR has increased stability in a particular conformation relative to the parent GPCR; b) providing a test compound; c) determining whether the test compound binds to the mutant GPCR when residing in a particular conformation; and d) isolating a test compound that binds to the mutant GPCR when residing in the particular formation. Methods of producing GPCRs with increased stability relative to a parent GPCR are also disclosed.Type: GrantFiled: April 17, 2014Date of Patent: February 16, 2016Assignee: Heptares Therapeutics LimitedInventors: Malcolm Peter Weir, Fiona Hamilton Marshall
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Patent number: 9249160Abstract: The disclosures herein relate to novel compounds of formula wherein W, X and Y1, Y2, Y3 and Y4 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of neurological or psychiatric disorders associated with orexin receptors.Type: GrantFiled: July 3, 2013Date of Patent: February 2, 2016Assignee: Heptares Therapeutics LimitedInventors: Miles Stuart Congreve, John Andrew Christopher, Benjamin Gerald Tehan, Sukhbinder Singh Klair, Sarah Joanne Aves
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Patent number: 9249130Abstract: According to the invention there is provided a compound of formula A1 which may be useful in the treatment of a condition or disorder ameliorated by the inhibition of the A1-A2b or, particularly, the A2a receptor wherein the compound of formula A1 has the structure, wherein, A represents Cy1 or HetA; Cy1 represents a 5- to 14-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one, two or three rings, which Cy1 group is optionally substituted by one or more R4a substituents; HetA represents a 5- to 14-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, which heterocyclic group may comprise one, two or three rings and which HetA group is optionally substituted by one or more R4b substituents; B represents a Cy2 or HetB; Cy2 represents a 3- to 10-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one or two rings, whicType: GrantFiled: July 2, 2014Date of Patent: February 2, 2016Assignee: Heptares Therapeutics LimitedInventors: Miles Stuart Congreve, Stephen Philippe Andrews, Jonathan Stephen Mason, Christine Mary Richardson, Giles Albert Brown
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Patent number: 9187451Abstract: This invention relates to compounds that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula I, where n is 1 or 2; p is 0, 1 or 2; q is 0, 1 or 2; and R1-R6 are as defined herein.Type: GrantFiled: November 16, 2012Date of Patent: November 17, 2015Assignee: Heptares Therapeutics LimitedInventors: Miles Congreve, Giles Brown, Julie Cansfield, Benjamin Tehan
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Publication number: 20150261911Abstract: The invention provides a method of predicting a three dimensional structural representation of a target protein of unknown structure, or part thereof, comprising: providing the coordinates of the human corticotropin-releasing factor receptor-1 (CRF1R) structure listed in Table A, Table B or Table C, optionally varied by a root mean square deviation of residue backbone atoms of not more than 4.383 ?, or selected coordinates thereof; and predicting the three-dimensional structural representation of the target protein, or part thereof, by modelling the structural representation on all or the selected coordinates of the CRF1R structure. The invention also provides the use of the CRF1R coordinates to select or design one or more binding partners of CRF1R.Type: ApplicationFiled: March 13, 2014Publication date: September 17, 2015Applicant: Heptares Therapeutics LimitedInventors: Andrea Bortolato, Kin Yip Cheng, Andrew Stephen Dore, Kaspar Hollenstein, Seyed Ali Jazayeri-Dezfuly, James Kean, Fiona Hamilton Marshall
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Patent number: 9081020Abstract: A method for selecting a membrane protein with increased stability, the method comprising: a) providing one or more mutants of a parent membrane protein in a membrane-containing composition, wherein the one or more mutants are exposed to an amount of a membrane destabilizing agent which is effective to destabilize the parent membrane protein in-situ, b) determining whether the or each mutant membrane protein has increased stability with respect to its structure and/or a biological activity compared to the stability of the parent membrane protein with respect to its structure and/or the same biological activity, and c) selecting the one or more mutants which have increased stability compared to the stability of the parent membrane protein.Type: GrantFiled: February 5, 2009Date of Patent: July 14, 2015Assignee: Heptares Therapeutics LimitedInventors: Malcolm Peter Weir, Richard Henderson, Christopher Gordon Tate, Edward Christopher Hulme
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Publication number: 20150147822Abstract: The invention provides an assay for assessing the conformational stability of a membrane protein, comprising: (a) providing a sample comprising a first population and a second population of a membrane protein; wherein the membrane protein in the first population is labelled with a donor label and the membrane protein in the second population is labelled with an acceptor label, or the membrane protein in the first population is labelled with an acceptor label and the membrane protein in the second population is labelled with a donor label, (b) exposing the first and second populations of the membrane protein to a stability modulating agent and/or condition, (c) and assessing aggregation between membrane proteins of the first and second populations by activating the donor label to permit a distance-dependent interaction with the acceptor label, which interaction produces a detectable signal.Type: ApplicationFiled: May 31, 2013Publication date: May 28, 2015Applicant: Heptares Therapeutics LimitedInventors: Fiona Hamilton Marshall, Seyed Ali Jazayeri-Dezfuly, Jayesh Chhotubhai Patel
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Patent number: 8900591Abstract: There is provided a G protein coupled receptor (GPCR) or a polynucleotide encoding said GPCR for use as a vaccine. There is also provided methods of antagonizing or agonizing A GPCR in vivo comprising the administration of a GPCR or a polynucleotide encoding a GPCR to a subject. The invention further provides a GPCR for use in inhibiting an activity of a GPCR binding partner in a subject.Type: GrantFiled: August 5, 2011Date of Patent: December 2, 2014Assignee: Heptares Therapeutics LimitedInventors: Catherine Jane Hutchings, Malcolm Peter Weir, Fiona Hamilton Marshall
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Publication number: 20140316116Abstract: A method of producing a conformational specific binding partner of a GPCR, the method comprising: a) providing a mutant GPCR of a parent GPCR, wherein the mutant GPCR has increased stability in a particular conformation relative to the parent GPCR; b) providing a test compound; c) determining whether the test compound binds to the mutant GPCR when residing in a particular conformation; and d) isolating a test compound that binds to the mutant GPCR when residing in the particular formation. Methods of producing GPCRs with increased stability relative to a parent GPCR are also disclosed.Type: ApplicationFiled: April 17, 2014Publication date: October 23, 2014Applicant: Heptares Therapeutics LimitedInventors: Malcolm Peter Weir, Fiona Hamilton Marshall
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Publication number: 20140315299Abstract: The invention provides a fusion protein comprising, from N-terminus to C-terminus: a) a first portion of a Family B G-protein coupled receptor (GPCR) that comprises transmembrane helix (TM)-1, TM2 and TM3 of the GPCR; b) a stable protein domain; and c) a second portion of the GPCR comprising TM4, TM5, TM6 and TM7 of the GPCR. The invention also provides a method of crystallising a GPCR comprising providing the fusion protein of the invention and crystallising it to obtain crystals.Type: ApplicationFiled: August 9, 2012Publication date: October 23, 2014Applicant: Heptares Therapeutics LimitedInventors: Seyed Ali Jazayeri-Dezfuly, Fiona Hamilton Marshall
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Patent number: 8809525Abstract: According to the invention there is provided a compound of formula A1 which may be useful in the treatment of a condition or disorder ameliorated by the inhibition of the A1-A2b or, particularly, the A2a receptor wherein the compound of formula A1 has the structure, wherein, A represents Cy1 or HetA; Cy1 represents a 5- to 14-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one, two or three rings, which Cy1 group is optionally substituted by one or more R4a substituents; HetA represents a 5- to 14-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, which heterocyclic group may comprise one, two or three rings and which HetA group is optionally substituted by one or more R4b substituents; B represents a Cy2 or HetB; Cy2 represents a 3- to 10-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one or two rings, whicType: GrantFiled: February 7, 2011Date of Patent: August 19, 2014Assignee: Heptares Therapeutics LimitedInventors: Miles Stuart Congreve, Stephen Philippe Andrews, Jonathan Stephen Mason, Christine Mary Richardson, Giles Albert Brown
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Patent number: 8790933Abstract: A method of producing a conformational specific binding partner of a GPCR, the method comprising: a) providing a mutant GPCR of a parent GPCR, wherein the mutant GPCR has increased stability in a particular conformation relative to the parent GPCR; b) providing a test compound; c) determining whether the test compound binds to the mutant GPCR when residing in a particular conformation; and d) isolating a test compound that binds to the mutant GPCR when residing in the particular conformation. Methods of producing GPCRs with increased stability relative to a parent GPCR are also disclosed.Type: GrantFiled: December 19, 2008Date of Patent: July 29, 2014Assignee: Heptares Therapeutics LimitedInventors: Malcolm Peter Weir, Fiona Hamilton Marshall
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Patent number: 8785135Abstract: The present invention relates in some aspects to mutant G protein coupled receptors (GPCRs) and methods for selecting those with increased stability. In certain aspects, the invention relates to the selection and preparation of mutant GPCRs which have increased stability under a particular condition compared to their respective parent proteins.Type: GrantFiled: March 20, 2008Date of Patent: July 22, 2014Assignee: Heptares Therapeutics LimitedInventors: Richard Henderson, Christopher Gordon Tate, Francesca Magnani, Maria Josefa Serrano-Vega, Yoko Shibata, Antony Johannes Warne, Malcolm Peter Weir