Patents by Inventor Jeffery W. Kelly
Jeffery W. Kelly has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 11945806Abstract: In immunoglobulin light chain amyloidosis (AL), the unique antibody light chain (LC) protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. For treating AL patients, such as those with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, provided herein are small molecule compounds of Formula Ia, Formula Ib, and Formula II that are kinetic stabilizers of the native dimeric structure of full-length LCs, which compounds can slow or stop the amyloidogenicity cascade at its origin.Type: GrantFiled: March 29, 2020Date of Patent: April 2, 2024Inventors: Jeffery W. Kelly, Gareth John Morgan, Nicholas Lok Yan, Hank Michael James Petrassi
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Publication number: 20240092757Abstract: Provided herein are compounds that activate IRE1/XBP1s, and pharmaceutically acceptable derivatives thereof. Also provided are pharmaceutical compositions containing the compounds and methods of using the compounds for treating a subject having a disease or disorder that may be ameliorated by increasing IRE1/XBP1s activity.Type: ApplicationFiled: November 8, 2023Publication date: March 21, 2024Inventors: Richard F. Labaudiniere, Bradley Dean Tait, Hank Michael James Petrassi, Jeffery W. Kelly, R. Luke Wiseman, Kyunga Lee, Adrian Marco Guerrero
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Publication number: 20220313624Abstract: Described herein are compounds comprising a biologically active organic core group with one to five —Z—(X1—S(O)(X2)F)m groups attached thereto, wherein Z is O, NR, or N; X1 is a covalent bond or CH2CH2; m can be 1 or 2 depending on the identity of Z; and X2 is O or NR. In some embodiments, the core group is an amino acid or a protein. In some embodiments the core group is a compound that has therapeutic activity toward a therapeutic target.Type: ApplicationFiled: May 27, 2022Publication date: October 6, 2022Applicant: THE SCRIPPS RESEARCH INSTITUTEInventors: Jiajia DONG, K. Barry SHARPLESS, Jeffery W. KELLY, Aleksandra BARANCZAK, Wentao CHEN
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Patent number: 11426402Abstract: Disclosed herein are compounds, their pharmaceutical salts, and pharmaceutical compositions that selectively activate the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1s) signaling pathway of the unfolded protein response (UPR), but that do not target the IRE1 kinase domain. The compounds are useful in treating diseases or conditions characterized by imbalances in proteostasis within the endoplasmic reticulum (ER) or secretory pathway, including those not associated with ER stress or activation of UPR.Type: GrantFiled: May 26, 2020Date of Patent: August 30, 2022Assignee: The Scripps Research InstituteInventors: R. Luke Wiseman, Jeffery W. Kelly, Julia M. D. Grandjean, Christina B. Cooley, Lars Plate, Enrique Saez, Aparajita Madhavan, Bernard Kok
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Publication number: 20220204485Abstract: In immunoglobulin light chain amyloidosis (AL), the unique antibody light chain (LC) protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. For treating AL patients, such as those with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, provided herein are small molecule compounds of Formula Ia, Formula Ib, and Formula II that are kinetic stabilizers of the native dimeric structure of full-length LCs, which compounds can slow or stop the amyloidogenicity cascade at its origin.Type: ApplicationFiled: March 29, 2020Publication date: June 30, 2022Inventors: Jeffery W. Kelly, Gareth John Morgan, Nicholas Lok Yan, Hank Michael James Petrassi
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Publication number: 20220000799Abstract: This application describes modified amino acids and polypeptides comprising a SO2F or CH2CH2SO2F group bound to the side chain of an amono acid or amino acid residue of a polypeptide in place of a hydrogen of a hydroxyl or amino substituent thereof. Methods of covalently binding the polypeptides to receptot sites of receptor proteins are also described herein.Type: ApplicationFiled: September 10, 2021Publication date: January 6, 2022Applicant: THE SCRIPPS RESEARCH INSTITUTEInventors: Jiajia DONG, K. Barry SHARPLESS, Jeffery W. KELLY, Aleksandra BARANCZAK, Wentao CHEN
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Publication number: 20210393557Abstract: The invention provides compounds for activating the activating transcription factor 6 (ATF6) arm of the unfolded protein response (UPR), or activating the transcriptional targets of ATF6, in the endoplasmic reticulum of a cell, the compounds being of any of formulas (I) through (IX) as described herein. The compounds can be used for treatment of conditions involving gain-of-toxic-function and loss-of-function folding disorders including lysosomal storage diseases, antitrypsin-associated emphysema and similar diseases. These molecules are also expected to have disease-ameliorating effects in Alzheimer's disease and diabetes.Type: ApplicationFiled: August 19, 2021Publication date: December 23, 2021Inventors: Christina Cooley, Jeffery W. Kelly, Ryan Paxman, Lars Plate, R. Luke Wiseman
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Patent number: 11141385Abstract: This application describes a compound represented by Formula (I): wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.Type: GrantFiled: September 4, 2020Date of Patent: October 12, 2021Assignee: THE SCRIPPS RESEARCH INSTITUTEInventors: Jiajia Dong, K Barry Sharpless, Jeffery W. Kelly, Aleksandra Baranczak, Wentao Chen
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Patent number: 11135186Abstract: The invention provides compounds for activating the activating transcription factor 6 (ATF6) arm of the unfolded protein response (UPR), or activating the transcriptional targets of ATF6, in the endoplasmic reticulum of a cell, the compounds being of any of formulas (I) through (IX) as described herein. The compounds can be used for treatment of conditions involving gain-of-toxic-function and loss-of-function folding disorders including lysosomal storage diseases, antitrypsin-associated emphysema and similar diseases. These molecules are also expected to have disease-ameliorating effects in Alzheimer's disease and diabetes.Type: GrantFiled: December 29, 2016Date of Patent: October 5, 2021Assignee: The Scripps Research InstituteInventors: Christina Cooley, Jeffery W. Kelly, Ryan Paxman, Lars Plate, R. Luke Wiseman
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Publication number: 20210008064Abstract: Disclosed herein are compounds, their pharmaceutical salts, and pharmaceutical compositions that selectively activate the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1s) signaling pathway of the unfolded protein response (UPR), but that do not target the IRE1 kinase domain.Type: ApplicationFiled: May 26, 2020Publication date: January 14, 2021Inventors: R. Luke Wiseman, Jeffery W. Kelly, Julia M.D. Grandjean, Christina B, Cooley, Lars Plate, Enrique Saez, Aparajita Madhavan, Bernard Kok
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Publication number: 20200397719Abstract: This application describes a compound represented by Formula (I): wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.Type: ApplicationFiled: September 4, 2020Publication date: December 24, 2020Applicant: THE SCRIPPS RESEARCH INSTITUTEInventors: Jiajia DONG, K. Barry SHARPLESS, Jeffery W. KELLY, Aleksandra BARANCZAK, Wentao CHEN
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Patent number: 10765645Abstract: This application describes a compound represented by Formula (I): YZX1—S(O)(X2)F)m]n??(I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.Type: GrantFiled: October 12, 2018Date of Patent: September 8, 2020Assignee: THE SCRIPPS RESEARCH INSTITUTEInventors: Jiajia Dong, K. Barry Sharpless, Jeffery W. Kelly, Aleksandra Baranczak, Wentao Chen
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Publication number: 20190029972Abstract: This application describes a compound represented by Formula (I): Y?Z?X1—S(O)(X2)F)m]n??(I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.Type: ApplicationFiled: October 12, 2018Publication date: January 31, 2019Applicant: THE SCRIPPS RESEARCH INSTITUTEInventors: Jiajia Dong, K. Barry Sharpless, Jeffery W. Kelly, Aleksandra Baranczak, Wentao Chen
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Publication number: 20190008809Abstract: The invention provides compounds for activating the activating transcription factor 6 (ATF6) arm of the unfolded protein response (UPR), or activating the transcriptional targets of ATF6, in the endoplasmic reticulum of a cell, the compounds being of any of formulas (I) through (IX) as described herein. The compounds can be used for treatment of conditions involving gain-of-toxic-function and loss-of-function folding disorders including lysosomal storage diseases, antitrypsin-associated emphysema and similar diseases. These molecules are also expected to have disease-ameliorating effects in Alzheimer's disease and diabetes.Type: ApplicationFiled: December 29, 2016Publication date: January 10, 2019Inventors: Christina Cooley, Jeffery W. Kelly, Ryan Paxman, Lars Plate, R. Luke Wiseman
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Patent number: 10117840Abstract: This application describes a compound represented by Formula (I): (I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.Type: GrantFiled: June 5, 2015Date of Patent: November 6, 2018Assignee: The Scripps Research InstituteInventors: Jiajia Dong, K. Barry Sharpless, Jeffery W. Kelly, Wentao Chen
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Publication number: 20180022797Abstract: The present invention provides compositions comprising anti-transthyretin antibodies. The compositions are particularly useful for diagnosis, prognosis and/or treatment of amyloid diseases or symptoms thereof.Type: ApplicationFiled: September 26, 2017Publication date: January 25, 2018Inventors: Xin JIANG, Jeffery W. KELLY, Justin CHAPMAN
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Patent number: 9790269Abstract: The present invention provides compositions comprising anti-transthyretin antibodies. The compositions are particularly useful for diagnosis, prognosis and/or treatment of amyloid diseases or symptoms thereof.Type: GrantFiled: February 7, 2014Date of Patent: October 17, 2017Assignee: MISFOLDING DIAGNOSTICS, INC.Inventors: Xin Jiang, Jeffery W. Kelly, Justin Chapman
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Patent number: 9771321Abstract: A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and reacts chemoselectively with one or two of four Lys-15 ?-amino groups within the transthyretin tetramer. The crystal structure confirms the binding orientation of the compound substructure and the conjugating amide bond. A covalent transthyretin kinetic stabilizer exhibits superior amyloid inhibition potency, compared to a non-covalent counterpart, and inhibits cytotoxicity associated with amyloidogenesis.Type: GrantFiled: April 14, 2014Date of Patent: September 26, 2017Assignee: THE SCRIPPS RESEARCH INSTITUTEInventors: Jeffery W Kelly, Sungwook Choi
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Publication number: 20170196985Abstract: This application describes a compound represented by Formula (I): (I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.Type: ApplicationFiled: June 5, 2015Publication date: July 13, 2017Inventors: Jiajia DONG, K. Barry SHARPLESS, Jeffery W. KELLY, Aleksandra BARANCZAK, Wentao CHEN
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Publication number: 20170190660Abstract: A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and reacts chemoselectively with one or two of four Lys-15 ?-amino groups within the transthyretin tetramer. The crystal structure confirms the binding orientation of the compound substructure and the conjugating amide bond. A covalent transthyretin kinetic stabilizer exhibits superior amyloid inhibition potency, compared to a non-covalent counterpart, and inhibits cytotoxicity associated with amyloidogenesis.Type: ApplicationFiled: April 14, 2014Publication date: July 6, 2017Inventors: Jeffery W. Kelly, Sungwook Choi