Patents by Inventor William S. Sly
William S. Sly 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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Publication number: 20180321220Abstract: A method for monitoring the metabolic state of an organism, cell, tissue, group of cells, organelles or organelle with or without a metabolic modulating agent or with or without a genetic alteration capable of modulating metabolism is disclosed. The biological material of interest is placed in a conductive solution in close proximity to a first electrode that is electrically coupled to a second electrode. A potential is applied to the electrodes sufficient enough to create a potential gradient between the two. If the biological material of interest is undergoing oxidation reactions, reduction reactions, or producing electrochemically active compounds as a result of metabolism, these will react at the first electrode, and in some cases, achieve direct electron transfer to the first electrode and generate a detectable electrical current. This current is directly proportional to the metabolic rate of the biological material of interest.Type: ApplicationFiled: November 8, 2016Publication date: November 8, 2018Applicant: Saint Louis UniversityInventors: Robert Louis ARECHEDERRA, Abdul WAHEED, William S. SLY
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Patent number: 8784833Abstract: Transplacental enzyme replacement therapy (ERT) is disclosed for deficiency of a polypeptide such as a tissue-nonspecific alkaline phosphatase (TNSALP) by administering a pharmaceutical composition that comprises a water-soluble TNSALP portion, e.g., C-terminus-truncated TNSALP peptide-bonded to an IgG1 antibody Fc portion, to a pregnant animal whose fetus or embryo is in need of such therapy. Also contemplated is a method for treating a metabolic disorder, such as HPP, in a fetus or embryo where a fusion protein that comprises a Fc fragment of an IgG1 antibody peptide-bonded to TNSALP is administered to a pregnant mother. The protein crosses the placenta of the mother and enters the fetal blood stream. The protein is taken up into fetal tissue such that the TNSALP restores normal metabolic activity in the fetus.Type: GrantFiled: January 17, 2011Date of Patent: July 22, 2014Assignee: Saint Louis UniversityInventors: William S. Sly, Jeffrey H. Grubb, Shunjl Tomatsu, Adriana Maria Monta{umlaut over (n)}o Suarez, Hirotaka Oikawa
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Patent number: 8492338Abstract: Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.Type: GrantFiled: May 25, 2012Date of Patent: July 23, 2013Assignee: Biomarin Pharmaceutical Inc.Inventors: Jonathan LeBowitz, Stephen M. Beverley, William S. Sly
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Publication number: 20130011381Abstract: Disclosed is a method for the treatment of lysosomal storage disease in mammals wherein the mammal is administered a therapeutically effective amount of an isolated, modified recombinant ?-glucuronidase whereby said storage diseased disease is relieved in the brain and visceral organs of the mammal. There is also disclosed an isolated, modified recombinant ?-glucuronidase wherein the modification is having its carbohydrate moieties chemically modified so as to reduce its activity with respect to mannose and mannose 6-phosphate cellular delivery system while retaining enzymatic activity. Also disclosed are other lysosomal enzymes within the scope of the invention.Type: ApplicationFiled: April 24, 2012Publication date: January 10, 2013Applicant: SAINT LOUIS UNIVERSITYInventors: William S. Sly, Jeffrey H. Grubb, Carole A. Vogler
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Publication number: 20120295327Abstract: Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.Type: ApplicationFiled: May 25, 2012Publication date: November 22, 2012Applicant: Biomarin Pharmaceutical Inc.Inventors: Jonathan H. LeBowitz, Stephen M. Beverley, William S. Sly
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Patent number: 8226940Abstract: The present invention provides a polypeptide therapeutic agent, useful in enzyme replacement therapy, with increased therapeutic benefits for the central nervous system. The invention provides a method of enhancing the effect of a polypeptide or protein on the central nervous system by the attachment of a short acidic amino acid sequence. Specifically the inventors disclose the attachment of a 4-15 acidic amino acid sequence to human ?-glucuronidase by construction of a fusion protein. This molecule is useful in the treatment of type VII mucopolysaccharidosis when administered to a patient.Type: GrantFiled: February 28, 2010Date of Patent: July 24, 2012Assignee: Saint Louis UniversityInventors: Shunji Tomatsu, Adriana Montano, Tatsuo Nishioka, Jeffrey H. Grubb, William S. Sly, Monica A. Gutierrez, Amelia Ortigoza Rodriguez, legal representative
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Patent number: 8207114Abstract: Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.Type: GrantFiled: November 2, 2009Date of Patent: June 26, 2012Assignee: Biomarin Pharmaceutical Inc.Inventors: Jonathan H. LeBowitz, Stephen M. Beverley, William S. Sly
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Publication number: 20110300143Abstract: The invention contemplates transplacental enzyme replacement therapy (ERT) for deficiency of a polypeptide such as a tissue-nonspecific alkaline phosphatase (TNSALP) by administering a before-described pharmaceutical composition to a pregnant animal whose fetus or embryo is in need of such therapy. The fusion protein of such a composition comprises a water-soluble TNSALP portion, e.g., C-terminus-truncated TNSALP peptide-bonded to an IgG1 antibody Fc portion. The invention also contemplates a method for treating a metabolic disorder, such as HPP, in a fetus or embryo were a protein is administered to a pregnant mother. The fusion protein comprises a Fc fragment of an IgG1 antibody peptide-bonded to TNSALP. The protein crosses the placenta of the mother and enters the fetal blood stream. The protein is taken up into fetal tissue such that the TNSALP restores normal metabolic activity in the fetus.Type: ApplicationFiled: January 17, 2011Publication date: December 8, 2011Applicant: SAINT LOUIS UNIVERSITYInventors: William S. Sly, Jeffrey H. Grubb, Shunji Tomatsu, Adriana Maria MontaƱo Suarez, Hirotaka Oikawa
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Patent number: 7943126Abstract: The present invention provides compositions and methods for use in enzyme replacement therapy. The inventors disclose a method of producing membrane bound enzymes in an active soluble form by eliminating the glycosylphosphatidylinositol (GPI) membrane anchor. In particular the inventors disclose a soluble active form of the membrane bound enzyme TNSALP which they produced by deleting the GPI anchor single peptide sequence. They have further shown that this composition is useful for treatment of hypophosphatasia. The inventors also disclose oligo acid amino acid variants thereof which specifically target bone tissue.Type: GrantFiled: March 17, 2009Date of Patent: May 17, 2011Assignee: Saint Louis UniversityInventors: Shunji Tomatsu, William S Sly, Jeffrey H Grubb, Tatsuo Nishioka, Ken-ichi Miyamoto, Seiji Yamaguchi
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Patent number: 7871624Abstract: The invention is directed to chimeral fusion proteins having an IgG1 antibody Fc portion and a lysosomal storage enzyme, particularly a Fc-GUS fusion protein useful in treating Sly's disease in an embryo or fetus. The invention is also directed to methods of treating in born errors of metabolism, particularly Sly's disease, in a fetus by delivering to a pregnant mother a Fc-MPS emzyme fusion protein.Type: GrantFiled: June 27, 2007Date of Patent: January 18, 2011Assignee: Saint Louis UniversityInventors: Jeffrey H. Grubb, William S. Sly
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Publication number: 20100158889Abstract: The present invention provides a polypeptide therapeutic agent, useful in enzyme replacement therapy, with increased therapeutic benefits for the central nervous system. The invention provides a method of enhancing the effect of a polypeptide or protein on the central nervous system by the attachment of a short acidic amino acid sequence. Specifically the inventors disclose the attachment of a 4-15 acidic amino acid sequence to human ?-glucuronidase by construction of a fusion protein. This molecule is useful in the treatment of type VII mucopolysaccharidosis when administered to a patient.Type: ApplicationFiled: February 28, 2010Publication date: June 24, 2010Applicant: Saint Louis University, a non-profit organizationInventors: Shunji Tomatsu, Adriana Montano, Tatsuo Nishioka, Jeffrey H. Grubb, William S. Sly, Monica A. Gutierrez, Amelia Ortigoza Rodriguez
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Publication number: 20100075906Abstract: Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.Type: ApplicationFiled: November 2, 2009Publication date: March 25, 2010Applicant: Zystor Therapeutics, Inc.Inventors: Jonathan H. LeBowitz, Stephen M. Beverley, William S. Sly
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Patent number: 7629309Abstract: Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.Type: GrantFiled: November 3, 2004Date of Patent: December 8, 2009Assignee: Zystor Therapeutics, Inc.Inventors: Jonathan H. LeBowitz, Stephen M. Beverley, William S. Sly
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Publication number: 20090238814Abstract: The present invention provides compositions and methods for use in enzyme replacement therapy. The inventors disclose a method of producing membrane bound enzymes in an active soluble form by eliminating the glycosylphosphatidylinositol (GPI) membrane anchor. In particular the inventors disclose a soluble active form of the membrane bound enzyme TNSALP which they produced by deleting the GPI anchor single peptide sequence. They have further shown that this composition is useful for treatment of hypophosphatasia. The inventors also disclose oligo acid amino acid variants thereof which specifically target bone tissue.Type: ApplicationFiled: March 17, 2009Publication date: September 24, 2009Applicant: SAINT LOUIS UNIVERSITYInventors: SHUNJIT TOMATSU, WILLIAM S. SLY, JEFFERY H. GRUBB, TATSUO NISHIOKA, KEN-ICHI MIYAMOTO, SEIJI YAMAGUCHI
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Publication number: 20090041741Abstract: There is disclosed an isolated, modified recombinant ?-glucuronidase wherein the modification is having its carbohydrate moeties chemically modified so as to reduce its activity with respect to mannose and mannose 6-phosphate cellular delivery system while retaining enzymatic activity Also disclosed are methods for the treatment of lysosomal storage disease in mammals wherein the mammal is administered a therapeutically effective amount of isolated, modified recombinant ?-glucuronidase whereby said storage diseased is relieved in the brain and visceral organs of the mammal. Also disclosed are other lysosomal enzymes within the scope of the invention.Type: ApplicationFiled: March 5, 2008Publication date: February 12, 2009Applicant: SAINT LOUIS UNIVERSITYInventors: William S. Sly, Jeffrey H. Grubb, Carole A. Vogler
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Publication number: 20040005309Abstract: Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.Type: ApplicationFiled: October 16, 2002Publication date: January 8, 2004Applicant: Symbiontics, Inc.Inventors: Jonathan H. LeBowitz, Stephen M. Beverley, William S. Sly