Patents by Inventor Karl-Heinz Eisele
Karl-Heinz Eisele 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: 10921312Abstract: The present invention pertains to a method for standardizing the sensitivity of induced pluripotent stem cell (iPS)-derived neurons to a neurotoxin polypeptide, comprising the steps of: a) cultivating different batches of induced pluripotent stem cell-derived neurons in a cell culture medium comprising GT1b for at least 3 hours; b) contacting the different batches of induced pluripotent stem cell-derived neurons of step a) with a neurotoxin polypeptide; c) cultivating the different batches of induced pluripotent stem cell-derived neurons of step b) for at least 24 hours in the presence of GT1b under conditions which allow for the neurotoxin polypeptide to exert its biological activity, thereby standardizing the sensitivity of the induced pluripotent stem cell-derived neurons to a neurotoxin polypeptide.Type: GrantFiled: February 18, 2015Date of Patent: February 16, 2021Assignee: MERZ PHARMA GMBH & CO. KGAAInventor: Karl-Heinz Eisele
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Patent number: 10781421Abstract: The present invention pertains to a method for the generation of neurotoxin-sensitive, neuronal differentiated cells comprising the steps of: a) cultivating tumor cells which are able to differentiate into neuronal cells in a culture medium under conditions and for a time which primes said tumor cells for neuronal differentiation; and b) cultivating the tumor cells primed for neuronal differentiation of a) in a differentiation medium having an osmolality of 100 to 270 mOsm/kg, and comprising (i) B27 supplement and/or (ii) N2 supplement, for at least 3 days, thereby obtaining neurotoxin-sensitive, neuronal differentiated cells. The invention further relates to neurotoxin-sensitive, neuronal differentiated cells obtainable by the method of the invention.Type: GrantFiled: September 27, 2018Date of Patent: September 22, 2020Assignee: MERE PHARMA GmbH & CO. KGaAInventors: Karl-Heinz Eisele, Kai Harting
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Patent number: 10725025Abstract: The present invention provides a method for enhancing the specific uptake of a neurotoxin polypeptide into cells, the method comprising: incubating cells susceptible to neurotoxin intoxication with a neurotoxin polypeptide for a time and under conditions which allow for the neurotoxin polypeptide to exert its biological activity, the incubation comprising at least one of the following steps: (i) K+-mediated depolarization of the cells, (ii) a reduced neurotoxin polypeptide exposition time and/or (iii) agitation of the cells during neurotoxin polypeptide exposition, thereby enhancing the specific uptake of the neurotoxin polypeptide into said cells.Type: GrantFiled: March 3, 2016Date of Patent: July 28, 2020Assignee: MERZ PHARMA GMBH & CO. KGAAInventors: Claudia Jatzke, Karl-Heinz Eisele, Gerd Mander, Klaus Fink
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Patent number: 10634683Abstract: The present invention pertains to a method for determining the biological activity of a neurotoxin, the method comprising the steps of: (a) expressing a fusion protein comprising (i) an anchor protein, (ii) a reporter protein and (iii) a neurotoxin cleavage site intervening the anchor protein and the reporter protein, in neurotoxin-sensitive cells; (b) incubating the neurotoxin-sensitive cells of (a) with a neurotoxin and cultivating the cells under conditions which allow the neurotoxin to exert its biological activity; (c) permeabilizing the neurotoxin-sensitive cells of (b) under conditions which allow the release of the reporter protein but not the release of the anchor protein from the permeabilized neurotoxin-sensitive cells; and (d) quantifying the activity of the reporter protein released from the cells, thereby determining the biological activity of the neurotoxin.Type: GrantFiled: November 20, 2015Date of Patent: April 28, 2020Assignee: MERZ PHARMA GMBH & CO. KGAAInventor: Karl-Heinz Eisele
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Publication number: 20190032009Abstract: The present invention pertains to a method for the generation of neurotoxin-sensitive, neuronal differentiated cells comprising the steps of: a) cultivating tumor cells which are able to differentiate into neuronal cells in a culture medium under conditions and for a time which primes said tumor cells for neuronal differentiation; and b) cultivating the tumor cells primed for neuronal differentiation of a) in a differentiation medium having an osmolality of 100 to 270 mOsm/kg, and comprising (i) B27 supplement and/or (ii) N2 supplement, for at least 3 days, thereby obtaining neurotoxin-sensitive, neuronal differentiated cells. The invention further relates to neurotoxin-sensitive, neuronal differentiated cells obtainable by the method of the invention.Type: ApplicationFiled: September 27, 2018Publication date: January 31, 2019Inventors: Karl-Heinz EISELE, Kai HARTING
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Patent number: 10125350Abstract: The present invention pertains to a method for the generation of neurotoxin-sensitive, neuronal differentiated cells comprising the steps of: a) cultivating tumor cells which are able to differentiate into neuronal cells in a culture medium under conditions and for a time which primes said tumor cells for neuronal differentiation; and b) cultivating the tumor cells primed for neuronal differentiation of a) in a differentiation medium having an osmolality of 100 to 270 mOsm/kg, and comprising (i) B27 supplement and/or (ii) N2 supplement, for at least 3 days, thereby obtaining neurotoxin-sensitive, neuronal differentiated cells. The invention further relates to neurotoxin-sensitive, neuronal differentiated cells obtainable by the method of the invention.Type: GrantFiled: October 15, 2013Date of Patent: November 13, 2018Assignee: MERZ PHARMA GmbH & CO. KGaAInventors: Karl-Heinz Eisele, Kai Harting
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Publication number: 20180238861Abstract: The present invention provides a method for enhancing the specific uptake of a neurotoxin polypeptide into cells, the method comprising: incubating cells susceptible to neurotoxin intoxication with a neurotoxin polypeptide for a time and under conditions which allow for the neurotoxin polypeptide to exert its biological activity, the incubation comprising at least one of the following steps: (i) K+-mediated depolarization of the cells, (ii) a reduced neurotoxin polypeptide exposition time and/or (iii) agitation of the cells during neurotoxin polypeptide exposition, thereby enhancing the specific uptake of the neurotoxin polypeptide into said cells.Type: ApplicationFiled: March 3, 2016Publication date: August 23, 2018Inventors: Claudia JATZKE, Karl-Heinz EISELE, Gerd MANDER, Klaus FINK
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Patent number: 9963502Abstract: The present invention relates to an antibody which specifically binds to unprocessed and/or partially processed neurotoxin polypeptide or an antibody which specifically binds an epitope consisting of a peptide having an amino acid sequence as shown in any one of SEQ ID NOs: 1 to 16 and to methods for the manufacture of such antibodies. Moreover, the present invention relates to a composition comprising processed neurotoxin polypeptide free of unprocessed or partially processed neurotoxin polypeptide and a method for manufacturing said neurotoxin polypeptide based on the antibodies of the invention. The present invention also relates to the use of the aforementioned antibody for separating processed neurotoxin polypeptides from unprocessed or partially processed neurotoxin polypeptides or for determining unprocessed or partially processed neurotoxin polypeptides. The present invention relates to a method for the manufacture of a medicament.Type: GrantFiled: August 8, 2016Date of Patent: May 8, 2018Assignee: MERZ PHARMA GmbH & CO. KGaAInventors: Michael Pfeil, Josef Friedrich, Harold Victor Taylor, Karl-Heinz Eisele, Cornelia Brünn
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Publication number: 20180045733Abstract: The present invention pertains to a method for determining the biological activity of a neurotoxin, the method comprising the steps of: (a) expressing a fusion protein comprising (i) an anchor protein, (ii) a reporter protein and (iii) a neurotoxin cleavage site intervening the anchor protein and the reporter protein, in neurotoxin-sensitive cells; (b) incubating the neurotoxin-sensitive cells of (a) with a neurotoxin and cultivating the cells under conditions which allow the neurotoxin to exert its biological activity; (c) permeabilizing the neurotoxin-sensitive cells of (b) under conditions which allow the release of the reporter protein but not the release of the anchor protein from the permeabilized neurotoxin-sensitive cells; and (d) quantifying the activity of the reporter protein released from the cells, thereby determining the biological activity of the neurotoxin.Type: ApplicationFiled: November 20, 2015Publication date: February 15, 2018Inventor: Karl-Heinz EISELE
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Publication number: 20170059558Abstract: The present invention pertains to a method for standardizing the sensitivity of induced pluripotent stem cell (iPS)-derived neurons to a neurotoxin polypeptide, comprising the steps of: a) cultivating different batches of induced pluripotent stem cell-derived neurons in a cell culture medium comprising GT1b for at least 3 hours; b) contacting the different batches of induced pluripotent stem cell-derived neurons of step a) with a neurotoxin polypeptide; c) cultivating the different batches of induced pluripotent stem cell-derived neurons of step b) for at least 24 hours in the presence of GT1b under conditions which allow for the neurotoxin polypeptide to exert its biological activity, thereby standardizing the sensitivity of the induced pluripotent stem cell-derived neurons to a neurotoxin polypeptide.Type: ApplicationFiled: February 18, 2015Publication date: March 2, 2017Inventors: Karl-Heinz EISELE, Gerd MANDER
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Publication number: 20160340417Abstract: The present invention relates to an antibody which specifically binds to unprocessed and/or partially processed neurotoxin polypeptide or an antibody which specifically binds an epitope consisting of a peptide having an amino acid sequence as shown in any one of SEQ ID NOs: 1 to 16 and to methods for the manufacture of such antibodies. Moreover, the present invention relates to a composition comprising processed neurotoxin polypeptide free of unprocessed or partially processed neurotoxin polypeptide and a method for manufacturing said neurotoxin polypeptide based on the antibodies of the invention. The present invention also relates to the use of the aforementioned antibody for separating processed neurotoxin polypeptides from unprocessed or partially processed neurotoxin polypeptides or for determining unprocessed or partially processed neurotoxin polypeptides. The present invention relates to a method for the manufacture of a medicament.Type: ApplicationFiled: August 8, 2016Publication date: November 24, 2016Inventors: Michael PFEIL, Josef Friedrich, Harold Victor Taylor, Karl-Heinz Eisele, Cornelia Brünn
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Publication number: 20160289731Abstract: The present invention is concerned with means and methods for determining neurotoxin activity. Specifically, it relates to a polynucleotide encoding a fusion polypeptide comprising (i) a transcription factor domain and (ii) a cytoplasmic retention domain, separated by a linker comprising a neurotoxin cleavage site and to a fusion polypeptide encoded by the polynucleotide of the invention. Also contemplated is a vector comprising the polynucleotide of the invention and a host cell comprising the polynucleotide, vector or fusion polypeptide of the invention. Moreover, envisaged is a method for determining neurotoxin activity in a sample. In addition, the invention pertains to the use of the polynucleotide, vector, fusion polypeptide or host cell of the invention for determining neurotoxin activity in a sample. Finally, the invention relates to a kit for determining neurotoxin activity comprising the polynucleotide, vector, fusion polypeptide or host cell of the invention.Type: ApplicationFiled: November 20, 2013Publication date: October 6, 2016Inventors: Karl-Heinz EISELE, Klaus FINK
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Patent number: 9447175Abstract: The present invention relates to an antibody which specifically binds to unprocessed and/or partially processed neurotoxin polypeptide or an antibody which specifically binds an epitope consisting of a peptide having an amino acid sequence as shown in any one of SEQ ID NOs: 1 to 16 and to methods for the manufacture of such antibodies. Moreover, the present invention relates to a composition comprising processed neurotoxin polypeptide free of unprocessed or partially processed neurotoxin polypeptide and a method for manufacturing said neurotoxin polypeptide based on the antibodies of the invention. The present invention also relates to the use of the aforementioned antibody for separating processed neurotoxin polypeptides from unprocessed or partially processed neurotoxin polypeptides or for determining unprocessed or partially processed neurotoxin polypeptides. The present invention relates to a method for the manufacture of a medicament.Type: GrantFiled: February 17, 2010Date of Patent: September 20, 2016Assignee: MERZ PHARMA GmbH & CO. KGaAInventors: Michael Pfeil, Josef Friedrich, Harold Victor Taylor, Karl-Heinz Eisele, Cornelia Brunn
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Patent number: 9314514Abstract: The present invention is concerned with modified neurotoxins. Specifically, it relates to a modified biologically active neurotoxin polypeptide comprising at least one poly-Glycine domain. Also contemplated is a polynucleotide encoding the modified neurotoxin polypeptide having a poly-Glycine domain fused to the N-terminus, to the C-terminus or to both of the heavy and/or light chain of the mature neurotoxin polypeptide, vector comprising it and a host cell comprising such a polynucleotide or a vector. Moreover, envisaged are the aforementioned compounds for use as a medicament for treating various diseases.Type: GrantFiled: November 8, 2012Date of Patent: April 19, 2016Assignee: MERZ PHARMA GmbH & CO. KGaAInventor: Karl-Heinz Eisele
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Patent number: 9310386Abstract: Novel methods for determining the unknown biological activity of a clostridial neurotoxin in a sample with respect to the known biological activity of a clostridial neurotoxin in a reference sample, comprising the step of comparing the biological activity of a clostridial neurotoxin preparation with the biological activity of a standard preparation of a reference clostridial neurotoxin in certain in vitro systems.Type: GrantFiled: January 19, 2011Date of Patent: April 12, 2016Assignee: MERZ PHARMA GmbH & CO. KGaAInventors: Thomas Wilk, Harold Victor Taylor, Karl-Heinz Eisele
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Patent number: 9213026Abstract: The present invention is concerned with tools for the quality control and safety during manufacture of neurotoxins. In particular, it relates to a method for the determination of the amount of partially processed and/or unprocessed Botulinum neurotoxin A polypeptide (BoNT/A) in a solution comprising processed and partially processed and/or unprocessed BoNT/A comprising the steps of contacting a sample of the solution with a capture antibody which specifically binds to the partially processed and unprocessed BoNT/A under conditions which allow for binding of the antibody to the partially processed and unprocessed BoNT/A, whereby a complex is formed, and determining the amount of the formed complex, whereby the amount of the complex is indicative for the amount of the partially processed and/or unprocessed BoNT/A in the solution. Moreover, the present invention contemplates a device and a kit for carrying out the method.Type: GrantFiled: August 13, 2014Date of Patent: December 15, 2015Assignee: MERZ PHARMA GmbH & CO. KGaAInventors: Harold Victor Taylor, Karl-Heinz Eisele, Cornelia Brunn
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Publication number: 20150267168Abstract: The present invention pertains to a method for the generation of neurotoxin-sensitive, neuronal differentiated cells comprising the steps of: a) cultivating tumor cells which are able to differentiate into neuronal cells in a culture medium under conditions and for a time which primes said tumor cells for neuronal differentiation; and b) cultivating the tumor cells primed for neuronal differentiation of a) in a differentiation medium having an osmolality of 100 to 270 mOsm/kg, and comprising (i) B27 supplement and/or (ii) N2 supplement, for at least 3 days, thereby obtaining neurotoxin-sensitive, neuronal differentiated cells. The invention further relates to neurotoxin-sensitive, neuronal differentiated cells obtainable by the method of the invention.Type: ApplicationFiled: October 15, 2013Publication date: September 24, 2015Inventor: Karl-Heinz Eisele
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Publication number: 20150044709Abstract: The present invention is concerned with test systems for determining the activity of neurotoxin polypeptides. Specifically, it relates to a polynucleotide encoding a single chain luciferase fusion polypeptide comprising: (i) a LuxB subunit, (ii) a linker comprising a neurotoxin cleavage site, and (iii) a LuxA subunit and a polypeptide encoded by the polynucleotide. Further provided in accordance with the invention are a vector and a host cell comprising the polynucleotide. Moreover, the present invention relates to a method for determining a proteolytically active neurotoxin polypeptide in a sample and a kit for carrying out the method.Type: ApplicationFiled: March 7, 2013Publication date: February 12, 2015Inventor: Karl-Heinz Eisele
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Publication number: 20140349322Abstract: The present invention is concerned with tools for the quality control and safety during manufacture of neurotoxins. In particular, it relates to a method for the determination of the amount of partially processed and/or unprocessed Botulinum neurotoxin A polypeptide (BoNT/A) in a solution comprising processed and partially processed and/or unprocessed BoNT/A comprising the steps of contacting a sample of the solution with a capture antibody which specifically binds to the partially processed and unprocessed BoNT/A under conditions which allow for binding of the antibody to the partially processed and unprocessed BoNT/A, whereby a complex is formed, and determining the amount of the formed complex, whereby the amount of the complex is indicative for the amount of the partially processed and/or unprocessed BoNT/A in the solution. Moreover, the present invention contemplates a device and a kit for carrying out the method.Type: ApplicationFiled: August 13, 2014Publication date: November 27, 2014Inventors: Harold Victor TAYLOR, Karl-Heinz Eisele, Cornelia Brunn
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Publication number: 20140308266Abstract: The present invention is concerned with modified neurotoxins. Specifically, it relates to a modified biologically active neurotoxin polypeptide comprising at least one poly-Glycine domain. Also contemplated is a polynucleotide encoding the modified neurotoxin polypeptide having a poly-Glycine domain fused to the N-terminus, to the C-terminus or to both of the heavy and/or light chain of the mature neurotoxin polypeptide, vector comprising it and a host cell comprising such a polynucleotide or a vector. Moreover, envisaged are the aforementioned compounds for use as a medicament for treating various diseases.Type: ApplicationFiled: November 8, 2012Publication date: October 16, 2014Inventor: Karl-Heinz Eisele