Patents by Inventor William Joseph ISSA
William Joseph ISSA 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: 20230416324Abstract: The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them. In some aspects, the disclosure provides mRNA wherein the uracil content has been modified and which may be particularly effective for use in therapeutic compositions, because they may benefit from both high expression levels and limited induction of the innate immune response. In some aspects, the disclosure provides methods for the production of pharmaceutical compositions including mRNA without reverse phase chromatography.Type: ApplicationFiled: October 25, 2022Publication date: December 28, 2023Inventors: Stephen G. HOGE, William Joseph ISSA, Edward John MIRACCO, Jennifer NELSON, John REYNDERS, Matthew STANTON
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Patent number: 11845772Abstract: Disclosed herein are methods for purifying RNA comprising poly A. Also disclosed herein are compositions such as surfaces and oligonucleotides for purifying RNA comprising polyA. Other embodiments are also disclosed. Commercially-available resins having polythymidine oligonucleotide ligands typically contain less than 30 thymidine (2?deoxy) residues and some commercial resin suppliers utilize a distribution of dT chain lengths, not of a discreet length.Type: GrantFiled: June 30, 2022Date of Patent: December 19, 2023Assignee: ModernaTX, Inc.Inventors: William Joseph Issa, John Grant Aunins, Stephane Bancel
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Publication number: 20230203086Abstract: Disclosed herein are methods for purifying RNA comprising poly A. Also disclosed herein are compositions such as surfaces and oligonucleotides for purifying RNA comprising polyA. Other embodiments are also disclosed. Commercially-available resins having polythymidine oligonucleotide ligands typically contain less than 30 thymidine (2?deoxy) residues and some commercial resin suppliers utilize a distribution of dT chain lengths, not of a discreet length.Type: ApplicationFiled: June 30, 2022Publication date: June 29, 2023Inventors: William Joseph ISSA, John Grant AUNINS, Stephane BANCEL
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Patent number: 11377470Abstract: Disclosed herein are methods for purifying RNA comprising poly A. Also disclosed herein are compositions such as surfaces and oligonucleotides for purifying RNA comprising polyA. Other embodiments are also disclosed. Commercially-available resins having polythymidine oligonucleotide ligands typically contain less than 30 thymidine (2?deoxy) residues and some commercial resin suppliers utilize a distribution of dT chain lengths, not of a discreet length.Type: GrantFiled: March 13, 2014Date of Patent: July 5, 2022Assignee: ModernaTX, Inc.Inventors: William Joseph Issa, John Grant Aunins, Stephane Bancel
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Publication number: 20210230578Abstract: The present invention describes methods of removing DNA from an RNA transcript during the mRNA production process. The method embodies procedures for obtaining an in vitro transcription product, and removing any DNA from the product. The DNA can be removed by adding either free DNase or a resin containing immobilized DNase to the product, and recovering the RNA transcript. Alternatively, the DNA template used in the in vitro transcription reaction is labeled. After transcription, the product is applied to a resin that is configured to bind the label, and the RNA transcript is recovered. To detect whether any residual impurities are left in the RNA transcript product, the product is subjected to nuclease digestion and subsequently to liquid chromatography-tandem mass spectrometry analysis to quantitate any residual DNA. The present invention demonstrates efficient and effective methods of isolating an RNA transcript from an in vitro transcription product.Type: ApplicationFiled: December 7, 2020Publication date: July 29, 2021Inventors: William Joseph ISSA, Yuxun WANG, Stephane BANCEL
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Patent number: 10858647Abstract: The present invention describes methods of removing DNA from an RNA transcript during the mRNA production process. The method embodies procedures for obtaining an in vitro transcription product, and removing any DNA from the product. The DNA can be removed by adding either free DNase or a resin containing immobilized DNase to the product, and recovering the RNA transcript. Alternatively, the DNA template used in the in vitro transcription reaction is labeled. After transcription, the product is applied to a resin that is configured to bind the label, and the RNA transcript is recovered. To detect whether any residual impurities are left in the RNA transcript product, the product is subjected to nuclease digestion and subsequently to liquid chromatography-tandem mass spectrometry analysis to quantitate any residual DNA. The present invention demonstrates efficient and effective methods of isolating an RNA transcript from an in vitro transcription product.Type: GrantFiled: July 30, 2018Date of Patent: December 8, 2020Assignee: ModernaTX, Inc.Inventors: William Joseph Issa, Yuxun Wang, Stephane Bancel
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Patent number: 10590161Abstract: The current landscape for preparative chromatographic RNA purification uses reversed phase HPLC, but this technique presents many issues with process scale up and ion exchange for preparative purification has only been used for short RNAs. The invention provides preparative purification of RNA (e.g., mRNA) using ion (e.g., anion) exchange chromatography that allows for separation of longer RNAs up to 10,000 nucleotides in length via a scalable method. This method avoids problems with current techniques by using low pressure chromatography that is agreeable with existing equipment in cGMP commercial facilities, that uses aqueous-bases solutions as the mobile phase (rather than flammable of greater than 10 mg RNA/mL resin (e.g., using larger pore sorbents, >500 Angstroms, that display greater mRNA binding capacities), and that yields desired RNA salt forms for downstream formulation with no additional manipulation necessary (unlike ion pair reverse phase techniques).Type: GrantFiled: March 14, 2014Date of Patent: March 17, 2020Assignee: ModernaTX, Inc.Inventors: William Joseph Issa, Joseph Louis Barberio, John Grant Aunins, Noubar B. Afeyan
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Publication number: 20190100748Abstract: The present invention describes methods of removing DNA from an RNA transcript during the mRNA production process. The method embodies procedures for obtaining an in vitro transcription product, and removing any DNA from the product. The DNA can be removed by adding either free DNase or a resin containing immobilized DNase to the product, and recovering the RNA transcript. Alternatively, the DNA template used in the in vitro transcription reaction is labeled. After transcription, the product is applied to a resin that is configured to bind the label, and the RNA transcript is recovered. To detect whether any residual impurities are left in the RNA transcript product, the product is subjected to nuclease digestion and subsequently to liquid chromatography-tandem mass spectrometry analysis to quantitate any residual DNA. The present invention demonstrates efficient and effective methods of isolating an RNA transcript from an in vitro transcription product.Type: ApplicationFiled: July 30, 2018Publication date: April 4, 2019Inventors: William Joseph ISSA, Yuxun WANG, Stephane BANCEL
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Publication number: 20190092828Abstract: The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them. In some aspects, the disclosure provides mRNA wherein the uracil content has been modified and which may be particularly effective for use in therapeutic compositions, because they may benefit from both high expression levels and limited induction of the innate immune response. In some aspects, the disclosure provides methods for the production of pharmaceutical compositions including mRNA without reverse phase chromatography.Type: ApplicationFiled: July 30, 2018Publication date: March 28, 2019Inventors: Stephen G. HOGE, William Joseph ISSA, Edward John MIRACCO, Jennifer NELSON, John REYNDERS, Matthew STANTON
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Publication number: 20190085368Abstract: Described are methods for production of RNA transcripts using a non-amplified, linearized DNA tempate in an in vitro transcription reaction. Enzymatic 5? capping and oligo dT purification can also be included in the methods.Type: ApplicationFiled: September 27, 2018Publication date: March 21, 2019Inventors: Stephane BANCEL, William Joseph ISSA, John Grant AUNINS, Tirtha CHAKRABORTY
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Patent number: 10138507Abstract: Described are methods for production of RNA transcripts using a non-amplified, linearized DNA template in an in vitro transcription reaction. Enzymatic 5? capping and oligo dT purification can also be included in the methods.Type: GrantFiled: March 13, 2014Date of Patent: November 27, 2018Assignee: ModernaTX, Inc.Inventors: Stephane Bancel, William Joseph Issa, John Grant Aunins, Tirtha Chakraborty
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Patent number: 10077439Abstract: The present invention describes methods of removing DNA from an RNA transcript during the mRNA production process. The method embodies procedures for obtaining an in vitro transcription product, and removing any DNA from the product. The DNA can be removed by adding either free DNase or a resin containing immobilized DNase to the product, and recovering the RNA transcript. Alternatively, the DNA template used in the in vitro transcription reaction is labeled. After transcription, the product is applied to a resin that is configured to bind the label, and the RNA transcript is recovered. To detect whether any residual impurities are left in the RNA transcript product, the product is subjected to nuclease digestion and subsequently to liquid chromatography-tandem mass spectrometry analysis to quantitate any residual DNA. The present invention demonstrates efficient and effective methods of isolating an RNA transcript from an in vitro transcription product.Type: GrantFiled: March 13, 2014Date of Patent: September 18, 2018Assignee: ModernaTX, Inc.Inventors: William Joseph Issa, Yuxun Wang, Stephane Bancel
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Patent number: 10072057Abstract: The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them. In some aspects, the disclosure provides mRNA wherein the uracil content has been modified and which may be particularly effective for use in therapeutic compositions, because they may benefit from both high expression levels and limited induction of the innate immune response. In some aspects, the disclosure provides methods for the production of pharmaceutical compositions including mRNA without reverse phase chromatography.Type: GrantFiled: July 21, 2017Date of Patent: September 11, 2018Assignee: ModernaTX, Inc.Inventors: Stephen G. Hoge, William Joseph Issa, Edward John Miracco, Jennifer Nelson, John Reynders, Matthew Stanton
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Publication number: 20180009866Abstract: The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them. In some aspects, the disclosure provides mRNA wherein the uracil content has been modified and which may be particularly effective for use in therapeutic compositions, because they may benefit from both high expression levels and limited induction of the innate immune response. In some aspects, the disclosure provides methods for the production of pharmaceutical compositions including mRNA without reverse phase chromatography.Type: ApplicationFiled: July 21, 2017Publication date: January 11, 2018Inventors: Stephen G. Hoge, William Joseph Issa, Edward John Miracco, Jennifer Nelson, John Reynders, Matthew Stanton
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Patent number: 9751925Abstract: The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them. In some aspects, the disclosure provides mRNA wherein the uracil content has been modified and which may be particularly effective for use in therapeutic compositions, because they may benefit from both high expression levels and limited induction of the innate immune response. In some aspects, the disclosure provides methods for the production of pharmaceutical compositions including mRNA without reverse phase chromatography.Type: GrantFiled: December 4, 2015Date of Patent: September 5, 2017Assignee: ModernaTX, Inc.Inventors: Stephen G. Hoge, William Joseph Issa, Edward John Miracco, Jennifer Nelson, John Reynders, Matthew Stanton
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Publication number: 20160237134Abstract: The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them. In some aspects, the disclosure provides mRNA wherein the uracil content has been modified and which may be particularly effective for use in therapeutic compositions, because they may benefit from both high expression levels and limited induction of the innate immune response. In some aspects, the disclosure provides methods for the production of pharmaceutical compositions including mRNA without reverse phase chromatography.Type: ApplicationFiled: December 4, 2015Publication date: August 18, 2016Inventors: Stephen G. HOGE, William Joseph ISSA, Ed MIRACCO, Jennifer NELSON, John REYNDERS, Matthew STANTON
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Publication number: 20160024141Abstract: The current landscape for preparative chromatographic RNA purification uses reversed phase HPLC, but this technique presents many issues with process scale up and ion exchange for preparative purification has only been used for short RNAs. The invention provides preparative purification of RNA (e.g., mRNA) using ion (e.g., anion) exchange chromatography that allows for separation of longer RNAs up to 10,000 nucleotides in length via a scalable method. This method avoids problems with current techniques by using low pressure chromatography that is agreeable with existing equipment in cGMP commercial facilities, that uses aqueous-bases solutions as the mobile phase (rather than flammable of greater than 10 mg RNA/mL resin (e.g., using larger pore sorbents, >500 Angstroms, that display greater mRNA binding capacities), and that yields desired RNA salt forms for downstream formulation with no additional manipulation necessary (unlike ion pair reverse phase techniques).Type: ApplicationFiled: March 14, 2014Publication date: January 28, 2016Applicant: Modema Therapeutics, Inc.Inventors: William Joseph ISSA, Joseph Louis BARBERIO, John Grant AUNINS, Noubar B. AFEYAN
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Publication number: 20160024140Abstract: Disclosed herein are methods for purifying RNA comprising poly A. Also disclosed herein are compositions such as surfaces and oligonucleotides for purifying RNA comprising polyA. Other embodiments are also disclosed. Commercially-available resins having polythymidine oligonucleotide ligands typically contain less than 30 thymidine (2?deoxy) residues and some commercial resin suppliers utilize a distribution of dT chain lengths, not of a discreet length.Type: ApplicationFiled: March 13, 2014Publication date: January 28, 2016Inventors: William Joseph ISSA, John Grant AUNINS, Stephane BANCEL
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Publication number: 20160024492Abstract: The present invention describes methods of removing DNA from an RNA transcript during the mRNA production process. The method embodies procedures for obtaining an in vitro transcription product, and removing any DNA from the product. The DNA can be removed by adding either free DNase or a resin containing immobilized DNase to the product, and recovering the RNA transcript. Alternatively, the DNA template used in the in vitro transcription reaction is labeled. After transcription, the product is applied to a resin that is configured to bind the label, and the RNA transcript is recovered. To detect whether any residual impurities are left in the RNA transcript product, the product is subjected to nuclease digestion and subsequently to liquid chromato graphy-tandem mass spectrometry analysis to quantitate any residual DNA. The present invention demonstrates efficient and effective methods of isolating an RNA transcript from an in vitro transcription product.Type: ApplicationFiled: March 13, 2014Publication date: January 28, 2016Applicant: MODERNA THERAPEUTICS, INC.Inventors: William Joseph ISSA, Yuxun WANG, Stephane BANCEL
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Publication number: 20160024547Abstract: Described are methods for production of RNA transcripts using a non-amplified, linearized DNA template in an in vitro transcription reaction. Enzymatic 5? capping and oligo dT purification can also be included in the methods.Type: ApplicationFiled: March 13, 2014Publication date: January 28, 2016Inventors: Stephane BANCEL, William Joseph ISSA, John Grant AUNINS, Tirtha CHAKRABORTY