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).

  • Publication number: 20210230578
    Abstract: 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: Application
    Filed: December 7, 2020
    Publication date: July 29, 2021
    Inventors: William Joseph ISSA, Yuxun WANG, Stephane BANCEL
  • Patent number: 10858647
    Abstract: 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: Grant
    Filed: July 30, 2018
    Date of Patent: December 8, 2020
    Assignee: ModernaTX, Inc.
    Inventors: William Joseph Issa, Yuxun Wang, Stephane Bancel
  • Patent number: 10590161
    Abstract: 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: Grant
    Filed: March 14, 2014
    Date of Patent: March 17, 2020
    Assignee: ModernaTX, Inc.
    Inventors: William Joseph Issa, Joseph Louis Barberio, John Grant Aunins, Noubar B. Afeyan
  • Publication number: 20190100748
    Abstract: 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: Application
    Filed: July 30, 2018
    Publication date: April 4, 2019
    Inventors: William Joseph ISSA, Yuxun WANG, Stephane BANCEL
  • Publication number: 20190092828
    Abstract: 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: Application
    Filed: July 30, 2018
    Publication date: March 28, 2019
    Inventors: Stephen G. HOGE, William Joseph ISSA, Edward John MIRACCO, Jennifer NELSON, John REYNDERS, Matthew STANTON
  • Publication number: 20190085368
    Abstract: 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: Application
    Filed: September 27, 2018
    Publication date: March 21, 2019
    Inventors: Stephane BANCEL, William Joseph ISSA, John Grant AUNINS, Tirtha CHAKRABORTY
  • Patent number: 10138507
    Abstract: 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: Grant
    Filed: March 13, 2014
    Date of Patent: November 27, 2018
    Assignee: ModernaTX, Inc.
    Inventors: Stephane Bancel, William Joseph Issa, John Grant Aunins, Tirtha Chakraborty
  • Patent number: 10077439
    Abstract: 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: Grant
    Filed: March 13, 2014
    Date of Patent: September 18, 2018
    Assignee: ModernaTX, Inc.
    Inventors: William Joseph Issa, Yuxun Wang, Stephane Bancel
  • Patent number: 10072057
    Abstract: 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: Grant
    Filed: July 21, 2017
    Date of Patent: September 11, 2018
    Assignee: ModernaTX, Inc.
    Inventors: Stephen G. Hoge, William Joseph Issa, Edward John Miracco, Jennifer Nelson, John Reynders, Matthew Stanton
  • Publication number: 20180009866
    Abstract: 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: Application
    Filed: July 21, 2017
    Publication date: January 11, 2018
    Inventors: Stephen G. Hoge, William Joseph Issa, Edward John Miracco, Jennifer Nelson, John Reynders, Matthew Stanton
  • Patent number: 9751925
    Abstract: 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: Grant
    Filed: December 4, 2015
    Date of Patent: September 5, 2017
    Assignee: ModernaTX, Inc.
    Inventors: Stephen G. Hoge, William Joseph Issa, Edward John Miracco, Jennifer Nelson, John Reynders, Matthew Stanton
  • Publication number: 20160237134
    Abstract: 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: Application
    Filed: December 4, 2015
    Publication date: August 18, 2016
    Inventors: Stephen G. HOGE, William Joseph ISSA, Ed MIRACCO, Jennifer NELSON, John REYNDERS, Matthew STANTON
  • Publication number: 20160024141
    Abstract: 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: Application
    Filed: March 14, 2014
    Publication date: January 28, 2016
    Applicant: Modema Therapeutics, Inc.
    Inventors: William Joseph ISSA, Joseph Louis BARBERIO, John Grant AUNINS, Noubar B. AFEYAN
  • Publication number: 20160024140
    Abstract: 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: Application
    Filed: March 13, 2014
    Publication date: January 28, 2016
    Inventors: William Joseph ISSA, John Grant AUNINS, Stephane BANCEL
  • Publication number: 20160024547
    Abstract: 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: Application
    Filed: March 13, 2014
    Publication date: January 28, 2016
    Inventors: Stephane BANCEL, William Joseph ISSA, John Grant AUNINS, Tirtha CHAKRABORTY
  • Publication number: 20160024492
    Abstract: 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: Application
    Filed: March 13, 2014
    Publication date: January 28, 2016
    Applicant: MODERNA THERAPEUTICS, INC.
    Inventors: William Joseph ISSA, Yuxun WANG, Stephane BANCEL
  • Publication number: 20160017313
    Abstract: Reversed phase-High Performance (High Pressure) Liquid Chromatography (RP-HPLC) and Size Exclusion Chromatography (SEC) methods have been developed for monitoring structural and size heterogeneity as well as stability of large RNA transcripts, including lengths of up to at least 10,000 nucleotides. The methods are designed for significantly larger mRNAs that could be monitored in the past, including lengths of up to at least 10,000 nucleotides, and including chemically modified RNA transcripts. SEC techniques are also used in the preparative purification of large RNA transcripts to remove impurities, including hybridized nucleic acid impurities and multimeric RNA species. All of these techniques are also beneficial in that they can be used for large scale manufacturing of therapeutics.
    Type: Application
    Filed: March 14, 2014
    Publication date: January 21, 2016
    Inventors: Vlad Boris SPIVAK, Zahra SHAHROKH, William Joseph ISSA