Patents by Inventor David Ralph

David Ralph 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: 20240092944
    Abstract: Disclosed herein is method for conjugating a metal chelating agent to a functionalized dextran by reacting a chelator with an aminated dextran backbone, where the chelator comprises a one, and only one, derivatized carboxylic acid group to form a chelator-dextran complex. In certain aspects, the dextran-chelator complex is substantially free of intra- or intermolecular crosslinking. In certain aspects, the functionalized dextran is an amine dextran, an alkynyl dextran, or a thiol dextran. In exemplary implementations, the functionalized dextran is an amine dextran. In further embodiments, one and only one carboxylic acid group on the chelating agent is derivatized as a N-hydroxysuccinimide (NHS) ester.
    Type: Application
    Filed: November 17, 2023
    Publication date: March 21, 2024
    Inventors: Jeffrey Arnold, David A. Ralph
  • Publication number: 20240075057
    Abstract: Provided are compounds, compositions, methods, and kits for increasing target specificity of a mannosylated carbohydrate polymeric therapeutic or diagnostic compound to reduce or eliminate localization of the mannosylated carbohydrate polymeric therapeutic or diagnostic compound to off-target sites. Mannosylated carbohydrate polymers are synthesized to be modified to be either polyanionic (i.e., net negatively charged) or electrostatically neutral, and using these polyanionic or neutral mannosylated carbohydrate polymers as competitors for polycationic (i.e., net positively charged) mannosylated carbohydrate polymers carrying small molecule drug payloads or imaging moieties to CD206 expressing cells in target tissues, such as tumors or other sites of inflammation.
    Type: Application
    Filed: October 27, 2023
    Publication date: March 7, 2024
    Inventors: David A. Ralph, Jeffrey Scott Arnold
  • Publication number: 20240024491
    Abstract: Provided are compounds, compositions, and methods of repolarizing a tumor associated macrophage (TAM), reducing macrophage-mediated inflammation, and treating a disease. A compound or pharmaceutical composition may be administered to a subject in need thereof, where the compound comprises a polymeric carbohydrate backbone, one or more mannose-binding C-type lectin receptor targeting moieties, and a therapeutic agent comprises one or more reactive hydroxyl groups and coupled to the polymeric carbohydrate backbone via a degradable linker. The degradable linker may comprise one or more carbonate and/or disulfide moieties. The disease to be treated may include cancer, an autoimmune disease, an inflammatory disorder, Non-Alcoholic Steatohepatitis (NASH), acute respiratory distress syndrome (ARDS), sepsis, coronavirus infection, influenza infection, cytokine storms, and other macrophage involved diseases.
    Type: Application
    Filed: July 13, 2023
    Publication date: January 25, 2024
    Inventors: Jeffrey Scott Arnold, David A. Ralph
  • Patent number: 11880656
    Abstract: A method for execution by a computing device includes obtaining a phrase that includes string of words and generating a valid sequence of words utilizing the phrase. The method further includes identifying a set of identigens for each word of the valid sequence of words to produce sets of identigens. The method further includes identifying, for each identigen of the sets of identigens, a word type associated with phrase structure grammar rules to produce sets of identigen-type associations. The method further includes interpreting, utilizing the phrase structure grammar rules, the sets of identigen-type associations to produce an entigen group. The entigen group represents a most likely interpretation of the phrase.
    Type: Grant
    Filed: January 31, 2023
    Date of Patent: January 23, 2024
    Assignee: entigenlogic LLC
    Inventors: Frank John Williams, David Ralph Lazzara, Donald Joseph Wurzel, Stephen Emerson Sundberg, Ameeta Vasant Reed, Dennis Arlen Roberson, Thomas James MacTavish, Karl Olaf Knutson, Jessy Thomas, Niklas Josiah MacTavish, David Michael Corns, II, Andrew Chu, Theodore Mazurkiewicz, Gary W. Grube
  • Patent number: 11859023
    Abstract: Disclosed herein is method for conjugating a metal chelating agent to a functionalized dextran by reacting a chelator with an aminated dextran backbone, where the chelator comprises a one, and only one, derivatized carboxylic acid group to form a chelator-dextran complex. In certain aspects, the dextran-chelator complex is substantially free of intra- or intermolecular crosslinking. In certain aspects, the functionalized dextran is an amine dextran, an alkynyl dextran, or a thiol dextran. In exemplary implementations, the functionalized dextran is an amine dextran. In further embodiments, one and only one carboxylic acid group on the chelating agent is derivatized as a N-hydroxysuccinimide (NHS) ester.
    Type: Grant
    Filed: July 8, 2021
    Date of Patent: January 2, 2024
    Assignee: Navidea Biopharmaceuticals, Inc.
    Inventors: Jeffrey Arnold, David A. Ralph
  • Publication number: 20230420162
    Abstract: Bundled cables and methods for preparing bundled cable are disclosed herein. In the method, a plurality of subunits is wound about a central member. The subunits include a subunit jacket made of a first thermoplastic composition and has a first outer surface, and the central member includes a central member jacket made of a second thermoplastic composition and has a second outer surface. A metal element is provided at an interface of the second outer surface and the first outer surface of the subunits. The metal element is heated such that at least one of the first thermoplastic composition or the second thermoplastic composition forms bonds with the other of the first thermoplastic composition or the second thermoplastic composition.
    Type: Application
    Filed: September 12, 2023
    Publication date: December 28, 2023
    Inventors: David Ralph Maack, Lars Kristian Nielsen, James Arthur Register, III, William Taylor Rowell
  • Patent number: 11833170
    Abstract: Provided are compounds, compositions, methods, and kits for increasing target specificity of a mannosylated carbohydrate polymeric therapeutic or diagnostic compound to reduce or eliminate localization of the mannosylated carbohydrate polymeric therapeutic or diagnostic compound to off-target sites. Mannosylated carbohydrate polymers are synthesized to be modified to be either polyanionic (i.e., net negatively charged) or electrostatically neutral, and using these polyanionic or neutral mannosylated carbohydrate polymers as competitors for polycationic (i.e., net positively charged) mannosylated carbohydrate polymers carrying small molecule drug payloads or imaging moieties to CD206 expressing cells in target tissues, such as tumors or other sites of inflammation.
    Type: Grant
    Filed: February 3, 2023
    Date of Patent: December 5, 2023
    Assignee: Navidea Biopharmaceuticals, Inc.
    Inventors: David A. Ralph, Jeffrey Scott Arnold
  • Publication number: 20230374055
    Abstract: Provided are novel compounds containing a polymeric carbohydrate backbone, one or more mannose-binding C-type lectin receptor targeting moieties, and a nitrogenous bisphosphonate compound coupled to the backbone via a thiol-maleimide conjugation, in addition to pharmaceutical compositions, methods of synthesizing, and methods of use. The thiol-maleimide conjugation of a bisphosphonate to a polymeric carbohydrate backbone provides for methods of using the compounds and compositions thereof for releasing the therapeutic payload when internalized into a mannose-binding C-type lectin receptor-expressing cell, such as tumor associated macrophages (TAMs) for the treatment of various diseases, including, cancer, autoimmune diseases, and inflammatory disorders.
    Type: Application
    Filed: May 19, 2023
    Publication date: November 23, 2023
    Inventors: David A. Ralph, Jeffrey Scott Arnold
  • Patent number: 11791067
    Abstract: Bundled cables and methods for preparing bundled cable are disclosed herein. In the method, a plurality of subunits is wound about a central member. The subunits include a subunit jacket made of a first thermoplastic composition and has a first outer surface, and the central member includes a central member jacket made of a second thermoplastic composition and has a second outer surface. A metal element is provided at an interface of the second outer surface and the first outer surface of the subunits. The metal element is heated such that at least one of the first thermoplastic composition or the second thermoplastic composition forms bonds with the other of the first thermoplastic composition or the second thermoplastic composition.
    Type: Grant
    Filed: August 11, 2020
    Date of Patent: October 17, 2023
    Assignee: CORNING RESEARCH & DEVELOPMENT CORPORATION
    Inventors: David Ralph Maack, Lars Kristian Nielsen, James Arthur Register, III, William Taylor Rowell
  • Publication number: 20230302041
    Abstract: Disclosed is a method for increased target specificity of a mannosylated carbohydrate polymeric therapeutic and/or diagnostic compound by administering a blocking composition comprising a backbone and one or more C-type lectin receptor targeting moieties attached thereto with an effective amount of the mannosylated dextran therapeutic and/or diagnostic compound. The administration of the blocking compound results in higher localization of the mannosylated dextran therapeutic and/or diagnostic compounds to a desired target other than the liver and/or spleen compared to without the administration of the blocking compound. The molecular weight of the blocking composition backbone is between about 1 kDa and about 35 kDa.
    Type: Application
    Filed: March 24, 2023
    Publication date: September 28, 2023
    Inventor: David A. Ralph
  • Publication number: 20230248757
    Abstract: Provided are compounds, compositions, methods, and kits for increasing target specificity of a mannosylated carbohydrate polymeric therapeutic or diagnostic compound to reduce or eliminate localization of the mannosylated carbohydrate polymeric therapeutic or diagnostic compound to off-target sites. Mannosylated carbohydrate polymers are synthesized to be modified to be either polyanionic (i.e., net negatively charged) or electrostatically neutral, and using these polyanionic or neutral mannosylated carbohydrate polymers as competitors for polycationic (i.e., net positively charged) mannosylated carbohydrate polymers carrying small molecule drug payloads or imaging moieties to CD206 expressing cells in target tissues, such as tumors or other sites of inflammation.
    Type: Application
    Filed: February 3, 2023
    Publication date: August 10, 2023
    Inventors: David A. Ralph, Jeffrey Scott Arnold
  • Publication number: 20230252019
    Abstract: A method executed by a computing device includes determining whether a set of words are included in a word set. When the set of words are in the word set, the method further includes determining a set of identigens for each word of the word set to produce sets of identigens, where a set of identigens of the sets of identigens represents one or more different meanings of a word of the word set. The method further includes interpreting, using identigen pairing rules, the sets of identigens to produce an entigen set. The method further includes assigning a single new entigen to represent the entigen set, where the single new entigen represents a most likely meaning interpretation of the word set.
    Type: Application
    Filed: April 10, 2023
    Publication date: August 10, 2023
    Applicant: entigenlogic LLC
    Inventors: Frank John Williams, David Ralph Lazzara, Donald Joseph Wurzel, Paige Kristen Thompson, Stephen Emerson Sundberg, Stephen Chen, Karl Olaf Knutson, Jessy Thomas, David Michael Corns, II, Andrew Chu, Eric Andrew Faurie, Theodore Mazurkiewicz, Gary W. Grube
  • Publication number: 20230218770
    Abstract: Disclosed are methods and compositions for repolarizing a tumor associated macrophage (TAM) from M2 to M1 comprising administering to a subject in need thereof an effective dose of a compound comprising a dextran backbone and one or more CD206 targeting moieties conjugated thereto. In certain aspects, the compound further comprises a therapeutic agent selected from: paclitaxel, gemcitabine, lapatinib, and doxorubicin. In further aspect, the therapeutic agent comprises a chelator and at least one metal ion. In certain implementations, the at least one metal ion comprises at least one Cu(II) ions.
    Type: Application
    Filed: February 27, 2023
    Publication date: July 13, 2023
    Inventor: David A. Ralph
  • Publication number: 20230210998
    Abstract: Methods, compounds, and compositions of conjugating anthracyclines to a carbohydrate polymer backbone via click chemistry are provided. The conjugation of anthracyclines utilizing a reaction between a hydrazone azide moiety and alkyne moiety provide for compositions with less crosslinking, and thereby increasing the efficacy of targeted drug delivery. The methods further provide for controlled loading of anthracycline to a carbohydrate polymer backbone.
    Type: Application
    Filed: December 29, 2022
    Publication date: July 6, 2023
    Inventors: David A. Ralph, Jeffrey Arnold
  • Patent number: 11693893
    Abstract: A method executed by a computing device includes determining a set of identigens for each query word of a query to produce sets of identigens. The method further includes interpreting the sets of identigens to produce different first and second query entigen groups. The method further includes generating an interim response based on the first and second query entigen groups. The method further includes determining a set of identigens for each updated query word of an updated query to produce updated sets of identigens. The method further includes selecting one of the first or second query entigen group based on the updated sets of identigens to produce a selected query entigen group. The method further includes generating a response entigen group utilizing the selected query entigen group and generating a response to the query utilizing the response entigen group.
    Type: Grant
    Filed: May 24, 2021
    Date of Patent: July 4, 2023
    Assignee: entigenlogic LLC
    Inventors: Frank John Williams, David Ralph Lazzara, Donald Joseph Wurzel, Stephen Emerson Sundberg, Ameeta Vasant Reed, Dennis Arlen Roberson, Thomas James MacTavish, Karl Olaf Knutson, Jessy Thomas, Niklas Josiah MacTavish, David Michael Corns, II, Andrew Chu, Theodore Mazurkiewicz, Gary W. Grube
  • Publication number: 20230177361
    Abstract: A method performed by a computing device includes generating a comparative query entigen group set based on a comparative query in accordance with identigen rules, where the comparative query entigen group set represents a most likely interpretation of the comparative query. The method further includes obtaining a first response entigen group from a knowledge database based on a first comparative query entigen group of the comparative query entigen group set, where the first response entigen group substantially includes the first comparative query entigen group. The method further includes obtaining a second response entigen group from the knowledge database based on a second comparative query entigen group of the comparative query entigen group set, where the second response entigen group substantially includes the second comparative query entigen group. The method further includes generating a comparative response based on the first response entigen group and the second response entigen group.
    Type: Application
    Filed: January 31, 2023
    Publication date: June 8, 2023
    Applicant: entigenlogic LLC
    Inventors: Frank John Williams, David Ralph Lazzara, Stephen Emerson Sundberg, Ameeta Vasant Reed, Dennis Arlen Roberson, Thomas James MacTavish, Karl Olaf Knutson, Jessy Thomas, Niklas Josiah MacTavish, David Michael Corns, II, Andrew Chu, Theodore Mazurkiewicz, Gary W. Grube
  • Publication number: 20230177268
    Abstract: A method for execution by a computing device includes obtaining a phrase that includes string of words and generating a valid sequence of words utilizing the phrase. The method further includes identifying a set of identigens for each word of the valid sequence of words to produce sets of identigens. The method further includes identifying, for each identigen of the sets of identigens, a word type associated with phrase structure grammar rules to produce sets of identigen-type associations. The method further includes interpreting, utilizing the phrase structure grammar rules, the sets of identigen-type associations to produce an entigen group. The entigen group represents a most likely interpretation of the phrase.
    Type: Application
    Filed: January 31, 2023
    Publication date: June 8, 2023
    Applicant: entigenlogic LLC
    Inventors: Frank John Williams, David Ralph Lazzara, Donald Joseph Wurzel, Stephen Emerson Sundberg, Ameeta Vasant Reed, Dennis Arlen Roberson, Thomas James MacTavish, Karl Olaf Knutson, Jessy Thomas, Niklas Josiah MacTavish, David Michael Corns, II, Andrew Chu, Theodore Mazurkiewicz, Gary W. Grube
  • Patent number: 11650979
    Abstract: A method executed by a computing device includes obtaining a string of words and determining whether two or more words of the string of words are in a word group. When the two or more words are in the word group, the method further includes determining a set of identigens for each word of the word group to produce sets of identigens, where a set of identigens of the sets of identigens represents one or more different meanings of a word of the word group. The method further includes interpreting, using identigen pairing rules, the sets of identigens to produce an entigen group. The method further includes assigning a new entigen to represent the entigen group, where the new entigen represents a most likely meaning interpretation of the word group.
    Type: Grant
    Filed: March 5, 2021
    Date of Patent: May 16, 2023
    Assignee: entigenlogic LLC
    Inventors: Frank John Williams, David Ralph Lazzara, Donald Joseph Wurzel, Paige Kristen Thompson, Stephen Emerson Sundberg, Stephen Chen, Karl Olaf Knutson, Jessy Thomas, David Michael Corns, II, Andrew Chu, Eric Andrew Faurie, Theodore Mazurkiewicz, Gary W. Grube
  • Publication number: 20230070258
    Abstract: Disclosed herein are methods of treating a subject with rheumatoid arthritis (RA) and methods of predicting the subject's likelihood of responding to a new RA therapy. The methods include administering to the subject a composition comprising a macrophage targeting construct and an imaging moiety conjugated thereto to acquiring planar images of a plurality of joints of the subject, and determining at least one TUVGlobal value for the subject from the planar images. Covariates comprising the quantification of serological RA markers and/or clinical assessments may be further obtained to apply statistical modeling to the combination of the at least one TUVGlobal and the one or more covariates. The statistical modeling is used to determine a likelihood of response to an RA therapy, and a treatment is administered to the subject based on the likelihood of response to the RA therapy.
    Type: Application
    Filed: August 19, 2022
    Publication date: March 9, 2023
    Inventors: David A. Ralph, Michael Rosol
  • Tap
    Patent number: D1016230
    Type: Grant
    Filed: May 10, 2022
    Date of Patent: February 27, 2024
    Assignee: ZIP HEATERS (AUSTRALIA) PTY LIMITED
    Inventors: David Mansueto, Gary Christopher Noble, Kevin Ralph Moult