Patents by Inventor W. Mark Saltzman
W. Mark Saltzman 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: 20250101136Abstract: A platform technology provides particle and nucleic acid conjugates, and compositions thereof, with enhanced targeting to cells, tissues, organs. The particles and nucleic acids and other deliverables contain a synthetic binding protein such as a polypeptide monobody covalently conjugated to the surface of the particle or the nucleic acid, for linking a targeting agent to the particle's surface or the nucleic acid. The particles and nucleic acids and other deliverables optionally contain an antibody non-covalently conjugated to the binding protein, via an Fc domain of the antibody. The particles can include therapeutic agents, diagnostic agents, prophylactic agents, or a combination thereof, to be delivered to desired cells, tissues, and/or organs. The particles and nucleic acids and other deliverables can be used in a wide array of applications including, but not limited to, ex vivo perfusion of mammalian organs and in vivo disease treatment.Type: ApplicationFiled: December 9, 2024Publication date: March 27, 2025Inventors: W. Mark Saltzman, Gregory T. Tietjen, Shohei Koide, Claire Albert, Jordan Pober, Akiko Koide, Laura Bracaglia
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Patent number: 12233140Abstract: Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.Type: GrantFiled: November 20, 2023Date of Patent: February 25, 2025Assignee: YALE UNIVERSITYInventors: Yang Deng, Asiri Ediriwickrema, W. Mark Saltzman
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Publication number: 20240423972Abstract: A bioadhesive nanoparticle (BNP) for long-lasting local drug delivery to treat cancer was developed. The bioadhesive nanoparticles (BNP) are composed of biodegradable polymer such as poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG), encapsulating a chemotherapeutic such as camptothecin (CPT). Nanoparticles (NPs) of PLA-HPG are non-adhesive NPs (NNPs), which are stealthy in their native state, but conversion of the vicinal diols of HPG to aldehydes confers the ability to form strong covalent bonds with amine-rich surfaces. The formulation is administered in combination with immunostimulatory molecules such as CPG and shows unexpectedly better killing of cancer cells.Type: ApplicationFiled: February 1, 2022Publication date: December 26, 2024Inventors: Hee-Won Suh, Julia M. Lewis, W. Mark Saltzman, Michael Girardi
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Patent number: 12162953Abstract: A platform technology provides particle and nucleic acid conjugates, and compositions thereof, with enhanced targeting to cells, tissues, organs. The particles and nucleic acids and other deliverables contain a synthetic binding protein such as a polypeptide monobody covalently conjugated to the surface of the particle or the nucleic acid, for linking a targeting agent to the particle's surface or the nucleic acid. The particles and nucleic acids and other deliverables optionally contain an antibody non-covalently conjugated to the binding protein, via an Fc domain of the antibody. The particles can include therapeutic agents, diagnostic agents, prophylactic agents, or a combination thereof, to be delivered to desired cells, tissues, and/or organs. The particles and nucleic acids and other deliverables can be used in a wide array of applications including, but not limited to, ex vivo perfusion of mammalian organs and in vivo disease treatment.Type: GrantFiled: December 4, 2020Date of Patent: December 10, 2024Assignees: YALE UNIVERSITY, NEW YORK UNIVERSITYInventors: W. Mark Saltzman, Gregory T. Tietjen, Shohei Koide, Claire Albert, Jordan Pober, Akiko Koide, Laura Bracaglia
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Publication number: 20240343859Abstract: Embodiments of the present invention comprises one or more of an article composed of a copolymer, a copolymer made from a process, and a process for the preparation of a copolymer composition by metal free enzyme ring-opening polymerization of a monomer composition comprising i) an ethylene brassylate monomer; ii) a 1-4 dioxan-2-one (DO); iii) lipase B from Candida antarctica (Novozyme® 435) and at an elevated temperature, processing the monomer reactants i) and ii) to a copolymer via ring-opening polymerization under solvent-free conditions and a nitrogen atmosphere in the absence of a metal and the presence of the lipase to produce a random EB-co-DO copolymer.Type: ApplicationFiled: April 5, 2024Publication date: October 17, 2024Applicants: University of Rhode Island Board of Trustees, Yale UniversityInventors: Matthew Kiesewetter, Kassie Picard, Jinal Pothupitiya, W. Mark Saltzman
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Patent number: 12030985Abstract: Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.Type: GrantFiled: July 28, 2023Date of Patent: July 9, 2024Assignee: YALE UNIVERSITYInventors: W. Mark Saltzman, Yuhang Jiang
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Publication number: 20240207172Abstract: Compositions and methods for fetal or in utero delivery of active agents are provided. The compositions are most typically administered intravenously via the vitelline vein, umbilical vein, or directly into the amniotic cavity of a pregnant mother. Fibroblast growth factor is to correct structural defects of neural tissue.Type: ApplicationFiled: December 27, 2023Publication date: June 27, 2024Inventors: W. Mark Saltzman, Adele S. Ricciardi, David H. Stitelman, James Stephen Farrelly, Anthony Bianchi
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Publication number: 20240173216Abstract: Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.Type: ApplicationFiled: November 20, 2023Publication date: May 30, 2024Inventors: Yang Deng, Asiri Ediriwickrema, W. Mark Saltzman
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Publication number: 20240092968Abstract: Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.Type: ApplicationFiled: July 28, 2023Publication date: March 21, 2024Inventors: W. Mark Saltzman, Yuhang Jiang
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Patent number: 11826438Abstract: Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.Type: GrantFiled: May 22, 2020Date of Patent: November 28, 2023Assignee: YALE UNIVERSITYInventors: Yang Deng, Asiri Ediriwickrema, W. Mark Saltzman
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Patent number: 11814464Abstract: Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.Type: GrantFiled: April 29, 2020Date of Patent: November 14, 2023Assignee: YALE UNIVERSITYInventors: W. Mark Saltzman, Yuhang Jiang
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Publication number: 20230355801Abstract: Encapsulation of MPLA in HPG-PLA nanoparticles having bioadhesive functional groups on the surface (“BNPs”) prolongs the local antitumor immune response in melanoma and boosts the adaptive immune response conferred by MPLA due to the polymer's bioadhesive properties. Delivery of MPLA in BNP prolongs the host's antitumor response with lower quantities of MPLA. Studies in mice showed that NPs delivered intratumorally have good lymphatic drainage and accumulate in lymph nodes, with prolonged dendritic cell maturation in vivo with intratumoral delivery of BNP-MPLA compared to free MPLA and NNP-MPLA.Type: ApplicationFiled: May 9, 2023Publication date: November 9, 2023Inventors: Kwangsoo Shin, Jungsoo Chang, W. Mark Saltzman, Michael Girardi
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Patent number: 11766400Abstract: Biodegradable contraceptive implants and methods of making and using thereof, are preferably formed of poly(?-pentadecalactone-co-p-dioxanone) [poly(PDL-co-DO)], a family of polyester copolymers that degrade slowly in the presence of water. The material is suitable as the basis of a biodegradable contraceptive implant that provides sustained release of a progestin at a rate similar to a commercially available nondegradable implant. In a preferred embodiment, the progestin is levonorgestrel (LNG), a hormone that prevents pregnancy by preventing the release of an egg from the ovary or by preventing fertilization of the egg by sperm. The implant may be inserted subcutaneously, allowing degradation over a period of up to about 18 or 24 months, eliminating the need for removal by a trained practitioner.Type: GrantFiled: October 24, 2017Date of Patent: September 26, 2023Assignees: YALE UNIVERSITY, FAMILY HEALTH INTERNATIONALInventors: W. Mark Saltzman, Elias Quijano, Fan Yang, Zhaozhong Jiang, Derek Owen
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Publication number: 20230293448Abstract: Compositions and methods for inducing a protective mucosal immunity against an antigen in a subject include the step of administering to a mucosal tissue an effective amount of a vaccine composition including the antigen or polynucleotide encoding an antigen associated or encapsulated within carriers such as poly(amine-co-ester) polymers in the form of particles (e.g., solid nanoparticles formed of PACE) or PACE copolymers and/or blends. Typically, the subject has previously been exposed to the antigen, for example, by administering to the same subject via a systemic or mucosal route of administration a priming antigen. In some embodiments, the polynucleotides-based vaccines are messenger RNAs encoding a viral antigen such as a coronavirus spike protein sequence, or a portion thereof. In preferred embodiments, the vaccine composition is administered intranasally.Type: ApplicationFiled: December 8, 2022Publication date: September 21, 2023Inventors: Akiko Iwasaki, Tianyang Mao, Benjamin Goldman-Israelow, W. Mark Saltzman, Alexandra Suberi, Melanie Reschke, Alexandra Piotrowski-Daspit, Hee Won Suh
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Publication number: 20230277658Abstract: Compositions for improved gene editing and methods of use thereof are disclosed. In a preferred method, gene editing involves use of a cell-penetrating anti-DNA antibody, such as 3E10, as a potentiating agent to enhance gene editing by nucleases and triplex forming oligonucleotides. Genomic modification occurs at a higher frequency when cells are contacted with the potentiating agent and nuclease or triplex forming oligonucleotide, as compared to the absence of the potentiating agent. The methods are suitable for both ex vivo and in vivo approaches to gene editing and are useful for treating a subject with a genetic disease or disorder. Nanoparticle compositions for intracellular delivery of the gene editing compositions are provided and are particularly advantageous for use with in vivo applications.Type: ApplicationFiled: November 9, 2022Publication date: September 7, 2023Applicant: Yale UniversityInventors: Elias QUIJANO, Adele RICCIARDI, Raman BAHAL, Audrey TURCHICK, Nicholas ECONOMOS, W. Mark SALTZMAN, Peter GLAZER
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Publication number: 20230265214Abstract: Compositions and methods of use thereof for delivering nucleic acid cargo into cells are provided. The compositions typically include (a) a 3E10 monoclonal antibody or an antigen binding, cell-penetrating fragment thereof; a monovalent, divalent, or multivalent single chain variable fragment (scFv); or a diabody; or humanized form or variant thereof, and (b) a nucleic acid cargo including, for example, a nucleic acid encoding a polypeptide, a functional nucleic acid, a nucleic acid encoding a functional nucleic acid, or a combination thereof. Elements (a) and (b) are typically non-covalently linked to form a complex.Type: ApplicationFiled: August 31, 2021Publication date: August 24, 2023Inventors: Elias Quijano, Peter Glazer, Bruce C. Turner, Audrey Turchick, W. Mark Saltzman
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Publication number: 20230233693Abstract: Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition. For poly(amine-co-ester) polymers with specific amine or hydroxyl group containing end-groups in admixture with PEGylated poly(amine-co-ester) polymers, in vivo delivery to the lung by inhalation has been shown.Type: ApplicationFiled: May 27, 2021Publication date: July 27, 2023Inventors: W. Mark Saltzman, Yuhang Jiang, Molly Grun, Alexandra Suberi
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Publication number: 20230172870Abstract: Nanoparticles useful for drug delivery are described. In one aspect, the nanoparticles contain poly(amine-co-ester)s or poly(amine-co-amide)s (PACE) modified with poly(ethylene glycol) (PACE-PEG), and can be optionally blended with a second PACE polymer optionally containing endgroup modifications. In another aspect, the nanoparticles contain a core containing a PACE polymer optionally containing endgroup modifications, and a polymeric surfactant non-covalently conjugated to the surface of the nanoparticles. The nanoparticles contain a peptide or protein targeting moiety that is covalently conjugated to the PACE-PEG polymer or to the surfactant on the surface of the nanoparticles via a linkage that contains a succinimide or substituted sulfone moiety, respectively. The nanoparticles provide as a versatile platform for the delivery of nucleic acids, such as mRNA.Type: ApplicationFiled: December 8, 2022Publication date: June 8, 2023Inventors: Alexandra Piotrowski-Daspit, Claire Albert, W. Mark Saltzman
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Publication number: 20220372474Abstract: Peptide nucleic acid (PNA) oligomers having one or more hydroxymethyl ?-substitutions, also referred to herein as “ser?PNA”, are provided. The hydroxymethyl ?-substitution preserves and amplifies the helical preorganization that is valuable for DNA duplex invasion by the oligomer. ser?PNA-containing triplex-forming molecules can be used in combination with a donor DNA fragment to facilitate genome modification in vitro and in vivo.Type: ApplicationFiled: June 22, 2020Publication date: November 24, 2022Inventors: Elias Quijano, Stanley Oyaghire, W. Mark Saltzman, Peter Glazer
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Publication number: 20220339294Abstract: Compositions containing populations of nanoparticles that show selective uptake by tissues and other cell types such as lung cells and/or bone marrow cells are described. The nanoparticles show this uptake by virtue of their size and in the absence of a targeting agent on the surface of the nanoparticles, i.e., passive targeting. The population of nanoparticles contain poly(lactic acid-co-glycolic acid), have a diameter between about 70 nm and about 220 nm, and at least 90% of the nanoparticles have a diameter between about 110 nm and about 129 nm. The nanoparticles are manufactured using a microfluidic system. The compositions can be used to treat lung- and/or blood-related genetic disorders in in vivo gene editing technologies.Type: ApplicationFiled: September 9, 2020Publication date: October 27, 2022Inventors: Hanna Mandl, Elias Quijano, W. Mark Saltzman, Peter Glazer