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Patents Assigned to The Wistar Institute of Anatomv and Biologv
Patent number: 11596678
Abstract: Nucleic acid molecules and compositions comprising one or more nucleic acid sequences that encode a consensus Marburgvirus filovirus glycoprotein immunogens. Immunomodulatory methods and methods of inducing an immune response against Marburgvirus are disclosed. Method of preventing infection by Marburgvirus and methods of treating individuals infected with Marburgvirus are disclosed. Consensus Marburgvirus filovirus glycoprotein immunogens are disclosed.
Type: Grant
Filed: December 1, 2017
Date of Patent: March 7, 2023
Assignees: The Trustees of the University of Pennsylvania, The Wistar Institute of Anatomv and Biologv
Inventors: David Weiner, Ami Patel, Sarah Elliott
Nov 8 2019
https://www.eurekalert.org/news-releases/746401
DNA technology as a novel strategy for delivery of anti-HIV antibodies
DNA technology as a novel strategy for delivery of anti-HIV antibodies
Co-authors: Megan C. Wise from Inovio Pharmaceuticals and Ziyang Xu from The Wistar Institute are co-first authors. Other co-authors include: Edgar Tello-Ruiz, Aspen Trautz, Ami Patel, Sarah T.C. Elliott, Neethu Chokkalingam, Sophie Kim, Kar Muthumani, and Daniel W. Kulp from Wistar; Jingjing Jiang, Paul Fisher, Stephany J. Ramos, Trevor R.F. Smith, Janess Mendoza, Kate E. Broderick, and Laurent Humeau from Inovio; Charles Beck, Melissa G. Kerkau, Guido Ferrari, and David C. Montefiori from Duke University.
(also https://www.sciencedaily.com/releases/2017/07/170706071919.htm )
Health News July 6, 2017 / 11:17 AM
DNA-based strategy protects against multiple flu strains in study
DNA-based strategy protects against multiple flu strains in study
Influenza vaccines work by prompting a person's immune system to produce soluble proteins known as antibodies to target the exact type of influenza virus.
Influenza vaccines work by prompting a person's immune system to produce soluble proteins known as antibodies to target the exact type of influenza virus.
By Amy Wallace
Researchers have developed a new DNA-based strategy to protect against several different strains of the influenza virus. Photo by Roger L. Wollenberg/UPI | License Photo
July 6 (UPI) -- Researchers at The Wistar Institute have created a new synthetic, DNA-based strategy that provides protection against several different influenza viruses.
Influenza vaccines work by triggering the body's immune system to produce antibodies that target the exact types of flu virus in each year's seasonal flu vaccine.
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Scientists from The Wistar Institute collaborated with MedImmune and Inovio Pharmaceuticals, Inc., to develop a method involving DNA sequences that encode protective antibodies into a vaccine. The antibodies protect against certain strains of the flu but do not provide protection from all flu virus strains.
"We devised a different method from the traditional vaccine strategy, and instead of relying on the immune system to respond to a vaccine, this new strategy delivers DNA sequences that directly encode the protective antibodies rather than inciting the production of antibodies through an immune response," Sarah T.C. Elliott, a postdoctoral fellow in Wistar's Vaccine and Immune Therapy Center in the Weiner lab, said in a press release. "This new synthetic DNA-based strategy -- termed DMAb's -- delivers monoclonal antibodies that provide protection against highly diverse strains of influenza."
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Traditionally, seasonal flu vaccines are only effective against strains identified each spring in sentinel laboratories and vaccines must then be rushed into production to have enough available when flu season starts.
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"The matching process is not a perfect science, therefore, in some flu seasons, the vaccine available in the fall is not a good match for the circulating virus strains and is less effective," David Weiner, executive vice president and director of the Vaccine and Immune Therapy Center at The Wistar Institute, said.
"Flu occasionally can also shift strains dramatically resulting in a pandemic strain that requires a new strategy for developing the vaccine, leaving the U.S. population at risk of major health consequences. Furthermore, some vulnerable populations may not respond well to vaccines, and new approaches that are simple, rapid and can broadly protect against influenza would be a major step forward."
Researchers tested their method by studying the DNA sequences for two human monoclonal antibodies -- one that broadly targets the influenza A virus and one that targets influenza B viruses.
Results from mouse models showed that the delivery of the DMAb sequence for influenza A targeted monoclonal antibody protected against lethal doses of two different influenza A viruses. The same results were shown for influenza B viruses.
The study was published July 6 in NPJ Vaccines.
Synthetic DNA-delivered Antibodies Protect Against Ebola in Preclinical Studies Representing a Novel Platform for Antibody Therapies for Outbreak Infections
Synthetic DNA-delivered Antibodies Protect Against Ebola in Preclinical Studies Representing a Novel Platform for Antibody Therapies for Outbreak Infections
PHILADELPHIA — (Nov. 13, 2018) — Scientists at The Wistar Institute and collaborators have successfully engineered novel DNA-encoded monoclonal antibodies (DMAbs) targeting Zaire Ebolavirus that were effective in preclinical models. Study results, published online in Cell Reports, showed that DMAbs were expressed over a wide window of time and offered complete and long-term protection against lethal virus challenges. DMAbs may also provide a novel powerful platform for rapid screening of monoclonal antibodies enhancing preclinical development.
Ebola virus infection causes a devastating disease, known as Ebola virus disease, for which no licensed vaccine or treatment are available. The 2014-2016 Zaire Ebola virus epidemic in West Africa was the most severe reported to date, with more than 28,600 cases and 11,325 deaths according to the Center for Disease Control. A new outbreak is ongoing in the Democratic Republic of Congo, with a death toll of more than 200 people since August. One of the experimental avenues scientists are pursuing is evaluating the safety and efficacy of monoclonal antibodies isolated from survivors as promising candidates for further development as therapeutics against Ebola virus infection. However, this approach requires high doses and repeated administration of recombinant monoclonal antibodies that are complex and expensive to manufacture, so meeting the global demand while keeping the cost affordable is challenging.
“Our studies show deployment of a novel platform that rapidly combines aspects of monoclonal antibody discovery and development technology with the revolutionary properties of synthetic DNA technology,” said lead researcher David B. Weiner, Ph.D., executive vice president and director of Wistar’s Vaccine & Immunotherapy Center, and W.W. Smith Charitable Trust Professor in Cancer Research.
Weiner’s lab designed and enhanced optimized DMAbs that, when injected locally, provide the genetic blueprint for the body to make functional and protective Ebola virus-specific antibodies, circumventing multiple steps in the antibody development and manufacturing process. Dozens of DMAbs were tested in mice and the best-performing ones were selected for further studies. These proved to be highly effective for providing complete protection from disease in challenge studies.
“Due to intrinsic biochemical properties, some monoclonal antibodies might be difficult and slow to develop or even impossible to manufacture, falling out of the development process and causing loss of potentially effective molecules,” added Weiner. “The DMAb platform allows us to collect protective antibodies from protected persons and engineer and compare them rapidly and then deliver them in vivo to protect against infectious challenge. Such an approach could be important during an outbreak, when we need to design, evaluate and deliver life-saving therapeutics in a time-sensitive manner.”
“We started with antibodies isolated from survivors and compared the activity of anti-Ebola virus DMAbs and recombinant monoclonal antibodies over time,” said Ami Patel, Ph.D., first author on the study and associate staff scientist in the Wistar Vaccine and Immunotherapy Center. “We showed that in vivo expression of DMAbs supports extended protection over traditional antibody approaches.”
The researchers also looked at how DMAbs physically interact with their Ebola virus targets, called epitopes, and confirmed that DMAbs bind to identical epitopes as the corresponding recombinant monoclonal antibodies made in traditional bioprocess facilities.
The Weiner Laboratory is also developing an anti-Ebola virus DNA vaccine. Preclinical results from this efforts were published recently in the Journal of Infectious Diseases.
Co-authors of this study from The Wistar Institute include Daniel H. Park, Marguerite E. Gorman, Sarah T.C. Elliott, Rianne Esquivel, and Kar Muthumani. Other co-authors include Carl W. Davis and Rafi Ahmed from Emory University; Trevor R.F. Smith, Charles Reed, Megan C. Wise, Jian Yan, Jing Chen, Kate E. Broderick, Laurent Humeau, and Niranjan Y. Sardesai from Inovio Pharmaceuticals; Anders Leung, Kevin Tierney, Trina Racine, Shihua He, Xiangguo Qiu, and Darwyn Kobasa from Public Health Agency of Canada; Aubrey Bryan, Edgar Davidson and Benjamin J. Doranz from Integral Molecular; Xiaoying Yu and Erica Ollmann Saphire from The Scripps Research Institute, La Jolla; James E. Crowe from Vanderbilt University; and Gary P. Kobinger from Université Laval, Canada.
This work was supported by a grant from the Defense Advanced Research Projects Agency (DARPA) awarded to Inovio Pharmaceuticals and by National Institutes of Health contract HHSN272201400058C.
In Vivo-delivered Synthetic Human DMAbs Protect Against Ebolavirus Infection in a Mouse Model,
Cell Reports (2018). Advanced online publication.
###
The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7175322/
Nanoparticle Vaccines: In Vivo Assembly of Nanoparticles Achieved through Synergy of Structure‐Based Protein Engineering and Synthetic DNA Generates Enhanced Adaptive Immunity (Adv. Sci. 8/2020)
Nanoparticle Vaccines: In Vivo Assembly of Nanoparticles Achieved through Synergy of Structure‐Based Protein Engineering and Synthetic DNA Generates Enhanced Adaptive Immunity (Adv. Sci. 8/2020)
Ziyang Xu 1,2, Megan C Wise 3, Neethu Chokkalingam 1, Susanne Walker 1, Edgar Tello‐Ruiz 1, Sarah T C Elliott 1, Alfredo Perales‐Puchalt 1, Peng Xiao 1, Xizhou Zhu 1, Ruth A Pumroy 2, Paul D Fisher 3, Katherine Schultheis 3, Eric Schade 3, Sergey Menis 4,5,6, Stacy Guzman 1, Hanne Andersen 7, Kate E Broderick 3, Laurent M Humeau 3, Kar Muthumani 1, Vera Moiseenkova‐Bell 2, William R Schief 4,5,6,8, David B Weiner 1, Daniel W Kulp 1,9
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PMCID: PMC7175322
https://www.linkedin.com/in/stcelliott/
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- Skilled in leading pre-clinical due diligence, informing indication strategy, & developing novel technologies from proof-of-concept to clinical IND.
- Accomplished scientist with patented/licensed innovations in non-viral gene delivery & immunology.
Jul 2022 to Present · 2 yrs 8 mos
Strategy & comprehensive product development for AAV gene therapies in hematology, metabolic disease, and several other exploratory therapeutic areas.
Due diligence, external engagement, & contracting to onboard platform-enabling emerging technologies.
Strategy & comprehensive product development for AAV gene therapies in hematology, metabolic disease, and several other exploratory therapeutic areas. Due diligence, external engagement, & contracting to onboard platform-enabling emerging technologies.
Postdoctoral Fellow - Center for Vaccines & Immune Therapeutics
Postdoctoral Fellow - Center for Vaccines & Immune Therapeutics
The Wistar Institute
The Wistar Institute
May 2016 - Apr 2019 · 3 yrs
May 2016 to Apr 2019 · 3 yrs
Philadelphia, Pennsylvania, United States
Philadelphia, Pennsylvania, United States
Engineered, established proof-of-concept, & patented non-viral nucleic acid gene delivery of therapeutic antibodies and/or antigens for indications in oncology, autoimmunity, virology, and bacteriology.
(Penn Medicine Pathology & Laboratory Medicine co-appointment.)
Engineered, established proof-of-concept, & patented non-viral nucleic acid gene delivery of therapeutic antibodies and/or antigens for indications in oncology, autoimmunity, virology, and bacteriology. (Penn Medicine Pathology & Laboratory Medicine co-appointment.)
Postdoctoral Fellow - Pathology & Lab Medicine
Postdoctoral Fellow - Pathology & Lab Medicine
Penn Medicine, University of Pennsylvania Health System
Penn Medicine, University of Pennsylvania Health System
Jan 2015 - May 2016 · 1 yr 5 mos
Jan 2015 to May 2016 · 1 yr 5 mos
Research Associate II
Research Associate II
Institute for Systems Biology
Institute for Systems Biology
Jan 2006 - Aug 2008 · 2 yrs 8 mos
Jan 2006 to Aug 2008 · 2 yrs 8 mos
Seattle, Washington, United States
Seattle, Washington, United States
Tech-enabling research supporting diagnostic applications of the nascent fields of glycoproteomics & computational biology.
Tech-enabling research supporting diagnostic applications of the nascent fields of glycoproteomics & computational biology.
Owner / Entrepreneur
Owner / Entrepreneur
UVillage Tutoring · Self-employed
UVillage Tutoring · Self-employed
2005 - 2008 · 3 yrs
2005 to 2008 · 3 yrs
Seattle, Washington, United States
Seattle, Washington, United States
Built a private tutoring service company & tutoring network to serve clients in high school STEM & graduate admissions test prep (MCAT, GRE, GMAT).
Built a private tutoring service company & tutoring network to serve clients in high school STEM & graduate admissions test prep (MCAT, GRE, GMAT).
Research Assistant - Anesthesiology
Research Assistant - Anesthesiology
University of Washington - School of Medicine
University of Washington - School of Medicine
Sep 2003 - Sep 2005 · 2 yrs 1 mo
Sep 2003 to Sep 2005 · 2 yrs 1 mo
Seattle, Washington, United States
Seattle, Washington, United States
Skills: Cell Biology
Activities and societies: President of Penn Biotech Group @ Wharton.
Activities and societies: President of Penn Biotech Group @ Wharton.
Sarah T Elliott
Sarah T Elliott
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Name
Sarah T Elliott
Birth Date
Jan 1983
Residence Date
2016-2020
Address
1151 E Hector St Apt 220
Residence
Conshohocken, Pennsylvania, USA
Postal Code
19428
Second Residence Date
2012-2017
Second Address
2323 Race St Unit 819
Second Residence
Philadelphia, Pennsylvania, USA
Second Postal Code
19103
Third Residence Date
2009-2012
Third Address
2300 Walnut St Apt 503
Third Residence
Philadelphia, Pennsylvania, USA
Third Postal Code
19103
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