NYBCe Patents & Licensing

NYBC 717: Light Detection Device For Alerting An External Monitoring System

Patent Number: Pending

Title: LIGHT DETECTION DEVICE FOR ALERTING AN EXTERNAL MONITORING SYSTEM

Inventor: Benjamin Matthew Bloomquist

Abstract:

Facilities around the world are reliant on monitoring systems to assess bacterial contamination in platelet donations. From hospitals to blood banks and research institutions, these facilities prioritize maintaining the safety and integrity of donated platelets. Monitoring systems equipped with advanced technologies play a pivotal role in swiftly identifying potential bacterial infections, preventing their transmission to recipients, and safeguarding the overall quality of the blood supply chain. 

NYBC researchers have engineered a method and apparatus designed to support the detection of laboratory instrument activation. This technology fills the gap left by the need for accurate bacterial screening of donated platelets and the lack of interoperability between laboratory instruments and external monitoring systems. The existing process relies on indicator lights within the laboratory instrument to alert operators of bacterial infection detection. However, current equipment requires constant operator presence for continual evaluation. This device alleviates this burden enabling operators to conduct continual evaluation for multiple systems simultaneously.   

NYBC 632: Megakaryocyte and Platelet Production from Stem Cells

Patent Number: US-9574178-B2

Title: MEGAKARYOCYTE AND PLATELET PRODUCTION FROM STEM CELLS

United States Patent: MEGAKARYOCYTE AND PLATELET PRODUCTION FROM STEM CELLS

Investigators(s): W. Beau Mitchell; Mauro P. Avanzi

Abstract:

NYBC researchers have developed a method to provide platelet production ex vivo. This method is employed to culture stem cells into megakaryocyte progenitor cells, which are then matured in a bioreactor (NYBC 654) to maximize platelet production. By harnessing this approach, a reliable and efficient platelet production process is achieved.

Each year, millions of patients in the United States are affected by conditions like thrombocytopenia, necessitating frequent platelet treatments. Despite the annual donation of over 10 million platelets from volunteer donors, the demand for platelets continues to outpace supply. Obtaining platelets is a time-consuming and costly process, further compounded by their short shelf life of a few days. This technology has the potential to improve the availability and accessibility of platelet transfusions, ensuring a steady supply of these vital products for patients suffering from blood disorders.

Related Publications:

Avanzi MP, Mitchell WB. Ex vivo production of platelets from stem cells. British journal of haematology. 2014 Apr;165(2):237-47.

Avanzi MP, Oluwadara OE, Cushing MM, Mitchell ML, Fischer S, Mitchell WB. A novel bioreactor and culture method drives high yields of platelets from stem cells. Transfusion. 2016 Jan;56(1):170-8.

Avanzi MP, Izak M, Oluwadara OE, Mitchell WB. Actin inhibition increases megakaryocyte proplatelet formation through an apoptosis-dependent mechanism. PloS one. 2015 Apr 14;10(4):e0125057.

Avanzi MP, Goldberg F, Davila J, Langhi D, Chiattone C, Mitchell WB. Rho kinase inhibition drives megakaryocyte polyploidization and proplatelet formation through MYC and NFE 2 downregulation. British journal of haematology. 2014 Mar;164(6):867-76.

NYBC 654: Megakaryocyte and Platelet Production from Stem Cells

Patent Number: US-9803164-B2

Title: MEGAKARYOCYTE AND PLATELET PRODUCTION FROM STEM CELLS

United States Patent: MEGAKARYOCYTE AND PLATELET PRODUCTION FROM STEM CELLS

Investigator(s): Beau W. Mitchell

Abstract:

NYBC researchers have developed a system for platelet production ex vivo using a 3-dimensional system that mimics the natural bone marrow niche environment. This method involves a proprietary medium-containing system for the differentiation, maturation and expansion of megakaryocytes. Additionally, within the system, there is an application of shear stress at a predetermined oxygen concentration that enhances platelet production.

Each year, millions of patients in the United States are affected by conditions like thrombocytopenia, necessitating frequent platelet treatments. Despite the annual donation of over 10 million platelets from volunteer donors, the demand for platelets continues to outpace supply. Obtaining platelets is a time-consuming and costly process, further compounded by their short shelf life of a few days. This technology has the potential to improve the availability and accessibility of platelet transfusions, ensuring a steady supply of these vital products for patients suffering from blood disorders.

Related Publications:

Avanzi MP, Oluwadara OE, Cushing MM, Mitchell ML, Fischer S, Mitchell WB. A novel bioreactor and culture method drives high yields of platelets from stem cells. Transfusion. 2016 Jan;56(1):170-8.

Avanzi MP, Mitchell WB. Ex vivo production of platelets from stem cells. British journal of haematology. 2014 Apr;165(2):237-47.

Thon JN, Dykstra BJ, Beaulieu LM. Platelet bioreactor: accelerated evolution of design and manufacture. Platelets. 2017 Jul 4;28(5):472-7.

NYBC 720: Interferon-gamma-mediated Anti-cancer Therapy

Patent Number: Pending

Title: INTERFERON-GAMMA-MEDIATED ANTI-CANCER THERAPY

International Patent Application: WIPO – SEARCH INTERNATIONAL AND NATIONAL PATENT COLLECTION

Investigator(s): Hui Zhong; Karina Yazdanbakhsh

Abstract:

NYBC researchers have unveiled the therapeutic potential of interferon-γ treated intermediate monocytes (IFN-IMo) in combating metastatic cancer. By subjecting the intermediate monocyte (Imo) subset to interferon-γ (IFN-γ) treatment, researchers can stimulate their expansion, presenting a promising avenue for direct cellular therapy. Moreover, when these IFN- γ treated IMo are co-cultured with NK cells, a potent pro-NK (Natural Killer) effect is generated, enhancing the immune system’s anti-tumor activity. 

Considering the global impact of cancer metastasis, with millions of patients at risk, the IFN-IMo technology holds immense therapeutic potential. Notably, it extends beyond metastasis treatment alone, presenting a versatile application as both a standalone therapy and a co-stimulatory approach with NK cell therapy. The broad scope of this technology positions it as a transformative force in the field of cancer treatment. 

Related Publications: 

Zhong H, Bao W, Liu Y, Yazdanbakhsh K. Inflammation Response Cytokines IFN-γ and IL-10 Regulate Monocyte Subset Differentiation. Blood. 2019 Nov 13;134:3586. 

Wang R, Bao W, Pal M, Liu Y, Yazdanbakhsh K, Zhong H. Intermediate monocytes induced by IFN-γ inhibit cancer metastasis by promoting NK cell activation through FOXO1 and interleukin-27. Journal for ImmunoTherapy of Cancer. 2022;10(1). 

Mouse Models of Autoimmune Hemolytic Anemia

Title: Mouse Models of Autoimmune Hemolytic Anemia

Abstract:

Researchers at the NYBC have developed mouse models of autoimmune hemolytic anemia (AIHA). These models mimic the key processes in human disease and allow for testing and identification of therapeutic strategies for AIHA. 

Autoimmune hemolytic anemia is a type of hemolytic anemia in which the immune system attacks and destroys red blood cells, leading to a decrease in the number of circulating red blood cells and subsequent symptoms such as fatigue, shortness of breath, and jaundice. While the exact cause of AIHA is not fully understood, it impacts approximately 1-3 people per 100,000 in the United States each year. For those that experience AIHA, there are significant limitations in efficacy and safety of the current-standard-of-care. These mouse models provide an opportunity for non-clinical therapeutic development and testing.   

Related Publications:

Yu J, Heck S, Yazdanbakhsh K. Prevention of red cell alloimmunization by CD25 regulatory T cells in mouse models. American journal of hematology. 2007 Aug;82(8):691-6. 

Mqadmi A, Zheng X, Yazdanbakhsh K. CD4+ CD25+ regulatory T cells control induction of autoimmune hemolytic anemia. Blood. 2005 May 1;105(9):3746-8. 

NYBC 711: Compounds for Treatment of Hemolysis -associated Diseases

Patent Number: Pending

Title: COMPOUNDS FOR TREATMENT OF HEMOLYSIS-AND INFLAMMASOME-ASSOCIATED DISEASES

International Patent Application: COMPOUNDS FOR TREATMENT OF HEMOLYSIS-AND INFLAMMASOME-ASSOCIATED DISEASES

Investigator(s): Hui Zhong; Karina Yazdanbakhsh

Abstract: 

NYBC researchers have discovered a novel method of reducing alloimmunization in chronically transfused patients by administering a therapeutically effective dose of combined hemin and quinine. This approach has been shown to decrease alloimmunization rates in vivo and leverages well-known medications that have been demonstrated to be safe. This combination technology has the potential to significantly improve the quality of life for chronically transfused patients and reduce healthcare costs associated with complications from alloimmunization. 

Hemolysis is a major concern for individuals who require regular blood transfusions due to underlying medical conditions, such as sickle cell disease and thalassemia. Chronic transfusions can lead to alloimmunization, where the recipient’s immune system develops antibodies against donor blood cells, causing complications and limiting the effectiveness of transfusions. Current treatments for alloimmunization, such as immunosuppressants, have shown limited improvement and significant side effects. There is a need for alternative approaches to reduce alloimmunization and improve the quality of life for chronically transfused patients. 

Related Publications: 

Pal M, Bao W, Wang R, Liu Y, An X, Mitchell WB, Lobo CA, Minniti C, Shi PA, Manwani D, Yazdanbakhsh K. Hemolysis inhibits humoral B-cell responses and modulates alloimmunization risk in patients with sickle cell disease. Blood. 2021 Jan 14;137(2):269-80. 

Zhong H, Yazdanbakhsh K. Hemolysis and immune regulation. Current opinion in hematology. 2018 May;25(3):177. 

NYBC 536: Universal Multi-Variant Detection System

Patent Number: 7348164

Title: UNIVERSAL MULTI-VARIANT DETECTION SYSTEM

United States Patent: UNIVERSAL MULTI-VARIANT DETECTION SYSTEM

Investigator(s): Linda Andrus; Carmen Nichols

Abstract:

NYBC researchers have developed a method of detecting variants of a pathogen with the use of a single detection probe, i.e., a universal multi-variant detection system. This technology entails a convenient and efficient diagnostic assay for detecting multiple variants of a specific nucleic acid target including viruses, bacteria, and multicellular parasites. This novel technology has the potential to significantly improve early detection and treatment of infections regardless of variant, particularly in settings where access to sophisticated laboratory equipment is limited.

There is an urgent need for sensitive, convenient nucleic acid-based screening assays capable of detecting closely related genetic variants of viruses, bacteria and other pathogens in contaminated blood. Such assays are needed to detect blood or plasma units from individuals in the early acute stages of a pathogen infection, i.e., before the individual has developed diagnostic antibodies to the virus.

Related Publications:

Wu X, Thi VL, Liu P, Takacs CN, Xiang K, Andrus L, Gouttenoire J, Moradpour D, Rice CM. Pan-genotype hepatitis E virus replication in stem cell–derived hepatocellular systems. Gastroenterology. 2018 Feb 1;154(3):663-74.

Catanese MT, Uryu K, Kopp M, Edwards TJ, Andrus L, Rice WJ, Silvestry M, Kuhn RJ, Rice CM. Ultrastructural analysis of hepatitis C virus particles. Proceedings of the National Academy of Sciences. 2013 Jun 4;110(23):9505-10.

Schwartz RE, Trehan K, Andrus L, Sheahan TP, Ploss A, Duncan SA, Rice CM, Bhatia SN. Modeling hepatitis C virus infection using human induced pluripotent stem cells. Proceedings of the National Academy of Sciences. 2012 Feb 14;109(7):2544-8.

NYBC 573: Babesia Subtilisin Technology for Detection and Treatment of Babesiosis

Patent Number: 7704508

Title: BABESIA SUBTILISIN

United States Patent: BABESIA SUBTILISIN

Investigator: Cheryl Lobo, PhD

Abstact:

NYBC researchers have discovered subtilisin, a protein in Babesia, which can be used for the diagnosis of Babesia sp. infection and provide potential opportunities for targeted therapy. The technology includes an isolated protein produced by a naturally occurring Babesia sp. as well as an antibody that specifically binds to the subtilisin protein. These tools have the potential to support the development of diagnostics and therapeutics to improve the early detection and treatment of Babesiosis and can lead to the development of more effective therapies for the disease. 

Babesiosis is a tick-borne parasitic disease caused by various species of Babesia, which can be life-threatening in some cases. The disease is challenging to diagnose due to its nonspecific symptoms and the lack of sensitive and specific diagnostic tools. Moreover, currently available treatments for babesiosis are limited in their efficacy, leading to a need for new therapeutic approaches. 

Related Publications:

Elton CM, Rodriguez M, Mamoun CB, Lobo CA, Wright GJ. A library of recombinant Babesia microti cell surface and secreted proteins for diagnostics discovery and reverse vaccinology. International journal for parasitology. 2019 Feb 1;49(2):115-25. 

Ord RL, Lobo CA. Human babesiosis: Pathogens, prevalence, diagnosis, and treatment. Current clinical microbiology reports. 2015 Dec;2:173-81. 

Lobo CA, Cursino-Santos JR, Alhassan A, Rodrigues M. Babesia: an emerging infectious threat in transfusion medicine. PLoS pathogens. 2013 Jul 11;9(7):e1003387. 

Montero E, Gonzalez LM, Rodriguez M, Oksov Y, Blackman MJ, Lobo CA. A conserved subtilisin protease identified in Babesia divergens merozoites. Journal of Biological Chemistry. 2006 Nov 24;281(47):35717-26. 

NYBC 589: Highly Potent Synergistic Combinations of Human Immunodeficiency Virus (HIV) Fusion Inhibitors

Patent Number: 7919101

Title: HIGHLY POTENT SYNERGISTIC COMBINATIONS OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) FUSION INHIBITORS

United States Patent: HIGHLY POTENT SYNERGISTIC COMBINATIONS OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) FUSION INHIBITORS

Investigator(s): Shibo Jiang; Chungen Pan

Abstract:

NYBC researchers have discovered a new approach for the treatment of HIV infection. This technology is a combination of two or more HIV fusion/entry small molecule inhibitors that are independently validated and enhance protection against HIV infection. These combinations of GMP-ready drugs provide an alternative avenue for the prevention and treatment of HIV infection.

Despite significant progress in the treatment and prevention of HIV, it remains a major global health concern, with an estimated 38 million people living with the virus worldwide. While current antiretroviral therapies (ARTs) are effective in controlling the virus, there are still significant limitations, including drug resistance, toxicity, and poor adherence. Moreover, the development of a vaccine against HIV has been challenging due to the high genetic variability of the virus and the lack of highly effective vaccine candidates.

Related Publications:

Pan C, Cai L, Lu H, Qi Z, Jiang S. Combinations of the first and next generations of human immunodeficiency virus (HIV) fusion inhibitors exhibit a highly potent synergistic effect against enfuvirtide-sensitive and-resistant HIV type 1 strains. Journal of virology. 2009 Aug 15;83(16):7862-72

Pan C, Liu S, Jiang S. HIV-1 gp41 fusion intermediate: a target for HIV therapeutics. Journal of the Formosan Medical Association. 2010 Feb 1;109(2):94-105.

Yu F, Lu L, Du L, Zhu X, Debnath AK, Jiang S. Approaches for identification of HIV-1 entry inhibitors targeting gp41 pocket. Viruses. 2013 Jan 11;5(1):127-49.

Xu W, Li H, Wang Q, Hua C, Zhang H, Li W, Jiang S, Lu L. Advancements in developing strategies for sterilizing and functional HIV cures. BioMed research international. 2017 Oct;2017.

NYBC 594: Immunoenhancer-linked Oligomeric HIV Vaccines

Patent Number: 8936789

Title: IMMUNOENHANCER-LINKED OLIGOMERIC HIV VACCINES

United States Patent: IMMUNOENHANCER-LINKED OLIGOMERIC HIV VACCINES

Investigator(s): Chungen Pan; Zhi Qi; Shibo Jiang

Abstract: 

NYBC researchers have discovered a novel HIV vaccine approach. The technology comprises immunogenic compositions that elicit potent and broad HIV neutralizing antibody responses in immunized hosts. This technology entails a subunit vaccine that leverages a gp41 fragment combined with IgG1 Fc and stabilizing Foldon (Fd) sequence derived from the natural trimerization domain of bacteriophage T4 fibritin. This vaccine demonstrates significant inhibition of HIV 6-helix bundle formation in vitro. 

Despite significant progress in the treatment and prevention of HIV, it remains a major global health concern, with an estimated 38 million people living with the virus worldwide. Current antiretroviral therapies (ARTs) have limitations, including drug resistance, toxicity, and poor adherence. Additionally, the development of a vaccine against HIV has been challenging due to the high genetic variability of the virus and the lack of highly effective vaccine candidates. Additional potent vaccine candidates would provide a much-needed prophylactic option for this global patient group. 

Related Publications: 

Qi Z, Pan C, Lu H, Shui Y, Li L, Li X, Xu X, Liu S, Jiang S. A recombinant mimetics of the HIV-1 gp41 prehairpin fusion intermediate fused with human IgG Fc fragment elicits neutralizing antibody response in the vaccinated mice. Biochemical and biophysical research communications. 2010 Jul 30;398(3):506-12. 

Lu L, Wei M, Chen Y, Xiong W, Yu F, Qi Z, Jiang S, Pan C. F (ab′) 2 fragment of a gp41 NHR-trimer-induced IgM monoclonal antibody neutralizes HIV-1 infection and blocks viral fusion by targeting the conserved gp41 pocket. Microbes and Infection. 2013 Nov 1;15(13):887-94. 

NYBC 595: Stabilized trimeric HIV-1 GP41 fusion inhibitor polypeptides comprising the N-terminal heptad repeat (NHR) and foldon (FD) trimerization motif

Patent Number: 9724383

TITLE: STABILIZED TRIMERIC HIV-1 GP41 FUSION INHIBITOR POLYPEPTIDES COMPRISING THE N-TERMINAL HEPTAD REPEAT (NHR) AND FOLDON (FD) TRIMERIZATION MOTIF

United States Patent: STABILIZED TRIMERIC HIV-1 GP41 FUSION INHIBITOR POLYPEPTIDES COMPRISING THE N-TERMINAL HEPTAD REPEAT (NHR) AND FOLDON (FD) TRIMERIZATION MOTIF

Investigator(s): Shibo Jiang; Zhi Qi; Xi Chen; Chungen Pan

Abstract: 

NYBC researchers have discovered a new approach to blocking HIV entry for the treatment and prevention of HIV infection, that uses a trimeric fusion inhibitor. This technology is comprised of peptides derived from the glycoprotein envelop of HIV itself and provide an alternative method to counteract HIV activity. This novel technology has been demonstrated to provide potent inhibition of HIV infection in vitro. 

Despite significant progress in the treatment and prevention of HIV, it remains a major global health concern, with an estimated 38 million people living with the virus worldwide. While current antiretroviral therapies (ARTs) are effective in controlling the virus, there are still significant limitations, including drug resistance, toxicity, and poor adherence. Moreover, the development of a vaccine against HIV has been challenging due to the high genetic variability of the virus and the lack of effective vaccine candidates. 

Related Publications: 

Liu S, Wu S, Jiang S. HIV entry inhibitors targeting gp41: from polypeptides to small-molecule compounds. Current pharmaceutical design. 2007 Jan 1;13(2):143-62. 

Pan C, Liu S, Jiang S. HIV-1 gp41 fusion intermediate: a target for HIV therapeutics. Journal of the Formosan Medical Association. 2010 Feb 1;109(2):94-105. 

Cai L, Jiang S. Development of peptide and small‐molecule HIV‐1 fusion inhibitors that target gp41. ChemMedChem. 2010 Nov 8;5(11):1813-24. 

Chen X, Lu L, Qi Z, Lu H, Wang J, Yu X, Chen Y, Jiang S. Novel recombinant engineered gp41 N-terminal heptad repeat trimers and their potential as anti-HIV-1 therapeutics or microbicides. Journal of Biological Chemistry. 2010 Aug 13;285(33):25506-15. 

NYBC 610: Immunopotentiator-linked Oligomeric Influenza Immunogenic Compositions

Patent Number: US-9592287-B2

Title: IMMNOPOTENTIATOR-LINKED OLIGOMERIC INFLUENZA IMMUNOGENIC COMPOSITIONS

United States Patent: IMMNOPOTENTIATOR-LINKED OLIGOMERIC INFLUENZA IMMUNOGENIC COMPOSITIONS

Investigator(s): Shibo Jiang; Lanying Du

Abstract:

NYBC researchers have developed an immunopotentiating platform that provides a highly potent influenza vaccine candidate. This technology entails a subunit vaccine that leverages a hemagglutinin (HA) trimer combined with IgG1 Fc and stabilizing sequence Fd. This novel vaccine produces a strong immune responses and neutralizing antibodies against multiple highly pathogenic H5N1 strains in vivo.

Seasonal influenza leads to 300,000-700,000 annual deaths globally. Current seasonal influenza vaccines include several strains of influenza. However, as the seasonal vaccines are designed to predict prominent strains in the coming year, there are often mismatches between circulating viruses and strains included in vaccines, leading to low vaccine efficacy. Development of a multi-valent influenza vaccine that promotes strong immune responses across antigenically distinct influenza strains is much needed.

Related Publications:

Du L, Jin L, Zhao G, Sun S, Li J, Yu H, Li Y, Zheng BJ, Liddington RC, Zhou Y, Jiang S. Identification and structural characterization of a broadly neutralizing antibody targeting a novel conserved epitope on the influenza virus H5N1 hemagglutinin. Journal of virology. 2013 Feb 15;87(4):2215-25.

Du L, Zhao G, Sun S, Zhang X, Zhou X, Guo Y, Li Y, Zhou Y, Jiang S. A critical HA1 neutralizing domain of H5N1 influenza in an optimal conformation induces strong cross-protection. PLoS One. 2013 Jan 8;8(1):e53568.

Du L, Leung VH, Zhang X, Zhou J, Chen M, He W, Zhang HY, Chan CC, Poon VK, Zhao G, Sun S. A recombinant vaccine of H5N1 HA1 fused with foldon and human IgG Fc induced complete cross-clade protection against divergent H5N1 viruses. PloS one. 2011 Jan 27;6(1):e16555

NYBC 647, 671 & 674: Immunogenic Composition for MERS coronavirus infection

Patent Numbers: 9889194, 11103575 and 2018094241

Title: IMMUNOGENIC COMPOSITION FOR MERS CORONAVIRUS INFECTION

United States Patent 9889194: IMMUNOGENIC COMPOSITION FOR MERS CORONAVIRUS INFECTION

United States Patent 11103575: IMMUNOGENIC COMPOSITION FOR MERS CORONAVIRUS INFECTION

United States Patent 2018094241: IMMUNOGENIC COMPOSITION FOR MERS CORONAVIRUS INFECTION

Investigator(s):  Lanying Du; Fang Li; Shibo Jiang; Yusen Zhou AND Shibo JIANG; Lanying Du; Yusen Zhou; Guangyu Zhao

Abstract: 

NYBC researchers have coined the concept of “neutralizing immunogenicity index” (NII) to determine an epitope’s immunogenicity and potential to induce neutralizing antibodies. By masking the epitope with a glycan probe and assessing its contribution to the vaccine’s overall neutralizing immunogenicity, the NII can be measured for different epitopes on an immunogen. Through this quantitative method, NYBC researchers have developed a variant form of a receptor-binding domain (RBD) vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV) by masking an epitope that has a negative NII score at residue T579N. This engineered vaccine has demonstrated significantly enhanced efficacy in protecting transgenic (hDPP4-Tg) mice from lethal MERS-CoV challenge. This technology also builds on this MERS-CoV RBD platform to include engineered vaccine candidates without the residue mutation and to include various immunopotentiating moieties such as IgG1 Fc. 

MERS-CoV is a highly pathogenic virus that has caused numerous outbreaks with significant morbidity and mortality. While there is currently no specific treatment or vaccine for MERS-CoV, the development of an effective vaccine is crucial to controlling future outbreaks and reducing the impact of the disease. 

Related Publications: 

Du L, Zhao G, He Y, Guo Y, Zheng BJ, Jiang S, Zhou Y. Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model. Vaccine. 2007 Apr 12;25(15):2832-8. 

Du L, Zhao G, Kou Z, Ma C, Sun S, Poon VK, Lu L, Wang L, Debnath AK, Zheng BJ, Zhou Y. Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development. Journal of virology. 2013 Sep 1;87(17):9939-42. 

Du L, Kou Z, Ma C, Tao X, Wang L, Zhao G, Chen Y, Yu F, Tseng CT, Zhou Y, Jiang S. A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines. PloS one. 2013 Dec 4;8(12):e81587. 

Jiang Y, Zhao G, Song N, Li P, Chen Y, Guo Y, Li J, Du L, Jiang S, Guo R, Sun S. Blockade of the C5a–C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV. Emerging microbes & infections. 2018 Dec 1;7(1):1-2 

NYBC 668: Biomarkers and Immunogenic Compositions for Filarial Parasites

Patent Number: Pending

Title: BIOMARKERS AND IMMUNOGENIC COMPOSTIIONS FOR FILARIAL PARASITES

Patent Pending: WO2017173369 BIOMAKERS AND IMMUNOGENIC COMPOSITIONS FOR FILARIAL PARASITES (wipo.int)

Investigator(s): Sara Lustigman; Thomas B. Nutman; Sasisekhar Bennuru

Abstract: 

NYBC researchers have developed novel immunogens that can be used to detect and prevent infection by Dirofilaria immitis, a parasite that causes heartworm disease in dogs. The composition is a series of immunogenic peptides derived from Onchocerca volvulus, with significant sequence homology to D. immitis. When administered to a canine subject at risk of D. immitis infection, the composition induces an immune response that may prevent infection. Additionally, these immunogens can be used for the development of lateral flow assays in order to detect anti-D. immitis antibodies in an infected animal. This scientific breakthrough has the potential to revolutionize heartworm detection and prevention in dogs and improve the health and well-being of millions of pets worldwide. 

There is an urgent need for an effective detection and prevention strategy in heartworm. Heartworm infection is a serious and potentially life-threatening condition for dogs, and prevention is key. Currently, there is a multi-billion dollar market in the US around the monthly prevention medications and post-infection treatment. However, there is significant evidence of increasing drug resistance in many regions where heartworm is endemic. Additionally, detection of infection relies on severe symptoms and expensive imaging. Therefore, it is particularly important to provide additional diagnostic and prophylactic options that might capitalize on the immune system of canines and provide a more long-term prevention strategy. 

Related Publications: 

Lustigman S, James ER, Tawe W, Abraham D. Towards a recombinant antigen vaccine against Onchocerca volvulus. Trends in parasitology. 2002 Mar 1;18(3):135-41. 

Lustigman S, Zhang J, Liu J, Oksov Y, Hashmi S. RNA interference targeting cathepsin L and Z-like cysteine proteases of Onchocerca volvulus confirmed their essential function during L3 molting. Molecular and biochemical parasitology. 2004 Dec 1;138(2):165-70.  

Hess JA, Zhan B, Bonne-Année S, Deckman JM, Bottazzi ME, Hotez PJ, Klei TR, Lustigman S, Abraham D. Vaccines to combat river blindness: expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model. International journal for parasitology. 2014 Aug 1;44(9):637-46. 

Grote A, Lustigman S, Ghedin E. Lessons from the genomes and transcriptomes of filarial nematodes. Molecular and biochemical parasitology. 2017 Jul 1;215:23-9. 

NYBC 684: ZIKA Virus Immunogenic Compositions

Patent Number: Pending

Title: ZIKA VIRUS IMMUNOGENIC COMPOSITIONS

Patent Pending: ZIKA VIRUS IMMUNOGENIC COMPOSITIONS

Investigator(s): Lanying Du, Wanbo Tai, Fang Li

Abstract:

NYBC researchers have developed a mutant Zika virus antigen that provides a highly potent neutralizing antibody response. This technology builds on the concept of “neutralizing immunogenicity index” (NII) to determine an epitope’s immunogenicity and potential to induce neutralizing antibodies. By masking the epitope with a glycan probe and assessing its contribution to the vaccine’s overall neutralizing immunogenicity, the NII can be measured for different epitopes on an immunogen. Through this quantitative method, NYBC researchers have developed a variant form of the EDIII polypeptide that has demonstrated a strong protective response in multiple in vivo lethal challenge models as well as through passive immunization via sera transfer. Importantly, this mutant EDIII polypeptide shows significant improvement over the native EDIII in preventing fetal development issues in challenged pregnant mice. 
 

Zika virus infection poses a significant global health threat, with transmission persisting in 89 countries globally. The existing prevention measures primarily focus on mosquito control and precautions for pregnant women due to the virus’s association with congenital birth defects. However, the development of a safe and efficacious Zika vaccine is crucial to provide widespread protection and mitigate the risk of Zika-related complication. 

Related Publications:

Tai W, He L, Wang Y, Sun S, Zhao G, Luo C, Li P, Zhao H, Fremont DH, Li F, Jiang S. Critical neutralizing fragment of Zika virus EDIII elicits cross-neutralization and protection against divergent Zika viruses. Emerging microbes & infections. 2018 Dec 1;7(1):1-8. 

Tai W, Chen J, Zhao G, Geng Q, He L, Chen Y, Zhou Y, Li F, Du L. Rational design of Zika virus subunit vaccine with enhanced efficacy. Journal of virology. 2019 Sep 1;93(17):10-128. 

Wang X, Tai W, Zhang X, Zhou Y, Du L, Shen C. Effects of adjuvants on the immunogenicity and efficacy of a Zika Virus envelope domain III subunit vaccine. Vaccines. 2019 Oct 27;7(4):161. 

NYBC 703 Substituted Heterocyclics with Therapeutic Activity in HIV

Patent Number: Pending

Title: SUBSTITUTED HETEROCYCLICS WITH THERAPEUTIC ACTIVITY IN HIV

Patent Pending: SUBSTITUTED HETEROCYCLICS WITH THERAPEUTIC ACTIVITY IN HIV

Investigator(s): Asim Kumar Debnath; Francesca Curreli

Abstract: 

NYBC researchers have discovered a new family of HIV fusion/entry small molecule inhibitors for the treatment of HIV infection. This technology is a family of salts that bind to envelope glycoprotein GP120 to prevent entry into host cells. These compounds can be formulated for oral delivery and provide an alternative for the prevention and treatment of HIV infection. 

Despite significant progress in the treatment and prevention of HIV, it remains a major global health concern, with an estimated 38 million people living with the virus worldwide. While current antiretroviral therapies (ARTs) are effective in controlling the virus, there are still significant limitations, including drug resistance, toxicity, and poor adherence. Moreover, the development of a vaccine against HIV has been challenging due to the high genetic variability of the virus and the lack of highly effective vaccine candidates. 

Related Publications: 

Curreli F, Belov DS, Do Kwon Y, Ramesh R, Furimsky AM, O’Loughlin K, Byrge PC, Iyer LV, Mirsalis JC, Kurkin AV, Altieri A. Structure-based lead optimization to improve antiviral potency and ADMET properties of phenyl-1H-pyrrole-carboxamide entry inhibitors targeted to HIV-1 gp120. European journal of medicinal chemistry. 2018 Jun 25;154:367-91. 

Iusupov IR, Curreli F, Spiridonov EA, Markov PO, Ahmed S, Belov DS, Manasova EV, Altieri A, Kurkin AV, Debnath AK. Design of gp120 HIV-1 entry inhibitors by scaffold hopping via isosteric replacements. European Journal of Medicinal Chemistry. 2021 Nov 15;224:113681. 

Curreli F, Kwon YD, Belov DS, Ramesh RR, Kurkin AV, Altieri A, Kwong PD, Debnath AK. Synthesis, antiviral potency, in vitro ADMET, and X-ray structure of potent CD4 mimics as entry inhibitors that target the Phe43 cavity of HIV-1 gp120. Journal of medicinal chemistry. 2017 Apr 13;60(7):3124-53. 

NYBC 706: Zika Virus Immunogenic Compositions

Patent Number: Pending

Title: ZIKA VIRUS IMMUNOGENIC COMPOSITIONS

Patent Pending: ZIKA VIRUS IMMUNOGENIC COMPOSITIONS

Investigator(s): Lanying Du; Liang Qiao; Frank Gambino; Wanbo Tai

Abstract: 

NYBC researchers have developed a Zika Virus vaccine for the protection of at-risk pregnant mothers and their fetuses while mitigating risk of antibody-dependent enhancement. This DNA vaccine induces only specific cytotoxic T lymphocytes, therefore circumventing antibody-dependent enhancement of Zika virus infection found when non-neutralizing antibodies are generated. This technology builds on our researchers’ expertise in protein engineering and immunology, resulting in ubiquinated and rearranged Zika non-structural protein that is processed immediately and degraded for presentation via MHC Class I.  This vaccine demonstrates efficacy in lethal challenge models in mice as well as demonstrated full protection of fetuses in pregnant mice. 

Zika virus infection poses a significant global health threat, with transmission persisting in 89 countries globally. The existing prevention measures primarily focus on mosquito control and precautions for pregnant women due to the virus’s association with congenital birth defects. Further, antibody dependent enhancement of disease remains a significant risk for patients previously infected or even for children with maternally acquired antibodies. Therefore, the development of a safe, efficacious Zika vaccine that focuses on cytotoxic T lymphocytes response rather than antibody response is crucial to provide widespread protection and mitigate the risk of Zika-related complication. 

Related Publications: 

Gambino F, Tai W, Voronin D, Zhang Y, Zhang X, Shi J, Wang X, Wang N, Du L, Qiao L. A vaccine inducing solely cytotoxic T lymphocytes fully prevents Zika virus infection and fetal damage. Cell reports. 2021 May 11;35(6). 

Gambino Jr F. Induction of Zika Virus-Specific Cd8+ T Cells by Means of DNA Vaccine (Doctoral dissertation, Loyola University Chicago). 

NYBC 672: Small Molecule Antagonists of PF4

Patent Number: Pending

Title: SMALL MOLECULE ANTAGONISTS OF PF4

Patent Pending: SMALL MOLECULE ANTAGONISTS OF PF4

Investigator(s): Bruce SACHAIS; Jay E. WROBEL; Allen B. REITZ; Steven E. MCKENZIE; Mark E. MCDONNELL; Haiyan BIAN; Thomas A. FORD-HUTCHINSON; Robert J. ROSANO; Yuhang ZHOU; Nandan MANDAYAM; Jennifer CLEMENS; Justin Sausker

Abstract:

NYBC researchers have developed a small molecule that inhibits immune complex formation between heparin and platelet factor 4 (PF4), thereby preventing the PF4 contribution to atherogenesis. Preliminary in vivo data using PF4 knockout athero-susceptible mice indicates that this mechanism of action may lower aortic atherosclerotic burden by 37%.  

Patients suffering from atherosclerosis exhibit activated platelets that release PF4. Remarkably, PF4 hinders the binding and degradation of LDL via its receptor, a process that may foster the generation of oxidized LDL (ox-LDL) and subsequent binding of ox-LDL to vascular cells. With approximately half of Americans aged 45 to 84 affected by atherosclerosis, it is a pervasive health concern. Atherosclerosis significantly contributes to cardiovascular disease, responsible for roughly 610,000 deaths annually in the United States alone. This technology has the potential to provide a novel therapeutic treatment to reduce mortality and morbidity in patients at-risk of atherosclerosis.  

Related Publications:

Sachais BS, Turrentine T, McKenna JM, Rux AH, Rader D, Kowalska AM. Elimination of platelet factor 4 (PF4) from platelets reduces atherosclerosis in C57Bl/6 and apoE-/-mice. Thrombosis and haemostasis. 2007;98(11):1108-13. 

Nassar T, Sachais BS, Akkawi SE, Kowalska MA, Bdeir K, Leitersdorf E, Hiss E, Ziporen L, Aviram M, Cines D, Poncz M. Platelet factor 4 enhances the binding of oxidized low-density lipoprotein to vascular wall cells. Journal of Biological Chemistry. 2003 Feb 21;278(8):6187-93. 

Sachais BS, Litvinov RI, Yarovoi SV, Rauova L, Hinds JL, Rux AH, Arepally GM, Poncz M, Cuker A, Weisel JW, Cines DB. Dynamic antibody-binding properties in the pathogenesis of HIT. Blood, The Journal of the American Society of Hematology. 2012 Aug 2;120(5):1137-42. 

Khandelwal S, Lee GM, Hester CG, Poncz M, McKenzie SE, Sachais BS, Rauova L, Kelsoe G, Cines DB, Frank M, Arepally GM. The antigenic complex in HIT binds to B cells via complement and complement receptor 2 (CD21). Blood, The Journal of the American Society of Hematology. 2016 Oct 6;128(14):1789-99. 

NYBC 675: Engineered Red Blood Cells Having Rare Antigen Phenotypes

Patent Number: Pending

Title: ENGINEERED RED BLOOD CELLS HAVING RARE ANTIGEN PHENOTYPES

Patent Pending: ENGINEERED RED BLOOD CELLS HAVING RARE ANTIGEN PHENOTYPES

Investigator(s):Stella Chou, Connie Westoff

Abstract:

NYBC researchers have developed a series of recombinant reagent cultured red blood cells (cRBCs) to standardize antibody testing and identify alloimmunization likelihood. These engineered red blood cells exhibit distinct blood antigen group profiles, including rare blood antigen groups. The technology allows for the generation of a diverse panel of antigenically distinct cRBCs, potentially encompassing up to fifteen distinct blood antigen groups.

Each year, approximately 29 million units of blood components are transfused annually in the United States. One of the largest challenges arises from the high rate of alloimmunization in transfused patients, particularly among individuals of African descent with hereditary anemia. The genetic diversity of blood group antigens in these patients, compared to the primarily European-based blood donor pool, contributes to the complexity and incidence of antibodies. Currently, the method used to screen for all-antibodies is complex, costly, and lacks standardization. Providing an improved testing system for the antibody identification in allo-immunized multiply transfused patients would improve care and reduce costs for patients suffering from blood disorders.

Related Publications:

An HH, Gagne AL, Maguire JA, Pavani G, Abdulmalik O, Gadue P, French DL, Westhoff CM, Chou ST. The use of pluripotent stem cells to generate diagnostic tools for transfusion medicine. Blood, The Journal of the American Society of Hematology. 2022 Oct 13;140(15):1723-34.

Lane WJ, Vege S, Mah HH, Lomas‐Francis C, Aguad M, Smeland‐Wagman R, Koch C, Killian JM, Gardner CL, De Castro M, Lebo MS. Automated typing of red blood cell and platelet antigens from whole exome sequences. Transfusion. 2019 Oct;59(10):3253-63.

Lane WJ, Westhoff CM, Gleadall NS, Aguad M, Smeland-Wagman R, Vege S, Simmons DP, Mah HH, Lebo MS, Walter K, Soranzo N. Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study. The Lancet Haematology. 2018 Jun 1;5(6):e241-51.

Chou ST, Flanagan JM, Vege S, Luban NL, Brown RC, Ware RE, Westhoff CM. Whole-exome sequencing for RH genotyping and alloimmunization risk in children with sickle cell anemia. Blood Advances. 2017 Aug 8;1(18):1414-22.

NYBC 712: Ferroportin-Inhibitors For The Use In The Treatment Of Myelodysplastic Syndromes (MDS)

Patent Number: Pending

Title: FERROPORTIN-INHIBTORS FOR THE USE IN THE TREATMENT OF MYELODYSPLASTIC SYNDROMES (MDS)

Patent Pending: FERROPORTIN-INHIBTORS FOR THE USE IN THE TREATMENT OF MYELODYSPLASTIC SYNDROMES (MDS)

Investigator(s): Francesa Vinchi

Abstract: 

NYBC researchers have unveiled a groundbreaking application for ferroportin inhibitors in the treatment of myelodysplastic syndromes (MDS), a group of disorders characterized by abnormal blood cell production in the bone marrow. MDS patients often suffer from iron overload due to ineffective erythropoiesis, which currently necessitates iron chelation therapy, a treatment approach fraught with limitations such as cost, administration challenges, and potential toxicities. The novel innovation here presents a series of compounds designed to target ferroportin, mitigating iron overload and subsequently reducing the risk of adverse outcomes associated with MDS. 

The pressing need for an effective solution to iron overload in MDS patients is underscored by the staggering prevalence of these disorders in the United States. With around 15,000 new MDS cases diagnosed each year and a substantial proportion experiencing iron overload, the urgency for innovative interventions becomes evident. The proposed technology not only offers the potential to alleviate iron-related complications but also opens new avenues for enhancing the well-being of MDS patients. By specifically addressing the iron imbalance inherent in these conditions, this breakthrough promises a transformative approach to managing MDS-associated challenges, highlighting the significant potential to enhance patient outcomes and quality of life. 

Related Publications: 

Ginzburg YZ, Vinchi F. Iron overload. In Transfusion Medicine and Hemostasis 2019 Jan 1 (pp. 433-436). Elsevier. 

Vinchi F, Porto G, Simmelbauer A, Altamura S, Passos ST, Garbowski M, Silva AM, Spaich S, Seide SE, Sparla R, Hentze MW. Atherosclerosis is aggravated by iron overload and ameliorated by dietary and pharmacological iron restriction. European heart journal. 2020 Jul 21;41(28):2681-95. 

Vinchi F, Hell S, Platzbecker U. Controversies on the consequences of iron overload and chelation in MDS. Hemasphere. 2020 Jun;4(3).