# data[].attributes.title
Monoclonal Antibody for Specific Detection of the Transcription Factor Eos (Ikzf4) in Regulatory T Cells

# data[].attributes.body.value
Regulatory T cells (Tregs) are immune cells that keep the immune system balanced and prevent autoimmunity. Tregs depend on a protein called Eos (Ikzf4) that helps turn genes on and off for their development and function, but until now, antibodies used to detect and study Eos were unreliable.
Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) have created monoclonal antibody 18H2 to accurately detect Eos in mouse and human Treg cells. To make 18H2, they immunized hamsters with a segment of the Eos protein and used advanced techniques to select the best antibody-producing cells. The resulting 18H2 antibody specifically detects Eos and does not react with cells lacking Eos.
The 18H2 antibody stands out by reliably detecting both human and mouse Eos and performing better in laboratory tests, such as flow cytometry, used to analyze Treg cells. This technology offers a powerful new way to study Treg cell development and how Eos helps protect against autoimmune conditions.

# data[].attributes.body.processed
Regulatory T cells (Tregs) are immune cells that keep the immune system balanced and prevent autoimmunity. Tregs depend on a protein called Eos (Ikzf4) that helps turn genes on and off for their development and function, but until now, antibodies used to detect and study Eos were unreliable.
Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) have created monoclonal antibody 18H2 to accurately detect Eos in mouse and human Treg cells. To make 18H2, they immunized hamsters with a segment of the Eos protein and used advanced techniques to select the best antibody-producing cells. The resulting 18H2 antibody specifically detects Eos and does not react with cells lacking Eos.
The 18H2 antibody stands out by reliably detecting both human and mouse Eos and performing better in laboratory tests, such as flow cytometry, used to analyze Treg cells. This technology offers a powerful new way to study Treg cell development and how Eos helps protect against autoimmune conditions.

# data[].attributes.field_collaboration_description.value
The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Areas of specific interest include (a) application in pre-clinical models of autoimmunity, cancer, and transplantation, (b) development of diagnostic assays for immune monitoring and biomarker discovery, and (c) inclusion in high-throughput screening platforms for drug discovery targeting Treg pathways. For collaboration opportunities, please contact Yogikala Prabhu at 202-365-4785, or yogikala.prabhu@nih.gov.

# data[].attributes.field_collaboration_description.processed
The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Areas of specific interest include (a) application in pre-clinical models of autoimmunity, cancer, and transplantation, (b) development of diagnostic assays for immune monitoring and biomarker discovery, and (c) inclusion in high-throughput screening platforms for drug discovery targeting Treg pathways. For collaboration opportunities, please contact Yogikala Prabhu at 202-365-4785, or yogikala.prabhu@nih.gov.

# data[].attributes.field_commercial_applications.value
Development of tests that track Treg cell function and Eos protein levels in patients and monitor Eos levels in autoimmune diseases, cancer treatments, and organ transplants.

# data[].attributes.field_commercial_applications.processed
Development of tests that track Treg cell function and Eos protein levels in patients and monitor Eos levels in autoimmune diseases, cancer treatments, and organ transplants.

# data[].attributes.field_competitive_advantages.value
Eos-specific detection, confirmed by lack of reactivity in cells that lack Eos.

Detection of both mouse and human Eos, enabling application to human research.

Precise detection and measurement of Treg cells in diverse sample types.

# data[].attributes.field_competitive_advantages.processed
Eos-specific detection, confirmed by lack of reactivity in cells that lack Eos.

Detection of both mouse and human Eos, enabling application to human research.

Precise detection and measurement of Treg cells in diverse sample types.

# data[].attributes.field_licensingcontact_hrefs[]
yogikala.prabhu@nih.gov?subject=Web Inquiry on [TAB-5103] Monoclonal Antibody for Specific Detection of the Transcription Factor Eos (Ikzf4) in Regulatory T Cells&body=Please send me information about technology [TAB-5103] Monoclonal Antibody for Specific Detection of the Transcription Factor Eos (Ikzf4) in Regulatory T Cells.

# data[].attributes.field_licensingcontact_htmls[]
Prabhu, Yogikala
yogikala.prabhu@nih.gov

# data[].attributes.field_licensing_contacts[].value
Prabhu, Yogikala
yogikala.prabhu@nih.gov

# data[].attributes.field_licensing_contacts[].processed
Prabhu, Yogikala
yogikala.prabhu@nih.gov

# data[].attributes.field_licensing_contacts_uris[]
yogikala.prabhu@nih.gov?subject=Web Inquiry on [TAB-5103] Monoclonal Antibody for Specific Detection of the Transcription Factor Eos (Ikzf4) in Regulatory T Cells&body=Please send me information about technology [TAB-5103] Monoclonal Antibody for Specific Detection of the Transcription Factor Eos (Ikzf4) in Regulatory T Cells.

# data[].attributes.field_publications[].value
Xie X, et al. Eos plays a critical role in Treg homeostasis and modulates the function of recirculating thymic Tregs in the control of Treg development. Cell Rep. 2026;45(1):116838. (doi:10.1016/j.celrep.2025.116838)

# data[].attributes.field_publications[].processed
Xie X, et al. Eos plays a critical role in Treg homeostasis and modulates the function of recirculating thymic Tregs in the control of Treg development. Cell Rep. 2026;45(1):116838. (doi:10.1016/j.celrep.2025.116838)

# data[].attributes.field_technology_names[]
Anti-mouse Ikzf4 (Eos) Monoclonal Antibody

# data[].attributes.field_technology_owners[]
National Institute of Allergy and Infectious Diseases (NIAID/NIH), NIAID - DIR

# data[].attributes.body.value
Rotavirus is a major cause of severe diarrhea and dehydration in infants and young children. Vaccines that cover the most important rotavirus serotypes could help reduce serious illness worldwide.

Researchers at NIAID’s Laboratory of Infectious Diseases developed a multivalent human-bovine reassortant rotavirus vaccine using vaccine strains created by combining selected genes from human and bovine (cow) rotaviruses. This approach targets the most important rotavirus serotypes at once, including G1, G2, G3, and G4, with the potential to expand coverage to G5, G9, and G10.

These multivalent vaccine candidates trigger immune responses against multiple rotavirus serotypes in a single formulation at lower doses than earlier human-bovine vaccine approaches. The multivalent formulation does not cause the low-grade, short-lived fever seen with prior candidates.

# data[].attributes.body.processed
Rotavirus is a major cause of severe diarrhea and dehydration in infants and young children. Vaccines that cover the most important rotavirus serotypes could help reduce serious illness worldwide.

Researchers at NIAID’s Laboratory of Infectious Diseases developed a multivalent human-bovine reassortant rotavirus vaccine using vaccine strains created by combining selected genes from human and bovine (cow) rotaviruses. This approach targets the most important rotavirus serotypes at once, including G1, G2, G3, and G4, with the potential to expand coverage to G5, G9, and G10.

These multivalent vaccine candidates trigger immune responses against multiple rotavirus serotypes in a single formulation at lower doses than earlier human-bovine vaccine approaches. The multivalent formulation does not cause the low-grade, short-lived fever seen with prior candidates.

# data[].attributes.field_collaboration_description.value
The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. For collaboration opportunities, please contact Elizabeth Pitts at 240–669–5299, or elizabeth.pitts@nih.gov.

# data[].attributes.field_collaboration_description.processed
The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. For collaboration opportunities, please contact Elizabeth Pitts at 240–669–5299, or elizabeth.pitts@nih.gov.

# data[].attributes.field_commercial_applications.value
Multivalent rotavirus vaccine that covers several clinically important rotavirus serotypes in a single product, including G1, G2, G3, and G4, with potential to expand coverage to the additional serotypes G5, G9, and G10.

# data[].attributes.field_commercial_applications.processed
Multivalent rotavirus vaccine that covers several clinically important rotavirus serotypes in a single product, including G1, G2, G3, and G4, with potential to expand coverage to the additional serotypes G5, G9, and G10.

# data[].attributes.field_competitive_advantages.value
Designed for lower-dose immunogenicity than earlier human-bovine reassortant approaches described in the literature.

No low-grade, transient fever observed compared with prior candidates.

Flexible reassortant design that may support addition of newly important rotavirus serotypes.

# data[].attributes.field_competitive_advantages.processed
Designed for lower-dose immunogenicity than earlier human-bovine reassortant approaches described in the literature.

No low-grade, transient fever observed compared with prior candidates.

Flexible reassortant design that may support addition of newly important rotavirus serotypes.

# data[].attributes.field_inventor_companies[]
National Institute of Allergy and Infectious Diseases (NIAID/NIH)

# data[].attributes.field_inventor_companies[]
National Institute of Allergy and Infectious Diseases (NIAID/NIH)

# data[].attributes.field_inventor_companies[]
National Institute of Allergy and Infectious Diseases (NIAID/NIH)

# data[].attributes.field_licensingcontact_hrefs[]
elizabeth.pitts@nih.gov?subject=Web Inquiry on [TAB-5101] Human-Bovine Reassortant Rotavirus Vaccine&body=Please send me information about technology [TAB-5101] Human-Bovine Reassortant Rotavirus Vaccine.

# data[].attributes.field_licensingcontact_htmls[]
Pitts, Elizabeth
elizabeth.pitts@nih.gov

# data[].attributes.field_licensing_contacts[].value
Pitts, Elizabeth
elizabeth.pitts@nih.gov

# data[].attributes.field_licensing_contacts[].processed
Pitts, Elizabeth
elizabeth.pitts@nih.gov

# data[].attributes.field_licensing_contacts_uris[]
elizabeth.pitts@nih.gov?subject=Web Inquiry on [TAB-5101] Human-Bovine Reassortant Rotavirus Vaccine&body=Please send me information about technology [TAB-5101] Human-Bovine Reassortant Rotavirus Vaccine.

# data[].attributes.field_patents[].value
US
Provisional (PRV) 60/094,425
Filed on 1998-07-28
Status: Abandoned

# data[].attributes.field_patents[].processed
US
Provisional (PRV) 60/094,425
Filed on 1998-07-28
Status: Abandoned

# data[].attributes.field_patents[].value
Patent Cooperation Treaty
(PCT) PCT/US1999/017036
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
Patent Cooperation Treaty
(PCT) PCT/US1999/017036
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
US Patent 7,932,074
Filed on 2001-01-04
Status: Expired

# data[].attributes.field_patents[].processed
US Patent 7,932,074
Filed on 2001-01-04
Status: Expired

# data[].attributes.field_patents[].value
Australia
National Stage 53221/99
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
Australia
National Stage 53221/99
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
Brazil
National Stage PI9912485-8
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
Brazil
National Stage PI9912485-8
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
Canada
National Stage 2336875
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
Canada
National Stage 2336875
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
China
National Stage 99810311.X
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
China
National Stage 99810311.X
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
European Patent
National Stage 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
European Patent
National Stage 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
India
National Stage IN/PCT/2001/0106/CHE
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
India
National Stage IN/PCT/2001/0106/CHE
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
Japan
National Stage 2000-562050
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
Japan
National Stage 2000-562050
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
South Korea
National Stage 10-2001-7001236
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
South Korea
National Stage 10-2001-7001236
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
Germany
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
Germany
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
France
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
France
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
United Kingdom
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
United Kingdom
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
Ireland
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
Ireland
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
Italy
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].processed
Italy
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patents[].value
China
Divisional (DIV) 200810090397.2
Filed on 2008-04-11
Status: Expired

# data[].attributes.field_patents[].processed
China
Divisional (DIV) 200810090397.2
Filed on 2008-04-11
Status: Expired

# data[].attributes.field_patents[].value
Japan
Divisional (DIV) 2009-148918
Filed on 2009-06-23
Status: Abandoned

# data[].attributes.field_patents[].processed
Japan
Divisional (DIV) 2009-148918
Filed on 2009-06-23
Status: Abandoned

# data[].attributes.field_patent_htmls[]
US
Provisional (PRV) 60/094,425
Filed on 1998-07-28
Status: Abandoned

# data[].attributes.field_patent_htmls[]
Patent Cooperation Treaty
(PCT) PCT/US1999/017036
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
US Patent 7,932,074
Filed on 2001-01-04
Status: Expired

# data[].attributes.field_patent_htmls[]
Australia
National Stage 53221/99
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
Brazil
National Stage PI9912485-8
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
Canada
National Stage 2336875
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
China
National Stage 99810311.X
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
European Patent
National Stage 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
India
National Stage IN/PCT/2001/0106/CHE
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
Japan
National Stage 2000-562050
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
South Korea
National Stage 10-2001-7001236
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
Germany
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
France
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
United Kingdom
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
Ireland
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
Italy
European patent (EP) 99938819.2
Filed on 1999-07-27
Status: Expired

# data[].attributes.field_patent_htmls[]
China
Divisional (DIV) 200810090397.2
Filed on 2008-04-11
Status: Expired

# data[].attributes.field_patent_htmls[]
Japan
Divisional (DIV) 2009-148918
Filed on 2009-06-23
Status: Abandoned

# data[].attributes.title
Human antibodies with anti-lymphocyte specificities and lytic activity

# data[].attributes.body.value
Antibody therapies that target human B cells are a promising way to treat diseases like B-cell cancers and autoimmune conditions like lupus and multiple sclerosis. Traditionally, these antibodies are made in animals and modified to resemble human antibodies to reduce immune rejection. Researchers in the Laboratory of Immunoregulation (LIR) at the National Institute of Allergy and Infectious Diseases (NIAID) have developed a new approach of using blood plasma from a patient with the rare immune disorder idiopathic CD4 lymphocytopenia (ICL) to find naturally occurring human antibodies.

By using advanced genetic sequencing, the researchers discovered and reproduced several new antibodies that could effectively attack and kill B-cell tumors, normal B cells, and T cells, demonstrating potential for eliminating cancerous or disease-causing immune cells. One potent antibody, NIH58.9, killed B cells at low concentrations of 0.01 nanomolar. These new antibodies may be used as treatments, combined with other therapies, or engineered into special formats like bispecific antibodies or antibody-drug conjugates.

# data[].attributes.body.processed
Antibody therapies that target human B cells are a promising way to treat diseases like B-cell cancers and autoimmune conditions like lupus and multiple sclerosis. Traditionally, these antibodies are made in animals and modified to resemble human antibodies to reduce immune rejection. Researchers in the Laboratory of Immunoregulation (LIR) at the National Institute of Allergy and Infectious Diseases (NIAID) have developed a new approach of using blood plasma from a patient with the rare immune disorder idiopathic CD4 lymphocytopenia (ICL) to find naturally occurring human antibodies.

By using advanced genetic sequencing, the researchers discovered and reproduced several new antibodies that could effectively attack and kill B-cell tumors, normal B cells, and T cells, demonstrating potential for eliminating cancerous or disease-causing immune cells. One potent antibody, NIH58.9, killed B cells at low concentrations of 0.01 nanomolar. These new antibodies may be used as treatments, combined with other therapies, or engineered into special formats like bispecific antibodies or antibody-drug conjugates.

# data[].attributes.field_collaboration_description.value
The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. For collaboration opportunities, please contact Benjamin Hurley at 240-276-5489, or benjamin.hurley@nih.gov.

# data[].attributes.field_collaboration_description.processed
The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. For collaboration opportunities, please contact Benjamin Hurley at 240-276-5489, or benjamin.hurley@nih.gov.

# data[].attributes.field_commercial_applications.value
Development of monoclonal antibody therapies, bispecific antibodies, and antibody-targeted drugs for use in organ transplantation, B-cell lymphomas, and autoimmune conditions

# data[].attributes.field_commercial_applications.processed
Development of monoclonal antibody therapies, bispecific antibodies, and antibody-targeted drugs for use in organ transplantation, B-cell lymphomas, and autoimmune conditions

# data[].attributes.field_competitive_advantages.value
First fully human IgM antibody that binds to and kills B cells

Fully human monoclonal antibodies eliminating humanization steps associated with antibodies derived from animal models and lowering risk of anti-drug antibody response

B-cell death observed at concentrations as low as 0.01Nm

Versatile antibody that may be used directly, engineered as IgG1 antibody, and possibly developed into bispecifics or antibody-drug conjugates

# data[].attributes.field_competitive_advantages.processed
First fully human IgM antibody that binds to and kills B cells

Fully human monoclonal antibodies eliminating humanization steps associated with antibodies derived from animal models and lowering risk of anti-drug antibody response

B-cell death observed at concentrations as low as 0.01Nm

Versatile antibody that may be used directly, engineered as IgG1 antibody, and possibly developed into bispecifics or antibody-drug conjugates

# data[].attributes.field_inventor_companies[]
National Institute of Allergy and Infectious Diseases (NIAID/NIH)

# data[].attributes.field_licensingcontact_hrefs[]
benjamin.hurley@nih.gov?subject=Web Inquiry on [TAB-5100] Human antibodies with anti-lymphocyte specificities and lytic activity&body=Please send me information about technology [TAB-5100] Human antibodies with anti-lymphocyte specificities and lytic activity.

# data[].attributes.field_licensingcontact_htmls[]
Hurley, Benjamin
benjamin.hurley@nih.gov

# data[].attributes.field_licensing_contacts[].value
Hurley, Benjamin
benjamin.hurley@nih.gov

# data[].attributes.field_licensing_contacts[].processed
Hurley, Benjamin
benjamin.hurley@nih.gov

# data[].attributes.field_licensing_contacts_uris[]
benjamin.hurley@nih.gov?subject=Web Inquiry on [TAB-5100] Human antibodies with anti-lymphocyte specificities and lytic activity&body=Please send me information about technology [TAB-5100] Human antibodies with anti-lymphocyte specificities and lytic activity.

# data[].attributes.field_patents[].value
US
Provisional (PRV) 63/787,190
Filed on 2025-04-11
Status: Expired

# data[].attributes.field_patents[].processed
US
Provisional (PRV) 63/787,190
Filed on 2025-04-11
Status: Expired

# data[].attributes.field_patents[].value
Patent Cooperation Treaty
(PCT) PCT/US2026/022767
Filed on 2026-04-08
Status: Pending

# data[].attributes.field_patents[].processed
Patent Cooperation Treaty
(PCT) PCT/US2026/022767
Filed on 2026-04-08
Status: Pending

# data[].attributes.field_patent_htmls[]
US
Provisional (PRV) 63/787,190
Filed on 2025-04-11
Status: Expired

# data[].attributes.field_patent_htmls[]
Patent Cooperation Treaty
(PCT) PCT/US2026/022767
Filed on 2026-04-08
Status: Pending

# data[].attributes.field_patent_titles[]
MONOCLONAL ANTI-LYMPHOCYTE ANTIBODIES AND THEIR USE

# data[].attributes.field_patent_titles[]
MONOCLONAL ANTI-LYMPHOCYTE ANTIBODIES AND THEIR USE

# data[].attributes.field_technology_names[]
Human antibodies with anti-lymphocyte specificities and lytic activity linked to ICL.

# data[].attributes.field_technology_owners[]
National Institute of Allergy and Infectious Diseases (NIAID/NIH), NIAID - DIR

# data[].attributes.title
Chimeric Adaptor Proteins (CAPs) Containing a Linker for Activation of T Cells (LAT) and a Kinase Domain for Use in T Cell-Based Immunotherapy

# data[].attributes.body.value
T cell immunotherapy is used in the treatment of various pathologies – including cancers and infections. Current therapies employ chimeric antigen receptors (CARs) consisting of the intracellular fragment of CD3-zeta as the signaling domain with varied combinations of co-stimulatory, transmembrane, spacer/hinge, and extracellular targeting domains. While effective in treating hematological malignancies, CAR T cells need to be activated through T cell receptor (TCR) activation. Such activation is subject to various regulatory and inhibitory mechanisms that can limit their full therapeutic potential. Moreover, CAR T cells are less effective in the treatment of solid tumors due to exhaustion. There remains a need for effective immunotherapies to treat solid tumors as well as hematological malignancies. Researchers at the National Cancer Institute (NCI) have found that after T cell receptor (TCR) activation, the linker for activation of T cells (LAT) forms a distinct signaling complex and its formation is sufficient to cause full T-cell activation independent of the TCR complex. As activation of the TCR complex is highly regulated by a number of competing kinases and phosphatases, the downstream LAT molecule offers several advantages over CD3-zeta as the signaling domain in CARs.

Researchers at the NCI have developed chimeric adaptor proteins (CAPs) consisting of an extracellular targeting domain, transmembrane domain, intracellular LAT domain, and the kinase domain of ZAP70. The inventors have observed that the formation of these complexes is sufficient to cause full T-cell activation independent of TCR activation. It is expected that the circumvention of the regulatory mechanisms targeting upstream TCR activation will increase the potency of T-cell signaling and the sensitivity of immunotherapy. Furthermore, T cells prepared with these recombinant molecules may be more resistant to exhaustion by molecules targeting TCR activation, and tunable, as the activity of the kinase domain can be altered with small molecules.

The Laboratory of Cellular and Molecular Biology, is seeking statements of capability or interest from parties interested in licensing this invention and/or collaborative research to further develop, evaluate, or commercialize CAPs for the treatment of solid tumors and hematological malignancies.

Competitive Advantages:

Potential for demonstrable efficacy against solid cancers previously refractory to cellular immunotherapy via:

Signaling through LAT allows circumvention of regulatory and inhibitory mechanisms involved in TCR activation

Directly triggering the downstream signaling cascade could cause more potent activation of T cells

LAT-based CAP-expressing T cells may be more resistant to PD-1-mediated T-cell exhaustion

Signaling from CAPs consisting of LAT and ZAP70 kinase domain may be tunable

Commercial Applications:

Treatment of hematological malignancies and solid tumors

Therapeutic use as a combination therapy with immune checkpoint inhibitors and/or chemotherapy

# data[].attributes.body.processed
T cell immunotherapy is used in the treatment of various pathologies – including cancers and infections. Current therapies employ chimeric antigen receptors (CARs) consisting of the intracellular fragment of CD3-zeta as the signaling domain with varied combinations of co-stimulatory, transmembrane, spacer/hinge, and extracellular targeting domains. While effective in treating hematological malignancies, CAR T cells need to be activated through T cell receptor (TCR) activation. Such activation is subject to various regulatory and inhibitory mechanisms that can limit their full therapeutic potential. Moreover, CAR T cells are less effective in the treatment of solid tumors due to exhaustion. There remains a need for effective immunotherapies to treat solid tumors as well as hematological malignancies. Researchers at the National Cancer Institute (NCI) have found that after T cell receptor (TCR) activation, the linker for activation of T cells (LAT) forms a distinct signaling complex and its formation is sufficient to cause full T-cell activation independent of the TCR complex. As activation of the TCR complex is highly regulated by a number of competing kinases and phosphatases, the downstream LAT molecule offers several advantages over CD3-zeta as the signaling domain in CARs.

Researchers at the NCI have developed chimeric adaptor proteins (CAPs) consisting of an extracellular targeting domain, transmembrane domain, intracellular LAT domain, and the kinase domain of ZAP70. The inventors have observed that the formation of these complexes is sufficient to cause full T-cell activation independent of TCR activation. It is expected that the circumvention of the regulatory mechanisms targeting upstream TCR activation will increase the potency of T-cell signaling and the sensitivity of immunotherapy. Furthermore, T cells prepared with these recombinant molecules may be more resistant to exhaustion by molecules targeting TCR activation, and tunable, as the activity of the kinase domain can be altered with small molecules.

The Laboratory of Cellular and Molecular Biology, is seeking statements of capability or interest from parties interested in licensing this invention and/or collaborative research to further develop, evaluate, or commercialize CAPs for the treatment of solid tumors and hematological malignancies.

Competitive Advantages:

Potential for demonstrable efficacy against solid cancers previously refractory to cellular immunotherapy via:

Signaling through LAT allows circumvention of regulatory and inhibitory mechanisms involved in TCR activation

Directly triggering the downstream signaling cascade could cause more potent activation of T cells

LAT-based CAP-expressing T cells may be more resistant to PD-1-mediated T-cell exhaustion

Signaling from CAPs consisting of LAT and ZAP70 kinase domain may be tunable

Commercial Applications:

Treatment of hematological malignancies and solid tumors

Therapeutic use as a combination therapy with immune checkpoint inhibitors and/or chemotherapy

# data[].attributes.field_licensingcontact_hrefs[]
suna.gulay@nih.gov?subject=Web Inquiry on [TAB-3924] Chimeric Adaptor Proteins (CAPs) Containing a Linker for Activation of T Cells (LAT) and a Kinase Domain for Use in T Cell-Based Immunotherapy&body=Please send me information about technology [TAB-3924] Chimeric Adaptor Proteins (CAPs) Containing a Linker for Activation of T Cells (LAT) and a Kinase Domain for Use in T Cell-Based Immunotherapy.&cc=michael.salgaller@nih.gov, tdiaz@mail.nih.gov

# data[].attributes.field_licensingcontact_htmls[]
Gulay French, Suna
suna.gulay@nih.gov

# data[].attributes.field_licensing_contacts[].value
Gulay French, Suna
suna.gulay@nih.gov

# data[].attributes.field_licensing_contacts[].processed
Gulay French, Suna
suna.gulay@nih.gov

# data[].attributes.field_licensing_contacts_uris[]
suna.gulay@nih.gov?subject=Web Inquiry on [TAB-3924] Chimeric Adaptor Proteins (CAPs) Containing a Linker for Activation of T Cells (LAT) and a Kinase Domain for Use in T Cell-Based Immunotherapy&body=Please send me information about technology [TAB-3924] Chimeric Adaptor Proteins (CAPs) Containing a Linker for Activation of T Cells (LAT) and a Kinase Domain for Use in T Cell-Based Immunotherapy.&cc=michael.salgaller@nih.gov, tdiaz@mail.nih.gov

# data[].attributes.field_patents[].value
Patent Cooperation Treaty
(PCT) PCT/US2020/022752
Filed on 2020-03-13
Status: Expired

# data[].attributes.field_patents[].processed
Patent Cooperation Treaty
(PCT) PCT/US2020/022752
Filed on 2020-03-13
Status: Expired

# data[].attributes.field_patents[].value
US
Provisional (PRV) 62/819,386
Filed on 2019-03-15
Status: Abandoned

# data[].attributes.field_patents[].processed
US
Provisional (PRV) 62/819,386
Filed on 2019-03-15
Status: Abandoned

# data[].attributes.field_patents[].value
European Patent
National Stage 20718061.3
Filed on 2020-03-13
Status: Pending

# data[].attributes.field_patents[].processed
European Patent
National Stage 20718061.3
Filed on 2020-03-13
Status: Pending

# data[].attributes.field_patents[].value
China
National Stage 202080021582.5
Filed on 2020-03-13
Status: Pending

# data[].attributes.field_patents[].processed
China
National Stage 202080021582.5
Filed on 2020-03-13
Status: Pending

# data[].attributes.field_patents[].value
Hong Kong
European patent (EP) 62022051308.4
Filed on 2020-03-13
Status: Pending

# data[].attributes.field_patents[].processed
Hong Kong
European patent (EP) 62022051308.4
Filed on 2020-03-13
Status: Pending

# data[].attributes.field_patents[].value
US
Continuation in Part (CIP) 17/475,810
Filed on 2021-09-15
Status: Pending

# data[].attributes.field_patents[].processed
US
Continuation in Part (CIP) 17/475,810
Filed on 2021-09-15
Status: Pending

# data[].attributes.field_patents[].value
Patent Cooperation Treaty
(PCT) PCT/US2022/076358
Filed on 2022-09-13
Status: Expired

# data[].attributes.field_patents[].processed
Patent Cooperation Treaty
(PCT) PCT/US2022/076358
Filed on 2022-09-13
Status: Expired

# data[].attributes.field_patent_htmls[]
Patent Cooperation Treaty
(PCT) PCT/US2020/022752
Filed on 2020-03-13
Status: Expired

# data[].attributes.field_patent_htmls[]
US
Provisional (PRV) 62/819,386
Filed on 2019-03-15
Status: Abandoned

# data[].attributes.field_patent_htmls[]
European Patent
National Stage 20718061.3
Filed on 2020-03-13
Status: Pending

# data[].attributes.field_patent_htmls[]
China
National Stage 202080021582.5
Filed on 2020-03-13
Status: Pending

# data[].attributes.field_patent_htmls[]
Hong Kong
European patent (EP) 62022051308.4
Filed on 2020-03-13
Status: Pending

# data[].attributes.field_patent_htmls[]
US
Continuation in Part (CIP) 17/475,810
Filed on 2021-09-15
Status: Pending

# data[].attributes.field_patent_htmls[]
Patent Cooperation Treaty
(PCT) PCT/US2022/076358
Filed on 2022-09-13
Status: Expired

# data[].attributes.field_patent_titles[]
CHIMERIC ADAPTOR AND KINASE SIGNALING PROTEINS AND THEIR USE IN IMMUNOTHERAPY

# data[].attributes.field_patent_titles[]
RECOMBINANT MOLECULES CONTAINING LINKER FOR ACTIVATION OF T CELLS AND THEIR USE IN IMMUNOTHERAPY

# data[].attributes.field_patent_titles[]
CHIMERIC ADAPTOR AND KINASE SIGNALING PROTEINS AND THEIR USE IN IMMUNOTHERAPY

# data[].attributes.field_patent_titles[]
CHIMERIC ADAPTOR AND KINASE SIGNALING PROTEINS AND THEIR USE IN IMMUNOTHERAPY

# data[].attributes.field_patent_titles[]
CHIMERIC ADAPTOR AND KINASE SIGNALING PROTEINS AND THEIR USE IN IMMUNOTHERAPY

# data[].attributes.field_patent_titles[]
CHIMERIC ADAPTOR AND KINASE SIGNALING PROTEINS  AND THEIR USE IN IMMUNOTHERAPY

# data[].attributes.field_patent_titles[]
Chimeric adaptor and kinase signaling proteins and their use in immunotherapy

# data[].attributes.field_publications[].value
Yi J, et al. TCR microclusters form spatially segregated domains and sequentially assemble in calcium-dependent kinetic steps

# data[].attributes.field_publications[].processed
Yi J, et al. TCR microclusters form spatially segregated domains and sequentially assemble in calcium-dependent kinetic steps

# data[].attributes.field_publications[].value
Balagopalan L, et al. Plasma membrane LAT activation precedes vesicular recruitment defining two phases of early T-cell activation

# data[].attributes.field_publications[].processed
Balagopalan L, et al. Plasma membrane LAT activation precedes vesicular recruitment defining two phases of early T-cell activation

# data[].attributes.field_publications[].value
Balagopalan L, et al. Generation of antitumor chimeric antigen receptors incorporating T cell signaling motifs (PMID: 39042728)

# data[].attributes.field_publications[].processed
Balagopalan L, et al. Generation of antitumor chimeric antigen receptors incorporating T cell signaling motifs (PMID: 39042728)

# data[].attributes.field_related_inventions[].processed
E-159-2009

# data[].attributes.field_technology_names[]
Recombinant Molecule Containing LAT For Use In T Cell Immunotherapy

# data[].attributes.field_technology_names[]
Chimeric Adaptor Proteins (CAPs) For Improved T-Cell Immunotherapy

# data[].attributes.title
Levonorgestrel Butanoate Formulation and Methods Relating Thereto

# data[].attributes.body.value
Summary:

The National Institute of Child Health and Human Development (NICHD) seeks licensees and/or research co-development partners for the development of an injectable contraceptive for women with a pharmaceutical formulation containing levonorgestrel butanoate (LB), a steroidal progestin.

Description of Technology:

This invention is a potential subcutaneous or intramuscular progestin-only, injectable contraceptive for women. Forty-five percent (45%) of pregnancies in the United States are unintended. In this group, one-third of reproductive age women are obese – increasing the risk of diabetes, hypertension and venous thromboembolism (VTE). All these are conditions for which most hormonal methods are contraindicated. Thus, additional safe and effective injectable contraceptive options are needed. A subcutaneous formulation may be self-injected without the need of a skilled care provider or medical office visit. Levonorgestrel butanoate (LB) serves as a pro-drug to deliver Levonorgestrel (LNG) to serum after hydrolysis of the ester. It addresses the demand for estrogen-free contraception with no increased risk of VTE. The lack of increased risk is a benefit for all women, especially those obese.

Injectables have lower failure rates than combined hormonal birth control pills or patches or progestin-only pills (POP). Also, POPs require strict adherence to a daily administration schedule. Currently, the only injectable contraceptive on the U.S. market is depomedroxyprogesterone acetate (DMPA). While popular, DMPA contraceptive with certain risks. DMPA may cause weight gain, moodiness, and a decrease in bone mineral density leading to a higher risk of bone fracture.

Levonorgestrel butanoate (LB) is a butyl prodrug of levonorgestrel, a widely-used steroidal progestin. It was in development as a long-acting injectable contraceptive since the 1980s by the World Health Organization (WHO) in collaboration with institutions around the world, including NICHD. However, conventional LB formulations, including the WHO formulation, exhibit undesirable stability issues reducing contraceptive activity and the ability to large-scale manufacture.

NICHD developed an injectable pharmaceutical formulation of LB with a potential for self-administration. The formulation promotes increased stability through a longer lasting and more concentrated dosage than previous LB formulations. This invention also involves a unique manufacturing process requiring only one vendor for more efficient production. NICHD is testing this formulation in an ongoing Phase I subcutaneous study. Results so far indicate promise as a long-lasting, reversible, injectable female contraceptive. Further, there is a competitive advantage as patients in the Phase I study thus far did not report some side effects associated with other contraceptive agents such as DMPA; e.g., weight gain or mood swings.

Potential Commercial Applications:

Injectable contraceptive use by humans

Use in the treatment of progestin-related diseases

Competitive Advantages:

Safer for women with high-risk conditions

Self-subcutaneous and reversible injectable

Long-lasting contraceptive effects

Increased stability relative to previous formulations

Amenable to large-scale manufacture relative to previous formulations

Estrogen free contraceptive

Progestin only self-injectable contraceptive

# data[].attributes.body.processed
Summary:

The National Institute of Child Health and Human Development (NICHD) seeks licensees and/or research co-development partners for the development of an injectable contraceptive for women with a pharmaceutical formulation containing levonorgestrel butanoate (LB), a steroidal progestin.

Description of Technology:

This invention is a potential subcutaneous or intramuscular progestin-only, injectable contraceptive for women. Forty-five percent (45%) of pregnancies in the United States are unintended. In this group, one-third of reproductive age women are obese – increasing the risk of diabetes, hypertension and venous thromboembolism (VTE). All these are conditions for which most hormonal methods are contraindicated. Thus, additional safe and effective injectable contraceptive options are needed. A subcutaneous formulation may be self-injected without the need of a skilled care provider or medical office visit. Levonorgestrel butanoate (LB) serves as a pro-drug to deliver Levonorgestrel (LNG) to serum after hydrolysis of the ester. It addresses the demand for estrogen-free contraception with no increased risk of VTE. The lack of increased risk is a benefit for all women, especially those obese.

Injectables have lower failure rates than combined hormonal birth control pills or patches or progestin-only pills (POP). Also, POPs require strict adherence to a daily administration schedule. Currently, the only injectable contraceptive on the U.S. market is depomedroxyprogesterone acetate (DMPA). While popular, DMPA contraceptive with certain risks. DMPA may cause weight gain, moodiness, and a decrease in bone mineral density leading to a higher risk of bone fracture.

Levonorgestrel butanoate (LB) is a butyl prodrug of levonorgestrel, a widely-used steroidal progestin. It was in development as a long-acting injectable contraceptive since the 1980s by the World Health Organization (WHO) in collaboration with institutions around the world, including NICHD. However, conventional LB formulations, including the WHO formulation, exhibit undesirable stability issues reducing contraceptive activity and the ability to large-scale manufacture.

NICHD developed an injectable pharmaceutical formulation of LB with a potential for self-administration. The formulation promotes increased stability through a longer lasting and more concentrated dosage than previous LB formulations. This invention also involves a unique manufacturing process requiring only one vendor for more efficient production. NICHD is testing this formulation in an ongoing Phase I subcutaneous study. Results so far indicate promise as a long-lasting, reversible, injectable female contraceptive. Further, there is a competitive advantage as patients in the Phase I study thus far did not report some side effects associated with other contraceptive agents such as DMPA; e.g., weight gain or mood swings.

Potential Commercial Applications:

Injectable contraceptive use by humans

Use in the treatment of progestin-related diseases

Competitive Advantages:

Safer for women with high-risk conditions

Self-subcutaneous and reversible injectable

Long-lasting contraceptive effects

Increased stability relative to previous formulations

Amenable to large-scale manufacture relative to previous formulations

Estrogen free contraceptive

Progestin only self-injectable contraceptive

# data[].attributes.field_keywords[]
National Institute of Child Health and Human Development

# data[].attributes.field_licensingcontact_htmls[]
Gunas, Heather
gunash@mail.nih.gov

# data[].attributes.field_licensing_contacts[].value
Gunas, Heather
gunash@mail.nih.gov

# data[].attributes.field_licensing_contacts[].processed
Gunas, Heather
gunash@mail.nih.gov

# data[].attributes.field_patents[].value
US
Provisional (PRV) 63/289,965
Filed on 2021-12-15
Status: Expired

# data[].attributes.field_patents[].processed
US
Provisional (PRV) 63/289,965
Filed on 2021-12-15
Status: Expired

# data[].attributes.field_patents[].value
Patent Cooperation Treaty
(PCT) PCT/US2022/052704
Filed on 2022-12-13
Status: Expired

# data[].attributes.field_patents[].processed
Patent Cooperation Treaty
(PCT) PCT/US2022/052704
Filed on 2022-12-13
Status: Expired

# data[].attributes.field_patents[].value
India
National Stage 202417045561
Filed on 2024-06-13
Status: Pending

# data[].attributes.field_patents[].processed
India
National Stage 202417045561
Filed on 2024-06-13
Status: Pending

# data[].attributes.field_patent_htmls[]
US
Provisional (PRV) 63/289,965
Filed on 2021-12-15
Status: Expired

# data[].attributes.field_patent_htmls[]
Patent Cooperation Treaty
(PCT) PCT/US2022/052704
Filed on 2022-12-13
Status: Expired

# data[].attributes.field_patent_htmls[]
India
National Stage 202417045561
Filed on 2024-06-13
Status: Pending

# data[].attributes.field_patent_titles[]
LEVONORGESTREL BUTANOATE FORMULATION AND METHODS RELATING THERETO

# data[].attributes.field_patent_titles[]
LEVONORGESTREL BUTANOATE FORMULATION AND METHODS RELATING THERETO

# data[].attributes.field_patent_titles[]
LEVONORGESTREL BUTANOATE FORMULATION AND METHODS RELATING THERETO

# data[].attributes.field_technology_names[]
Levonorgestrel Prodrug Formulation And Methods Relating Thereto