Samuel Bernal

US Patent:

20030017158, Jan 23, 2003

Filed:

Mar 8, 2002

Appl. No.:

10/019494

Inventors:

Samuel Bernal - Woodland Hills CA, US
Douglas Burkett - Gilbert AZ, US
Ralph Green - Scottsdale AZ, US
Seth Rose - Tempe AZ, US

International Classification:

A61K039/395
G01N033/574

US Classification:

424/155100, 435/007230

Abstract:

A diagnostic method for detecting cancerous epithelial cells by selectively marking the mitochondria of the cancer cells, by delivering to the epithelium a cationic supravital mitochondrial marking agent. Selective killing of cancerous epithelial cells in the presence of normal cells is effected by delivering a cationic supravital mitochondrial marking agent to epithelial cancer cells. The killing agent can also comprise the reaction product of the marking agent and a cancer chemotherapeutic drug or in admixture

US Patent:

20210238245, Aug 5, 2021

Filed:

Jan 19, 2021

Appl. No.:

17/248288

Inventors:

Samuel Dequina Bernal - Woodland Hills CA, US

Assignee:

Globetek Science Foundation - Makati

International Classification:

C07K 14/495

Abstract:

This invention discloses a bifunctional TGF-B/immune checkpoint fusion gene and protein with anti-inflammatory activity that represents a new class of therapy for Immune disorders, immune dysregulation, and autoimmune diseases. The bifunctional TGF-B/immune checkpoint fusion gene and protein include: (i) a TGF-B domain is selected from the group consisting of TGF-B1, TGF-B2, and TGF-B3, (ii) an immune checkpoint domain selected from the group of immune checkpoints consisting of PD-L1, PD-L2, and CTLA-4, (iii) a flexible peptide linker that links two TGF-B domains resulting in a dimeric TGF-B construct wherein the dimeric form of the TGF-B ligand is important for its binding and functional activity, and (iv) a rigid peptide linker, wherein the dimeric TGF-B ligand is linked to the immune checkpoint ligand.The functional domains of the fusion protein act in concert to maintain tolerance for self-antigens by stimulating regulatory cells and to regulate the activities of effector cells, respectively. The immune regulatory activity of the bifunctional TGF-B/immune checkpoint fusion gene and protein was demonstrated using a TGF-B1/PD-L1 fusion pair, showing that the domains functionally bind their respective receptors and inhibit NF-kB activation in a reporter assay, downregulate NF-kB-responsive genes, suppress the growth of PHA/IFN-γ-activated effector-like Jurkat T cells with subsequent upregulation of Foxp3 and downregulation of NF-kB1 and IL-6. The fusion protein described in this invention elicits a high frequency of cell-to-cell contact that induced upregulation of Treg-associated markers (Foxp3 and IL2RA). The bifunctional fusion protein described herein modulates immune reactions and represents a new class of therapy for Immune disorders, immune dysregulation, and autoimmune diseases.