Abbott Laboratories Corporation

Other

Creative Biotherapeutics

Donald J Davidson

Jack Henkin

George S Sheppard

Keith W Woods

Jieyi Wang

Earl J Gubbins

Richard W McCroskey

COVID-19 results from the infection of the SARS-CoV-2 virus and has spread quickly to literally infected the world. Although coronavirus spike proteins can recognize a broad range of host cell-surface proteins, inhibiting spike protein binding to a survival factor called GRP78 results in a significant reduction in SARS-CoV-2 attachment, entry and replication in lung and kidney cells. This inhibition is accomplished with a novel type of inhibitor that potently blocks the binding of SARS-CoV-2 spike protein and whole virus to surface-bound GRP78. These novel GRP78 inhibitors also down regulate cytokines (IL10, IL6), immune co-inhibitory checkpoint proteins (PD-L1, B7H3, B7H4), and up regulate immune co-stimulatory proteins (MHC-II, CD-86) resulting in the reduction of the immune suppressive nature of infected lung alveolar epithelial cells in vitro and in vivo. Finally, these novel GRP78 inhibitors inhibit the hyperfibrinolysis of infected lung cells by reducing the activation of plasmin on cell surfaces.

Antivirus proteins having a Kringle 5 subunit

Glucose-regulated protein (GRP78) antagonists that block, interfere, and/or inhibit binding of receptor tyrosine kinase orphan receptors (RORs) are described for use as immunotherapy anticancer. These GRP78 antagonists inhibit surface bound GRP78 binding and receptor signaling and are believed to mimic the behavior of anti-angiogenic kringles found in mammalian plasminogen and in receptor tyrosine kinase orphan receptors. These GRP78 antagonist may be free peptide fragments, or peptide fragments covalently fused to blood borne proteins such as albumin or immunoglobins, or modified peptide fragments that a designed to bind to blood or tissue peptides when introduced in vivo into the blood stream of a patient.

GRP78 antagonist that block binding of receptor tyrosine kinase orphan receptors as immunotherapy anticancer agents

Mammalian kringle 5 fragments and kringle 5 fusion proteins are disclosed as a compounds for treating angiogenic diseases. Methods and compositions for inhibiting angiogenic diseases are also disclosed.

Antiangiogenic peptides, polypeptides encoding same and methods for inhibiting angiogenesis

Antiangiogenic peptides

Triazine angiogenesis inhibitors

Mammalian kringle 5 fragments are disclosed as a compounds for treating angiogenic diseases. Methods and compositions for inhibiting angiogenic diseases are also disclosed.

Antiangiogenic peptides and methods for inhibiting angiogenesis

Compounds having Formula I ##STR1## or pharmaceutically acceptable salts or prodrugs thereof, are useful for treating pathological states which arise from or are exacerbated by angiogenesis. The invention also relates to pharmaceutical compositions comprising these compounds and to methods of inhibiting anglogenesis in a mammal.

Antiangiogenic peptides polynucleotides encoding same and methods for

Mammalian kringle 5 peptide fragments are disclosed for treating angiogenic diseases Methods and compositions for inhibiting angiogenic diseases are also disclosed.

Mammalian kringle 5 is disclosed as a compound for treating angiogenic diseases. Methods and compositions for inhibiting angiogenic diseases are also disclosed.

Growing community of inventors

Gurnee, IL, United States of America

Donald J Davidson