A Novel Chemical Series for Inhibiting Bromodomain-containing Protein 4 (BRD4) for Treating Cancer

This technology includes the design, synthesis, and use of a novel chemical series for multiple treatments, including for treating cancer. A series of substituted bicyclic heteroaryl small molecules were found to be a potent inhibitor of bromodomain-containing protein 4 (BRD4) for multiple uses, including cancer. A BRD4 inhibitor is in a class of drugs known as BET inhibitors that are used broadly as anti-inflammatories and as anti-cancer agents. The chemical series exhibited less hepatocyte toxicity compared to existing treatments.

Treatment of primary hyperoxalurias with small molecule lactate dehydrogenase inhibitors such as WO2018005807A1

This technology includes the use of novel lactate dehydrogenase (LDH) inhibitors, including WO2018005807A1, for the treatment of primary hyperoxalurias (PHs). PHs are rare autosomal recessive disorders caused by overproduction of oxalate, leading to recurrent calcium oxalate kidney stone disease, and in some cases end-stage renal disease. One potential strategy to treat PHs is to reduce the production of oxalate by diminishing the activity of LDH, the proposed key enzyme responsible for converting glyoxylate to oxalate.

Attenuated Host-Range Restricted Dengue Viruses Derived by Site-Directed Mutagenesis of the Conserved 3-Stem and Loop Structure in Genomic RNA for Use as Vaccines

Although flaviviruses cause a great deal of human suffering and economic loss, there is a shortage of effective vaccines. The present invention is directed toward vector stage replication-defective flaviviruses that are replication-defective in mosquito vectors that transmit them to humans. The replication-defective flaviviruses of the present invention demonstrate a limited ability to replicate in the vector organisms that transmit flaviviruses from one host to another.

Dengue Tetravalent Vaccine Containing a Common 30 Nucleotide Deletion in the 3'-UTR of Dengue Types 1, 2, 3, and 4

The invention relates to a dengue virus tetravalent vaccine containing a common 30-nucleotide deletion (delta30) in the 3'-untranslated region (UTR) of the genome of dengue virus serotypes 1, 2, 3, and 4. The previously identified delta30 attenuating mutation, created in dengue virus type 4 (DEN4) by the removal of 30 nucleotides from the 3'-UTR, is also capable of attenuating a wild-type strain of dengue virus type 1 (DEN1).

Activation of Recombinant Diphtheria Toxin Fusion Proteins by Specific Proteases Highly Expressed on the Surface of Tumor Cells

This invention relates to diphtheria toxin fusion proteins comprising a diphtheria toxin (DT) cell-killing component and a cell-binding component such as granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 2 (IL-2), or epidermal growth factor (EGF). Receptors for the latter three materials are present on many types of cancer cells; therefore, these fusion proteins bind preferentially to these cancer cells. A key feature is that these toxins are altered so as to require activation by a cell-surface protease that is overexpressed on many types of cancers.

Transgenic Mouse Models for Studying HLA-B57:01 and HLA-B15:02 Linked Immune Responses and Hypersensitivity Reactions

Transgenic mouse models expressing human HLA-B57:01 and HLA-B15:02 molecules have emerged as invaluable tools for unraveling the intricacies of immune responses and hypersensitivity reactions. The major histocompatibility complex (MHC) encoded proteins play a pivotal role in the immune system by presenting peptide fragments to T lymphocytes, and HLA-B57:01 has been associated with severe hypersensitivity reactions triggered by abacavir, a widely used anti-retroviral drug.

New Cholera Vaccine and Method for Conjugating Bacterial Polysaccharides to Proteins

A new conjugate vaccine for cholera has been developed. The invention includes a new method to conjugate the O-specific polysaccharide-core part of the bacterial lipopolysaccharide and protein subcomponents. Conventional technology has entailed chemical treatment of both components to introduce linkers, which made them amenable for covalent linking. The new method simplifies production by utilizing squaric acid chemistry for conjugating the free amine-containing species (e.g. polysaccharides) directly to amine-containing species (e.g.

Naphthalene-containing Selective Inhibitors of BMP type 1 Receptors for the Treatment of Fibrodysplasia Ossificans Progressiva

This technology includes the use of a new class of molecules (nanomolar ALK2 inhibitor) to impede bone morphogenetic proteins (BMP) signaling for the treatment of Fibrodysplasia ossificans progressiva (FOP). FOP is a rare disease, characterized by malformation of the great (big) toes during embryonic development. Individuals with FOP have identical heterozygous activating mutation (R206H) in the gene encoding ACRV1 (also known as ALK2), a BMP type 1 receptor.

Cancer Therapeutic Based on Hypoxia Inducible Factor 1 (HIF-1) Inhibitors

Hypoxia is a characteristic of many solid tumors resulting from accelerated cellular proliferation and inadequate vascularization. HIF-1 is a transcription factor critical for maintaining cellular homeostasis in, and adaptively responding to, low oxygen environments. HIF-1 becomes activated through binding to the transcriptional co-activator protein p300. Disruption of the HIF-1/p300 interaction could potentially modulate HIF-1 activity.

Photoactivatable Lipid-based Nanoparticles as a Vehicle for Dual Agent Delivery

The invention relates to novel lipid-based nanoparticles (liposomes) for use in targeted, on demand and on site drug delivery. The particles include a wall surrounding a cavity, wherein the wall is comprised of:

  1. A lipid bilayer comprising 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC), dipalmitoylphosphatidylcholine (DPPC), and 1,2-distearoyl-sn-glycero-3-

phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000), and

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