Pharmaceuticals & Vitamin D

Most Recent Inventions

New Hormone Analogs for Treating Hypoparathyroidism

UW–Madison researchers have developed backbone-modified analogs of PTH(1-34). The analogs exhibit advantageous properties; they are biased toward Gs activation/cAMP production relative to β arrestin recruitment.

The analogs were generated via an unconventional strategy in which the backbone of a natural PTHR-1 agonist was altered, rather than the side-chain complement. More specifically, selected α-amino acid residues were systemically replaced with either β-amino acid residues or with unnatural D-stereoisomer α-amino acid residues.

The researchers have shown that backbone-modification can rapidly identify potent agonists with divergent receptor-state selectivity patterns relative to a prototype peptide.

Nylon-3 Polymers to Treat Fungal Infections

UW–Madison researchers have found that nylon-3 polymers developed in their lab display potent antifungal activity against a broad spectrum of common fungal pathogens, with minimal toxicity towards mammalian cells. The polymers have some activity alone, and when used in combination with existing drugs provide synergistic effects against Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus strains, including some resistant strains.

Synergistic combination offers efficacy with significantly reduced amounts of drug and corresponding toxicity, which could potentially expand the relevant patient population.

The polymers were designed to resemble host-defense peptides (HDPs), which are natural molecules that exhibit antimicrobial activities.

Phospholipid Ether Analogs for Treating and Imaging Pediatric Solid Tumors

UW–Madison researchers have developed radiolabeled, tumor-targeted alkylphosphocholine analogs shown to diagnose and treat malignant pediatric solid cancers, including pediatric brain cancers across a wide range of histological subtypes.

Disease indication – Malignant pediatric solid tumors including (but not limited to): neuroblastoma; Ewing sarcoma; rhabdomyosarcoma; osteosarcoma; retinoblastoma; Wilms tumor; and pediatric brain tumors such as medulloblastoma, high-grade glioma, glioblastoma.

Drug format – The analogs can be designed as targeted agents for local delivery of radiation therapy by incorporating a radioactive iodine isotope, or for targeted delivery of detection/imaging moieties by incorporating a fluorophore or radioactive iodine isotope.

Drug class – Potential to become the first targeted radiotherapeutic agent for multiple pediatric solid tumors, including malignant brain tumors.

Research stage and preliminary data – Demonstrated selective in vivo uptake in 10 different malignant pediatric solid tumor cell lines and in various pediatric brain tumor cell lines, while exhibiting negligible uptake in various normal human primary cells. Demonstrated anti-tumor activity in vivo against five different pediatric solid tumor types in murine xenograft models. A pediatric phase I trial is in progress.

Inhibiting Quorum Sensing in Staphylococcus Epidermidis, a Health Care Pathogen

UW–Madison researchers have synthesized a set of potent peptidic modulators of Staphylococcus epidermidis quorum sensing. Targeting the AgrC receptor, these compounds include the first universal QS inhibitors active against all known groups of S. epidermidis. Others are strongly group- or species-selective and could be applied to selectively modulate either S. epidermidis or S. aureus quorum sensing.

Improved Influenza B Virus Replication for Vaccine Development

UW–Madison researchers led by Yoshihiro Kawaoka and Gabriele Neumann have identified growth enhancing mutations that increase the yield of influenza B viruses, potentially enabling more rapid and cost-effective vaccine production.

Virus libraries were generated for each lineage (B/Victoria and B/Yamagata) and passaged in cultured cells to identify several mutations in the ‘internal’ genes of influenza B viruses that confer high-yield in cultured cells and/or embryonated chicken embryos. The use of one or more of these mutations in vaccine virus master strains results in higher viral titers (e.g., 108 PFU/mL or more) in cultured cells and/or embryonated chicken eggs.

Most Recent Patents

Natural Antibiotic to Treat Clostridium Infection and More

UW–Madison researchers have identified a potential new antibiotic to treat infections caused by C. difficile, Staphylococcus and other drug-resistant strains. The compound is a natural product called ecteinamycin. It was discovered and isolated from a sea squirt bacterium (Actinomadura). Preliminary data suggests ecteinamycin is potent, selective and able to protect cells against bacterial toxins.

Effective and Robust Method of T Cell Expansion and Activation

UW–Madison researchers have shown for the first time that the addition of inhibitors which block the binding of BAFF to its receptor BAFF-R/BR3 activates both CD4+ and CD8+ cytolytic T cells such that the killing of target human tumor cell lines is significantly augmented.

Specifically, the researchers demonstrated in vitro that a neutralization antibody to the BAFF receptor, BR3, significantly increased CRTAM+ CD4+ and CD8+ T cell proliferation and their anti-tumor cytotoxic activity via increases in granzyme B. This was shown for even aggressive melanoma cell lines such as A375 whereby a four day co-culture with BR3 neutralized T cells almost completely eradicated the tumor cells from culture. This innovation removes a significant roadblock in the industrial production/manufacture of T cells ex vivo for T cell and chimeric antigen receptor (CAR) T cell immunotherapy, which is currently one of the most exciting new cancer therapies.

Analogs of Diptoindonesin G for Breast Cancer Drug Development

UW–Madison researchers have synthesized analogs of Dip G that have shown a greater ability than the parent molecule to decrease ERα expression and stabilize ERβ in cultured breast cancer cells. The compounds are active for ameliorating, attenuating and halting the growth/metastasis of breast cancers.