Technologies

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.
P180053US02

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.
P170021US02

Method and Compounds for Treating Friedreich’s Ataxia

UW–Madison researchers have developed a chimeric synthetic molecule capable of inducing increases in FXN mRNA levels in Friedreich’s ataxia patient cell lines.

The complex has the formula A-L-B wherein A- is a bromodomain inhibitor, -L- is a linker, and -B is a polyamide that specifically binds to one or more repeats of a GAA oligonucleotide sequence. Mechanistically, when the complex binds to the repeat sequence, the bromodomain inhibitor (ex., Brd4) recruits the superelongation complex (SEC) to restart the paused transcription complex.
P160232US05

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.
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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.
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Most Recent Patents

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.
P170010US02

Hormone Analogs for Treating Hypoparathyroidism

UW–Madison researchers have developed backbone-modified peptide analogs of PTH (1-34) that could be used to treat hypoparathyroidism, a condition caused by decreased gland function resulting in low blood calcium levels, abnormal muscle activity and other symptoms. The analogs were generated by replacing certain α-amino acid resides with β-amino acid residues.

The analogs were used to assess the impact of backbone modifications on receptor state-selectivity. The results show that diverse binding profiles can be achieved via this strategy and give rise to distinct behaviors in vivo.
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Vitamin D Analog “UW-05” for Skin Therapy, Parathyroid and Autoimmune Disease Treatment

UW–Madison researchers have developed a vitamin D analog, 2-methylene-(22E)-25-hexanoyl-24-oxo-26,27-cyclo-22-dehydro-19-nor-1α-hydroxyvitamin D3. Known as UW-05, the compound shows high transcription activity, pronounced activity in arresting proliferating cells and inducing their differentiation. Bone calcium mobilization activity is lower compared to the native hormone. UW-05 may be useful against autoimmune diseases, some cancers, skin wrinkles and disorders, inflammatory problems and obesity.
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