Syracuse University

Xeragenx LLC

Robert Patrick Doyle

Joshua J Lensbouer

Jonathan David Bortz

David S Hermelin

Ron Bonaccorso

Kelsey Moody

Anthony Vortherms

The invention involves the coupling of compounds that can be bound by Haptocorrin (R-binder; Transcobalamin I; HC) to a target drug to improve pharmacokinetics, avoid undesirable side effects, and/or modify CNS access and localization. The pharmaceutical effect may be improved by conjugating the drug to haptocorrin binding substrate. This allows the conjugate to become bound to unsaturated haptocorrin in the blood, thereby protecting the drug from metabolism or excretion to increase protein half-life while not interfering with the efficacy of the protein drug. The conjugation may additionally prevent the drug from reaching the central nervous system or modify where the drug localizes and produces undesirable side effects such as nausea or hypophagia. Such a route also would prevent, in all case save for actual vitamin B, binding by serum transcobalamin II (TCII), and thus not cause Bdeficiency with long term use.

Peptide drug improvement using vitamin Band Haptocorrin binding substrate conjugates

The present invention provides compositions and methods for lowering blood glucose. More specifically, the present invention provides compositions comprising a complex comprising IF and Bconjugated to a peptide comprising a GLP-1 agonist. Advantageously, the composition may be delivered subcutaneously.

Glycemic control using intrinsic factor bound to a vitamin Bconjugate of a glucagon-like peptide-1 receptor agonist

Peptide drug improvement using vitamin B12 and haptocorrin binding substrate conjugates

Disclosed herein are methods and compositions useful in the treatment and/or prevention of a disease or indication associated with accumulation of a bisretinoid, for example A2E. In many embodiments, the disclosed methods and compositions are useful in treating an eye disease, for example macular degeneration.

Saposin B binds the lipofuscin bisretinoid A2E and prevents its enzymatic and photo degradation

The present invention relates to the digestion of peptides by pancreatic proteases and, more specifically, to compositions and methods for protecting against protease digestion.

Compositions and methods for enhancing peptide stability against protease digestion

A method for the avoidance of side effects associated with glucagon-like peptide-1 receptor (GLP-1R) agonists through vitamin Bconjugation prior to administration. Vitamin Bmay be bound to a GLP-1R agonist, such as exendin-4 (Ex4), to provide enhanced proteolytic stability while retaining GLP-1R agonism. The conjugate (B-Ex4) also improves glucose tolerance without producing anorexia and malaise. A GLP-1R agonist that is resistant to DPP-IV degradation and does not penetrate readily into the CNS, but retains the enhanced pharmacokinetic and pharmacodynamic profile on pancreatic &#x3b2;-cells provide a pharmacological tool for glycemic control in type 2 diabetes mellitus (T2DM) patients without eliciting unwanted hypophagia and nausea.

Preventing central nervous system induced nausea through use of vitamin Bconjugation

Peptide sequences that can serve as agonists of both the glucagon-like peptide 1 receptor (GLP-IR) and the neuropeptide Y2 receptor (NPYR2). The peptide sequences include regions that correspond to certain aspect of natural substrates and known agonists of the glucagon-like peptide 1 receptor (GLP-IR) and the neuropeptide Y2 receptor (NPYR2) in a single sequence.

Coagonists of glucagon-like peptide 1 receptor and neuropeptide Y2 receptor

Improved delivery of zinc using haptocorrin or intrinsic factor modified to include a zinc binding sequence that can outcompete dietary zinc inhibitors such as phytin. Known zinc binding sequences can be assayed to determine competitiveness with respect to phytin and, if successful, incorporated into the Bbinding site of haptocorrin or intrinsic factor. Thus a method of producing functional human haptocorrin or intrinsic factor which binds to zinc includes the steps of modifying human TCN1 or GIF to comprise one or more zinc-binding site sequences, constructing a vector containing the modified human TCN1 or GIF sequence, and introducing the vector into a host cell for a time and under conditions sufficient for expression of the functional human haptocorrin or intrinsic factor. The resulting zinc binding complex can be orally administered to zinc deficient individuals to improve the amount of dietary zinc available to the individuals.

Methods and systems for zinc delivery using intrinsic factor or haptocorrin

A method of producing butanal by optimizing the growth ofusing cellulose as food source, overexpressing a key 'gate' enzyme in butyric acid/butyraldehyde production, and knocking out the isobutyryl-CoA synthase gene to shunt the pathway. Optionally, the produced butanal can be isolated and converted into butanol.

[object Object]

The present invention relates to an isolated antigen fromthat is useful for developing, inter alia, vaccines against pathogenic bacteria of humans and animals. The present invention also relates to vaccines and antibodies developed using the isolated antigen. The present invention also relates to methods of using the antigen, vaccines, and antibodies of the present invention to detect, treat, and prevent infection and diseases associated with pathogenic bacteria.

Compositions containing a therapeutic peptide covalently linked to Vitamin Bat the 5'-hydroxyl group of the ribose moiety of &#x3b1;-ligand are described. The length of the linkage is optimized so that the biological activity of both the Vitamin Band the therapeutic peptide is maintained. Therapeutic peptide includes insulin, PYY, NPY and GLP-1. Attachment to Vitamin Bprovides uptake of the therapeutic peptide from the digestive tract and longer residence time.

Growing community of inventors

Syracuse, NY, United States of America

Robert Patrick Doyle