(to drug -NH2r -OH,-SH)
You may have noticed that Prolynx scientists value publishing their novel research in high-quality, peer-reviewed-journals. We are proud to be the sole non-academic group recognized as one of the "selected highly-prolific authors" in the past 5 years for Bioconjugate Chemistry on their Journal Stars website: http://journalstars.acs.org/biological/journal/bioconjugate-chemistry.
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Schneider, E. et al, Bioconjugate Chemistry 2016, 27, 2534-2539 "Approach For Half-Life Extension of Small Antibody Fragments That Does Not Affect Tissue Uptake"
Henise, J. et al, Journal of Biomedical Materials Research B 2016, 00B:000-000; doi: 10.1002/jbm.b.33701 "Surgical Sealants with Tunable Swelling, Burst Pressures, and Biodegradation Rates"
Cerchiari, A.E. et al, Scientific Reports 2016, 6,33148; doi: 10.1038/srep33148 "Probing the Luminal Microenvironment of Reconstituted Epithelial Microtissues"
Schneider, E. et al, Bioconjugate Chemistry 2016, 27, 1638-1644 "Subcutaneously Administered Self-Cleaving Hydrogel-Octreotide Conjugated Provide Very Long-Acting Octreotide"
Schneider, E. et al, Bioconjugate Chemistry 2016, 27, 1210-1215 "Hydrogel Drug Delivery System Self-Cleaving Covalent Linkers for Once-a-Week Administration of Exenatide"
Reid, R. et al, Macromolecules 2015, 48, 7359-7369 "Analytical and Simulation-Based Models for Drug Release and Gel-Degradation in a Tetra-PEG Hydrogel Drug-Delivery System"
Schneider, E. et al, European Journal of Pharmaceuticals and Biopharmaceutics 2015, 93, 254-259 "Half-Life Extension of the HIV-Fusion Inhibitor Peptide TRI-1144 Using a Novel Linker Technology"
Henise, J. et al, Bioconjugate Chem. 2015, 26, 270-278 "Biodegradable Tetra-PEG Hydrogels as Carriers for a Releasable Drug Delivery System"
Fontaine, S. et al, Bioconjugate Chem. 2015, 26, 145-152 "Long-Term Stabilization of Maleimide−Thiol Conjugates"
Lawrence, M. et al, ARVO 2014 Annual Meeting, "The Intravitreal Pharmacokinetics of Fluorophores Conjugated to PEGs by Non-Cleavable and Self-Cleaving Linkers in Non-human Primates"
Santi, D.V. et al, J.MedChem. 2014, 57, 2303-2314 "Macromolecular Prodrug that provides the Irinotecan Active-Metabolite SN-38 with Ultralong Half-Life, Low Cmax, and Low Glucuronide Formation"
Schneider, E. et al, Bioconjugate Chem. 2013, 24, 1990-1997 "Beta-Eliminative Releasable Linkers Adapted for Bioconjugation of Macromolecules to Phenols"
Henise, J. et al, Peptide Conference 2013 "An optimized hydrogel offers tunable half-life extension of peptides and proteins"
Schneider, E.L., et al, Peptide Conference 2013 "Self-administered long-acting octreotide conjugates"
Ashley, G.W. et al, PNAS 2013, 110(6), 2318-2323 "Hydrogel drug delivery system with predictable and tunable drug release and degradation rates"
Schneider, E.L. et al, Peptide Conference 2012 "Predictable half-life extension demonstrated through peptide TRI-1144"
Henise, J. et al, Peptide Conference 2012 "A biodegradable hydrogel drug delivery system for tunable half-life extension"
Santi, D.V. et al, PNAS 2011, 109(16), 6211-6216 "Predictable and tunable half-life extension of therapeutic agents by controlled chemical release from macromolecular conjugates"
Schneider, E. et al, Peptide Conference 2011 "Predictable and tunable drug release from macro-molecular conjugates"
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ProLynx β-Eliminative Drug Delivery System
One major challenge in drug development is achieving the optimal residence time for a drug – often measured by its “half-life” in the body. The half-life of a drug is rarely too long, but often too short. When the half-life is short the drug must either be administered frequently or in very high doses so it lasts longer. Very frequent administration is inconvenient for the patient and leads to non-compliance; high doses lead to high drug level spikes – a high Cmax – and large excursions from high-to-low drug levels – peak/trough or Cmax/Cmin – that can cause toxicities. The ideal drug has an appropriately long half-life, low Cmax and low Cmax/Cmin.
Prolynx has a novel, proprietary technology for half-life extension of peptide, protein and small molecule drugs. It can achieve a long half-life and low Cmax for a drug that normally has a short half-life. First, we developed a library of “self-cleaving” β-eliminative linkers that are programmed to release a native, unmodified drug from a carrier over periods of hours to years. Each linker in the library contains a specific “modulator” that controls the drug release rate independent of enzymes or the species the system is used in. Second, we developed technology to use these linkers for releasable attachment of drugs to macromolecular carriers. In one format, the carrier is a circulating macromolecule, such as polyethylene glycol (PEG), that is administered by s.c. or i.v injection; with this format, we can usually extend the drug’s half-life to about one week – the limit dictated by the elimination of the circulating conjugate.
The second carrier format is a porous PEG-hydrogel fabricated as 40 um
microspheres and injected as subcutaneous depots. Here, the drug is covalently
tethered to the microspheres by a releasable linker, and is slowly released to give
a half-life ranging from about a week to a month. Slower-cleaving linkers are also
installed in the polymer crosslinks so gel degradation can be balanced with drug
ProLynx has numerous examples of half-life extension of short-lived therapeutics
to periods of weeks to months. In addition to small molecules and peptides, we have recently shown the same technology can be applied to larger proteins – in one case increasing the half-life of a 25 kDa single chain antibody fragment to that typically seen with monoclonal antibodies. We are interested in applying our technology to extend half-lives of proprietary drugs of pharma companies, and also seeking collaborations on development of ProLynx’s long-lasting drug conjugates.
For more detailed info, select publications of interest below:
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