Quintessence Biosciences Inc.

Madison, WI, United States

Quintessence Biosciences Inc.

Madison, WI, United States
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Rutkoski T.J.,University of Wisconsin - Madison | Rutkoski T.J.,Deciphera Pharmaceuticals LLC | Kink J.A.,Quintessence Biosciences Inc. | Strong L.E.,Quintessence Biosciences Inc. | And 2 more authors.
Bioconjugate Chemistry | Year: 2010

Site-specific cross-linking can generate homogeneous multimeric proteins of defined valency. Pancreatic-type ribonucleases are an especially attractive target, as their natural dimers can enter mammalian cells, evade the cytosolic ribonuclease inhibitor (RI), and exert their toxic ribonucleolytic activity. Here, we report on the use of eight distinct thiol-reactive cross-linking reagents to produce dimeric and trimeric conjugates of four pancreatic-type ribonucleases. Both the site of conjugation and, to a lesser extent, the propinquity of the monomers within the conjugate modulate affinity for RI, and hence cytotoxicity. Still, the cytotoxicity of the multimers is confounded in vitro by their increased hydrodynamic radius, which attenuates cytosolic entry. A monomeric RI-evasive variant of bovine pancreatic ribonuclease (RNase A) inhibits the growth of human prostate and lung tumors in mice. An RI-evasive trimeric conjugate inhibits tumor growth at a lower dose and with less frequent administration than does the monomer. This effect is attributable to an enhanced persistence of the trimers in circulation. On a molecular basis, the trimer is ∼300-fold more efficacious and as well tolerated as erlotinib, which is in clinical use for the treatment of lung cancer. These data encourage the development of mammalian ribonucleases for the treatment of human cancers. © 2010 American Chemical Society.


Rutkoski T.J.,University of Wisconsin - Madison | Kink J.A.,Quintessence Biosciences Inc | Strong L.E.,Quintessence Biosciences Inc | Raines R.T.,University of Wisconsin - Madison
Translational Oncology | Year: 2013

Human pancreatic ribonuclease (RNase 1) is a small secretory protein that catalyzes the cleavage of RNA. This highly cationic enzyme can enter human cells spontaneously but is removed rapidly from circulation by glomerular filtration. Here, this shortcoming is addressed by attaching a poly(ethylene glycol) (PEG) moiety to RNase 1. The pendant no effect on ribonucleolytic activity but does increase persistence in circulation. The RNase 1-PEG conjugates inhibit the growth of tumors in a xenograft mouse model of human lung cancer. Both retention in circulation and tumor growth inhibition correlate with the size of the pendant PEG. A weekly dose of the 60-kDa conjugate at 1 μmol/kg inhibited nearly all tumor growth without affecting body weight. Its molecular efficacy is ~5000-fold greater than that of erlotinib, which is a small molecule in clinical use for the treatment of lung cancer. These data demonstrate that the addition of a PEG moiety can enhance the in vivo efficacy of human proteins that act within cells and highlight a simple means of converting an endogenous human enzyme into a cytotoxin with potential clinical utility. © 2013 Neoplasia Press, Inc. All rights reserved.


Patent
Quintessence Biosciences Inc. | Date: 2013-06-20

The present invention is directed toward the delivery of a toxic protein to pathogenic cells, particularly cancer cells. In preferred embodiments, the toxic protein is a ribonuclease that has been modified to make it toxic to target cells and that can be conjugated to a target cell-specific delivery vector, such as an antibody, for delivery to pathogenic cells.


Patent
Quintessence Biosciences Inc. | Date: 2015-04-27

The present invention is directed toward the delivery of toxic agents to pathogenic cells, particularly cancer cells. In some embodiments, the toxic agent is a human ribonuclease or similar agent that is toxic to cells.


Patent
Quintessence Biosciences Inc. | Date: 2012-07-10

The present invention relates to the use of ribonucleases (RNases) in the treatment or prevention of disease.


Patent
Quintessence Biosciences Inc. | Date: 2016-07-18

The present invention is directed toward the delivery of a toxic protein to pathogenic cells, particularly cancer cells. In preferred embodiments, the toxic protein is a ribonuclease that has been modified to make it toxic to target cells and that can be conjugated to a target cell-specific delivery vector, such as an antibody, for delivery to pathogenic cells.


Patent
Quintessence Biosciences Inc. | Date: 2011-09-13

The present invention relates to the use of ribonucleases (RNases) in the treatment or prevention of disease.


Patent
Quintessence Biosciences Inc. | Date: 2015-04-14

The present invention relates to the use of ribonucleases (RNases) in the treatment or prevention of disease.


Patent
Quintessence Biosciences Inc. | Date: 2014-04-14

The present invention is directed toward the delivery of a toxic protein to pathogenic cells, particularly cancer cells. In preferred embodiments, the toxic protein is a ribonuclease that has been modified to make it toxic to target cells and that can be conjugated to a target cell-specific delivery vector, such as an antibody, for delivery to pathogenic cells.


Patent
Quintessence Biosciences Inc. | Date: 2014-01-07

The present invention relates to the use of ribonucleases (RNases) in the treatment or prevention of disease.

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