University of Louisville Research Foundation, Inc.

Advanced Cancer Therapeutics, LLC

Antisoma Research Limited

Paula J Bates

John Olaf Trent

Donald Miller

Gerald B Hammond

Xiaohua Xu

Mohammad Tariq Malik

Bo Xu

Kyung Aih Kang

Sarah A Andres

Francesca R Salipur

Elsa Merit Reyes-Reyes

Donald M Miller

Joseph A Burlison

Martin G O'Toole

Robert M Buchanan

Nagaraju Miriyala

Craig A Grapperhaus

Abraham Vaisberg

Caleb Aaron Calvary

Nicholas S Vishnosky

Jason O E Young

Levi Beverly

Zhuang Jin

Yingchang Mi

Some embodiments of the invention include methods of using a compound such as Formula (I), Formula (II), or I-1 (e.g., in compositions or in pharmaceutical compositions) for treating diseases (e.g., cancer such as chemo-resistant cancer or cancer-therapy-resistant cancer). Additional embodiments of the invention are also discussed herein.

Methods for treating diseases

A composition comprises an anti-nucleolin agent conjugated to nanoparticles. The nanoparticles are non-magnetic, not iron oxide and not polyacrylamide. Furthermore, a pharmaceutical composition for treating cancer comprises a composition including an anti-nucleolin agent conjugated to nanoparticles, and a pharmaceutically acceptable carrier.

Anti-nucleolin agent-conjugated nanoparticles

Some embodiments of the invention include inventive compounds (e.g., compounds of Formula (I) or (Ia)). Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the inventive compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer). Further embodiments include methods for making the inventive compounds. Additional embodiments of the invention are also discussed herein.

Compounds, compositions, methods for treating diseases, and methods for preparing compounds

A composition comprises an anti-nucleolin agent conjugated to nanoparticles, and optionally containing gadolinium. Furthermore, a pharmaceutical composition for treating cancer comprises a composition including an anti-nucleolin agent conjugated to nanoparticles, and a pharmaceutically acceptable carrier. The composition enhances the effectiveness of radiation therapy, enhancing contrast in X-ray imaging techniques, and when gadolinium is present, provide cancer selective MRI contrast agents.

Anti-nucleolin agent-conjugated nanoparticles as radio-sensitizers and MRI and/or X-ray contrast agents

Some aspects of the invention include attenuating DNMT1 inhibitor activity in an animal comprising administering an antioxidant. Other aspects of the invention include methods comprising administering a composition comprising a DNMT1 inhibitor and an antioxidant. In some instances in the methods, the animal is undergoing a treatment for cancer. Additional aspects of the invention include compositions comprising a DNMT1 inhibitor and an antioxidant.

Compositions and methods for modulating DNMT1 inhibitor activity

Certain embodiments of the invention include compositions comprising a compound of Formula (I), and salts, isomers, and derivatives thereof. Pharmaceutical compositions of some embodiments of the present invention comprise a compound of Formula (I), and salts, isomers, and derivatives thereof. Other embodiments of this invention include methods for treating disease (e.g., cancer) and methods for administering a compound of Formula (I), and salts, isomers, and derivatives thereof.

Compounds, compositions, pharmaceutical compositions, and methods of use

Provided herein are methods for predicting efficacy of a DNA (cytosine-5)-methyltransferase 1 (DNMT1) inhibitor treatment in a subject having a cancer, methods of identifying a subject having a cancer that is more likely to respond to a DNMT1 inhibitor treatment, and methods of selecting a treatment for a subject having a cancer that include determining a level of SOX9 in a sample containing cells from a subject having a cancer. Also provided are methods of treating a subject having a cancer that include selectively administering a DNMT1 inhibitor to a subject having cancer determined to have an elevated level of SOX9 in a sample containing cells from the subject compared to a reference level. Also provided are antibodies and antigen-binding antibody fragments that specifically bind to SOX9, and nucleic acid sequences that contain at least 10 nucleotides complementary to a contiguous sequence present in a SOX9 nucleic acid for use in these methods.

Predictive marker of DNMT1 inhibitor therapeutic efficacy and methods of using the marker

The invention provides compounds of Formula (I):R&#x2261;R&#x2003;&#x2003;(I)wherein Rand Rhave any of the values or specific values defined herein, as well as compositions comprising such compounds and therapeutic methods comprising the administration of such compounds.

Therapeutic compounds

The present invention provides a method for inhibiting the proliferation of malignant and/or hyperplastic cells in a subject by administering to the subject a therapeutically effective amount of a guanosine rich oligonucleotide. The present invention also provides oligonucleotides which are capable of being specifically bound to a specific cellular protein which is nucleolin and/or nucleolin in nature, which is implicated in the proliferation of cells, specifically malignant and/or hyperplastic cells, and a method for their selection.

Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin

Methods for the treatment of tumors and cancer by exploiting the surface expression of the usually nuclear-localized protein, nucleolin.

Method for the diagnosis and prognosis of malignant diseases

The invention provides compounds of Formula (I): wherein Rand Rhave any of the values or specific values defined herein, as well as compositions comprising such compounds and therapeutic methods comprising the administration of such compounds.

Compositions and methods for modulating tumor proliferation in an individual are provided. The methods employ nucleolin-binding agents, such as aptamers. The aptamers of the present invention can be used to modulate the proliferation of malignant, dysplastic, hyperproliferative, and/or metastatic cells through interference with molecular interactions and functions of nucleolin in the tumor cell.

Growing community of inventors

Louisville, KY, United States of America

Paula J Bates