Children's Medical Center Corporation

The General Hospital Corporation

The Brigham and Women's Hospital, Inc.

Beth Israel Deaconess Medical Center, Inc.

Children's Medical Center of Boston

Children's Medical Center Corporatioin

Bruce R Zetter

Lere Bao

Lijun Sun

Omid C Farokhzad

Jinjun Shi

Yingjie Xu

Sabarni K Chatterjee

Mohammad Ariful Islam

Robert Samuel Langer

David R Elmaleh

W Scott McDougal

Ivy Chung

Adam S Feldman

Earl Weinstein

Jacqueline Banyard Bhisitkul

Amy Holleman

Jacqueline Banyard

Scott W McDougal

The present disclosure provides compounds of Formula (I). The compounds described herein may be useful in treating and/or preventing proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.

Compounds for treating proliferative diseases

Compositions and methods for treating cancer that include administering a therapeutically effective amount of a tumor suppressor mRNA complexed with a delivery vehicle as described herein, e.g., a nanoparticle.

Restoration of tumor suppression using MRNA-based delivery system

Restoration of tumor suppression using mRNA-based delivery system

The present disclosure provides compounds of Formula (I). The compounds described herein may be useful in treating and/or preventing proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein. 

Provided herein are methods and assays relating to the diagnosis and treatment of a taxane-resistant cancer. Such methods and assays comprise determining the level of expression of miR-135in a biological sample from a subject having or suspected of having a taxane-resistant cancer or from a subject that was or is being treated with a taxane anti-cancer agent. Also provided herein are methods for treating such cancers by administering an inhibitor of the miR-135pathway and a taxane to a subject in need thereof.

Diagnosis and treatment of taxane-resistant cancers

Embodiments of the invention are directed to methods for predicting the resistance of cancer to members of the taxoid family by measuring the levels of prohibitin. Methods for treating cancer and taxoid family member resistant cancers using inhibitors of prohibitin, as well as therapeutic complexes that target prohibitin are also provided.

Methods to predict and prevent resistance to taxoid compounds

The present invention is based on the discovery that three proteins, Cystatin B, Chaperonin 10, and Profilin are present in the urine of patients with bladder cancer, a cancer of epithelial origin. Accordingly, the present invention is directed to methods for prognostic evaluation of cancers of epithelial origin and to methods for facilitating diagnosis of cancers of epithelial origin by monitoring the presence of these markers in biological samples. The invention is also directed to markers for therapeutic efficacy.

Method for diagnosis and prognosis of epithelial cancers

Novel biotinylated composition comprising a nucleic acid, e.g. siRNA, that are useful for targeting therapeutic and imaging agents to sites of infection and tumors are disclosed.

Biotinylated compositions

We have discovered a protein in humans, herein referred to as collagen like gene (CLG) product (SEQ ID NOS: 12 and 13), that is expressed in human prostate cancer and breast cancer cell lines but not in normal adult, placenta, lung, liver, skeletal muscle, kidney or pancreas tissues. We have also discovered that the level of CLG mRNA expression correlates positively with the metastatic potential of the cancer cell lines tested.

Methods for diagnosis and prognosis of cancer

The present invention provides a thymosin &bgr;15 promoter. The promoter comprises the nucleotide sequence of SEQ ID NO:1 or a fragment thereof capable of expressing an operably linked DNA. A DNA sequence having nucleotides &minus;400 to &plus;1 of FIG. is a preferred fragment. The invention also provides novel assays for identifying compounds useful in the treatment of malignancies involving modulation of thymosin &bgr;15 expression, e.g., breast, pancreas and prostate cancer. The invention further provides a method of human gene therapy for treating malignancies involving up-regulation of thymosin &bgr;15 expression.

Thymosin &bgr;-15 promoter and uses thereof

The present inventors have now discovered that humans have a gene that encodes a novel protein of the thymosin &bgr; family. This novel protein, herein referred to as thymosin &bgr;15, has the ability to bind and sequester G-actin, like other members of the thymosin &bgr; family, but unlike what is known about other members it also directly regulates cell motility in prostatic carcinoma cells. The present invention is direct to an isolated cDNA encoding the human thymosin &bgr;15 gene (SEQ ID NO: 1) and have deduced the amino acid sequence (SEQ ID NO: 2).

Antibodies specific for human thymosin &bgr;15 protein and uses thereof

The present inventors have discovered that humans have a gene that encodes a novel protein of the thymosin .beta. family. This novel protein, herein referred to as thymosin .beta.15, has the ability to bind and sequester G-actin, like other members of the thymosin .beta. family, but unlike what is known about other members also directly regulates cell motility in prostatic carcinoma cells. A cDNA of the human thymosin .beta.15 gene (SEQ ID NO: 1) and having the deduced the amino acid sequence (SEQ ID NO: 2) was isolated. The present inventors have shown that enhanced transcripts (mRNA) and expression of the thymosin .beta.15 gene in non-testicular cells has a high correlation to disease state in a number of cancers, such as prostate, lung, melanoma and breast cancer, particularly metastatic cancers. Accordingly, discovering enhanced levels of transcript or gene product in non-testicular tissues can be used in not only a diagnostic manner, but a prognostic manner for particular cancers.

Method for diagnosis of cancer

The present inventors have now discovered that humans have a gene that encodes a novel protein of the thymosin .beta. family. This novel protein, herein referred to as thymosin .beta.15, has the ability to bind and sequester G-actin, like other members of the thymosin .beta. family, but unlike what is known about other members it also directly regulates cell motility in prostatic carcinoma cells. The present invention is direct to an isolated cDNA encoding the human thymosin .beta.15 gene (SEQ ID NO: 1) and have deduced the amino acid sequence (SEQ ID NO: 2).

Growing community of inventors

W. Newton, MA, United States of America

Bruce R Zetter