Harvard College

Merrimack Pharmaceuticals, Inc.

The General Hospital Corporation

Grace Bio-labs, Inc.

Gavin MacBeath

Lin Nie

William Kubasek

Bambang Adiwijaya

Rachel C Nering

Taranjit S Gujral

Akos Czibere

Defne Yarar

Sharon Moulis

Stuart L Schreiber

Ravi Thadhani

Jennipher Lyn Grudzien

Angela N Koehler

Myles S Wolf

Tanya Lynn Knickerbocker

Kristopher M Depew

Paul Hergenrother

Olga Burenkova

Mark Sevecka

Alexei Finski

Taran S Gujral

Provided are methods for optimizing therapy of, treating a patient having, or selecting (identifying) patients who will benefit from treatment for, a cancer (e.g., a non-hematological cancer; e.g., a gynecological cancer). The methods comprise determining whether the patient will benefit from treatment with an ErbB3 inhibitor (e.g., an anti-ErbB3 antibody), with or without either a taxane or an aromatase inhibitor, or with a taxane or an aromatase inhibitor in the absence of an ErbB3 inhibitor, based on levels of particular biomarkers and combinations of biomarkers measured in a biological sample obtained from the patient. The methods further comprise optimizing the patient's therapy, selecting the patient for treatment, or treating the patient accordingly. In various aspects the biological samples are sections of a biopsy (e.g., a formalin fixed paraffin embedded biopsy). In oth6er aspects the biomarkers are proteins and/or nucleic acids. In other aspects the biomarkers function in ErbB-mediated signal transduction.

Biomarker profiles for predicting outcomes of cancer therapy with ERBB3 inhibitors and/or chemotherapies

Methods for predicting a therapeutic response in a patient (e.g., a cancer patient) to ErbB3 inhibitors, and methods of treating a cancer patient with targeted therapies.

Biomarkers for predicting outcomes of cancer therapy with ErbB3 inhibitors

The invention provides a method for lysing a single cell embedded in a tissue from the inside of the cell, and collecting the intracellular lysate for use in analytical methods. This method preserves the state of molecules of the cell, and therefore allows for transformation of a single target cell in live tissue into a format that can be evaluated using analytical methods.

Method for lysing a single cell in a solid tissue

Disclosed herein are methods of treating cancer in a subject, and methods for inhibiting growth, migration and/or invasion of a cancer cell in the subject, comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that downmodulates Fzd2. The antibody may specifically bind Fzd2, and may promote internalization of the Fzd2 receptor by the cancer cells and/or prevent ligand binding to Fzd2. Specific antibodies, and also specific portions of the Fzd2 molecule for antibody binding are disclosed. In one embodiment the antibody specifically binds to the epitope HGAEQICVGQNHSEDGAPAL (SEQ ID NO: 1). Specific cancers (e.g. late stage hepatocellular carcinoma), intended for treatment are provided, and include cancers that exhibit overexpression of Fzd2, and/or Wnt5a.

Frizzled 2 as a target for therapeutic antibodies in the treatment of cancer

Provided are methods for optimizing therapy of, treating a patient having, or selecting (identifying) patients who will benefit from treatment for, a cancer (e.g., a non-hematological cancer; e.g., a gynecological cancer). The methods comprise determining whether the patient will benefit from treatment with an ErbB3 inhibitor (e.g., an anti-ErbB3 antibody), with or without either a taxane or an aromatase inhibitor, or with a taxane or an aromatase inhibitor in the absence of an ErbB3 inhibitor, based on levels of particular biomarkers and combinations of biomarkers measured in a biological sample obtained from the patient. The methods further comprise optimizing the patient's therapy, selecting the patient for treatment, or treating the patient accordingly. In various aspects the biological samples are sections of a biopsy (e.g., a formalin fixed paraffin embedded biopsy). In other aspects the biomarkers are proteins and/or nucleic acids. In other aspects the biomarkers function in ErbB-mediated signal transduction.

The invention relates to methods and compositions for identifying pregnant subjects having, or predisposed to having, gestational diabetes, preeclampsia, and gestational hypertension. The methods are applicable to urine and/or blood samples and can be conducted prior to the third trimester of pregnancy, and as early as the first trimester.

Screening for gestational disorders

The invention describes a process for preparing a microtiter-microarray device that includes a bottomless microtiter plate attached to the first side of one or more substrates with microarrays of materials attached thereto. The microtiter plate and the one or more substrates are attached through one or more gaskets. Preferably, the microtiter plate is attached to one face of the one or more gaskets by an irreversible water-tight seal, and the first side of the one or more substrates is attached to the opposite face of the one or more gaskets by a reversible, water-tight seal.

Interface between substrates having microarrays and microtiter plates

The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support, wherein the density of the array of compounds is at least 1000 spots per cm . In particularly preferred embodiments, these compounds are attached to the solid support through a covalent interaction. In general, these inventive arrays are generated by: (1) providing a solid support, wherein said solid support is functionalized with a selected chemical moiety capable of interacting with a desired chemical compound to form an attachment; (2) providing one or more solutions of one or more types of compounds to be attached to the solid support; and (3) delivering said one or more types of compounds to the solid support, whereby an array is formed and the array of compounds has a density of at least 1000 spots per cm . In another aspect, the present invention provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest comprising: (1) providing an array of compounds, wherein the array has a density of at least 1000 spots per cm ; (2) contacting the array with one of more types of biological macromolecules of interest; and (3) determining the interaction of specific small molecule-biological macromolecule partners.

Small molecule printing

Growing community of inventors

Wakefield, MA, United States of America

Gavin MacBeath