Merrimack Pharmaceuticals, Inc.

Praecis Pharmaceuticals, Inc.

William Kubasek

Gavin MacBeath

Lin Nie

Bambang Adiwijaya

Sharon Moulis

Rachel C Nering

Defne Yarar

Akos Czibere

Malcolm L Gefter

Ulrik Bjerl Nielsen

Gary Fred Musso

Jonathan Basil Fitzgerald

Marc B Garnick

Mark A Findeis

Birgit Schoeberl

Matthew D Onsum

Ethan R Signer

Brian Harms

James Wakefield

Howard Benjamin

Michael Kelley

Arvind Hundal

Susan Molineaux

Joseph Chin

Jung-Ja Lee

Laura Kasman

Michael J Reed

Francis David Gibbons

Matthew David Onsum

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

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 provides methods for treating patients which methods comprise methods for predicting responses of cells, such as tumor cells, to treatment with therapeutic agents. These methods involve measuring, in a sample of the cells, levels of one or more components of a cellular network and then computing a Network Activation State (NAS) or a Network Inhibition State (NIS) for the cells using a computational model of the cellular network. The response of the cells to treatment is then predicted124 based on the NAS or NIS value that has been computed. The invention also comprises predictive methods for cellular responsiveness in which computation of a NAS or NIS value for the cells (e.g., tumor cells) is combined with use of a statistical classification algorithm. Biomarkers for predicting responsiveness to treatment with a therapeutic agent that targets a component within the ErbB signaling pathway are also provided.

Methods and systems for predicting response of cells to a therapeutic agent

Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural .beta. amyloid peptides (.beta.-AP). In a preferred embodiment, the .beta. amyloid modulator compounds of the invention are comprised of an A.beta. aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural .beta. amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural .beta.-AP aggregation when the natural .beta.-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

A.beta. peptides that modulate .beta.-amyloid aggregation

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Belmont, MA, United States of America

William Kubasek