Millennium Pharmaceuticals Limited

University of Texas System

Bayer Corporation

Promega Corporation

Millenium Pharmaceuticals, Inc.

Novartis Ag

Chiron Corporation

Chiron Diagnostics Corporation

John E Monahan

Robert Schlegel

Xumei Zhao

Donna M Ford

Karen Glatt

Manjula Gannavarapu

Shubhangi Kamatkar

Wilson O Endege

Sebastian Hoersch

Yan Chen

James Robert Hartnett

James W Schumm

Leopoldo G Mendoza

Richard A Martinelli

Steven J Ekenberg

Mark A Maffitt

Randall L Dimond

Eddie Carroll, Iii

Edward E Pahuski

Jon H Astle

Katharine M Miller

Geoffrey R Hudson

Christopher L Jones

Kathleen E Steinmann

Robert C Bast

Gabriel N Hortobagyi

Marcia E Lewis

Theodore J Catino

Christopher C Burgess

Lajos Pusztai

Yong Yao Xu

Rachel E Meyers

Say-Jong Law

Shifeng Pan

Todd B Sells

John T Unger

Guohan Yang

Poornima Dwivedi

Gary A Molino

Youzhen Wang

Steven E Bushnell

Jimmy Zhang

Juliet Williams

Douglas N Ludtke

Marion Dorsch

Adnan Derti

James Lillie

Maureen Mertens, Hattersley

Vickesh Myer

Yongyao Xu

Dustin L Anderson

Bella O Gorbatcheva

Maureen Mertens

Michael Patrick Morrissey

Sebastian Hoersh

The invention provides methods for modulating, e.g., antagonizing, the activity of the Hedgehog signaling pathway, and for treating Hedgehog related disorders such as cancers (e.g., medulloblastoma). In particular, the invention provides methods for inhibiting aberrant growth states resulting from phenotypes such as Ptch loss-of-function, Hedgehog gain-of-function, smoothened gain-of-function or Gli gain-of-function by administering to a mammal combinations of Smoothened inhibitors (e.g., a compound of Formula I, Formula II, or Formula III, or any of the compounds listed herein or incorporated by reference) and cholesterol biosynthesis pathway inhibitors (e.g., statins), Gli inhibitors, and/or Phosphatidylinositol 3-kinase (PI3K) inhibitors.

Smoothened antagonism for the treatment of hedgehog pathway-related disorders

The invention relates to newly discovered nucleic acid molecules and proteins associated with cervical cancer including pre-malignant conditions such as dysplasia. Compositions, kits, and methods for detecting, characterizing, preventing, and treating human cervical cancers are provided.

Genes, compositions, kits, and methods for identification, assessment, prevention and therapy of cervical cancer

The invention relates to newly discovered nucleic acid molecules and proteins associated with ovarian cancer. Compositions, kits, and methods for detecting, characterizing, preventing, and treating human ovarian cancers are provided.

Nucleic acid molecules and proteins for the identification, assessment, prevention, and therapy of ovarian cancer

The invention relates to newly discovered nucleic acid molecules and proteins associated with breast cancer. Compositions, kits, and methods for detecting, characterizing, preventing, and treating human breast cancers are provided.

Compositions, kits, and methods for identification, assessment, prevention, and therapy of breast cancer

The invention relates to nucleic acid molecules and proteins associated with breast cancer. Compositions, kits, and methods for detecting, characterizing, preventing, and treating human breast cancers are provided.

The invention relates to nucleic acid molecules and proteins associated with cervical cancer including pre-malignant conditions such as dysplasia. Compositions, kits, and methods for detecting, characterizing, preventing, and treating human cervical cancers are also provided.

Compositions, kits, and methods for identification, assessment, prevention, and therapy of cervical cancer

Genes, compositions, kits and methods for identification, assessment, prevention, and therapy of cervical cancer

The present invention entails methods and kits for carrying them out based on the discovery that an RNA replicase, such as Q&bgr; replicase, has DNA-dependent RNA polymerase (&ldquo;DDRP&rdquo;) activity with nucleic acid segments, including DNA segments and DNA:RNA chimeric segments, which comprise a 2&prime;-deoxyribonucleotide or an analog thereof and which have sequences of RNAs that are autocatalytically replicatable by the replicase.

Nucleic acid amplification with DNA-dependent RNA polymerase activity of RNA replicases

Highly hydrophilic non-nucleosidic tags with multiple labels are provided for use in nucleic acid probes. The tags are branched structures having a phosphodiester backbone, which have the advantages of a small dimensional size and high hydrophilicity. After the tag is labeled, its high negative charge and minimal size help to keep the carriers away from DNA or RNA molecules, due to repulsion between negative charges. Non-specific intercalation and steric hindrance are therefore minimized, and the hydrophobicity, if any of reporter molecules is reduced. The probes are used in place of conventionally labeled oligonucleotides for a variety of hybridization reactions.

Nucleic acid probes having highly hydrophilic non-nucleosidic tags with multiple labels, and uses thereof

This invention relates to novel human genes, to proteins expressed by the genes, and to variants of the proteins. The invention also relates to diagnostic and therapeutic agents related to the genes and proteins, including probes, antisense constructs, and antibodies. The invention further relates to polynucleotides differentially expressed in prostate cancer.

Genes and gene expression products that are differentially regulated in prostate cancer

The present invention entails methods, and kits for carrying them out, based on the discovery that an RNA replicase, such as Q&bgr; replicase, has DNA-dependent RNA polymerase (&ldquo;DDRP&rdquo;) activity with nucleic acid segments, including DNA segments and DNA:RNA chimeric segments, which comprise a 2&prime;-deoxyribonucleotide or an analog thereof and which have sequences of RNAs that are autocatalytically replicatable by the replicase. The discovery of this DDRP activity provides methods of the invention for nucleic acid amplification wherein a nucleic acid, with a DNA segment with the sequence of an RNA that is autocatalytically replicatable by an RNA replicase, is provided as a substrate for the replicase. The replicase catalyzes synthesis, from the DNA segment, of the RNA, which the replicase then autocatalytically replicates. The invention entails use of the amplification methods in detecting nucleic acid analytes, as in nucleic acid probe hybridization assays. Such assays of the invention include those wherein a nucleic acid analyte is hybridized with one or more nucleic acid probes, which include or are processed to generate a DNA segment which is amplifiable through production from the segment, catalyzed by the DDRP activity of an RNA replicase, of an autocatalytically replicatable RNA, which is autocatalytically replicated to provide an abundance of readily detectable reporter molecules. The invention permits replacement of an RNA, that is autocatalytically replicatable with an RNA replicase and employed as a reporter or label in prior art assays, such as nucleic acid probe hybridization assays or immunoassays, with a nucleic acid comprising a DNA segment with the same base sequence as the RNA. The invention also includes the methods of the invention with Mn , Co , or Zn in the solutions in which the DDRP activity occurs.

This invention relates to novel human genes, to proteins expressed by the genes, and to variants of the proteins. The invention also relates to diagnostic assays and therapeutic agents related to the genes and proteins, including probes, antisense constructs, and antibodies. The subject nucleic acids have been found to be differentially regulated in tumor cells, particularly in colon cancer tissue.

Human genes and expression products: II

This invention relates to novel human genes, to proteins expressed by the genes, and to variants of the proteins. The invention also relates to diagnostic assays and therapeutic agents related to the genes and proteins, including probes, antisense constructs. and antibodies. The subject nucleic acids have been found to be differentially regulated in tumor cells, particularly colon cancer cell lines and/or tissue.

Human genes and gene expression products

The present invention entails methods, and kits for carrying them out, based on the discovery that an RNA replicase, such as Q.beta. replicase, has DNA-dependent RNA polymerase ('DDRP') activity with nucleic acid segments, including DNA segments and DNA:RNA chimeric segments, which comprise a 2'-deoxyribonucleotide or an analog thereof and which have sequences of RNAs that are autocatalytically replicatable by the replicase. The discovery of this DDRP activity provides methods of the invention for nucleic acid amplification wherein a nucleic acid, with a DNA segment with the sequence of an RNA that is autocatalytically replicatable by an RNA replicase, is provided as a substrate for the replicase. Assays of the invention include those wherein a nucleic acid analyte is hybridized with one or more nucleic acid probes, which include or are processed to generate a DNA segment which is amplifiable through production from the segment, catalyzed by the DDRP activity of an RNA replicase, of an autocatalytically replicatable RNA, which is autocatalytically replicated to provide an abundance of readily detectable reporter molecules.

Nucleic acid amplification with DNA-dependent RNA polymerase activity of

Growing community of inventors

Walpole, MA, United States of America

John E Monahan