Bristol-myers Squibb Compnay

Merck Sharp + Dohme Corp.

Oncogen

Rosetta Inpharmatics, Inc.

Sarepta Therapeutics, Inc.

The Netherlands Cancer Institute

Oncogen Limited Partnership

Sanofi

Emory University

Other

Merck + Co., Inc.

Yale University

Fred Hutchinson Cancer Center

Cetus Corporation

Dharmacon, Inc.

Peter S Linsley

Jeffrey A Ledbetter

Nitin Krishnaji Damle

William Brady

Jurgen Bajorath

Robert Peach

Joseph P Brown

Joseph Naemura

Diane Horn

Lisa K Gilliland

Julja Burchard

Martha S Hayden

Karl E Hellstrom

Ingegerd E Hellstrom

H Perry Fell

Joyce M Zarling

Aimee L Jackson

Mao Mao

Mohammed Shoyab

Hans Marquardt

Yudong He

HongYue Dai

Christopher J Roberts

Peter A Kiener

Laura Johanna Van't Veer

Janell M Schelter

Brian James Leppert

Marc J Van De Vijver

Rene Bernards

Alejandro A Aruffo

Steven Bartz

Lee Lim

Christian P Larsen

Philip M Wallace

Thomas C Pearson

Patricia A Moran

Michael L Diegel

Gunnar J Hanson

Peter Senter

Guy L Cavet

Diane L Hollenbaugh

Michele A Cleary

Marcia B Hanson

Peter C Su

Susan F Radka

Jill F Magnus

Augustinus A M Hart

Andrew B Adams

Karl Erik Hellstrom

Robert J Peach

Anastasia Khvorova

William Marshall

Devin Leake

Angela Reynolds

Mark A Kay

Lieping Chen

Patrick A Baeuerle

Francisco A Leon

David B Ring

Gregory J Hannon

Roland Stoughton

Stephen H Friend

Scott William Lowe

Anthony F Purchio

Timothy M Rose

Jean-Claude Becker

Arthur E Frankel

David Hagerty

Robert Cohen

Hongyue Dai

Judith A Kapp

Lin He

Suzette Carr

Jerald P Radich

Xingyue He

Collin J Weber

Kevan C Herold

Susan A Safley

Karl Erik Hellstr&ouml;m

Ingegerd Hellstr&ouml;m

Vincent Ochs

Najma Malik

Ge Wei

Christopher B Wilson

Jeffery C Kallestad

Vincent W Ochs

Sarah Alice Long

Wei Ge

A A M Hart

Aa M Hart

Mary K Hagler

Miho Kibukawa

Joseph R Naemura

Steven R Bartz

Yuriy Fedorov

Joseph Patrick Brown

Provided herein, in one aspect, is a method of preventing or delaying the onset of clinical type 1 diabetes (T1D), comprising: providing a non-diabetic subject who is at risk for T1D; administering a prophylactically effective amount of an anti-CD3 antibody to the non-diabetic subject; and determining, prior to or after the administering step, that the non-diabetic subject has more than about 5% to more than about 10% TIGIT+KLRG1+CD8+ T-cells in all CD3+ T cells, which is indicative of successful prevention or delay of the onset of clinical T1D.

Methods and compositions for preventing type 1 diabetes

The invention provides for a method for selectively reducing the expression of a mutant mRNA and/or protein having an expanded nucleotide repeat relative to a wild-type mRNA, comprising contacting a cell with an antisense oligonucleotide of sufficient length and complementarity to the expanded nucleotide repeat. More particularly it relates to selectively reducing the expression of mutant Huntington protein associated with Huntington's disease. The antisense oligonucleotide comprising either a nucleotide or a repeated three nucleotide sequence as defined in the claims.

Oligonucleotides for treating expanded repeat diseases

The invention relates to the use of an antisense compound for inducing exon inclusion as a treatment for Spinal Muscle Atrophy (SMA). More particularly it relates to inducing inclusion of exon 7 to restore levels of Survival Motor Neuron (SMN) protein encoded by the Survival Motor Neuron (SMN) gene.

Induced exon inclusion in spinal muscle atrophy

The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Methods of treatment using CTLA4 mutant molecules

The present invention relates to genetic markers whose expression is correlated with breast cancer. Specifically, the invention provides sets of markers whose expression patterns can be used to differentiate clinical conditions associated with breast cancer, such as the presence or absence of the estrogen receptor ESR1, and BRCA1 and sporadic tumors, and to provide information on the likelihood of tumor distant metastases within five years of initial diagnosis. The invention relates to methods of using these markers to distinguish these conditions. The invention also relates to kits containing ready-to-use microarrays and computer software for data analysis using the statistical methods disclosed herein.

Diagnosis and prognosis of breast cancer patients

In one aspect, a method is provided of inhibiting proliferation of a mammalian cell comprising introducing into said cell an effective amount of at least one at least one small interfering RNA agent (iRNA), wherein said iRNA comprises a nucleotide sequence of at least 15 nucleotides, wherein the nucleotide sequence comprises a seed region consisting of nucleotide positions 1 to 12, wherein position 1 represents the 5' end of the iRNA nucleotide sequence and wherein said seed region comprises a nucleotide sequence of at least six contiguous nucleotides that is complementary to six contiguous nucleotides within positions 1 to 12 of a nucleotide sequence, wherein position 1 represents the 5&#x2033;end of the nucleotide sequence, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8. In some embodiments, the method comprises introducing at least one iRNA that inhibits the expression of at least one miR-16 responsive gene selected from TABLE 5 into the mammalian cell.

Methods and compositions for regulating cell cycle progression

The invention provides methods and compositions for gene silencing by RNA interference. In particular, the invention provides methods for gene silencing or RNA knockdown using small interfering RNAs (siRNAs) having partial sequence homology to its target gene. The invention also provides methods for identifying common and/or differential responses to a plurality of different siRNAs targeting a gene. The invention also provides methods for evaluating the relative activity of the two strands of an siRNA. The invention further provides methods of designing siRNAs for gene silencing. The invention further provides methods of using siRNAs as therapeutics for treatment of diseases.

Methods and compositions for RNA interference

The present invention provides a method for identifying siRNA target motifs in a transcript using a position-specific score matrix approach. The invention also provides a method for identifying off-target genes of an siRNA using a position-specific score matrix approach. The invention further provides a method for designing siRNAs with higher silencing efficacy and specificity. The invention also provides a library of siRNAs comprising siRNAs with high silencing efficacy and specificity.

Method for selecting SIRNAs from a plurality of SIRNAs for gene silencing

In one aspect, the invention generally relates to use of miR-34 as a biomarker to estimate TP53 function in a cell. In another aspect, the invention generally relates to multiple uses of miR-34 and siRNAs functionally and structurally related to miR-34 for the treatment of cancer.

Methods of using MIR34 as a biomarker for TP53 functional status

In one aspect, the invention generally relates to compositions comprising miR-34 and siRNAs functionally and structurally related to miR-34 for the treatment of cancer.

Compositions comprising MIR34 therapeutic agents for treating cancer

The invention provides molecular markers that are associated with the progression of chronic myeloid leukemia (CML), and methods and computer systems for monitoring the progression of CML in a patient based on measurements of these molecular markers. The present invention also provides CML target genes, and methods and compositions for treating CML patients by modulating the expression or activity of these CML target genes and/or their encoded proteins. The invention also provides genes that are associated with resistance to imatinib mesylate (Gleevec&#x2122;) treatment in CML patients, and methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate treatment based on measurements of these genes and/or their encoded proteins. The invention also provides methods and compositions for enhancing the effect of Gleevec&#x2122; by modulating the expression or activity of these genes and/or their encoded proteins.

Genes associated with progression and response in chronic myeloid leukemia and uses thereof

Growing community of inventors

Encinitas, CA, United States of America

Peter S Linsley