In accordance with the present invention, there are provided fully human monoclonal antibodies against human epidermal growth factor receptor (EGF-r). Nucleotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences from CDR1 through CDR3, are provided. Hybridomas expressing such immunoglobulin molecules and monoclonal antibodies are also provided.

Human monoclonal antibodies to epidermal growth factor receptor

The present invention provides novel human sequence antibodies against human CTLA-4 and methods of treating human diseases, infections and other conditions using these antibodies.

Human ctla-4 antibodies and their uses

In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucleotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly contiguous heavy and light chain sequences spanning the complementarity determining regions (CDRs), specifically from within FR1 and/or CDR1 through CDR3 and/or within FR4, are provided. Further provided are antibodies having similar binding properties and antibodies (or other antagonists) having similar functionality as antibodies disclosed herein.

Human monoclonal antibodies to CTLA-4

Human monoclonal antibodies directed against B7-H1 and uses of these antibodies in diagnostics and for the treatment of diseases associated with the activity and/or expression of B7-H1 are disclosed. Additionally, hybridomas or other cell lines expressing such antibodies are disclosed.

Targeted binding agents against b7-h1

Oligomeric compounds including oligoribonucleotides and oligoribonucleosides are provided that have subsequences of 2′-pentoribofuranosyl nucleosides that activate dsRNase. The oligoribonucleotides and oligoribonucleosides can include substituent groups for increasing binding affinity to complementary nucleic acid strand as well as substituent groups for increasing nuclease resistance. The oligomeric compounds are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics. Also included in the invention are mammalian ribonucleases, i.e., enzymes that degrade RNA, and substrates for such ribonucleases. Such a ribonuclease is referred to herein as a dsRNase, wherein “ds” indicates the RNase's specificity for certain double-stranded RNA substrates. The artificial substrates for the dsRNases described herein are useful in preparing affinity matrices for purifying mammalian ribonuclease as well as non-degradative RNA-binding proteins.

Oligoribonucleotides and ribonucleases for cleaving RNA

A method for synthesizing sulfurized oligonucleotide analogs, such as phosphorothioate and phosphorodithioate analogs, is provided that employs a thiophosphorus compound, such as a thiophosphoric, dithiophosphoric, thiophosphinic, or dithiophosphinic acid disulfide or polysulfide, as a sulfurizing agent. The method of the invention may be used to sulfurize any phosphorous(III)-containing intermediate. Preferably, the method is practiced on a commercial DNA synthesizer using phosphoramidite and/or phosphorthioamidite intermediates.

Method of synthesizing sulfurized oligonucleotide analogs

Bis(O,O-diisopropoxy phosphinothioyl) disulfide - a highly efficient sulfurizing reagent for cost-effective synthesis of oligo(nucleoside phosphorothioate)s

An improved method for the synthesis of N3′→P5′ phosphoramidate oligonucleotides

31P NMR is an extremely valuable tool for oligonucleotide research and development. This brief commentary, which is directed to scientists who do not regularly use 31P NMR in their work, attempts to outline some of the principles, considerations, and representative applications of 31P NMR spectroscopy in oligonucleotide research and development.

31P NMR spectroscopy in oligonucleotide research and development.

A method for synthesizing sulfurized oligonucleotide analogs, such as phosphorothioate and phosphorodithioate analogs, is provided that employs a thiuram disulfide as a sulfurizing agent. The method of the invention may be used to sulfurize any phosphorous(III)-containing intermediate. Preferably, the method is practiced on a commercial DNA synthesizer using phosphoramidite and/or phosphorthioamidite intermediates.

Bernard L. Hirschbein

Papers

Method of synthesizing sulfurized oligonucleotide analogs

Bis(O,O-diisopropoxy phosphinothioyl) disulfide - a highly efficient sulfurizing reagent for cost-effective synthesis of oligo(nucleoside phosphorothioate)s

An improved method for the synthesis of N3′→P5′ phosphoramidate oligonucleotides

31P NMR spectroscopy in oligonucleotide research and development.

Method of synthesizing sulfurized oligonucleotide analogs with thiuram disulfides