Tufts University

Wellesley College

New England Medical Center Hospitals. Inc.

Massachusetts Institute of Technology

M.i.t.

New England Medical Center

Other

Center for Blood Research, Inc.

Mass. Inst. of Technology

New England Med. Center Hospitals

Philip E Auron

Andrew C Webb

Charles A Dinarello

Alexander Rich

Lee Gehrke

Lanny J Rosenwasser

Sheldon M Wolff

Wayne R Waterman

Junichi Tsukada

Sheldon M Wolff, Deceased

The subject invention concerns a nucleic acid comprising a nucleotide sequence encoding human interleukin-1 (IL-1), and fragments thereof, and the polypeptides and peptides obtained. Specifically, the subject invention comprises the cloning of a cDNA synthesized by reverse transcription of poly(A)RNA isolated from adherent human monocytes stimulated with bacterial endotoxin. Human IL-1 is useful to induce the production of IL-2 by activated T-cells; it also acts on B-cells and NK-cells. The subject invention further concerns antibodies that are immunoreactive with human IL-1.beta. proteins.

Biologically active fragments of IL-1.beta.

The subject invention concerns a nucleic acid comprising a nucleotide sequence encoding human interleukin-1 (IL-1), and fragments thereof, and the polypeptides and peptides obtained. Specifically, the subject invention comprises the cloning of a cDNA synthesized by reverse transcription of poly(A)RNA isolated from adherent human monocytes stimulated with bacterial endotoxin. Human IL-1 is useful to induce the production of IL-2 by activated T-cells; it also acts on B-cells and NK-cells.

Recombinant DNA which codes for interleukin-1

A method for finding an agent which inhibits interaction between LIL-Stat protein and a nucleic acid having a LIL-Stat binding sequence is described. The LIL-Stat protein is contacted with the nucleic acid in the presence of an agent which inhibits or does not inhibit the interaction between the LIL-Stat protein and the nucleic acid. It is determined whether or not the agent inhibits this interaction. Also described are a method for treating an inflammatory response in a mammal, a therapeutic inhibitory agent suitable for treating or preventing an inflammatory response in a mammal, and DNA molecules having a DNA sequence encoding a binding site for the LIL-Stat protein.

LIL-Stat DNA binding sites and methods for identifying inhibitory

The subject invention concerns a nucleic acid comprising a nucleotide sequence encoding human interleukin-1 (IL-1), and fragments thereof, and the polypeptides and peptides obtained. Specifically, the subject invention comprises the cloning of a cDNA synthesized by reverse transcription of poly(A)RNA isolated from adherent human monocytes stimulated with bacterial endotoxin. The subject invention further concerns antibodies that are immunoreactive with human IL-1.beta. proteins. Human IL-1 is useful to induce the production of IL-2 by activated T-cells; it also acts on B-cells and NK-cells.

Antibodies to IL-1.beta.

The subject invention concerns a nucleic acid comprising a nucleotide sequence encoding human interleukin-1 (IL-1), and fragments thereof, and the polypeptides and peptides obtained. Specifically, the subject invention comprises the cloning of a cDNA synthesized by reverse transcription of poly(A)RNA isolated from adherent human monocytes-stimulated with bacterial endotoxin. Human IL-1 is useful to induce the production of IL-2 by activated T-cells; it also acts on B-cells and NK-cells.

IL-1.beta.protein precursor

Disclosed are novel muteins of IL-1 compounds which can be used to regulate excess IL-1 produced in various diseases in humans and animals. The IL-1 muteins can be prepared by site-directed mutagenesis whereby a positively charged residue is replaced with a negatively charged or neutral residue at a designated position in the molecule. The resulting IL-1 muteins have reduced biological activity but retain receptor binding affinity.

Interleukin-1 muteins, their preparation and method of use to inhibit

The subject invention concerns truncated human Il-1 cDNA sequences which encode biologically-active novel human IL-1 proteins. These truncated human IL-1 cDNA sequences can be obtained by genetic engineering procedures using a clone of human IL-1 cDNA, having the accession number NRRL B-15770, as a starting material. The truncated human IL-1 cDNA sequences of the subject invention are contained in specified plasmids whose constructions are described in detail. Biologically-active human IL-1 proteins are useful to induce the production of IL-2 by activated T-cells. They also act on B-cells and NK-cells.

Human IL-1 cDNA sequences encoding biologically-active human IL-1

The subject invention concerns truncated human IL-1 cDNA sequences which encode biologically-active novel human IL-1 proteins. These truncated human IL-1 cDNA sequences can be obtained by genetic engineering procedures using a clone of human IL-1 cDNA, having the accession number NRRL B-15770, as a starting material. The truncated human IL-1 cDNA sequences of the subject invention are contained in specified plasmids whose constructions are described in detail. Biologically-active human IL-1 proteins are useful to induce the production of IL-2 by activated T-cells. They also act on B-cells and NK-cells.

Truncated human IL-1 cDNA sequences which encode biologically-active

The invention is directed to an Arg-Serpin human plasminogen activator inhibitor designated PAI-2. This protein is prepared via recombinant DNA means. The invention also includes other serpins which can be made by amino acid substitutions or deletions in conserved regions of PAI-1 and PAI-2, as shown in FIG. 4. The proteins of the invention can be used to inhibit, or at least modulate, human plasminogen activator activity in a variety of physiological conditions, e.g., fibrinolysis, tumor metastasis, and tumor growth.

Growing community of inventors

Framingham, MA, United States of America

Philip E Auron