Oncogen

Lifespan Biosciences, Inc.

Sanofi

Other

The Boeing Company

Bristol-myers Company

Cetus Corporation

Genetic Systems Corporation

Oncogen Limited Partnership

Bristol-myers Squibb Compnay

Joseph P Brown

Peter S Linsley

Diane Horn

Karl E Hellstrom

Ingegerd E Hellstrom

Glenna C Burmer

Gregory D Plowman

James Johnathan Childress

Anthony F Purchio

Timothy M Rose

Shiu-Lok Hu

Mark S Alston

Sridhar Pennathur

Charles D Estin

Amanda A Ford

Mark George Saulnier

David B Ring

Hans Marquardt

Arthur E Frankel

David E Kerr

Vincent Ochs

Christine C Stewart

Vincent W Ochs

Karl Erik Hellstrom

This invention relates to the discovery of the association of certain nucleic acid sequences and proteins with breast cancer, the use of such sequences as a diagnostic indicator and treatments based on the association.

Breast cancer associated nucleic acid sequences and their associated proteins

This invention provides methods for the isolation of complete representation of cellular messenger ribonucleic acid from wax-embedded tissue samples. Expression of genes of interest can thus be fortuitously determined and cDNA probes can be readily developed.

Methods of measuring gene expression using wax-embedded tissue specimens

Novel hybridoma cell lines producing monoclonal antibodies reactive with purified mucin antigens from normal and tumor sources are generated using mucins, including purified mucins from tumor sources. Epitopes on mucin antigens from normal and tumor sources are demonstrated to be distinct, using these new antibodies. The antibodies may be useful alone or in combination, in the diagnosis and treatment of cancer including malignancies of the breast and lung.

Method for detecting cancer using monoclonal antibodies to new mucin

The present invention provides gene subtraction methods that can be used to identify and isolate from hybridization mixtures differentially expressed nucleic acid and/or commonly expressed nucleic acid between two populations of nucleic acid. The methods of the present invention employ a restriction endonuclease recognition site that is also recognized in whole or in part by a second restriction endonuclease (e.g., HinPI and BssHII or HhaI and HinP1I) to create different ends (e.g., sticky ends) between the first and second nucleic acid populations. In addition, the methods of the present invention use a selective ligation step, a biotinylated nucleotide extension step, or both to differentiate between homoduplexes, which allow for the identification of sequences that are different between the two nucleic acid populations, and heteroduplexes, which allow for the identification of sequences that are common to the two nucleic acid populations.

Subtractive hybridization techniques for identifying differentially

The strength of composite patches is improved over conventional bolted or bonded patches by including Z-pins in the patch/parent structure interface to provide a mechanical link with small stress concentration between the patch and the parent structure. In some cases, we achieve a stronger repair removing the pins to leave holes that fill with resin from the patch during the curing or bonding operation.

Composite patches having Z-pin reinforcement

Z-pin reinforced bonded composite repairs

Hybridomas producing monoclonal antibodies to new mucin epitopes

A method for treating serum samples to remove sialic acid from ligands to expose binding sites to enhance immunological binding, for use in assays and to generate novel anti-ligands is described. The method includes treatment of serum using neuraminidase.

Method for increasing the sensitivity of assays for target ligand

The present invention relates to a novel monoclonal antibody reactive with human colorectal mucin antigen. More particularly, the antibody of the invention is a murine monoclonal antibody, CT43, reactive with a novel antigenic determinant on much antigen highly correlated with human colorectal cancer. The antigenic determinant found by the CT43 has been characterized as neuraminidase and proteinase K resistant, periodate sensitive and unreactive with the glycoconjugates of Table 2. Methods are provided for the detection and quantitation of the CT43 antigenic determinant and its correlation with colorectal cancer. CT43, and CT66 specific for the sialylated Lewis a and Lewis a antigen have been deposited with the American Type Culture Collection, as accession numbers ATCC HB 10217 and ATCC HB 10218, deposited Sep. 6, 1989.

Hybridoma CT43 producing a monoclonal antibody to a novel mucin epitope

Peptides or proteins related to a melanoma associated antigen are described. These are produced in large quantities via recombinant DNA techniques and/or by chemical synthetic methods. The peptides or proteins can be used as immunogens in vaccine formulations which can induce an immune response that selectively destroys melanoma cells in a vaccinated individual. Where the peptides or proteins are expressed by a recombinant virus, inactivated or live virus vaccine formulations may be prepared.

Recombinant viruses encoding the human melanoma-associated antigen

The present invention is concerned with novel monoclonal antibodies which bind strongly to a protein antigen associated with human non-small cell lung carcinomas ('NSCLC') human small cell lung carcinomas and certain other human carcinomas including many carcinomas of the colon and breast. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use both in diagnostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods for treatment of human in NSCLC and certain other human carcinomas. Also disclosed is a novel 110,000 dalton glycoprotein antigen found on the cell surface of human non-small lung carcinoma tumor cells and on cells from certain other human cancers. The amino terminal amino acid sequence of this antigen is: ##STR1## in which X represents an unidentified amino acid.

Monoclonal antibodies and antigen for human non-small cell lung

Vaccines against melanoma

The present invention is concerned with novel monoclonal antibodies which define a glycolipid antigen associated with human non-small cell lung carcinomas ('NSCLC') and certain other human carcinomas. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use in diagnostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods. The invention also comprises a method for determining the presence of a malignant condition in lung tissue and other human tissue. The method involves examining the human tissue for the presence of a glycolipid antigen having the characteristics of a ganglio-N-triosylceramide.

Monoclonal antibodies for treatment of human non-small cell lung

This invention relates to a novel method for the delivery of cytotoxic drugs to tumor cells by the administration of a tumor-specific antibody-enzyme conjugate that binds to the tumor cells, and the additional administration of a prodrug that is converted at the tumor site, in the presence of the antibody-bound enzyme, to an active cytotoxic drug. According to preferred embodiments of this invention, antibody-enzyme conjugates containing the enzyme, alkaline phosphatase ('AP'), have been used in conjunction with the novel prodrug, etoposide-4'-phosphate or 7-(2'-aminoethyl phosphate)mitomycin or a combination thereof, to effect killing of tumor cells. According to another embodiment of the invention, an antibody-enzyme conjugate containing the enzyme, penicillin V amidase ('PVA'), has been used in conjunction with a novel prodrug, N-(p-hydroxyphenoxyacetyl)adriamycin to effect killing of tumor cells. Still another embodiment of the invention relates to the use of an antibody-enzyme conjugate containing the enzyme, cytosine deaminase ('CD'), in combination with the prodrug, 5-fluorocytosine, to effect killing of tumor cells. The method, antibody-enzyme conjugates, prodrugs, pharmaceutical compositions and combinations of this invention provide for enhanced selective killing of tumor cells and are thus useful in the treatment of cancers and other tumors.

Antibody-enzyme conjugates in combination with prodrugs for the delivery

The present invention is concerned with novel monoclonal antibodies which define a gylcolipid antigen associated with human non-small cell lung carcinomas ('NSCLC') and certain other human carcinomas. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use in diagonostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods. The invention also comprises a method for determining the presence of a malignant condition in lung tissue and other human tissue. The method involves examining the human tissue for the presence of a glycolipid antigen having the characteristics of a ganglio-N-triosylceramide.

Monoclonal antibodies to the L6 glycolipid antigenic determinant found

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Seattle, WA, United States of America

Joseph P Brown