The United States of America As Represented by the Department of Health

The United States of America As Represented by the Secretary of

Cetus Corporation

Mark C Willingham

Ira H Pastan

Kai Chang

Ulrich Brinkmann

David J Fitzgerald

David Fitzgerald

Lee Pai

David B Ring

David J FitzGerald

Walter J Laird

Arthur E Frankel

Michael J Bjorn

Jeffrey L Windelhake

This invention provides for recombinant single chain antibodies capable of specifically binding to a Lewis.sup.Y -related carbohydrate antigen and fusion proteins comprising these antibodies. More particularly, the invention provides for single chain Fv regions of the monoclonal antibody B3. The invention also provides for a method of improving the binding affinity of antibodies lacking a serine at position 95 of the V.sub.H region that involves mutating position 95 to a serine.

Single chain B3 antibody fusion proteins and their uses

The subject invention relates to methods for reducing tumor cell growth in a mammal by administering compositions which include an antibody having the binding specificity of a monoclonal antibody selected from the group comprising one of those referred to as B1, B3 or B5 conjugated to a toxin, radionuclide or drug.

Methods for reducing tumor cell growth by using antibodies with broad

The invention provides a novel treatment of cancer using a monoclonal antibody that recognizes cell surface antigens present on a number of tumor cells, including ovarian, esophageal and cervical carcinomas. A preferred monoclonal antibody is secreted by a hybridoma deposited with the ATCC and has Accession NO. HB 10570.

Monoclonal antibodies and conjugates thereof useful for the treatment of

The subject invention relates to monoclonal antibodies and uses thereof. In particular, the invention relates to three monoclonal antibodies, referred to as B1, B3, and B5, which are useful in the treatment and diagnosis of many forms of cancer.

Method for diagnosing tumors using mouse monoclonal antibodies

Monoclonal antibody K1 binds to an epitope on the surface of cells of some human tumors, but not to many important normal tissues. Unlike similar antigenic sites such as CA125, this epitope is not shed into the plasma of patients with mesothelioma, e.g. with ovarian cancer. Since the K1 monoclonal antibody is therefore not neutralized by circulating antigen immediately upon injection into the bloodstream, and since K1 allows efficient entry of coupled toxins into cells, the K1 monoclonal antibody can be used in the diagnosis of mesotheliomas.

Monoclonal antibody binding cell surface antigens for diagnosing cancer

The invention provides novel monoclonal antibodies and the hybridomas that secrete them. The antibodies can be used for the diagnosis of a number of cancers, such as ovarian, esophageal and cervical carcinomas. A preferred antibody is secreted by a hybridoma deposited with the ATCC and has Accession No. HB 10570.

Monoclonal antibody useful for the diagnosis of cancer

Mouse monoclonal antibodies specific for normal primate tissue,

Immunotoxins comprising a cytotoxic moiety and monoclonal antibodies which bind to human ovarian cancer tissue having at least one of the following capabilities are claimed: cytotoxic ID.sub.50 of 10 nM or less against human ovarian cancer cells, retardation of human ovarian cancer tumor growth in mammals or extension of survival of a mammal carrying a human ovarian cancer tumor. Antigens to which the monoclonal antibody of the immunotoxin bind are identified and characterize the immunotoxins. Methods of killing human ovarian cancer cells, retarding the growth of human ovarian cancer tumors in mammals or extending the survival of mammals carrying human ovarian cancer tumors are claimed.

Anti-human ovarian cancer immunotoxins and methods of use thereof

Monoclonal antibodies are produced which specifically bind to human ovarian cancer cells. These antibodies are conjugated to Pseudomonas exotoxin in order to produce an immunotoxin suitable for the chemotherapeutic treatment of human ovarian cancer.

Monoclonal antibody against ovarian cancer cells (OVB-3)

A method of modifying Pseudomonas exotoxin (PE) with methyl-4-mercaptobutyrimidate is disclosed so that after conjugating the exotoxin to a monoclonal antibody (ab) such as the antibody to the transferrin receptor, the PE-ab conjugate becomes a highly potent immunotoxin suitable for use against human tumor cells. This same method has been used to conjugate PE to epidermal growth factor (EGF) to create a highly potent growth factor-toxin conjugate for use against cells having large numbers of EGF receptors. Also disclosed are the immunotoxin conjugates for Pseudomonas exotoxin coupled to anti-TFR (antibody to the transferrin receptor) and anti-TAC (antibody to the human T-cell growth factor receptor) and to EGF.

Pseudomonas exotoxin conjugate immunotoxins

The entry of animal viruses into their host cells proceeds via a specialized internalization pathway involving clathrin coated regions of the plasma membrane. In the present invention, there has been examined the effect of dansylcadaverine compared with amantadine and other antiviral agents as to the entry of vesicular stomatitis virus (VSV) into mouse cells. It was found that both compounds inhibit VSV entry. Both compounds inhibit the uptake of .alpha..sub.2 macroglobulin (.alpha.2M), a protein that binds to specific membrane receptors and follows the same route of internalization. Dansylcadaverine is 20 fold more potent than amantadine to the blocking virus and also to the .alpha..sub.2 macroglobulin uptake.

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Bethesda, MD, United States of America

Mark C Willingham