The United States of America, As Represented by the Secretary, Department of Health and Human Services

Other

James Vincent

Ira H Pastan

Byungkook Lee

Curt Douglas Wolfgang

Tapan K Bera

Satoshi Nagata

Masanori Onda

George Vasmatzis

Robert Kreitman

Yasuo Tsutsumi

A new polypeptide is disclosed that is specifically detected in the cells of the prostate, termed Novel Gene Expressed in Prostate (NGEP). Polynucleotides encoding NGEP are also disclosed, as are vectors including these polynucleotides. Host cells transformed with these polynucleotides are also disclosed. Antibodies are disclosed that specifically bind NGEP. Methods are disclosed for using an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP. Assays are disclosed for the detection prostate cancer. Pharmaceutical compositions including an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP are also disclosed. These pharmaceutical compositions are of use in the treatment of prostate cancer.

Gene expressed in prostate cancer and methods of use

A new polypeptide is disclosed that is specifically detected in the cells of the prostate, termed Novel Gene Expressed in Prostate (NGEP). Polynucleotides encoding NGEP are also disclosed, as are vectors including these polynucleotides. Host cells transformed with these polynucleotides are also disclosed. Antibodies are disclosed that specfically bind NGEP. Methods are disclosed for using an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP. Assays are disclosed for the detection prostate cancer. Pharamaceutical compositions including an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP are also disclosed. These pharmaceutical compositions are of use in the treatment of prostate cancer.

The invention provides recombinant immunotoxins that have been modified from a parental immunotoxin to lower liver toxicity. The immunotoxins are created by specifically mutating charged residues in the framework regions of the heavy chain, the light chain, or both, of the antibody portion or antigen-binding fragment thereof of the parental immunotoxin to reduce the pI of the antibody or fragment. In preferred forms, the antibody portion of the parental is an anti-Tac, anti-mesothelin, or anti-LewisY antigen antibody or antigen-binding fragment, and in particularly preferred forms the antibody portion is an M16 dsFv, a St6 dsFv or a Mt9 dsFv, or a sequence that has at least 90% sequence identity to one of these molecules but retain the particular mutations that lower pI without affecting antibody activity. The invention further provides nucleic acids encoding the recombinant immunotoxins of the invention, expression cassettes comprising the nucleic acids, and host cells comprising the expression cassettes. The invention also provides a method for killing a cell comprising an antigen on the surface of the cell, the method comprising contacting the cell with a recombinant immunotoxin of the invention that has an antibody or antigen-binding fragment thereof that binds specifically to the antigen on the surface of the cell, and uses of immunotoxins of the invention for the manufacture of medicaments.

Reduction of the nonspecific animal toxicity of immunotoxins by mutating the framework regions of the Fv to lower the isoelectric point

A bobbin having a drum for winding thereon of filamentary materials such as fishing tackle. The bobbin includes a flat, circular disc having a first surface from which a cylindrical wall extends, and a second surface from which the drum and hub means extend. The wall means of one bobbin mates with the hub means of an identical bobbin with a releasable, interference, snap fit to permit interconnection of a plurality of such bobbins in coaxial, side by side, relatively rotatable relation.

Bobbin for rotatable, releasable attachment to identical bobbins

A retainer for use with a bobbin having filamentary material wound thereon to prevent unwanted unwinding of the material. The retainer is formed from a strip of elastic material with one end folded back upon an intermediate portion to form a minor loop, and the other end passed around and superposed with the first end to form a major loop. The three superposed layers in the areas of the intermediate portion and immediately adjacent the two ends are permanently secured and an opening therethrough defined by a grommet. The major loop is stretched to pass over the peripheral edge of the bobbin and engage the outer layer of filamentary material with the free end of the latter passing through the opening in the retainer.

Growing community of inventors

Takoma Park, MD, United States of America

James Vincent