Isis Pharmaceuticals, Inc.

Baylor College of Medicine

Biosciences Corporation of Texas

Harris Busch

Rose K Busch

James W Freeman

C Frank Bennett

Jacqueline R Wyatt

Clarence Frank Bennett

Karel Smetana

Laszlo Perlaky

Frances M Davis

Ferenc Gyorkey

Phyllis Gyorkey

Yasuo Saijo

Antisense compounds, compositions and methods are provided for modulating the expression of GU Protein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding GU Protein. Methods of using these compounds for modulation of GU Protein expression and for treatment of diseases associated with expression of GU Protein are provided.

Antisense modulation of GU protein expression

Oligonucleotides capable of inhibiting the production of proliferation-associated proteins are provided. Oligonucleotides designed to be hybridizable with nucleic acids encoding nucleolar proteins are believed to be therapeutically useful. Certain of such oligonucleotides, hybridizable to portions of the gene coding for p120, especially the 3' untranslated region, were made and found to inhibit the synthesis of p120. The oligonucleotides of the invention are useful for the treatment of diseases characterized by hyperproliferation of cells such as malignancies, inflammatory and cardiovascular diseases. Treatment of human breast cell carcinoma, human epitheloid cervix carcinoma, human amelanotic melanoma, human renal cell carcinoma and other tumors are indicated.

Oligonucleotide modulation of cell growth

Tumor nucleoli were treated with polyclonal antisera to normal human tissue nucleoli to block determinants common to tumor and normal tissue nucleoli. Immunization of mice with these immune-complexes resulted in the development of a monoclonal antibody (FB2) to a novel nucleolar proliferation associated antigen which has a molecular wei

Detection of human cancer cells with antibodies to human cancer

Specific common nucleolar antigens are found in a broad range of human malignant tumor specimens and have been isolated, extracted and purifed. Monoclonal antibodies specific to one of these nucleolar antigens (p145) are harvested from mouse ascites or culture supernatant and used for detection of human

Detection of human cancer cells with anitbodies to human cancer

Specific common nucleolar antigens are found in a broad range of human malignant tumor specimens and have been isolated, extracted and purified. Antibodies and antisera specific to these nucleolar antigens are harvested from non-human hosts and used for detection of human cancer cells. Disclosed are (1) methods for isolating the nucleolar antigens, obtaining them in substantially purified form, producing the specific antibodies, obtaining them in substantially purified form, and using the antisera and antibodies induced by the nucleolar antigens in diagnostic procedures for detecting human cancer cells, and (2) diagnostic kits comprising specific antibodies and antisera.

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Houston, TX, United States of America

Harris Busch