The Ohio State University

Aphton Corporation

Onconon, LLC

Vernon C Stevens

Pierre L Triozzi

Stephen Grimes

Pravin T P Kaumaya

Dov Michaeli

Edwin P Rock

Antibody compositions and methods for inhibition of the effects of gonadotropin hormones are provided. Methods for treating cancer and methods for regulating fertility are provided by administration of the antibody compositions to a mammalian subject in need thereof.

Antibody compositions, methods for treating neoplastic disease and methods for regulating fertility

Compositions for stimulating the immune system and for treating malignancies associated with overexpression of the HER-2 protein are provided. Such compositions include immunogenic epitopes of the HER-2 proteins and chimeric and multivalent peptides which comprise such epitopes. The present invention also relates to polynucleotides which encode the chimeric peptides. Also provided are pharmaceutical compositions comprising such immunogenic compositions. Methods for stimulating an immune response to HER-2 protein are provided. Methods for treating breast cancer, ovarian cancer, prostate cancer, colon cancer and lung cancer are provided.

Polypeptides and polynucleotides for enhancing immune reactivity to HER-2 protein

Chimeric peptide epitopes can serve as effective immunogens against hormones and other small peptides or proteins. Thus, immunogenic peptides are selected from promiscuous Th epitopes and synthesized together with self antigenic peptide sequences fused with or without end to end spacer peptide interconnections. A peptide sequence which may be of the gonadotropin releasing hormone is linked with an immunogenic peptide sequence selected from a promiscuous Th-epitope of measles virus protein F, tetanus toxoid, or malaria protein CSP. Compositions of the chimeric immunogen are found effective in eliciting high and specific anti-GnRH antibody titers.

Chimeric peptide immunogens

Endogenous protein hormones, fragments thereof including epitopes, and synthetic peptides mimicking epitope regions of hormones such as human chorionic gonadotropin can be conjugated to a foreign carrier or otherwise modified so as to produce antibodies in humans against the endogenous protein hormone. Synthetic analogs to the 38 to 57 sequence of the beta subunit of human chorionic gonadotropin have been found which upon conjugation to a suitable foreign carrier can be employed to raise a high level of antibodies to human chorionic gonadotropin with a significant decrease in antibodies reactive to human pituitary luteinizing hormones. Upon conjugation to a foreign carrier such analogs may be administered to humans to treat hormone-associated carcinomas and for purposes of contraception.

Antigenic modification of polypeptides

Endogenous and exogenous proteins, and fragments thereof, are chemically modified outside the body of an animal so that when injected into the animal they produce more antibodies against the unmodified protein than would injection of the unmodified protein or fragment alone. The chemical modification may be accomplished by attaching the proteins or fragments to carriers such as, for example, bacterial toxoids. The chemical modification can also be accomplished by polymerization of protein fragments. Proteins which can be modified include Follicle Stimulating Hormone and Human Chorionic Gonadotropin. The modified polypeptides may be administered to animals for the purpose of contraception, abortion or treatment of hormone-related disease states and disease disorders, treatment of hormone-associated carcinomas, and to boost the animals resistance to exogenous proteins, for example viral proteins.

Antigenic modification of HCG polypeptides

Endogenous and exogenous proteins, and fragments thereof, are chemically modified outside the body of an animal so that when injected into the animal they produce more antibodies against the unmodified protein than would injection of the unmodified protein or fragment alone. The chemical modification may be accomplished by attaching the proteins or fragments to carriers such as, for example, bacterial toxoids. The chemical modification can also be accomplished by polymerization of protein fragments. Proteins which can be modified include Follicle Stimulating Hormone and Human Chorionic Gonadotropin. The modified polypeptide may be administered to animals for the purpose of contraception, abortion or treatment of hormone-related disease states and disease disorders, treatment of hormone-associated carcinomas, and to boost the animals' resistance to exogenous proteins, for example viral proteins.

Method for treatment of antigenically modified polypeptides

Antigenically modified polypeptides composition

Antigenically modified HCG polypeptides

Endogenous and exogenous proteins, and fragments thereof, are chemically modified outside the body of an animal so that when injected into the animal they produce more antibodies against the unmodified protein than would injection of the unmodified protein or fragment alone. The chemical modification may be accomplished by attaching the proteins or fragments to carriers such as, for example, bacterial toxoids. The chemical modification can also be accomplished by polymerization of protein fragments. Proteins which can be modified include Follicle Stimulating Hormone and Human Chorionic Gonadotropin. The modified polypeptide may be administered to animals for the purpose of contraception, abortion or treatment of hormone-related disease states and disease disorders, treatment of hormone-associated carcinomas, and to boost the animals resistance to exogenous proteins, for example viral proteins.

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Dublin, OH, United States of America

Vernon C Stevens