University of Medicine and Dentistry of New Jersey

Columbia University

Gordon J MacDonald

William R Moyle

Robert E Canfield

Robert K Campbell

E Glenn Armstrong

Yanhong Wang

Donna M Anderson

Yi Han

The present invention pertains to an alpha, beta-heterodimeric polypeptide having binding affinity to vertebrate luteinizing hormone (LH) receptors and vertebrate follicle stimulating hormone (FSH) receptors comprising a glycoprotein hormone alpha-subunit polypeptide and a non-naturally occurring beta-subunit polypeptide, wherein the beta-subunit polypeptide is a chain of amino acids comprising the following four joined subsequences: (a) a first subsequence homologous to the amino acid sequence of residues 1-93 of the beta-subunit selected from the group consisting of human chorionic gonadotrophin (hCG), vertebrate luteinizing hormone (LH), vertebrate follicle stimulating hormone (FSH), and vertebrate thyroid stimulating hormone (TSH); (b) a second subsequence homo logous to the amino acid sequence of residues 94-97 of the beta-subunit selected from the group consisting of human chorionic gonadotrophin (hCG) and vertebrate luteinizing hormone (LH); (c) a third subsequence homologous to the amino acid sequence of residues 98-100 of the beta-subunit selected from the group consisting of human chorionic gonadotrophin (hCG), vertebrate luteinizing hormone (LH), vertebrate follicle stimulating hormone (FSH), and vertebrate thyroid stimulating hormone (TSH); and (d) a fourth subsequence homologous to the amino acid sequence of residues 101-110 of the beta-subunit of vertebrate follicle stimulating hormone.

Analogs of glycoprotein hormones having altered receptor binding

This invention provides a quantitative assay for determining the amount of a biologically active ligand selected from the group consisting of human chorionic gonadotropin and luetinizing hormone present in a sample comprising contacting the sample with both the receptor to which the ligand naturally binds in order to effect its biologicaly activity and a monoclonal antibody directed to the ligand or to a complex of the ligand and the receptor so as to form a complex of the ligand bound to both the receptor, at the site to which the ligand naturally binds to the receptor, and the monoclonal antibody. In the complex so formed, either the receptor or the monoclonal antibody is labeled with a detectable marker and a determination is made of the amount of labeled receptor or of labeled monoclonal antibody bound to the ligand or the amount of labeled receptor or of labeled monoclonal antibody not bound to the ligand, or both such amounts. This invention further provides a quantitative assay for determining the amount present in a sample of a receptor to which a biologically acitve ligand selected from the group consisting of human chorionic gonadotropin and luetinizing hormone naturally binds in order to effect its biological activity. Finally, this invention provides kits for quantitatively assaying for the amount present in a sample of a biologically active ligand or for a receptor to which the ligand naturally binds in order to effect its biological activity.

Sensitive bioassay using monoclonal antibodies which bind to

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Piscataway, NJ, United States of America

Gordon J MacDonald