Other

Columbia University

University of Medicine and Dentistry of New Jersey

Washington University

Merck Serono S. A.

William R Moyle

Robert E Canfield

Irving Boime

Paul H Ehrlich

Russell C Scaduto, Jr

Gordon J MacDonald

Robert K Campbell

Donna M Anderson

Yi Han

E Glenn Armstrong

Yanhong Wang

This invention relates to the field of glycoprotein hormone analogs and their uses as agonists, antagonists, targeting vectors, and immunogens. In particular, this invention describes a method for stabilizing a heterodimer that permits the preparation of functional glycoprotein hormone analogs. The analogs of present invention comprise at least one alpha subunit polypeptide and at least one beta subunit polypeptide, wherein the seatbelt region of the beta subunit is linked to the alpha subunit. The invention also provides for a beta subunit polypeptide wherein the C-terminal amino acid is from residue 10 to residue 20 of the seatbelt region.

Salmon follitropin hormone analogs

The invention relates to analogs of glycoprotein hormones with an intersubunit disulfide crosslink and their preparation and use. Corresponding DNA sequences and host cells, as well as pharmaceutical compositions are also disclosed.

Disulfide crosslinked glycoprotein hormone analogs, and their preparation and use

A sensor device is provided for detecting an analyte in a sample in which an analyte is bound to a detection reagent to form a bound complex. The device comprises (a) a sample () comprising an ionic analyte and a detection reagent in a conductive fluid, wherein the detection reagent has a net charge different from the analyte; (b) a first permeable polymeric hydrogel plate () and a first spacer plate (), which plates provide a compartment for the sample; (c) an anode () juxtaposed to the outside of the first hydrogel plate and not in contact with the sample; (d) a cathode () juxtaposed to the outside of the first spacer plate and not in contact with the sample; (e) a voltage generator () to apply an electric potential to the anode and cathode; and (f) a detector (). The bound complex formed from the analyte and detection reagent is detected by the detector because the bound complex has a charge that causes it to migrate in a direction opposite from that of the unbound analyte when the electric potential is applied.

Sensors for biomolecular detection and cell classification

The present invention relates to methods for enhancing fertility by reducing the activities and/or levels of circulating glycoprotein hormones having lutropin (LH) activity. The molecules of the invention are antibodies or other binding agents that reduce the biological activities of LH. The present invention also relates to novel methods for devising and/or selecting antibodies to specific portions of proteins including LH and human chorionic gonadotropin (hCG) to permit their biological activities to be reduced to desired degrees. The present invention also relates to the preparation of single subunit gonadotropins and gonadotropin antagonists for use in stimulating and inhibiting fertility and for controlling ovarian hyperstimulation. In a preferred embodiment, the present invention pertains to a method for stimulating fertility in mammals by reducing the activity of glycoprotein hormones having luteinizing hormone activity in circulation and thereby stimulating the production of follicle stimulating hormone which comprises administering to the mammal a therapeutically effective amount of a binding agent that binds luteinizing hormone.

Methods for altering fertility

The present invention relates to a method for preparing heterodimeric analogs of cysteine knot proteins. More specifically, the invention relates to a method for forming a subunit combination of a cysteine knot protein having an &agr;-subunit and a &bgr;-subunit to prepare a heterodimeric protein analog which comprises the steps of (a) attaching a dimerization domain to the amino termini of both an &agr;-subunit and &bgr;-subunit of a cysteine knot protein; and (b) dimerizing the &agr;-subunit and &bgr;-subunit to form a heterodimeric protein analog. In another embodiment, the invention relates to a method for forming a subunit combination of a cysteine knot protein having an &agr;-subunit and a &bgr;-subunit to prepare a heterodimeric protein analog which comprises the steps of (a) attaching a dimerization domain to the amino terminus of an &agr;-subunit and the carboxy terminus of a &bgr;-subunit of a cysteine knot protein; and (b) dimerizing the &agr;-subunit and &bgr;-subunit to form a heterodimeric protein analog.

Method for making hormone heterodimers

Single-chain forms of the glycoprotein hormone quartet, at least some members of which are found in most vertebrates, are disclosed. The &agr; and &bgr; subunits of the wild-type heterodimers or their variants or their fragments are covalently linked, optionally through a linker moiety. Some of the single-chain forms are agonists and others antagonists of the glycoprotein hormone activity.

Single-chain forms of the glycoprotein hormone quartet

Single chain forms of the glycoprotein hormone quartet

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

Mixtures of monoclonal antibodies which contain effective assaying amounts of each of at least two monoclonal antibodies that bind to different antigenic sites on the antigen and are capable under appropriate conditions of binding simultaneously to an antigen are useful in enhanced sensitivity assays for the antigen. By utilizing such mixtures in diagnostic assays for important antigens such as the polypeptide human chorionic gonadotropin enhanced sensitivity can be achieved as compared with assays employing individual monoclonal antibodies.

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Piscataway, NJ, United States of America

William R Moyle