Abstract: Modified follicle stimulating hormone (FSH), containing an amino acid sequence which differs from the wild-type FSH, said modified FSH comprising a modified ?-subunit, wherein the potency of said modified FSH is increased by at least about a ten fold as compared to wild type FSH. Nucleic acids encoding the modified FSH, vectors comprising the nucleic acids, and host cells comprising the vectors. Methods of assisting reproduction, diagnosing and/or treating conditions associated with glycoprotein hormone activity, reducing hyperstimulation syndrome, improving the quality of oocytes, inducing superovulation, and enhancing in vitro fertilization.

Abstract: Modified VEGF proteins that inhibit VEGF-mediated activation or proliferation of endothelial cells are disclosed. The analogs may be used to inhibit VEGF-mediated activation of endothelial cells in angiogenesis-associated diseases such as cancer, inflammatory diseases, eye diseases, and skin disorders.

Abstract: Modified VEGF proteins that inhibit VEGF-mediated activation or proliferation of endothelial cells are disclosed. The analogs may be used to inhibit VEGF-mediated activation of endothelial cells in angiogenesis-associated diseases such as cancer, inflammatory diseases, eye diseases, and skin disorders.

Abstract: This invention provides long-acting, superactive analogs of glycoprotein hormones demonstrating enhanced bioactivity both in vitro and in vivo as compared to wild type counterparts. The analogs are particularly useful for treating subjects showing low receptor expression or poor receptor responsiveness, and for the treatment of any condition associated with glycoprotein hormone activity.

Abstract: Modified VEGF proteins that inhibit VEGF-mediated activation or proliferation of endothelial cells are disclosed. The analogs may be used to inhibit VEGF-mediated activation of endothelial cells in angiogenesis-associated diseases such as cancer, inflammatory diseases, eye diseases, and skin disorders.

Abstract: Modified VEGF proteins that inhibit VEGF-mediated activation or proliferation of endothelial cells are disclosed. The analogs may be used to inhibit VEGF-mediated activation of endothelial cells in angiogenesis-associated diseases such as cancer, inflammatory diseases, eye diseases, and skin disorders.

Abstract: Modified VEGF proteins that inhibit VEGF-mediated activation or proliferation of endothelial cells are disclosed. The analogs may be used to inhibit VEGF-mediated activation of endothelial cells in angiogenesis-associated diseases such as cancer, inflammatory diseases, eye diseases, and skin disorders.

Abstract: This invention provides superactive analogs of FSH demonstrating enhanced bioactivity both in vitro and in vivo as compared to wild type FSH. In particular, the analogs of the invention demonstrate at least a ten fold increase in potency or at least a ten percent increase in maximal efficacy as compared to wild type protein. The analogs are particularly useful in treating subjects showing low FSH receptor expression or poor FSH receptor responsiveness, and for the treatment of any condition associated with glycoprotein hormone activity.

Abstract: This invention provides superactive analogs of FSH demonstrating enhanced bioactivity both in vitro and in vivo as compared to wild type FSH. In particular, the analogs of the invention demonstrate at least a ten fold increase in potency or at least a ten percent increase in maximal efficacy as compared to wild type protein. The analogs are particularly useful in treating subjects showing low FSH receptor expression or poor FSH receptor responsiveness, and for the treatment of any condition associated with glycoprotein hormone activity.

Abstract: The invention is directed toward a human glycoprotein hormone having at least one, two, three, four, or five basic amino acids in the ?-subunit at positions selected from the group consisting of positions 11, 13, 14, 16, 17, and 20. The invention is also directed to a human glycoprotein where at least one of the amino acids at position 58, 63, and 69 of the ?-subunit of the human thyroid stimulating hormone are basic amino acids. The invention is further directed to a modified human glycoprotein hormone having increased activity over a wild-type human glycoprotein hormone, where the modified human glycoprotein comprises a basic amino acid substituted at a position corresponding to the same amino acid position in a non-human glycoprotein hormone having an increased activity over the wild-type human glycoprotein hormone.

Abstract: Modified VEGF proteins that inhibit VEGF-mediated activation or proliferation of endothelial cells are disclosed. The analogs may be used to inhibit VEGF-mediated activation of endothelial cells in angiogenesis-associated diseases such as cancer, inflammatory diseases, eye diseases, and skin disorders.

Abstract: Compositions and methods based on mutant Cystine Knot Growth Factors (CKGFs) comprising amino acid substitutions relative to the wild type hormone/growth factor. Mutated glycoprotein hormones, including thyroid stimulating hormone (TSH) and chorionic gonadotropin (CG) are disclosed as exemplary mutant CKGFs. Mutant TSH heterodimers and hCH heterodimers possessed modified bioactivities, including superagonist activity. Accordingly, the present invention provides methods for using mutant CKGFs, CKGF analogs, fragments, and derivatives thereof for treating or preventing diseases. Pharmaceutical and diagnostic compositions, methods of using mutant TSH heterodimers and TSH analogs with utility for treatment and prevention of metabolic and reproductive diseases are also provided.

Abstract: The invention is directed toward a human glycoprotein hormone having at least one, two, three, four, or five basic amino acids in the ?-subunit at positions selected from the group consisting of positions 11, 13, 14, 16, 17, and 20. The invention is also directed to a human glycoprotein where at least one of the amino acids at position 58, 63, and 69 of the ?-subunit of the human thyroid stimulating hormone are basic amino acids. The invention is further directed to a modified human glycoprotein hormone having increased activity over a wild-type human glycoprotein hormone, where the modified human glycoprotein comprises a basic amino acid substituted at a position corresponding to the same amino acid position in a non-human glycoprotein hormone having an increased activity over the wild-type human glycoprotein hormone.

Abstract: The invention is directed toward a human glycoprotein hormone having at least one, two, three, four, or five basic amino acids in the ?-subunit at positions selected from the group consisting of positions 11, 13, 14, 16, 17, and 20. The invention is also directed to a human glycoprotein where at least one of the amino acids at position 58, 63, and 69 of the ?-subunit of the human thyroid stimulating hormone are basic amino acids. The invention is further directed to a modified human glycoprotein hormone having increased activity over a wild-type human glycoprotein hormone, where the modified human glycoprotein comprises a basic amino acid substituted at a position corresponding to the same amino acid position in a non-human glycoprotein hormone having an increased activity over the wild-type human glycoprotein hormone.

Abstract: The present invention provides improved methods of imaging, targeted therapy and detection and diagnostics using modified glycoprotein hormones having increased activity over wild-type hormones.

Abstract: The invention is directed toward a human glycoprotein hormone having at least one, two, three, four, or five basic amino acids in the ?-subunit at positions selected from the group consisting of positions 11, 13, 14, 16, 17, and 20. The inventions is also directed to a human glycoprotein where at least one of the amino acids at position 58, 63, and 69 of the ?-subunit of the human thyroid stimulating hormone are basic amino acids. The invention is further directed to a modified human glycoprotein hormone having increased activity over a wild-type human glycoprotein hormone, where the modified human glycoprotein comprises a basic amino acid substituted at a position corresponding to the same amino acid position in a non-human glycoprotein hormone having an increased activity over the wild-type human glycoprotein hormone.

Abstract: Compositions and methods based on mutant Cystine Knot Growth Factors (CKGFs) comprising amino acid substitutions relative to the wild type hormone/growth factor. Mutated glycoprotein hormones, including thyroid stimulating hormone (TSH) and chorionic gonadotropin (CG) are disclosed as exemplary mutant CKGFs. Mutant TSH heterodimers and hCH heterodimers possessed modified bioactivities, including superagonist activity. Accordingly, the present invention provides methods for using mutant CKGFs, CKGF analogs, fragments, and derivatives thereof for treating or preventing diseases. Pharmaceutical and diagnostic compositions, methods of using mutant TSH heterodimers and TSH analogs with utility for treatment and prevention of metabolic and reproductive diseases are also provided.

Abstract: The present invention is based upon the discovery that mutant &agr; subunits and mutant &bgr; subunits each comprising amino acid substitutions relative to the wild type can be produced and assembled to form a mutant TSH heterodimer or TSH analog that possesses higher bioactivity in vitro and longer half life in vivo. Accordingly, the present invention provides methods for using mutant TSH heterodimers, TSH analogs, fragments, and derivatives thereof for treating or preventing diseases of the thyroid, in particular thyroid cancer. The invention also relates to methods of diagnosis, prognosis and monitoring for thyroid-related functions. Pharmaceutical and diagnostic compositions, methods of using mutant TSH heterodimers and TSH analogs with utility for treatment and prevention of metabolic and reproductive diseases are also provided.

Abstract: Compositions and methods based on mutant Cystine Knot Growth Factors (CKGFs) comprising amino acid substitutions relative to the wild type hormone/growth factor. Mutated glycoprotein hormones, including thyroid stimulating hormone (TSH) and chorionic gonadotropin (CG) are disclosed as exemplary mutant CKGFs. Mutant TSH heterodimers and hCH heterodimers possessed modified bioactivities, including superagonist activity. Accordingly, the present invention provides methods for using mutant CKGFs, CKGF analogs, fragments, and derivatives thereof for treating or preventing diseases. Pharmaceutical and diagnostic compositions, methods of using mutant TSH heterodimers and TSH analogs with utility for treatment and prevention of metabolic and reproductive diseases are also provided.

Abstract: The invention is directed toward a human glycoprotein hormone having at least one, two, three, four, or five basic amino acids in the &agr;-subunit at positions selected from the group consisting of positions 11, 13, 14, 16, 17, and 20. The inventions is also directed to a human glycoprotein where at least one of the amino acids at position 58, 63, and 69 of the &bgr;-subunit of the human thyroid stimulating hormone are basic amino acids. The invention is further directed to a modified human glycoprotein hormone having increased activity over a wild-type human glycoprotein hormone, where the modified human glycoprotein comprises a basic amino acid substituted at a position corresponding to the same amino acid position in a non-human glycoprotein hormone having an increased activity over the wild-type human glycoprotein hormone.