Abstract: Preparations including recombinant FSH (rFSH).

Abstract: Novel ?10 polypeptides and heterodimers thereof, and nucleic acid molecules encoding the same are disclosed. The invention also provides vectors, host cells, selective binding agents, and methods for producing ?10 polypeptides and heterodimeric forms thereof, specifically ?2/?10. Also provided for are methods for the treatment, diagnosis, amelioration, or prevention of diseases with ?10 polypeptides and ?2/?10 heterodimers or their respective binding agents.

Abstract: Novel ?10 polypeptides and heterodimers thereof, and nucleic acid molecules encoding the same are disclosed. The invention also provides vectors, host cells, selective binding agents, and methods for producing ?10 polypeptides and heterodimeric forms thereof, specifically ?2/?10. Also provided for are methods for the treatment, diagnosis, amelioration, or prevention of diseases with ?10 polypeptides and ?2/?10 heterodimers or their respective binding agents.

Abstract: One aspect of the present invention is concerned with a method of controlled ovarian hyperstimulation in a mammalian female, said method comprising the co-administration to said female of —a substance having follicle stimulating hormone activity (FSH substance) in an amount effective to stimulate multiple follicular development; —gonadotropin releasing hormone (GnRH) antagonist in an amount equivalent to a daily subcutaneous dose of at least 0.5 mg ganirelix to prevent a premature LH-surge; and —a LH substance in an amount effective to prevent or suppress symptoms of luteinising hormone (LH) deficiency resulting from the administration of the GnRH antagonist; followed by administering a meiosis and luteinisation inducing substance (ML substance) in an amount effective to stimulate resumption of meiosis and luteinisation, and wherein the LH substance is not obtained from the urine of human females.

Abstract: This invention relates to Huntington's disease and more specifically to methods for testing and inhibiting the development of Huntington's disease.

Abstract: Method for increasing half-life of therapeutic agents in plasma and novel polypeptide derivatives.

Abstract: The invention provides a method for purifying recombinant FSH.

Abstract: Compositions and methods of producing components of protein biosynthetic machinery that include orthogonal tRNA's, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNA's/synthetases are provided. Methods for identifying these orthogonal pairs are also provided along with methods of producing proteins using these orthogonal pairs.

Abstract: The invention relates to a method for purifying recombinant human FSH or an FSH variant starting from crude FSH, comprising the following steps: 1) dye-affinity chromatography; 2) hydrophobic interaction chromatography; and 3) reverse phase chromatography.

Abstract: FSH mutants with increased glycosylation and longer half-lives are described. The use of FSH mutants for inducing folliculogenesis in human patients is also described.

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 relates to the use of gonadotrophins in the induction of folliculogenesis in anovulatory women. In particular, if relates to the use of LH (or an equivalent dosage of hCG) in the production of a medicament for inducing folliculogenesis in anovulatory women at a specified daily doses. In certain embodiments. LH may be used in conjunction with FSH.

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 concerns the use of an agonist of an hypothalamic hormone for the preparation of a pharmaceutical agent to support the luteal phase during infertility treatment of female mammals and more specifically of woman. According to this invention, the pharmaceutical agent is suitable to be used for supporting the luteal phase after a spontaneous ovulation or after stimulation of follicular growth, trigger of final follicular maturation and ovulation with one or several additional agents.

Abstract: A polypeptide and polynucleotides encoding same comprising one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to an amino terminus of a cytokine and two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a carboxy terminus of a cytokine are disclosed. Pharmaceutical compositions comprising the polypeptide and polynucleotides of the invention and methods of using same are also disclosed.

Abstract: The present invention relates to compositions and methods for fusion protein separation utilizing a peptide linker comprising a novel thrombin cleavage site.

Abstract: The invention relates to a method for purifying a glycoprotein, preferably FSH or a FSH mutant comprising the steps of subjecting a liquid containing said FSH or a FSH mutant to: (1) a dye affinity chromatography; (2) a weak anion exchange chromatography; (3) a hydrophobic interaction chromatography; and (4) a strong anion exchange chromatography; which may be carried out in any order.

Abstract: This invention relates to FSH or a FSH variant containing an alpha and beta subunit contained in formulations, and articles of manufacture. The invention provides advantageous new proteins and nucleic acids, multi-use pharmaceutical solutions, formulations and products of said proteins and nucleic acids where none approved for commercial use had previously existed having such extended use indications. These products are particularly useful in therapeutic regimens for increasing serum levels of FSH or a FSH variant over a period of treatment. Thus, inter alia, the invention fills the need for convenient products of FSH or from a FSH variant.

Abstract: Novel ?10 polypeptides and heterodimers thereof, and nucleic acid molecules encoding the same are disclosed. The invention also provides vectors, host cells, selective binding agents, and methods for producing ?10 polypeptides and heterodimeric forms thereof, specifically ?2/?10. Also provided for are methods for the treatment, diagnosis, amelioration, or prevention of diseases with ?10 polypeptides and ?2/?10 heterodimers or their respective binding agents.

Abstract: The present invention provides sequon polypeptides with an amino acid sequence including one or more exogenous O-linked glycosylation sequence of the invention. In addition, the present invention provides methods of making polypeptide conjugates as well as methods of using such conjugates and their pharmaceutical compositions. The invention further provides libraries of sequon polypeptides, wherein each member of such library includes at least one exogenous O-linked glycosylation sequence of the invention. Also provided are methods of making and using such libraries.

Abstract: FSH mutant with increased glycosylation and longer half-life is described. The use of this FSH mutant for inducing folliculogenesis in human patients is also described.

Abstract: This invention relates to FSH or a FSH variant containing an alpha and beta subunit contained in formulations, and articles of manufacture. The invention provides advantageous new proteins and nucleic acids, multi-use pharmaceutical solutions, formulations and products of said proteins and nucleic acids where none approved for commercial use had previously existed having such extended use indications. These products are particularly useful in therapeutic regimens for increasing serum levels of FSH or a FSH variant over a period of treatment. Thus, inter alia, the invention fills the need for convenient products of FSH or from a FSH variant.

Abstract: Forms of differentially acting glycoprotein hormones are disclosed. These compositions are of the formula ?1-(linker1)m-?-(linker2)n-?2;??(1) ?1-(linker1)m-?2-(linker2)n-?;??(2) ?-(linker1)m-?1-(linker2)n-?2;??(3) ?2??-(linker)m-?1; or??(4) ?1-(linker)m-???2??(5) wherein each of ?1 and ?2 has the amino acid sequence of the ? subunit of a vertebrate glycoprotein hormone or a variant of said amino acid sequence, as variants are defined herein. “?” designates the ? subunit of a vertebrate glycoprotein hormone or a variant thereof, “linker” refers to a covalently linked moiety that spaces the ?1 and ?2 subunits at appropriate distances from the ? subunit and from each other. “?” is a noncovalent link. Each of m and n is independently 0 or 1.

Abstract: The invention provides methods and compositions for in vivo incorporation of non-naturally encoded amino acids into polypeptides by Pseudomonas species and strains derived therefrom. Also provided are compositions including proteins with non-naturally encoded amino acids made by Pseudomonas species and strains derived therefrom.

Abstract: The invention provides a protocol leading to improved embryo implantation rates and/or decreased miscarriage rates in which hCG, or a bio-analogue, is administered during the follicular phase.

Abstract: A peptide that comprises a modified tandem GnRH decapeptide sequence which allows for a testosterone level that is essentially nondetectable after vaccination with the peptide in a suitable dosage and/or allows for an immunogenic response that allows for the effective discrimination between GnRH-I and GnRH-II and a method for the immunocastration of pigs.

Abstract: Novel ?10 polypeptides and heterodimers thereof, and nucleic acid molecules encoding the same are disclosed. The invention also provides vectors, host cells, selective binding agents, and methods for producing ?10 polypeptides and heterodimeric forms thereof, specifically ?2/?10. Also provided for are methods for the treatment, diagnosis, amelioration, or prevention of diseases with ?10 polypeptides and ?2/?10 heterodimers or their respective binding agents.

Abstract: The present invention provides conjugates between follicle stimulating hormone and PEG moieties. The conjugates are linked via an intact glycosyl linking group that is interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from both glycosylated and unglycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto either an amino acid or glycosyl residue on the peptide. Also provided are pharmaceutical formulations including the conjugates. Methods for preparing the conjugates are also within the scope of the invention.

Abstract: The inventors have designed novel FSH mutants with increased glycosylation and longer half-lives for use in inducing folliculogenesis in human patients. The use of a FSH mutant preparation of the invention permits the use of lower cumulative doses of FSH to achieve the same or better clinical result.

Abstract: A hybrid protein includes two coexpressed amino acid sequences forming a dimer. Each sequence contains the binding portion of a receptor, such as TBP1 or TBP2, or a ligand, such as IL-6, IFN-? and TPO, linked to ? subunit of a natural heterodimeric scaffold. Each coexpressed sequence contains a corresponding subunit so as to form a heterodimer upon expression. Corresponding DNA molecules, expression vectors and host cells are also disclosed as are pharmaceutical compositions and a method of producing such proteins.

Abstract: The present invention relates to a method for improving homogeneity and/or secretion of a recombinant protein of interest expressed in mammalian cells by replacing the endogenous signal peptide sequence of the DNA encoding the protein of interest with that of human hGH. Specifically, the present invention relates to a method wherein the protein of interest is a subunit of the follicle stimulating hormone (FSH). The invention also relates to DNA expression vectors containing the sequence encoding such proteins of interest fused to the signal peptide sequence of the hGH and to cells harbouring such vectors.

Abstract: This invention provides VEGF-FSH compounds having increased serum half-lives relative to either native VEGF or FSH, in which both VEGF and FSH are biologically active. This invention also provides related compositions and methods for increasing fertility, egg production and spermatogenesis in a subject, as well as methods for increasing vascularization in a tissue, particularly in ovarian tissue.

Abstract: Methods for treating FSH related conditions, such as prostatic intraepithelial neoplasia, pedophilia, infertility, or vaginal bleeding, with GnRH antagonists are disclosed. The methods of the invention generally feature administering to a subject a GnRH antagonist suitable for in vivo administration and able to reduce both plasma FSH and LH levels in a subject, in an amount or in a formulation effective to reduce plasma FSH levels in the subject to a symptom alleviating level. In vitro fertilization and male contraceptive methods 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 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: Purification process of humanPurification process of human urinary gonadotropins of high biological activity and chemical purity absolutely free of foreign contaminating materials derived from the use of biological reagents or chromatography dyes, from crude of gonadotropins. The high biological activity and chemically pure composition of human gonadotropins obtained by this process, are used for the treatment of infertility and are selected from the group of follitropin or menotropins, having a bioactivity greater than 2500 IU/mg protein as tested by biological assay in rats, for both FSH and LH hormones for menotropins and greater than 5000 IU/mg protein for follitropin having an FSH:LH ratio about 75:1. Pharmaceutical preparations of said gonadotropins free of these contaminating materials are also comprised within the present invention.

Abstract: Glycosylated or nonglycosylated molecules of the formula ?1-(linker1)n1-?2-(linker2)n2-?3-(linker3)n3-?;??(1) ?1-(linker1)n1-?2-(linker2)n2-?-(linker3)n3-?3 ;??(2) ?1-(linker1)n1-?-(linker2)n2-?2-(linker3)n3-?3 ;??(3) and ?-(linker1)n1-?1-(linker2)n2-?2-(linker3)n3-?3 ??(4) wherein ? is the ? subunit of a vertebrate glycoprotein hormone or a variant thereof; each ? is independently a glycoprotein ? subunit or a variant thereof, each “linker” is a hydrophilic, flexible spacer equivalent to a peptide containing 1–100 amino acid residues; and each n is a 0 or 1; said compound optionally comprising one or more additional ?x(linkerx)nx and/or one or more additional ? subunits are useful in protocols to enhance fertility in humans and in animals.

Abstract: The present invention relates to two novel Gonadotropin releasing hormones muGnRH I and muGnRH II of amino acid SEQ ID 1 as QHWSAWRLPG, and SEQ ID 2 QHWSWGILPG respectively, useful for induced breeding in fish both in combination and alone, by activating production of Gonadotropin, and a method of isolating the same from Indian Murrel brain, and further, a method of inducing breeding in fishes using the said novel gonadotropin releasing hormones.

Abstract: The subject invention provides a fusion protein for producing a dual immune response in a vertebrate, which fusion protein comprises: (a) a first proteinaceous portion analogous to all or part of a peptide endogenously synthesized within the vertebrate, the activity of which peptide is to be inhibited within the vertebrate, and which proteinaceous portion by itself is incapable of eliciting an effective immunoinhibitory response in said vertebrate; connected to (b) a second proteinaceous portion analogous to all or part of an immunogen from a pathogen, which pathogen is capable of pathogenically infecting the vertebrate; the portion (b) causing the vertebrate's immune system to recognize the portion (a) and produce a response that: (i) inhibits the activity of the peptide endogenously synthesized within the vertebrate; and (ii) protects the vertebrate from infection by the pathogen, when the vertebrate is vaccinated with an effective amount of the fusion protein.

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: A novel lyophilizate and method of preparation as well as the use of the lyophilizate to treat female infertility and for gonad protection. Cetrorelix is dissolved in acetic acid 30% v/v, the solution is transferred to water and freeze dried.

Abstract: A peptide that comprises a modified tandem GnRH decapeptide sequence which allows for a testosterone level that is essentially non-detectable after vaccination with the peptide in a suitable dosage and/or allows for a an immunogenic response that allows for the effective discrimination between GnRH-I and GnRH-II and a method for the immunocastration of pigs.

Abstract: 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.

Abstract: The invention refers to liquid pharmaceutical compositions containing hCG stabilised with a polyalcohol or a non-reducing sugar. Preferably, the compositions are stabilised with mannitol. In the preferred embodiments such compositions are aqueous solutions in a phosphate buffer at pH 7. Such compositions are ready to be injected and, therefore, the step of reconstitution of the lyophilised powder is avoided, thus simplifying the way of use.

Abstract: Single-chain forms of the glycoprotein hormones LH, FSH, TSH or CG which are lacking at least one disulfide bridge in the sequence representing the &agr; and/or &bgr; subunit are useful as agonists or antagonists of the native glycoprotein hormones.

Abstract: Glycosylated or nonglycosylated proteins of the formula FSH&bgr;-(linker1)n1-LH&bgr;(1-X)-(linker2)n2-&agr; wherein FSH&bgr; is a vertebrate follicle stimulating hormone &bgr; subunit or a variant thereof; LH&bgr;(1-X) refer's to a &bgr; subunit of a vertebrate luteinizing hormone containing positions 1-X where X is an integer of 114-121 or a variant thereof; each “linker” is a hydrophilic, flexible amino acid sequence containing 1-100 amino acid residues; each n is a 0 or 1; and &agr; is the &agr; subunit of a vertebrate glycoprotein hormone or a variant thereof are useful in protocols to enhance fertility in humans and in animals.

Abstract: Erythropoietin containing a CTP extension and secreted from CHO cells exhibits a favorably extended biological half-life.

Abstract: Novel isolated cDNA encoding the precursor of the novel gonadotropin-releasing hormones in four species of the fish lamprey is disclosed. The use of such cDNA's in studying the phylogenetic relationship of various species of fish and vertebrates overall; and the use of such cDNA's for controlling the gonadal development and spawning of fish, including inducing and inhibiting maturation, spawning and reproduction, is also described. Methods by which the novel peptides may be administered to fish to control their reproduction are also described.

Abstract: The present invention relates to two novel Gonadotropin releasing hormones muGnRH I and muGnRH II of amino acid SEQ ID 1 as QHWSAWRLPG, and SEQ ID 2 QHWSWGILPG respectively, useful for induced breeding in fish both in combination and alone, by activating production of Gonadotropin, and a method of isolating the same from Indian Murrel brain, and further, a method of inducing breeding in fishes using the said novel gonadotropin releasing hormones.

Abstract: Forms of differentially acting glycoprotein hormones are disclosed. These compositions are of the formula &bgr;1-(linker1)m-&agr;-(linker2)n-&bgr;2  (1); &bgr;1-(linker1)m-&bgr;2-(linker2)n-&agr;  (2); &agr;-(linker1)m-&bgr;1-(linker2)n-&bgr;2  (3); &bgr;2≈&agr;-(linker)m-&bgr;1  (4); or &bgr;1-(linker)m-&agr;≈&bgr;2  (5) wherein each of &bgr;1 and &bgr;2 has the amino acid sequence of the &bgr; subunit of a vertebrate glycoprotein hormone or a variant of said amino acid sequence as variants are defined herein. “&agr;” designates the a subunit of a vertebrate glycoprotein hormone or a variant thereof; “linker” refers to a covalently linked moiety that spaces the &bgr;1 and &bgr;2 subunits at appropriate distances from the &agr; subunit and from each other. “≈” is a noncovalent link. Each of m and n is independently 0 or 1.

Abstract: The present invention relates to peptides of one or more portions of the human chorionic gonadotropin &bgr;-chain as well as methods for treatment and prevention of diseases, including HIV infection, using human chorionic gonadotropin, employing the &bgr;-chain of human chorionic gonadotropin, peptides containing a sequence of one or more portions of the &bgr;-chain of human chorionic gonadotropin and derivatives and analogues thereof. The invention further relates to fractions of sources and or preparations of human chorionic gonadotropin, such as fractions of human early pregnancy urine, which fractions have anti-HIV activity. The present invention further relates to pharmaceutical compositions for treating and/or preventing HIV infection.