Abstract: The present invention provides methods of producing biologically active recombinant eFSH analogs and methods of increasing reproduction in mammals, particularly equine, using recombinant eFSH analogs. Also provided are methods of producing biologically active single chain recombinant eFSH. The recombinant eFSH analogs of the present invention increase superovulation, follicular development, embryo development, and reproductive efficiency in horses, cattle and other ungulates.

Abstract: The present invention provides methods of producing biologically active recombinant eFSH analogs and methods of increasing reproduction in mammals, particularly equine, using recombinant eFSH analogs. Also provided are methods of producing biologically active single chain recombinant eFSH. The recombinant eFSH analogs of the present invention increase superovulation, follicular development, embryo development, and reproductive efficiency in horses, cattle and other ungulates.

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

Abstract: Forms of differentially acting glycoprotein hormones are disclosed.

Abstract: The invention provides recombinant native and mutein forms of human follicle stimulating hormone beta subunit (FSH beta) with characteristic glycosylation patterns which are influential in the metabolic activity of the protein. The invention also provides recombinant mutant forms of the human alpha subunit common to FSH, LH, CG, and TSH, to obtain hormones which also have unique glycosylation patterns. Also provided are recombinant materials to produce these subunits separately or together to obtain complete heterodimeric hormones of regulated glycosylation pattern.

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: 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: Glycosylated or nonglycosylated molecules of the formula

Abstract: Recombinant materials are provided for the production of the &agr;-glycoprotein hormone subunit. These muteins have utility as antagonists and in altering pharmacokinetic activity of these hormones.

Abstract: The invention provides recombinant native and mutein forms of human follicle stimulating hormone beta subunit (FSH beta) with characteristic glycosylation patterns which are influential in the metabolic activity of the protein. The invention also provides recombinant mutant forms of the human alpha subunit common to FSH, LH, CG, and TSH, to obtain hormones which also have unique glycosylation patterns. Also provided are recombinant materials to produce these subunits separately or together to obtain complete heterodimeric hormones of regulated glycosylation pattern.

Abstract: 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.

Abstract: 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.

Abstract: The invention provides peptide and protein pharmaceuticals with extended half-lives. The modified peptides and proteins of the invention contain at least two tandem extensions at their C-terminus comprising the carboxy terminal portion of human chorionic gonadotropin. These “CTP units” consist essentially of the native HCG-&bgr; sequence from position 112-118 to position 145 or conservative modifications thereof.

Abstract: Single-chain agonists and/or antagonists of the glycoprotein hormones are disclosed. These proteins are of the formula.beta..sup.1 -(linker.sup.1).sub.m -.alpha.-(linker.sup.2).sub.n -.beta..sup.2 (1);or.beta..sup.1 -(linker.sup.1).sub.m -.beta..sup.2 -(linker.sup.2).sub.n -.alpha. (2);or.alpha.-(linker.sup.1).sub.m -.beta..sup.1 -(linker.sup.2).sub.n - .beta..sup.2 (3)wherein each of .beta..sup.1 and .beta..sup.2 has the amino acid sequence of the .beta. subunit of a vertabrate glycoprotein hormone or a variant thereof; ".alpha." designates the .alpha. subunit of a vertabrate glycoprotein hormone or a variant thereof; "linker" refers to a covalently linked moiety that spaces the .beta..sup.1 and .beta..sup.2 subunits at distances from the .alpha. subunit and from each other effective to retain said activity, and each of m and n is independently 0 or 1.

Abstract: Single-chain forms of the glycoprotein hormone quartet, at least some members of which are found in most vertebrates, are disclosed. In these single-chain forms, the .alpha. and .beta. subunits of the wild-type heterodimers or their variants are covalently linked, optionally through a linker moiety. A drug may further be included within the linker moiety to be targeted to receptors for these hormones. Some of the single-chain forms are agonists and others antagonists of the glycoprotein hormone activity. Kits comprising antibodies to these proteins can be used in immunodetection methods.

Abstract: Improved methods for recombinant production of human reproductive hormones are disclosed. These methods involve the use of animal-derived cells that contain regulated secretory granules as host cells for expression systems capable of expressing DNA encoding human reproductive hormones or their .beta. subunits.