Abstract: The present invention provides for circularly permuted ligands which possess specificity and binding affinity comparable to or greater than the specificity and binding affinity of the original (unpermuted) ligand. The invention further provides for novel chimeric molecules comprising a circularly permuted ligand joined to one or more molecules of interest.

Abstract: The present invention relates to polynucleotide and polypeptide molecules for stanniocalcin-2, a novel member of the stanniocalcin family. The polypeptides, and polynucleotides encoding them, modulate electrolyte homeostasis. The present invention also includes antibodies to the stanniocalcin-2 polypeptides.

Abstract: Methods are provided for the modulation of the effects of GDF-8 and BMP-11, particularly on neural and muscular disorders administration of follistatin for treating neural, muscle, disorders which are characterized by an abnormality in the levels or activity of GDF-8 or BMP-11.

Abstract: The present invention provides a method for purifying follicle stimulating hormone (FSH) from biological samples, for example, from human pituitary glands or human postmenopausal urine, wherein the FSH is contaminated with other proteins, by use of dye-ligand affinity chromatography (DAC). This process may be used to generate affinity pure FSH suitable for therapeutic applications.

Abstract: Disclosed is human haemopoietic maturation factor polypeptides and DNA (RNA) encoding such haemopoietic maturation factor polypeptides. Also provided is a procedure for producing such polypeptides by recombinant techniques and the use of such polypeptides for treating leukemia, auto-immune diseases and blood related disorders. Antagonists against such polypeptides and their use as a therapeutic to prevent expansion of T-cell populations is also disclosed. Diagnostic assays are also disclosed which detect the presence of mutations in the haemopoietic maturation factor nucleic acid sequences and altered levels of the protein.

Abstract: Described are new glycoprotein hormones capable of competing with natural hormones for the normal receptor binding sites but substantially incapable of effecting post receptor activities. The glycoprotein hormones of the present invention have had specific (rather than all) oligosaccharide chains removed so as to effectively diminish biologic activity while not significantly reducing plasma half-life, thus improving the molecules effectiveness as an antagonist compared with conventionally-produced molecules. The preferred glycoprotein hormones are ideally obtained by site-directed mutagenesis to selectively deglycosylate the protein. Also described are therapeutic treatments comprising the administration of the recombinant glycoprotein hormones of the present invention as hormone antagonists.

Abstract: There is provided a DNA (or RNA) polynucleotide sequences encoding naturally occurring splice variants of human growth hormone, hGHV-2(88) and hGHV-3(53) as well as analogs and derivatives thereof, which both lack nucleotide sequences normally present in the gene which codes for wild-type hGH. The growth hormone variants of the present invention are of human origin and are useful for diagnostic preventative and therapeutic purposes with respect to certain human diseases. The present invention is also related to a method for producing the human growth hormone variants by recombinant DNA techniques. A method of generating an antibody directed against and therefore inhibiting the activity of wild-type growth hormone is also provided.

Abstract: The instant invention is drawn to a sperm surface protein in substantially pure form selected from a human PH30 beta chain protein and a mouse PH30 beta chain proteins. Such proteins are useful as contraceptive vaccines in humans and mice respectively, and for identifying small molecules that will disrupt sperm-egg interaction and fertilization.

Abstract: The invention provides heterobifunctional cross-linking reagents and methods of using the cross-linking reagents. The cross-linking reagents of the invention combine a nucleophilic hydrazide residue with an electrophilic maleimide residue, allowing coupling of aldehydes to free thiols. In the methods of the invention, human immunodeficiency virus (HIV) infected cells can be detected using conjugates that include CD4 molecules conjugated to detectable markers via the disclosed cross-linking reagents.

Abstract: The invention relates to novel modified polypeptides, with or without variations in noncoding regions, with altered biological activity. The invention discloses methods of preparing the modified polypeptides and methods of use.

Abstract: Analogs of human erythropoietin, including the ?X.sup.33, Cys.sup.139, des-Arg.sup.166 ! and ?Cys.sup.139, des-Arg.sup.166 ! analogs, as well as methods for making and using such analogs and pharmaceutical compositions containing the same.

Abstract: The invention provides heterobifunctional cross-linking reagents and methods of using the cross-linking reagents. The cross-linking reagents of the invention combine a nucleophilic hydrazide residue with an electrophilic maleimide residue, allowing coupling of aldehydes to free thiols. In the methods of the invention, human immunodeficiency virus (HIV) infected cells can be detected using conjugates that include CD4 molecules conjugated to detectable markers via the disclosed cross-linking reagents.

Abstract: The invention is directed to a glycosylated or nonglycosylated protein which is composed of the amino acid sequence of a first .alpha. subunit common to the glycoprotein hormones linked covalently, optionally through a linker moiety, to the amino acid sequence of a second .alpha. subunit of said hormones, wherein said first and second .alpha. subunits consist of the native amino acid sequences or variants of said amino acid sequences. These proteins are useful as agonists or antagonists of glycoprotein hormone activity.

Abstract: A human chemotactic protein polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for preventing and/or treating for stem cell mobilization, myeloprotection and neuronal protection, to treat tumors, to promote wound healing, to combat parasitic infection and to regulate hematopoiesis. Also disclosed are antagonists against such polypeptides which may be employed to treat rheumatoid arthritis, lung inflammation, allergy, infectious diseases and to prevent inflammation and atherosclerosis. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention for detecting diseases are also disclosed.

Abstract: Methods useful for treating cancers are disclosed. The methods involve administering human chorionic gonadotropin (hCG) or human luteinizing hormone (hLH) to patients having cancers. Articles of manufacture that are useful for carrying out the described methods are also described. The claimed methods are effective against breast, prostate, ovary, and stomach carcinomas, as well as neuroblastomas, and Kaposi's sarcoma, among others.

Abstract: The three-dimensional structure of human chorionic gonadotrophin (hCG) has been determined by X-ray crystallography and the coordinates of the individual atoms are presented. Analogues of hCG and other glycoprotein hormones sharing a similar .alpha.-subunit structure are produced by inputting chemical changes to the structure into a computer loaded with three-dimensional molecular simulation software and representing visually on a computer display. The three-dimensional structures of the original glycoprotein and the chemically modified analogues are compared, and those analogues wherein the three-dimensional configuration and spatial arrangement of regions involved in receptor binding and signal transduction remain substantially preserved are selected for synthesis by molecular biology techniques and screening for biological activity. Glycoprotein analogues with additional glycosylation sites, and deletion of non-essential hairpins are disclosed.

Abstract: Erythropoietin isoforms having a specific number of sialic acids per erythropoietin molecule are disclosed. Also disclosed are mixtures of such isoforms, pharmaceutical compositions containing such isoforms or mixtures thereof and methods of obtaining the erythropoietin isoforms.

Abstract: Prophylaxis against viral infections, as well as treatment for individuals infected with a virus, can be achieved through the administration of human chorionic gonadotropin (HCG). Exemplary of the viral infections that are amenable to the use of HCG in this regard include those caused by HIV-1, Kaposi's sarcoma herpes virus, molluscipoxvirus and cytomegalovirus. In addition, HCG can be used as a neonatal immune booster via administration to a baby at delivery and, optionally, for the first several months of life, until the infantile immune system matures, in order to prevent HIV transmission and control any low-level viremia, as well as to protect against various other viruses, such as herpes viruses and oncogenic viruses.

Abstract: A pharmaceutical preparation comprising a growth hormone and histidine or a derivative of histidine as additive or buffering substance shows a very high stability against deamidation, oxidation and cleavage of peptide bonds. The stability of the product allows for the storing and shipment thereof in a lyophilized state or in the form of a dissolved or re-dissolved preparation at ambient temperature. Crystallization of growth hormone in the presence of histidine or a derivative thereof gives rise to a higher yield of crystals having a higher purity than known methods.

Abstract: A pharmaceutical preparation comprising a growth hormone and histidine or a derivative of histidine as additive or buffering substance shows a very high stability against deamidation, oxidation and cleavage of peptide bonds. The stability of the product allows for the storing and shipment thereof in a lyophilized state or in the form of a dissolved or re-dissolved preparation at ambient temperature. Crystallization of growth hormone in the presence of histidine or a derivative thereof gives rise to a higher yield of crystals having a higher purity than known methods.

Abstract: Compositions of proteins with chondrocyte and cartilaginous tissue inducing activity, as well as method of using those compositions, are disclosed. The compositions comprise one or more proteins of the transforming growth factor-.beta. (TGF-.beta.) superfamily of proteins, particularly bone morphogenetic proteins (BMPs), in combination with parathyroid hormone related polypeptide (PTHrP) or an equivalent PTH-like polypeptide. The compositions and methods are useful in the treatment of osteoarthritis, cartilage defects and in related tissue repair.

Abstract: Synthetic polypeptide analogs of parathyroid hormone PTH, parathyroid hormone related peptide PTHrp, and of the physiologically active truncated homologs and analogs of PTH and PTHrp, in which amino acid residues (22-31) form an amphipathic .alpha.-helix, said residues (22-31) selected from hydrophilic amino acids (Haa) and lipophilic amino acids (Laa) ordered in the sequence:Haa(Laa Laa Haa Haa).sub.2 Laaand their pharmaceutically acceptable salts are useful for the prophylaxis and treatment of ostoporosis in mammals. Processes for the production of the polypeptides via solid phase and recombinant methods are provided.

Abstract: The present invention provides novel megakaryocyte differentiation factors, which are useful as therapeutic agents due to their accelerating effects on the differentiation of megakaryocytes and their thrombopoietic effects. The megakaryocyte differentiation factors of the present invention include the megakaryocyte differentiation factor having the amino acid sequence shown in SEQ ID NO: 34. The present invention also provides DNA coding for the megakaryocyte differentiation factors of the present invention, expression vectors containing the DNA, hosts transformed with the expression vectors, and processes for production of the megakaryocyte differentiation factors using transformed hosts. The present invention further provides specific antibodies to the megakaryocyte differentiation factors of the present invention.

Abstract: The present invention is directed to a family of heparin-binding epithelial cell growth factors termed amphiregulins (AR). In particular, it relates to the isolation of AR genes from different animal species, expression of the genes, identification of various forms of biologically active AR products, purification of the AR products, antibodies specific for AR, and uses of AR. AR is detectable in several normal human epithelial cells and in a high percentage of human colon cancers. In addition to stimulating the growth of these cultured epithelial cells, AR may have a wide range of applications including, but not limited to, accelerating the growth of normal epithelial cells. In some tumor cell lines, primarily of breast or ovarian carcinomas, AR serves as a direct growth inhibitor. On the other hand, AR may function as a growth stimulatory molecule in colorectal carcinomas and other pathologies of increased epithelial proliferation.

Abstract: Growth differentiation factor-8 (GDF-8) polypeptides, polynucleotides encoding GDF-8 polypeptides, and vectors and host cells containing GDF-8 encoding polynucleotides are provided.

Abstract: Specific netrin proteins, nucleic acids which encode netrin proteins and hybridization reagents, probes and primers capable of hybridizing with netrin genes and methods for screening chemical libraries for lead compounds for pharmacological agents useful in the diagnosis or treatment of disease associated undesirable cell growth are provided. An exemplary screen involves forming a mixture comprising a recombinant netrin protein, a natural intracellular netrin protein binding target, and a candidate pharmacological agent; incubating the mixture under conditions whereby, but for the presence of said candidate pharmacological agent, said netrin protein selectively binds said binding target; and detecting the presence or absence of specific binding of said netrin protein to said binding target.

Abstract: Growth differentiation factor-9 (GDF-9) is disclosed along with its polynucleotide sequence and amino acid sequence. Also disclosed are diagnostic and therapeutic methods of using the GDF-9 polypeptide and polynucleotide sequences.

Abstract: Growth Differentiation factor-3 (GDF-3) is disclosed along with its polynucleotide sequence and amino acid sequence. Also disclosed are diagnostic and therapeutic methods of using the GDF-3 polypeptide and polynucleotide sequences.

Abstract: Mammalian proteins and muteins thereof, designated interleukin-4s (IL-4s), are provided which exhibit both B cell growth factor activity and T cell growth factor activity. Compounds of the invention include native human and murine IL-4s, muteins thereof, and nucleic acids which are effectively homologous to disclosed cDNAs, and/or which are capable of coding for mammalian IL-4s and their muteins.

Abstract: "Partial" and "complete" CTP units are used to modify biologically active proteins and peptides to alter their clearance patterns. "Complete" CTP units have the amino acid sequence found at positions 112-118 to position 145 of the .beta.-subunit of human chorionic gonadotropin; "partial" CTP units are missing at least one amino acid in the region of position 118-145 inclusive. Variants of these CTP units contain 1-5 conservative amino acid substitutions which do not destroy activity. Suitable peptides or proteins which may be modified in this manner include various hormones and cytokines.

Abstract: The present invention relates, in general, to a method of enhancing the production performance of avians, by administering to a bird a heterologous protein comprised of inhibin protein, or a fragment thereof, and a carrier protein. The present invention also relates to a method of enhancing the production performance of avians, by administering to a bird a fusion gene product comprising a gene encoded for the expression of alpha-subunit avian inhibin protein, or a fragment thereof, and a gene encoded for the expression of a carrier protein. An effective amount of the heterologous protein or fusion gene product is administered to an animal such that an immunological response occurs in the animal against the heterologous protein. The present invention further relates to the above heterologous protein and fusion gene product, and to methods of producing the same.

Abstract: Polypeptides, polynucleotides, fragments thereof, and monoclonal antibodies thereto are provided for antigen-specific and antigen-non-specific glycosylation inhibiting factor and a method for recombinant production of biologically active polypeptides from a structural gene encoding the polypeptide.

Abstract: The invention relates to methods and compositions for the prevention or treatment of patients suffering from respiratory distress syndrome and/or sepsis syndrome by administering directly into the lungs small or nicrocrystalline particles or droplets of at least one protease inhibitor alone or with an oxygen metabolite scavenger. The method can also include the treatment in combination with the monitoring of the urine desmosine level of the patients and the use of DNase.

Abstract: Growth differentiation factor-6 (GDF-6) polypeptides, polynucleotides encoding GDF-6 polypeptides, and vectors and host cells containing GDF-6 encoding polynucleotides are provided.

Abstract: Biologically active heterodimeric human fertility hormones composed of two different subunits, each subunit being synthesized in the same cell transformed by at least one cell expression vector having heterologous DNA encoding each subunit with each subunit being controlled by a separate promoter. Preferred human fertility hormones include hCG, hLH and hFSH.

Abstract: A stable, freeze-dried, and pharmaceutically acceptable formulation includes a protein, a buffer, alanine, and mannitol, at a mass ratio of mannitol/alanine being 0.1-1, wherein the formulation being useful in an assay kit.

Abstract: Disclosed are 1) osteogenic devices comprising a matrix containing osteogenic protein and methods of inducing endochondral bone growth in mammals using the devices; 2) amino acid sequence data, amino acid composition, solubility properties, structural features, homologies and various other data characterizing osteogenic proteins, 3) methods of producing osteogenic proteins using recombinant DNA technology, and 4) osteogenically and chondrogenically active synthetic protein constructs.

Abstract: The present disclosure relates to the application of genetic engineering to provide artificial .beta. cells, i.e. cells which can secrete insulin in response to glucose. This is achieved preferably through the introduction of one or more genes selected from the insulin gene, glucokinase gene, and glucose transporter gene, so as to provide an engineered cell having all three of these genes in a biologically functional and responsive configuration. Assays for detecting the presence of diabetes-associated antibodies in biological samples using these and other engineered cells expressing diabetes-associated epitopes are described. Also disclosed are methods for the large-scale production of insulin by perfusing artificial .beta. cells, grown in liquid culture, with glucose-containing buffers.

Abstract: Modified polypeptides with increased biological activity exhibited as either increased potency or prolonged circulating half-life are disclosed with methods of preparing the modified polypeptides and methods of use.

Abstract: Methods of removing protein contaminants from a solution comprising thrombopoietin are disclosed. The solution is exposed to hydroxyapatite, whereby protein contaminants are bound to the hydroxyapatite and the thrombopoietin remains substantially unbound, and the unbound thrombopoietin is recovered. The use of hydroxyapatite is advantageously combined with other purification and concentration techniques, including ion-exchange chromatography, ligand affinity chromatography, hydrophobic interaction chromatography, ultrafiltration, and differential precipitation.

Abstract: A protein which inhibits milk secretion by lactating goats has been isolated from milk by anion exchange of a defined whey fraction, optionally followed by chromatofocussing, and is defined by reference to peaks in which it is found, its molecular weight of 7.6 KDa and pI of 4.8.

Abstract: Blood coagulation normalizing agents comprising effective ingredient of TCF-II.The blood coagulation normalizing agents of the present invention comprised of glycoprotein TCF-II produced by human fibroblast cells and accelerates the production of blood coagulation factor and increases platelet count to treat abnormal blood coagulation such as disseminated intravascular coagulation (DIC) and decreased platelet count caused by administration of cisplatin.

Abstract: Single-chain forms of the glycoprotein hormone quartet, at least some members of which are found in most vertebrates, are disclosed. The single chain compounds of the invention comprise two .beta. subunits of the glycoprotein hormones, which .beta. subunits are the same or different. These "two-.beta." forms are antagonists of glycoprotein hormone activity.

Abstract: Prophylaxis against HIV, treatment for individuals infected with HIV, and treatment Kaposi's sarcoma can be effected, respectively, through the administration of human chorionic gonadotropin.

Abstract: Compositions of proteins with chondrocyte and cartilaginous tissue inducing activity, as well as method of using those compositions, are disclosed. The compositions comprise one or more proteins of the transforming growth factor-.beta. (TGF-.beta.) superfamily of proteins, particularly bone morphogenetic proteins (BMPs), in combination with parathyroid hormone related polypeptide (PTHrP) or an equivalent PTH-like polypeptide. The compositions and methods are useful in the treatment of osteoarthritis, cartilage defects and in related tissue repair.

Abstract: The present invention relates to gonadotropins consisting of an .alpha. and .beta. subunit, said gonadotropins comprising non-native disulfide bridges, preferably non-native intersubunit disulfide bridges. The gonadotropins according to the invention have improved stability. The present invention furthermore provides for pharmaceutical compositions comprising said gonadotropins.

Abstract: Polypeptides comprising an N-terminal amino acid sequence corresponding to amino acids 107-111 of parathyroid hormone related protein (PTHrP) having bone resorption inhibitory activity are provided. The polypeptides are provided in pharmaceutical compositions for the treatment of diseases and disorders where inhibition of bone resorption is indicated.

Abstract: The present invention provides a polypeptide represented by the following amino acid sequence: ##STR1## wherein n is 0 or 1 and X represents Pro Ala Gly Thr Arg Ala Asn Asn Thr Leu Leu Asp Ser Arg Gly Trp Gly Thr Leu Leu Ser Arg Ser Arg Ala Gly or a fragment thereof (n=0: SEQ ID NO:1, n=1: SEQ ID NO:2), a recombinant DNA coding for the polypeptide, a vector containing the recombinant DNA, the preparation of a transformant carrying the vector, and the production of the polypeptide with the transformant. The use of this peptide in pharmaceutical compositions is also provided.

Abstract: The present invention relates to a keratinocyte growth factor fragment, KGF.sub.des1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF.sub.163. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues, C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R- (SEQ ID NO: 2) of the KGF.sub.163 N-terminus. The present invention also relates to a DNA molecule encoding KGF.sub.des1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGF.sub.des1-23 by culturing the transformed host. The present invention further relates to a conjugate of KGF.sub.des1-23 and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGF.sub.

Abstract: Methods useful for treating cancers are disclosed. The methods involve administering human chorionic gonadotropin (hCG) or human luteinizing hormone (hLH) to patients having cancers. Articles of manufacture that are useful for carrying out the described methods are also described. The claimed methods are effective against breast, prostate, ovary, and stomach carcinomas, as well as neuroblastomas, and Kaposi's sarcoma, among others.