Abstract: The present invention relates to granulocyte colony-stimulating factor (“G-CSF”) hybrid molecules which retain the internal core helices of G-CSF. Also provided are pharmaceutical compositions containing hybrid molecules.

Abstract: The present invention provides novel isolated NOVX polynucleotides and polypeptides encoded by the NOVX polynucleotides. Also provided are the antibodies that immunospecifically bind to a NOVX polypeptide or any derivative, variant, mutant or fragment of the NOVX polypeptide, polynucleotide or antibody. The invention additionally provides methods in which the NOVX polypeptide, polynucleotide and antibody are utilized in the detection and treatment of a broad range of pathological states, as well as to other uses.

Abstract: The present invention broadly relates to the field of protein modification, and, more specifically, the attachment of water soluble polymers to novel erythropoietin stimulating protein (NESP).

Abstract: Conjugates of erythropoietin with poly(ethylene glycol) comprise an erythropoietin glycoprotein having at least one free amino group and having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells and selected from the group consisting of human erythropoietin and analogs thereof which have sequence of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites or a rearrangement of at least one glycosylation site; said glycoprotein being covalently linked to “n” poly(ethylene glycol) groups of the formula —CO—(CH2)x(OCH2CH2)m—OR with the carbonyl of each poly(ethylene glycol) group forming an amide bond with one of said amino groups; wherein R is lower alkyl; x is 2 or 3; m is about 450 to about 900; n is from 1 to 3; and n and m are chosen so that the molecular weight of the conjugate minus the erythropoietin glycoprotein is from 20 kilodaltons to 100 kilodaltons.

Abstract: Conjugates of erythropoietin with poly(ethylene glycol) comprise an erythropoietin glycoprotein having at least one free amino group and having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells and selected from the group consisting of human erythropoietin and analogs thereof which have sequence of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites or a rearrangement of at least one glycosylation site; the glycoprotein being covalently linked to “n” poly(ethylene glycol) groups of the formula —CO—(CH2)x(OCH2CH2)m—OR with the carbonyl of each poly(ethylene glycol) group forming an amide bond with one of said amino groups; wherein R is lower alkyl; x is 2 or 3; m is about 450 to about 900; n is from 1 to 3; and n and m are chosen so that the molecular weight of the conjugate minus the erythropoietin glycoprotein is from 20 kilodaltons to 100 kilodaltons.

Abstract: Methods and compositions are provided for protecting or enhancing an erythropoietin-responsive cell, tissue, organ or body part function or viability in vivo, in situ or ex vivo in mammals, including human beings, by systemic or local administration of an erythropoietin receptor activity modulator, such as an erythropoietin or a modified erythropoietin.

Abstract: A molecule is provided capable of promoting high affinity binding of a fibroblast growth factor (FGF) to a FGF receptor (FGFR), said molecule being selected from: (i) a recombinant chimeric fusion molecule comprising the extracellular domain of a syndecan or a fragment thereof fused to a tag suitable for proteoglycan purification, said fusion molecule being post-translationally glycosylated to carry at least one chain of a heparan sulfate having at least one highly sulfated domain; (ii) a DNA sequence encoding a chimeric fusion molecule comprising the extracellular domain of a syndecan or a fragment thereof fused to a tag suitable for proteoglycan purification; and (iii) a sugar molecule from a syndecan carrying at least one chain of a heparan sulfate having at least one highly sulfated domain. The compounds may be used for induction of angiogenesis, bone fracture healing, enhancement of wound healing, promotion of tissue regeneration and treatment of ischemic heart diseases and peripheral vascular diseases.

Abstract: The invention relates to polypeptide conjugates comprising a polypeptide exhibiting G-CSF activity and having an amino acid sequence that differs from the amino acid sequence of human G-CSF in at least one specified introduced and/or removed amino acid residue comprising an attachment group for a non-polypeptide moiety, and having at least one non-polypeptide moiety attached to an attachment group of the polypeptide. The attachment group may e.g. be a lysine, cysteine, aspartic acid or glutamic acid residue or a glycosylation site, and the non-polypeptide moiety may e.g. be a polymer such as polyethylene glycol or an oligosaccharide. The conjugate, which has a reduced in vitro bioactivity compared to hG-CSF, has one or more improved properties such as increased biological half-life and increased stimulation of neutrophils.

Abstract: The present invention relates to diagnosis aids and processes for detecting pregnancy in ruminants based on the relaxin-like factor detectable in ruminants. Antibodies against the relaxin-like factor from ruminants as well as against fragments and/or active derivatives of the same with the same immunogenicity are also provided.

Abstract: The present invention provides new interferon &bgr; conjugates, methods of preparing such conjugates and the use of such conjugates in therapy, in particular for the treatment of multiple sclerosis.

Abstract: Glycosylated polypeptides comprising the primary structure NH2—X—Pp—COOH, wherein X is a peptide addition comprising or contributing to a glycosylation site, and Pp is a polypeptide of interest or comprising the primary structure NH2-Px—X—Py-COOH, wherein Px is an N-terminal part of a polypeptide Pp of interest, Py is a C-terminal part of said polypeptide Pp, and X is a peptide addition comprising or contributing to a glycosylation site are provided. The glycosylated polypeptides possess improved properties as compared to the polypeptide of interest.

Abstract: 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.

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: Erythropoietin analog-human serum albumin (EPOa-hSA) fusion protein and methods of making and using the fusion protein.

Abstract: A method for quantitatively and/or qualitatively assaying an analyte in a sample, wherein the analyte is a receptor binding compound, has low detection limits equivalent to those of radioreceptor assays. The method comprises the steps of a) contacting the sample with material comprising a receptor for the analyte in order for receptor-analyte binding to occur and b) further contacting the sample with a detectable ligand for the receptor in order for receptor-ligand binding to occur, followed by c) separating the resulting receptor bound and free fractions, d) subjecting the receptor bound fraction to dissociating conditions releasing the ligand from the receptor and e) assaying for the dissociated ligand in a manner known per se for the detection of the detectable ligand.

Abstract: Heterodimeric polypeptide conjugates exhibiting FSH activity, comprising a dimeric polypeptide comprising an FSH-&agr; subunit and an FSH-&bgr; subunit, wherein at least one of the FSH-&agr; and FSH-&bgr; subunits differs from the corresponding wildtype subunit in that at least one amino acid residue acid residue comprising an attachment group for a non-polypeptide moiety has been introduced or removed, and having at least one non-polypeptide moiety bound to an attachment group of at least one of said subunits are provided. Preferably, at least one attachment group, e.g., an N- or O-glycosylation site or an attachment site for a polymer molecule such as polyethylene glycol, has been introduced, e.g., at an N-terminal. The polypeptide conjugates exhibit improved properties, in particular an increased half-life, compared to human FSH.

Abstract: The use of hCG, hCG &bgr;-subunit, as well as fragments and active derivatives thereof, or hCG &bgr;-core in the preparation of a medicament for the prophylaxis and/or the treatment of pathologies requiring inhibition of the matrix metalloprotease (MMP) enzymatic 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 &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.

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). Depending on the starting material used and the initial purity of FSH in the starting material, additional purification steps may be employed. These steps preferably involve the use of hydrophobic interaction chromatography. This process may be used to generate affinity pure FSH suitable for therapeutic applications. The methods of the invention provide high purity FSH with high overall yield. A further advantage is the ability to easily regenerate the chromatography media for re-use, thus providing added economy to the purification process.

Abstract: Disclosed are novel compositions of morphogenic proteins constituting soluble forms of these proteins, antibodies that distinguish between soluble and mature forms, and method for producing these morphogenic proteins and antibodies.

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 invention 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.

Abstract: The present invention relates to derivatives of hGLP-2 and analogues and/or fragments thereof having a lipophilic substituent have interesting pharmacological properties, in particular they have a more protracted profile of action than the parent peptides.

Abstract: The present invention relates to enhancer peptide sequences originally derived from various retroviral envelope (gp41) protein sequences that enhance the pharmacokinetic properties of any core polypeptide to which they are linked. The invention is based on the discovery that hybrid polypeptides comprising the enhancer peptide sequences linked to a core polypeptide possess enhanced pharmacokinetic properties such as increased half life. The invention further relates to methods for enhancing the pharmacokinetic properties of any core polypeptide through linkage of the enhancer peptide sequences to the core polypeptide. The core polypeptides to be used in the practice of the invention can include any pharmacologically useful peptide that can be used, for example, as a therapeutic or prophylactic reagent.

Abstract: Novel &bgr;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 &bgr;10 polypeptides and heterodimeric forms thereof, specifically &agr;2/&bgr;10. Also provided for are methods for the treatment, diagnosis, amelioration, or prevention of diseases with &bgr;10 polypeptides and &agr;2/&bgr;10 heterodimers or their respective binding agents.

Abstract: There can be provided a fungal antigen which is an insoluble fraction obtainable from fungal cells of which cell wall has been substantially removed or at least partially removed; a process for producing the same; a nucleic acid encoding the fungal antigen; a biologic product containing the fungal antigen; a method of stimulating immunological responses by using the biologic product; a method of suppressing allergic reaction to fungi in a vertebrate; and a method for diagnosing a disease caused by fungi in a vertebrate.

Abstract: The present invention is directed to a pharmaceutical combination preparation comprising 2,000-7,000 U of recombinant human erythropoietin (EPO) and 5-20 mg of an Fe(III) complex, wherein the rhEPO and the Fe(III) complex may be present in separate administration forms or in an integrated administration form. The pharmaceutical preparation is used in the treatment of anemias or hemodialysis patients.

Abstract: Disclosed herein are novel methods of obtaining osteogenic and other growth factor compositions from alternative nonbone sources such as tissue or bone marrow, and methods of using the same. Also disclosed are implants infused with growth factors obtained from the methods disclosed herein.

Abstract: Compositions of proteins with tendon/ligament-like tissue inducing activity are disclosed. The compositions are useful in the treatment of tendinitis and tendon or ligament defects and in related tissue repair.

Abstract: A proteoglycan (“azaftig”) with a molecular weight of approximately 24,000 Dalton has been isolated and partially characterized from the urine of cachectic cancer and non-cancer patients. Azaftig has been shown to bind to receptors on fat cell membranes, and to cause lipolysis. Azaftig does not bind to muscle cell membranes, or cause proteolysis in muscle tissue. Azaftig detection in urine or other body fluids will allow early identification of patients in which weight loss may become a problem. Azaftig may also aid fat loss in humans in which obesity is a threat to health.

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: The invention relates to Cytostatin III polypeptides, polynucleotides encoding the polypeptides, methods for producing the polypeptides, in particular by expressing the polynucleotides, and agonists and antagonists of the polypeptides. The invention further relates to methods for utilizing such polynucleotides, polypeptides, agonists and antagonists for applications, which relate, in part, to research, diagnostic and clinical arts.

Abstract: Transgenically produced prolactin and methods of making and using transgenically produced prolactin are disclosed.

Abstract: An isolated and purified polypeptide having heparin binding properties with the amino acid sequence of SQ ID No: 1 and pharmaceutical compositions for treating skin wounds.

Abstract: O-glycan is released from a glycoconjugate with a substantially anhydrous hydrazine reagent, the glycoconjugate being substantially salt-free and substantially anhydrous. Released O-glycan is recovered in substantially unreduced and intact form using a chromatographic material.

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: Proteins or peptidic substances, which may be prepared from naturally occurring proteins, enhance the bioavailability of proteolytically-labile therapeutic agents which, in the absence of the protein or peptidic substance would suffer enzymatic inactivation upon administration.

Abstract: Trophoblastic .beta.-I-glycoprotein (TBG) is used as a means for treating autoimmune diseases showing suppressors immunodeficit.A method of treating of autoimmune diseases comprises the administration of an immune correcting preparation, said preparation being trophoblastic .beta.-I-glycoprotein (TBG), indications with respect to said preparation being determined by testing TBG sensitivity of mononuclear cells (MNCs).

Abstract: Provided is an aqueous pharmaceutical composition comprising human growth hormone wherein said human growth hormone is dissolved in a benzalkonium chloride-containing, slightly to weakly acidic solution buffered, most preferably, with maleate. The composition is sufficiently stable to be supplied in liquid state and can be prepared as a less painful composition.

Abstract: Compositions and methods of treating disease and injuries wherein by sequentially or co-administering pulmonarily a polypeptide effective for the treatment of the injury or disease and a protease inhibitor capable of binding with elastase or cathepsin G.

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: 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: Described are modified Noggin muteins, compositions comprising the muteins, and DNA or RNA sequences comprising coding (sense) or antisense sequences for the muteins.

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: A protein is provided derived from human fibroblast having an N-terminal amino acid sequence represented by SEQ ID NOS: 1 and 2, having a molecular weight of approximately 15kD under reducing and non-reducing conditions by (dosium dodecyl sulfate-polyacrylamide gel electrophoresis), and having an activity to stimulate growth of osteoblast. The protein is produced by gene engineering procedures, contains the amino acid sequence represented by SEQ ID NO: 9 and has osteoblast growth activity. Also provided is a method for preparing the protein by culturing human fibroblast and treating the conditioned medium for purification. The protein is utilized for the treatment of diseases characterized by decreased bone mass such as osteoporosis or is utilized as an antigen for immunological diagnosis of diseases.

Abstract: The method for determining a suppressor component of human immune status comprises collecting peripheral blood, obtaining a suspension of mononuclear cells (MNCs), dividing said suspension into two equal portions, cultivating MNCs in the first portion without a suppressor activator, cultivating MNCs in the second portion with said suppressor activator (TBG), washing MNCs out of culture medium, blocking the proliferation, adding newly isolated MNCs from a normal donor, which MNCs have been stimulated with phytohemagglutinin, into each of MNC portions in equal proportions to obtain test cultures, cultivating said test cultures, further evaluating the proliferation in said test cultures and determining the suppression value on the basis of the ratios of proliferation levels in test cultures.

Abstract: The extracellular domain, or fragment thereof, of a gonadotropin glycoprotein hormone receptor is expressed and secreted in a soluble and functionally hormone-binding form. A recombinant baculovirus transfer vector is constructed to include a gene segment encoding the extracellular domain, or fragment thereof, of the glycoprotein hormone receptor joined in frame with a gene segment encoding a baculovirus signal peptide and operably linked to a baculovirus promoter. Recombinant baculovirus generated by transfection or co-transfection of insect cells are then used to infect insect host cells for the expression and secretion of soluble receptor.

Abstract: Human chemokine .beta.-6 agonist and antagonist polypeptides and DNA encoding such polypeptides and procedure for producing such polypeptides by recombinant technique are disclosed. The chemokine .beta.-6 antagonists of the present invention may be employed to treat rheumatoid arthritis, lung inflammation, allergy, asmtha, infectious diseases and to prevent inflammation and atherosclerosis. The chemokine .beta.-6 agonists may be employed to myeloprotect patients undergoing chemotherapy.

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: A pharmaceutical formulation comprising a growth hormone pretreated with zinc and optionally lysine or calcium ions 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 formulation at ambient temperature.