Abstract: The present invention relates to a keratinocyte growth factor fragment, KGFdes1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF163. 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 KGF163 N-terminus. The present invention also relates to a DNA molecule encoding KGFdes1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGFdes1-23 by culturing the transformed host. The present invention further relates to a conjugate of KGFdes1-23 and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis.

Abstract: Methods and compositions are provided for efficient production of human insulin-like growth factor. Synthetic IGF I and IGF II genes are joined to leader and processing signals which provide for expression and secretion of the gene product in yeast. Enhanced yields of the product may then be recovered from the nutrient medium. Yeast strains S. cerevisiae AB103 (pYIGF-I-10/1) and AB103 (pYIGF-II-10/1) were deposited at the American Type Culture Collection on Apr. 23, 1983 and granted Accession Nos. 20673 and 20674, respectively.

Abstract: Methods and compositions for the expression of nucleotide sequences are provided. Compositions comprise the nucleic acid sequences of the transcriptional regulatory region of the PpSEC10 gene of Pichia pastoris. Methods are provided to chemically regulate the PpSEC10 transcriptional control region by modulating the iron concentration in the culturing medium. The methods find use in regulating expression of nucleotide sequences. Furthermore, the methods of the invention can be used to regulate polypeptide expression, more particularly in regulating heterologous polypeptide expression, particularly using a yeast host cell as the expression system.

Abstract: Methods for preparing biodegradable microparticles are provided. Also provided are microparticles prepared by the method which include IGF-1 entrapped therein. The microparticles allow for controlled release of IGF-1 and other polypeptides over prolonged periods of time.

Abstract: A purified insulin-like growth factor binding protein (IGFBP) selected from the group consisting of insulin-like growth factor binding protein having an amino acid sequence that, preferably, is at least 70% homologous to the amino acid sequence of FIG. 1 and fragments thereof that are capable of binding to an antibody specific for the protein or to an insulin-like growth factor is described. This new IGFBP is designated herein as IGFBP-5. Recombinant DNA molecules encoding the binding proteins and subsequences thereof are also described along, with recombinant microorganisms and cell lines containing the DNA molecules and methods for producing the binding proteins using recombinant hosts containing the relevant DNA molecules. Antibodies to the protein, useful in various diagnostic applications, are also described.

Abstract: Purified C-terminally truncated insulin-like growth factor binding protein-5 (IGFBP-5) compounds are described. The compounds are mitogenic and bind to insulin-like growth factors (IGFs) with decreased affinity. The C-terminally truncated IGFBPs can be produced recombinantly.

Abstract: Regulatory nucleotide sequences for a novel Pichia pastoris gene, designated PpSEC10 gene, and the nucleotide sequences and respective amino acid sequences for the secretion leader and the mature Sec10p protein components of the precursor polypeptide encoded by this novel gene are provided. These compositions are useful in methods for expression and secretion of proteins when assembled in proper reading frame, individually or in combination, within a DNA construct that further comprises a nucleotide sequence encoding a protein of interest. Vectors comprising the DNA constructs of the invention can be used to transform a yeast host cell, which can then be cultured to obtain the secreted protein of interest. Kits useful in this method and in methods of detection of the Sec10p protein using antibodies are also disclosed.

Abstract: Disclosed is a method for transporting neurologic therapeutic agents to the brain by means of the olfactory neural pathway and a pharmaceutical composition useful in the treatment of brain disorders.

Abstract: Purified compounds comprising truncated insulin-like growth factor binding protein (IGFBP) capable of binding to an antibody specific for the compound or to an insulin-like growth factor wherein the truncated IGFBP has a decreased affinity for insulin-like growth factors (IGFs) are described. Recombinant DNA molecules encoding the truncated IGFBPs are also described along with recombinant microorganisms and cell lines containing the DNA molecules and methods for producing the truncated IGFBPs using recombinant hosts containing the relevant DNA molecules. Methods for stimulating mitogenic activity and also for treating a bone disorder in mammals are also described.

Abstract: Methods for stimulating osteogenesis using C-terminally truncated insulin-like growth factor binding protein-5 (IGFBP-5) compounds and derivatives thereof are described. The IGFBP-5 polypeptides used in the methods are mitogenic and can be combined in compositions with insulin-like growth factor (IGF).

Abstract: Disclosed is a method for transporting neurologic therapeutic agents to the brain by means of the olfactory neural pathway and a pharmaceutical composition useful in the treatment of brain disorders.

Abstract: Disclosed is a method for transporting neurologic therapeutic agents to the brain by means of the olfactory neural pathway and a pharmaceutical composition useful in the treatment of brain disorders.

Abstract: Compositions and methods are provided for endopeptidases and their production, and for enhanced efficiencies of processing heterologous precursor polypeptides to mature polypeptides. These compositions and methods utilize recombinant PACE 4 and 4.1, mammalian endopeptidases that are specific for dibasic amino acid sites. Therapeutic compositions and methods employing PACE 4 or 4.1 or their inhibitors are also provided.

Abstract: A new receptor for fibroblast growth factor has been cloned and expressed. The recombinant receptor is useful for inhibiting FGF activity, and for screening compounds for binding activity similar to that of FGF. A soluble, truncated recombinant receptor is also prepared, and is capable of binding FGF.

Abstract: Recombinant protein complexes having human Factor VIII:C activity are expressed in a eukaryotic host cell by transforming the host cell with first and second expression cassettes encoding a first polypeptide substantially homologous to human Factor VIII:C A domain and a second polypeptide substantially homologous to human Factor VIII:C C domain, respectively. In the present invention, the first polypeptide may be extended having at its C-terminal a human Factor VIII:C B domain N-terminal peptide, a polypeptide spacer of 3-40 amino acids, and a human Factor VIII:C B domain C-terminal peptide. Expression of the second polypeptide is improved by employing an &agr;1-antitrypsin signal sequence.

Abstract: Disclosed is a method for transporting neurologic therapeutic agents to the brain by means of the olfactory neural pathway and a pharmaceutical composition useful in the treatment of brain disorders.

Abstract: Methods for purifying authentic, properly folded IGF polypeptides from yeast transformants are disclosed. The methods include a refolding step and provide for high yields of authentic IGF from a variety of yeast strains.

Abstract: Polynucleotides, vectors, and host cells comprising a polynucleotide having a fragment of a leader sequence and a second nucleotide sequence that encodes a polypeptide heterologous to the leader sequence, wherein the leader sequence fragment is sufficient for secretion and comprises an amino acid sequence that comprises at least about 70% sequence identity to the leader sequence of Pichia acaciae killer toxin, wherein the heterologous polypeptide is not naturally contiguous to the leader sequence, and wherein upon expression of the polynucleotide molecule in a host cell suitable for expression thereof, the heterologous polypeptide is produced that is free of additional N-terminal amino acids.

Abstract: The present invention relates to 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 keratonocyte 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: A yeast &agr;-factor expression system is provided comprised of a truncated leader sequence, containing the &agr;-factor signal peptide and one glycosylation site, linked by a processing site to a non-yeast protein-encoding sequence.