Abstract: Full-length cDNA clones have been isolated encoding purified augmenter of liver regeneration (ALR) polypeptides prepared from the cytosol of livers from weanling rats and from humans. The full-length clone from the rat is a 1226 bp cDNA containing an 81 bp 5'-untranslated region, a 594 bp coding region and a 551 bp 3'-untranslated region. The coding region encodes three proteins with estimated molecular weights of 15,081, 20,193 and 22,835. The full-length clone from the human consists of a 727 bp cDNA containing a 4 bp 5'-untranslated region, a 615 bp coding region and a 108 bp 3'-untranslated region, including the termination codon TAG and the poly (A) region. The 615 bp coding region encodes four proteins, human ALR-V1, ALR-V2, ALR-V3 and ALR, having estimated molecular weights of 23,448, 20,834, 20,703 and 15,028, respectively.

Abstract: Stable, highly purified Factor VIII protein formulations are provided in high ionic strength media which comprises: sodium chloride, potassium chloride or mixtures thereof; calcium chloride; and histidine as the buffering agent.

Abstract: The present invention relates to novel purified and isolated nucleotide sequences encoding mammalian Ca.sup.2+ /calmodulin stimulated phosphodiesterases (CaM-PDEs) and cyclic-GMP-stimulated phosphodiesterases (cGS-PDEs). Also provided are the corresponding recombinant expression products of said nucleotide sequences, immunological reagents specifically reactive therewith, and procedures for identifying compounds which modulate the enzymatic activity of such expression products.

Abstract: A yeast .alpha.-factor expression system is provided comprised of a truncated leader sequence, containing the .alpha.-factor signal peptide and one glycosylation site, linked by a processing site to a non-yeast protein-encoding sequence.

Abstract: Recombinant organisms are disclosed that contain a pathway for glucose uptake other than the pathway normally utilized by the host cell. In particular, the host cell is one in which glucose transport into the cell normally is coupled to PEP production. This host cell is transformed so that it uses an alternative pathway for glucose transport that is not coupled to PEP production. In a preferred embodiment, the host cell is a bacterium other than Z. mobilis that has been transformed to contain the glf and glk genes of Z. mobilis. By uncoupling glucose transport into the cell from PEP utilization, more PEP is produced for synthesis of products of commercial importance from a given quantity of biomass supplied to the host cells.

Abstract: A process for producing cholesterol oxidase from a recombinant microorganism, the microorganism itself and its recombinant plasmid are disclosed. The cholesterol oxidase has a particular amino acid sequence, a high substrate affinity and a working pH in the acidic range. The gene for this cholesterol oxidase was derived from Brevibacterium sterolicum.

Abstract: Peptides which inhibit the binding of yon Willebrand Factor to Factor VIII. Monoclonal antibodies capable of specifically binding to the region of von Willebrand Factor containing the Factor VIII binding domain. Improved methods of preparing Factor VIII.

Abstract: The present invention provides derivatives of tissue plasminogen activator that lack the Finger, Growth Factor and Kringle 1 domains and comprise a Kringle 2 domain that is monoglycosylated at a site other than that of t-PA. Using recombinant DNA techniques, an alternate glycosylation sequence is provided within the Kringle 2 domain of these t-PA derivatives. This alternate glycosylation consensus sequence, as well as the glycosylation consensus sequence within the Serine Protease domain, is glycosylated upon the expression and secretion of these molecules from eucaryotic host cells. Thus, a homogeneous population of diglycosylated t-PA derivatives that lack the Finger, Growth Factor and Kringle 1 domains is produced.

Abstract: DNA constructs encoding human Factor VIII:C protein are disclosed. In particular, the DNA construct contains a nucleotide sequence that encodes a first polypeptide homologous to the A domain of human Factor VIII:C linked to a second polypeptide homologous to the C domain of human Factor VIII:C by a polypeptide spacer that comprises a peptide homologous to a human Ig heavy chain hinge region. Recombinant methods for producing human Factor VIII:C protein are also disclosed.

Abstract: The invention is transfected cells, substantially all of which contain at least one human collagen gene and express fibrillar collagen molecules derived using methods for synthesizing collagen and collagen fibrils in said cell lines, and methods for treatment of disorders in humans using said collagen derived from said stable cell lines.

Abstract: Endotoxin binding/neutralizing proteins capable of binding endotoxin in vivo, thereby neutralizing the toxic effect or bioactivity of endotoxin which are isolated from a horseshoe crab such as Limulus polyphemus, pharmaceutical compositions and pharmaceutical uses of the proteins, a method of purifying the proteins and an assay for endotoxin based on the proteins, are disclosed.

Abstract: DNA enclosing a tissue factor protein mutant capable of neutralizing the ability of endogenous tissue factor to induce coagulation is provided. A representative tissue factor mutant designated K165A, K166A TF is useful in a method for inhibiting thrombin-induced platelet aggregation in a mammal, either separately or in combination with a thrombolytic agent, an anticoagulant, or a GPII.sub.blll.sub.a inhibitor.

Abstract: A Bacillus cell contains a mutation in the epr gene resulting in inhibition of the production by the cell of the proteolytically active epr gene product; the cell may further contain mutations in the genes encoding proteolytically active residual protease I (bpr) and proteolytically active residual protease II (RP-II).

Abstract: Human tissue plasminogen activator (t-PA) is produced in useful quantities using recombinant DNA techniques. The invention disclosed thus enables the production of t-PA free of contaminants with which it is ordinarily associated in its native cellular environment. Methods, expression vehicles and various host cells useful in its production are also disclosed.

Abstract: Chimeric blood coagulation proteins are disclosed. The proteins are (i) coagulation factor V in which at least one A3, C1 or C2 domain exon thereof is replaced with the homologous exon of coagulation factor VIII; or (ii) coagulation factor VIII in which at least one A3, C1 or C2 domain exon thereof is replaced with the homologous exon of coagulation factor V. The chimeric proteins are useful for diagnostic purposes in epitope mapping and for therapeutic purposes in facilitating blood coagulations in patients in need of such treatment.

Abstract: Pharmaceutical composition containing Ecotin in a therapeutically effective amount for inhibition of blood coagulation.

Abstract: A cloned gene (epr) encoding a novel extracellular protease, Epr, from Bacillus subtilis is described. Also described is a triple extracellular neutral, alkaline and serine protease deficient Bacillus subtilis mutant strain having deletions in the (npr), (apr) and (epr) genes encoding these proteases. The triple mutant strain was constructed by the gene conversion technique and produces about 1% of the extracellular proteolytic activity of the wild type. It is a particularly useful host for the production of heterologous proteins that are secreted into the growth medium.

Abstract: A hybrid human/porcine coagulation factor VIII is produced by isolation and recombination of human and porcine factor VIII subunits, or by genetic engineering of the human and porcine factor VIII genes. Subunits of factor VIII that have been purified from human or porcine plasma are isolated, and hybrid human/porcine factor VIII is produced by mixing either porcine heavy chain subunits with human light chain subunits or by mixing human heavy chain subunits with porcine light chain subunits, thereby producing human light chain/porcine heavy chain and human heavy chain/porcine light chain hybrid molecules. These hybrid molecules are isolated by ion exchange chromatography. Alternatively, recombinant DNA methods are used to swap elements of porcine factor VIII for the corresponding elements of human factor VIII to produce hybrid human/porcine factor VIII.

Abstract: Novel single-chain hybrid plasminogen activators having an amino acid sequence composed of at least two subsequences corresponding in amino acid identity and number to subsequences of human t-PA and of human u-PA, and mutants thereof in which at least one of the N-glycosylation sites is modified such that glycosylation cannot take place at these sites exhibit valuable pharmacological properties. The hybrid plasminogen activators are produced by recombinant DNA technology.

Abstract: The present invention relates to novel purified and isolated nucleotide sequences encoding mammalian Ca.sup.2+ /calmodulin stimulated phosphodiesterases (CaM-PDEs) and cyclic-GMP-stimulated phosphodiesterases (cGS-PDEs). Also provided are the corresponding recombinant expression products of said nucleotide sequences, immunological reagents specifically reactive therewith, and procedures for identifying compounds which modulate the enzymatic activity of such expression products.