Abstract: The present invention relates to agents and methods that are capable of augmenting NK-mediated killing of target cells by reducing inhibitory KIR signalling without reducing the binding of KIR to HLA-C. As described herein, transduction of negative signaling via KIR, upon binding of KIR to its HLA class I ligand, can involve a ligand-binding induced, conformational reorientation of the KIR molecules allowing interactions to form between adjacent KIRs in specific domains, leading to accelerated clustering. Methods and agents such as monoclonal antibodies for reducing KIR-mediated inhibition of NK cell cytotoxicity without reducing or blocking HLA-binding by, e.g., reducing or blocking dimerization of KIR, are provided.

Abstract: Compositions and methods for regulating an immune response in a subject are described. More particularly, described are human antibodies that regulate the activity of NK cells and allow a potentiation of NK cell cytotoxicity in mammalian subjects, and antibodies having antigen-binding properties similar to those of human monoclonal antibody 1-7F9 or 1-4F1. Described also are also fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly for use in therapy, to increase NK cell activity or cytotoxicity in subjects.

Abstract: The present invention relates to a filamentous fungus useful for the production of heterologous polypeptides, having been modified by recombinant DNA technology in a manner by which the expression of alkaline proteases have been completely or partially inactivated. The invention also encompasses processes for the production of proteins of interest in high yields by using the fungi of the invention. The invention furthermore relates to methods for producing such fungi and DNA constructs to be used in these methods.

Abstract: The present invention relates to an enzyme exhibiting aminopeptidase activity, a method for producing said enzyme, an enzyme preparation containing said enzyme exhibiting aminopeptidase activity, and use of said enzyme for various industrial purposes.

Abstract: A method for in vivo production of a library in cells comprising a multitude of mutated genetic elements, wherein an error-prone polymerase is used in each ancestral cell to replicate all or a part of a genetic element independently of the host chromosomal replication machinery. The genetic element comprisesi) an origin of replication from which replication is initiated,ii) optionally a genetic marker, e.g. a gene conferring resistance towards an antibiotic,iii) a gene encoding the polypeptide of interest.Also methods for the generation of a DNA sequence encoding a desired variant of a polypeptide of interest, and for the determination of such a DNA sequence are described.

Abstract: The present invention relates to therapeutically active heterocyclic compounds, to methods for their preparation and to pharmaceutical compositions comprising the compounds. The novel compounds are useful in treating diseases in the central nervous system related to malfunctioning of the nicotinic cholinergic system.

Abstract: A method of selectively acylating an insulin, an insulin analogue or a precursor thereof having a free .epsilon.-amino group of a Lys residue contained therein and at least one free .alpha.-amino group which method comprises reacting the .epsilon.-amino group with an activated amide in a polar solvent in the presence of a base.

Abstract: The present invention provides novel crystalline (-)-3R,4R-trans-7-methoxy-2,2-dimethyl-3-phenyl-4-{4-?2-(pyrrolidin-1-yl)e thoxy!phenyl}chromane, hydrogen fumarate useful for reducing or preventing bone loss as well as pharmaceutical compositions containing the same. A process for preparing (-)-3R,4R-trans-7-methoxy-2,2-dimethyl-3-phenyl-4-{4-?2-(pyrrolidin-1-yl)e thoxy!phenyl}chromane, hydrogen fumarate is described.

Abstract: The invention provides crystalline 3-(4-hexyloxy-1,2,5-thiadiazol-3-yl)-1,2,5,6-tetrahydro-1-methylpyridine (+) L-hydrogentartrate, its preparation and use as a therapeutic agent.

Abstract: This invention is in the field of glucose isomerization enzymes. More specifically, the invention is directed to a novel xylose isomerase, a process for the preparation of this enzyme, the use of this enzyme in glucose isomerization processes, and glucose isomerization processes. The enzyme is preferably derived from Thermotoga maritima or Thermotoga neapolitana. The enzyme has a temperature optimum above 90.degree. C., pH optimum in the range of from 6 to 7 and a residual activity at 90.degree. C. of more than 40% after 30 minutes and/or residual activity at 98.degree. C. of more than 20% after 30 minutes. The enzyme can also be in immobilized form.