Abstract: The present invention relates to recombinant fusion proteins wherein erythropoietin (EPO) is linked via its C-terminus to an Fc fragment, and wherein the recombinant fusion proteins are further carbamoylated at the primary amines of the fusion protein. More specifically the invention relates to carbamoylated EPO-Fc fusion proteins, wherein at least one, preferably two or more, lysine amine residues and/or the N-terminal amino acid of the fusion protein are carbamoylated. The carbamoylated EPO-Fc fusion proteins of the present invention having a reduced hematopoietic activity whereas the tissue regenerative activity, i.e. the nerve cell regenerative activity remains unaltered or is even enhanced as compared to unmodified EPO-Fc fusion proteins. The invention further relates to a process for the manufacture of such fusion proteins and to pharmaceutical compositions containing them, as well as to the use of such fusion proteins and pharmaceutical compositions for medical therapy.

Abstract: The invention relates to a pharmaceutical composition made from an active ingredient included in liposomes for topical application, whereby the liposomes have an aqueous medium in the interior thereof and contain at least one active ingredient therein which exerts a direct or indirect relaxing effect on smooth musculature and is preferably selected from the group of prostaglandins, adenylate cyclases, cAMP, AMP, ATP, NO-synthetases, nitrogen monoxide (NO), NO compounds, nitrates, guanylate cyclases, cGMP, GMP, GTP and phosphodiesterases, in particular, Sildenafil. The invention further relates to a method for production of said composition, optionally, in sterile form and the use of the liposomes supporting the active ingredient in various galenic forms for external application in the genital region, for prophylaxis and/or therapy of sexual disorders in men or women and/or for increase of sexual sensitivity.

Abstract: The present invention relates to methods for increasing the secretion of a protein of interest (POI) from a eukaryotic cell comprising co-expression of a POI and of at least one protein that enhances protein secretion, said enhancing protein being selected from the group consisting of BMH2, BFR2, C0G6, C0Y1, CUP5, IMH 1, KIN2, SEC31, SSA4 and SSE1. The invention further relates to a yeast promoter sequence, in particular to a promoter sequence of the PET9 gene of P. pastoris, having, under comparable conditions, an increased promoter activity relative to a promoter sequence of the GAP protein. The invention further relates to an expression vector comprising such a promoter sequence and to the use of such an expression vector for expression of a POI in a host cell. The invention further relates to new yeast promoter sequences of genes from P. pastoris, which are useful for expression of a POI in yeast.

Abstract: The present invention relates to recombinant fusion proteins wherein erythropoietin (EPO) is linked via its C-terminus to an Fc fragment, and wherein said recombinant fusion proteins are further carbamoylated at the primary amines of the fusion protein. More specifically the invention relates to carbamoylated EPO-Fc fusion proteins, wherein at least one, preferably two or more, lysine amine residues and/or the N-terminal amino acid of said fusion protein are carbamoylated. The carbamoylated EPO-Fc fusion proteins of the present invention having a reduced hematopoietic activity whereas the tissue regenerative activity, i.e. the nerval cell regenerative activity remains unaltered or is even enhanced as compared to unmodified EPO-Fc fusion proteins. The invention further relates to a process for the manufacture of such fusion proteins and to pharmaceutical compositions containing them, as well as to the use of such fusion proteins and pharmaceutical compositions for medical therapy.

Abstract: The invention relates to a pharmaceutical composition made from an active ingredient included in liposomes for topical application, whereby the liposomes have an aqueous medium in the interior thereof and contain at least one active ingredient therein which exerts a direct or indirect relaxing effect on smooth musculature and is preferably selected from the group of prostaglandins, adenylate cyclases, cAMP, AMP, ATP, NO-synthetases, nitrogen monoxide (NO), NO compounds, nitrates, guanylate cyclases, cGMP, GMP, GTP and phosphodiesterases, in particular, Sildenafil. The invention further relates to a method for production of said composition, optionally, in sterile form and the use of the liposomes supporting the active ingredient in various galenic forms for external application in the genital region, for prophylaxis and/or therapy of sexual disorders in men or women and/or for increase of sexual sensitivity.

Abstract: The invention relates to Ab2-type anti-idiotypic antibodies and fragments thereof which mimic HVI-1 epitopes that are otherwise cryptic to the immune system and which antibodies or fragments thereof are directed against potently neutralizing anti-HIV-1 antibodies. The invention further relates to a hybridoma cell line 3H6 expressing the anti-idiotypic antibody and to pharmaceutical compositions containing the antibody or fragment thereof. The invention also relates to HIV-1 neutralizing Ab3-type antibodies elicited upon administration of the Ab2-type anti-idiotypic antibody or fragment thereof and to pharmaceutical compositions containing them. The invention also relates to the use of the present antibodies or fragments thereof as screening tools or as diagnostic or therapeutic agents.

Abstract: The invention relates to a simple and efficient process for isolating viruses from various sources and for producing live attenuated influenza vaccines in a serum-free Vero cell culture under conditions where alterations in the surface antigens of the virus due to adpative selection are minimized or prevented. The process does not require purification of the virus-containing supernatant harvested from the cell culture nor post-incubation treatment of the viruses for HA activation. The invention further relates to influenza A and B master strain candidates and to vaccines made thereof.

Abstract: The present invention relates to liposomes for drug delivery, wherein a liposome includes molecules of at least one desired drug distributed within an aqueous phase in the interior of the liposome and wherein the liposome further includes molecules of the same or of another drug attached to either or both sides of the liposomal membrane. More specifically, the invention relates to liposomes, wherein at least a part of the molecules of a desired drug bear a functional group that is reactive with a functional group present in at least one lipid fraction, and wherein the drug is covalently linked to the membrane lipids by chemical bonding, e.g. by ester bonding of a hydroxyl group of a lipid molecule and an acidic residue of the drug. In a preferred embodiment, the desired drug is a glycoprotein such as erythropoietin. The invention further relates to a method of manufacture of said liposomes and to pharmaceutical compositions containing them.

Abstract: The present invention relates to a method for the manufacture and purification of recombinant trypsinogen and trypsin in E. coli and yeast, using high yield expression vectors with and without secretion leader sequences. The invention further relates to an improved method and apparatus for carrying out protein refolding specifically useful for processing trypsinogen that has accumulated intracellularly in the form of inclusion bodies.

Abstract: The present invention relates to cell-regulatory proteins and to nucleotide sequences encoding said proteins wherein the proteins have been found to be potential tumor and/or senescense markers useful for medical diagnostics and additionally having therapeutical potential as well as antiapoptotic properties useful for improving cell viability in cell culture technology. The invention further relates to antibodies directed against the cell-regulatory proteins and to their use in medical diagnostics and therapy. The invention further relates to methods for the manufacture and application of the cell-regulatory proteins and of the corresponding nucleotide sequences.

Abstract: The invention relates to short 3- to 10-mer bioactive oligopeptides composed of amino acid residues selected from the group consisting of glycine, alanine, ?-alanine, serine, histidine, glutamic acid, aspartic acid, lysine and arginine. They are able to improve at least one cell culture parameter such as growth rate, viable cell number, viability on day 6 or 7, or final product yield, when added to the basal nutrient medium. The invention further relates to mixtures of such oligopeptides and to a method of improving cell culture parameters by incubating animal or plant cells in the presence of said oligopeptides.

Abstract: The invention relates to a recombinant NS gene of an influenza A virus comprising a functional RNA binding domain and a gene sequence modification after nucleotide position 400 of the NS1 gene segment, counted on the basis of influenza A/PR/8/34 Virus, wherein the modification bars transcription of the remaining portion of the NS1 gene segment. It further relates to embodiments, wherein the modification comprises deletions, insertions, or a shift of the open reading frame, and particularly to constructs comprising an insertion of an autocleavage site 2A, the nef gene from HIV-1 or the sequence encoding the ELDKWA-epitope of gp4l of HIV-1. The invention also relates to influenza virus transfectants that contain the modified NS gene and have an IFN inducing phenotype but which may or may not be sensitive towards IFN. The invention also relates to vaccines comprising such a chimeric virus.

Abstract: Disclosed are antibodies which can be used for the manufacture of vaccines for active and/or passive immunization of persons in need of such treatment. The invention also provides for human monoclonal antibodies that are functionally equivalent to the above-mentioned antibodies produced by any one of the cell lines CL1 through CL6 (deposited at the European Collection of Animal Cell Cultures (ECACC) at the PHLS in Porton Down, Salisbury, UK). Also provided are hybridoma and/or CHO cell lines producing any one of the antibodies disclosed and claimed herein, Also provided are mixtures of antibodies of the present invention, as well as methods of using individual antibodies or mixtures thereof for the detection, prevention and/or therapeutical treatment of HIV-1 infections in vitro and in vivo.

Abstract: Superoxide dismutase (SOD), preferably rhSOD, is used in liposomes, optionally mixed with hyaluronic acid and/or at least one physiologically acceptable carrier, and other optional additives, to prepare a pharmaceutical composition useful against increased concentrations of superoxide radicals and/or the damage caused thereby. These compositions can be administered topically, orally and/or parenterally to prevent and/or heal burns, skin lesions due to radiation, inflammations, rheumatic and arthritic diseases, bronchitis, ARDS, emphysema, allergic oedemas and other inflammatory process, possibly trigged by microbial infections. They may also be used in the cosmetic treatment of furuncles, acne and the like. They may also be used to improve the preservability of organic, preferably biogenic, materials, in particular organ transplants and liquids with organic components, as well as foodstuffs.