Funzyme Biotechnologies Sa

B.m.r.a. Corporation B.v.

Nestec S.a.

Centre Hospitalier Universitaire Vaudois (c.h.u.v.)

Michel Monod

Eric Grouzmann

Reto Stocklin

Jean-Silvain Lacroix

Michael Affolter

Peter Van Den Broek

Agnes Doumas

The present invention relates to micro-organisms and to methods of producing proteins. More specifically, the inventions relates to a host cell useful for the expression of heterozygous proteins in which the host cell,, has been genetically modified so that the gene for endogenous secreted subtilisin Sub2 protease is completely or partially inactivated.

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Disclosed herein are fungal nucleic acid sequences that encode novel dipetidyl peptidase IV (DPPIV) polypeptides. Also disclosed are polypeptides encoded by these nucleic acid sequences, as well as derivatives, variants, mutants, or fragments of the aforementioned polypeptide, polynucleotide, or antibody. The aminopeptidase polypeptides, referred to herein as DPPIV proteins of the invention are useful in a variety of medical, research, and commercial applications.

Fungal dipeptidyl peptidase IV (DPPIV) enzyme for reagent use

Disclosed herein are fungal nucleic acid sequences that encode novel polypeptides. Also disclosed are polypeptides encoded by these nucleic acid sequences, as well as derivatives, variants, mutants, or fragments of the aforementioned polypeptide, polynucleotide, or antibody. The novel leucine aminopeptidase (LAP) and other amino- and carboxypeptidases polypeptides, referred to herein as EXOX nucleic acids and proteins of the invention are useful in a variety of medical, research, and commercial applications.

Fungal proteins and nucleic acids encoding same

The present invention is directed to methods of treating a wide variety of diseases, disorders and conditions characterized by excessive activity of substance P. The treatment involves administering peptidases that recognize and selectively cleave polypeptides at Xaa-Pro sequences.

Treatment of substance P-related disorders

The present invention is directed to methods of treating mucosal inflammation associated with rhinitis or sinusitis by administering peptidases that recognize and cleave polypeptides at Xaa-Pro sequences. In addition, the invention encompasses therapeutic packages in which pharmaceutical compositions containing the peptidases are preloaded in a device suitable for intranasally delivering drug.

Method of treating rhinitis or sinusitis by intranasally administering a peptidase

The invention has for object the new recombinant prolyl-dipeptidyl-peptidase enzyme (DPP IV) from,comprising the amino-acid sequence from amino acid 1 to amino acid 755 of SEQ ID NO:2 or functional derivatives thereof, and providing a high level of hydrolyzing specificity towards proteins and peptides starting with X-Pro- thus liberating dipeptides of X-Pro type, wherein X is any amino acid. The invention also provides a DNA molecule encoding the enzyme according to the invention, cells expressing the enzyme according to the invention by recombinant technology, an Aspergillus naturally providing a prolyl-dipeptidyl-peptidase activity which has integrated multiple copies of the Aspergillus native promoter which naturally directs the expression of the gene encoding the prolyl-dipeptidyl-peptidase activity, Aspergillus naturally providing a prolyl-dipeptidyl-peptidase activity which is manipulated genetically so that the dppIV gene is inactivated. The invention provides a method for producing the enzyme according to the invention, comprising cultivating the cells of the invention in a suitable growth medium under conditions that the cells express the enzyme, and optionally isolating the enzyme in the form of a concentrate. The invention provides the use of the enzyme or the cells of the invention to hydrolyze protein containing materials. The invention provides the use of an enzyme and/or a cell providing a prolyl-dipeptidyl-peptidase activity, in combination with at least an enzyme providing a prolidase to hydrolyze protein containing materials. In a last further aspect, the invention provides a food product comprising a protein hydrolyzate obtainable by fermentation with at least a microorganism providing a prolyl-dipeptidyl-peptidase activity higher than 50 mU per ml when grown in a minimal medium containing 1% (w/v) of wheat gluten.

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Lausanne, Switzerland

Michel Monod