Novo Nordisk A/s

Novozymes A/s

Arne Agerlin Olsen

Helle Outtrup

Claus Dambmann

Martin Schulein

Henrik Bisgangrd-Frantzen

Erwin Ludo Roggen

Per Linaa Jorgensen

Lars Bo Hansen

Thomas Christian Beck

Claus Von Der Osten

Mads E Bjoernvad

Steffen Ernst

Tine Muxoll Fatum

Annette Prento

Allan Svendsen

Kim Borch

Kim Vilbour Andersen

Henrik Lund

Henrik Bisgard-Frantzen

Martin Sch&uuml;lein

Henrik Bisg&aring;rd-Frantzen

Marianne Thellersen

Niels Munk

Peter Rosholm

Heinz-Josef Deussen

Heinz Josef Deussen

Erwin Lugo Roggen

The present invention relates to a method of selecting a protein variant having reduced immunogenicity as compared with the parent protein. This method includes the steps of screening a random peptide display package library with antibodies raised against any protein of interest, sequencing the amino acid sequence of the antibody binding peptides, or the DNA sequence encoding the antibody binding peptides, identifying epitope patterns of a protein by sequence alignment of the reactive peptide sequence, localization of epitope patterns on the primary 3-dimensional structure of the parent protein, defining an epitope area including amino acids situated within 5 &angst; from the epitope amino acids, and affecting antibody binding to the epitope, changing the localized epitope patterns, or amino acids defining the epitope area of the parent protein by genetic engineering mutations of a DNA sequence encoding the parent protein without impairing functionality of the protein using the emerging epitode database for eliminating amino acid substitutions creating new or duplicating existing epitope patterns, introducing the mutated DNA sequence into a suitable host, culturing the host and expressing the protein variant, and evaluating the immunogenicity of the protein variant using the parent protein as reference. The invention further relates to the protein variant and its use, as well as to a method for producing said protein variant.

Low allergenic protein variants

A polypeptide-polymer conjugate is prepared having one or more polymers covalently bound to a polypeptide. The polymer has the general formula; EO PO wherein EO is ethylene oxide, PO is propylene oxide, x&equals;1&minus;99%, y&equals;1&minus;99%, x&plus;y&equals;100%, and x and y are in a ratio range of 10:90 to 90:10, more preferably 40:60 to 60:40, or in a 50/50 ratio. The polymer, which can be a block polymer, typically has a molecular weight in a range of 100 to 100,000 daltons, and the polypeptide may contain 1 to 100 polymer molecules. Coupling the polypeptide, in particular enzymes, to the polymer reduces respiratory allergenicity of the polypeptide. Industrial compositions such as detergent compositions, personal care compositions, compositions for processing/treating textiles, and food and feed compositions containing the polypeptide-polymer conjugate have reduced respiratory allergenicity.

Polypeptides conjugated to copolymers of ethylene oxide and propylene oxide to reduce allergenicity

The present invention relates to polypeptide-polymer conjugates having added and/or removed one or more attachment groups for coupling polymeric molecules on the surface of the polypeptide structure, a method for preparing polypeptide-polymer conjugates of the invention, the use of said conjugates for reducing the immunogenicity and allergenicity and compositions comprising said conjugate.

Modified enzymes having polymer conjugates

The present invention relates to polypeptides with reduced immune response including reduced allergenicity having one or more amino acid residues being substituted with other amino acid residues and/or having coupled one or more polymeric molecules in the vicinity of the polypeptides metal binding site, a method for preparing modified polypeptides of the invention, the use of the polypeptide for reducing the immunogenicity and allergenicity and compositions comprising the polypeptide.

Modified polypeptide

Modified enzymes are prepared for use in skin care products by covalently coupling to the enzymes from 4 to 70 polymeric molecules with or without a linker such as a triazine ring. Molecular weight of the polymeric molecules may be from 1 to 35 kDa and of the enzymes from 15 to 100 kDa. The number and weight of polymeric molecules coupled is balanced with the weight and/or surface area of the enzymes. Enzymes include proteases such as subtilisins, lipases and oxidoreductases such as laccases and superoxide dismutase, and polymeric molecules include polysaccharides such as dextran or pullulan and polyalkylene oxides such as polyethylene glycol. The polymeric molecules may be coupled to the enzymes at the N-terminal amino group and/or lysine residues, and preferably at a position more than 5 &angst; from the active site of the enzymes. A preferred modified enzyme is a protease having from 5 to 13 coupled polymeric molecules. Skin care products containing the modified enzymes have improved stability and reduced allergenicity as compared to the products containing the unmodified enzymes.

Modified protease having 5 to 13 covalently coupled polymeric molecules for skin care

The present invention relates to modified polypeptides with reduced respiratory allergenicity having polymeric molecules with a molecular weight from 100 up to 750 Da, coupled covalently to the parent polypeptide having a molecular weight from 5 to 100 kDa. The present invention also relates to industrial compositions comprising modified polypeptide with reduced respiratory allergenicity, skin care products, the use of modified polypeptides for reducing the allergenicity of industrial composition and products and finally a method for reducing the allergenicity of polypeptides.

Polypeptides conjugated with polymers

An isolated nucleic acid constructs encoding cellulytic enzymes derived from a strain of,recombinant vectors and host cells comprising such constructs, and methods for obtaining cellulytic enzymes.

DNA constructs and methods of producing cellulytic enzymes

The present invention relates to polypeptide-polymer conjugates having added and/or removed one or more attachment groups for coupling polymeric molecules on the surface of the polypeptide structure, a method for preparing polypeptide-polymer conjugates of the invention, the use of said conjugated for reducing the immunogenicity and allergenicity and compositions comprising said conjugate.

The invention relates to modified polypeptides with reduced respiratory allergenicity comprising a parent polypeptide with a molecular weight from between 10 kDa and 100 kDa conjugated to a polymer with a molecular weight (M,) in the range of 1 kDa and 60 kDa. The modified polypeptide are produced using a process including the step of conjugating from 1 to 30 polymer molecules with the parent polypeptide. Further the invention relates to compositions comprising said polypeptides and further ingredients normally used in e.g. detergents, including dishwashing detergents and soap bars, household article, agrochemicals, personal care products, cosmetics, toiletries, oral and dermal pharmaceuticals, composition for treating textiles, and compositions used for manufacturing food and feed. Finally the invention is directed to uses of polypeptides with reduced allergenicity or compositions thereof for reducing the allergenicity of products for a vast number of industrial applications.

Polypeptide with reduced respiratory allergenicity

The invention relates to modified polypeptides with reduced allergenicity comprising a parent polypeptide with a molecular weight from between 10 kDa and 100 kDa conjugated to a polymer with a molecular weight (M.sub.r) in the range of 1 kDa and 60 kDa. The modified polypeptide are produced using a process including the step of conjugating from 1 to 30 polymer molecules with the parent polypeptide. Further the invention relates to compositions comprising said polypeptides and further ingredients normally used in e.g. detergents, including dishwashing detergents and soap bars, household article, agrochemicals, personal care products, cosmetics, toiletries, oral and dermal pharmaceuticals, composition for treating textiles, and compositions used for manufacturing food and feed. Finally the invention is directed to uses of polypeptides with reduced allergenicity or compositions thereof for reducing the allergenicity of products for a vast number of industrial applications.

Polypeptide with reduced allergenicity

The present invention provides polypeptide conjugates with reduced allergenicity comprising a polymeric carrier molecule having two or more polypeptide molecules coupled thereto. The invention also provides methods for producing the conjugates, compositions comprising the conjugates, and the use of the conjugates in industrial applications, including personal care products and detergent compositions.

Conjugation of polypeptides

This invention relates to Alkalophilic Bacillus sp. AC13 microorganisms and cultures, and mutants and variants thereof, and to enzymes obtainable from the microorganism.

Alkalophilic Bacillus sp. AC13 and protease, xylanase, cellulase

The present invention relates to novel microorganisms, novel enzymes obtainable herefrom, and to a method of producing the novel enzymes. More specifically, the invention relates to novel enzymes obtainable from strains of the novel alkalophilic species Bacillus sp. AC13. Moreover, the invention relates to a method for producing the enzymes of the invention, and to the use of the enzymes in detergents or in the paper pulp industry.

The invention relates to modified polypeptides with reduced allergenicity comprising a parent polypeptide with a molecular weight from between 10 kDa and 100 kDa conjugated to a polymer with a molecular weight (M.sub.r) in the range of 1 kDa and 60 kDa. The modified polypeptide are produced using a process including the step of conjugating from 1 to 30 polymer molecules with the parent polypeptide. Further the invention relates to compositions comprising said polypeptides and fruther ingredients normally used in e.g. detergents, including dishwashing detergents and soap bars, household article, agrochemicals, personal care products, cosmetics, toiletries, oral and dermal pharmaceuticals, composition for treating textiles, and compositions used for manufacturing food and feed. Finally the invention is directed to uses of polypeptides with reduced allergenicity or compositions thereof for reducing the allergenicity of products for a vast number of industrial applications.

An isolated nucleic acid constructs encoding cellulytic enzymes derived from a strain of Bacillus agaradherens, recombinant vectors and host cells comprising such constructs, and methods for obtaining cellulytic enzymes.

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Virum, Denmark

Arne Agerlin Olsen