Modified bacterial hyaluronidase polypeptide, production process, pharmaceutical compositions and their uses

1 . A modified bacterial hyaluronidase polypeptide consisting of SEQ ID No. 1.

2 . A nucleic acid encoding the modified bacterial hyaluronidase polypeptide according to claim 1 , wherein the nucleic acid consists of SEQ ID No. 2.

3 . A recombinant expression vector comprising an expression vector and the nucleic acid according to claim 2 .

4 . A host cell transformed with the recombinant expression vector according to claim 3 , wherein the host cell is E. coli.

5 . A process of production of a purified bacterial hyaluronidase polypeptide comprising the following steps:

a. Culturing a transformed E. coli host cell as claimed in claim 4 in suitable growth medium under suitable conditions to express the bacterial hyaluronidase polypeptide,

b. Harvesting the cultured transformed host cell of step a),

c. Lysing the harvested host cell of step b) and separating resulting host cell fragments from resulting host cell content comprising the bacterial hyaluronidase polypeptide, and

d. Purifying the resulting host cell content of step c) with histidine-tagged (HIS) affinity chromatography and streptavidin-tagged (STREP) affinity chromatography to result in a purified form of the bacterial hyaluronidase polypeptide, so that the purified hyaluronidase polypeptide consists of SEQ ID No. 1 and exhibits a purity of >98.8% and a general specific activity ranging between 1,500,000 United States Pharmacopeia Units per mg (USP U/mg)+/−150,000 USP U/mg.

6 . A pharmaceutical composition comprising the modified bacterial hyaluronidase polypeptide according to claim 1 in a therapeutically effective amount and one or more pharmaceutically acceptable excipients.

7 . The pharmaceutical composition according to claim 6 , wherein a unit dose of the composition comprises the modified bacterial hyaluronidase polypeptide in an amount of 200 U per kg per day to 30,000 U per kg per day.

8 . The pharmaceutical composition according to claim 6 , wherein the composition is selected from a solid, semi-solid or liquid application form.

9 . The pharmaceutical composition according to claim 6 , wherein the composition is suitable for oral, nasal, transdermal, rectal, intravenous, or intramuscular application.

10 . A method of treating homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia, and/or diabetic foot syndrome comprising administering the modified bacterial hyaluronidase polypeptide according to claim 1 to a subject in need thereof.

11 . A method of treating homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia, and/or diabetic foot syndrome comprising administering the pharmaceutical composition according to claim 6 to a subject in need thereof.