PH20 POLYPEPTIDE VARIANTS, FORMULATIONS AND USES THEREOF

1 - 23 . (canceled)

24 . A nucleic acid encoding the modified PH20 polypeptide, the modified PH20 polypeptide comprising an amino acid sequence, wherein:

(a) at least 95% of the residues of the amino acid sequence of the modified PH20 polypeptide are identical to the residues in an amino acid sequence selected from the group consisting of SEQ ID NO: 35 when the sequence of the modified PH20 polypeptide is aligned at positions corresponding to the sequence selected from the group consisting of SEQ ID NO: 35 to maximize identical residues, and wherein terminal gaps are treated as non-identical; and

(b) the amino acid sequence of the modified PH20 polypeptide comprises an amino acid modification at a position corresponding to position 309 with reference to amino acid positions set forth in SEQ ID NO: 3; and

(c) the modification at position 309 is a replacement selected from among E, G, H, L, M, N, Q, R, S, and T.

25 . The nucleic acid of claim 24 , wherein the amino acid modification is at a position corresponding to position 309 with reference to amino acid positions set forth in SEQ ID NO: 3 is N.

26 . The nucleic acid of claim 25 , wherein at least 96% of the residues of the amino acid sequence of the modified PH20 polypeptide are identical to the residues in the amino acid sequence set forth in SEQ ID NO: 35.

27 . The nucleic acid of claim 24 , wherein the modified PH20 polypeptide exhibits increased hyaluronidase activity compared to the hyaluronidase activity of the polypeptide set forth in SEQ ID NO: 3, measured under identical conditions.

28 . The nucleic acid of claim 24 , wherein the hyaluronidase activity of the modified PH20 polypeptide is at least 120% of the hyaluronidase activity of the PH20 polypeptide of SEQ ID NO: 3, measured under identical conditions.

29 . The nucleic acid of claim 24 , wherein the modified PH20 polypeptide is a soluble PH20 polypeptide.

30 . A recombinant expression vector, comprising the nucleic acid of claim 24 .

31 . A host cell, comprising the vector of claim 30 .

32 . A method for administering a therapeutically active agent, comprising providing a pharmaceutical composition, and parenterally administering the pharmaceutical composition,

wherein the pharmaceutical composition comprises

a modified PH20 polypeptide comprising an amino acid sequence, wherein:

(a) at least 95% of the residues of the amino acid sequence of the modified PH20 polypeptide are identical to the residues in an amino acid sequence selected from the group consisting of SEQ ID NO: 35 when the sequence of the modified PH20 polypeptide is aligned at positions corresponding to the sequence selected from the group consisting of SEQ ID NO: 35 to maximize identical residues, and wherein terminal gaps are treated as non-identical, and

(b) the amino acid sequence of the modified PH20 polypeptide comprises an amino acid modification at a position corresponding to position 309 with reference to amino acid positions set forth in SEQ ID NO: 3, and

(c) the modification at position 309 is a replacement selected from among E, G, H, L, M, N, Q, R, S, and T; and

the therapeutically active agent.

33 . The method of claim 32 , wherein said parenterally administering is subcutaneously administering.

34 . A method for treating cancer, comprising administering a pharmaceutical composition, wherein the pharmaceutical composition comprises a modified PH20 polypeptide comprising an amino acid sequence, wherein:

(a) at least 95% of the residues of the amino acid sequence of the modified PH20 polypeptide are identical to the residues in an amino acid sequence selected from the group consisting of SEQ ID NO: 35 when the sequence of the modified PH20 polypeptide is aligned at positions corresponding to the sequence selected from the group consisting of SEQ ID NO: 35 to maximize identical residues, and wherein terminal gaps are treated as non-identical; and

(b) the amino acid sequence of the modified PH20 polypeptide comprises an amino acid modification at a position corresponding to position 309 with reference to amino acid positions set forth in SEQ ID NO: 3; and

(c) the modification at position 309 is a replacement selected from among E, G, H, L, M, N, Q, R, S, and T.

35 . The method of claim 34 , wherein said administering is to a subject receiving treatment with an anticancer drug.

36 . The method of claim 34 , wherein the amino acid modification is at a position corresponding to position 309 with reference to amino acid positions set forth in SEQ ID NO: 3 is N.

37 . The method of claim 34 , wherein at least 96% of the residues of the amino acid sequence of the modified PH20 polypeptide are identical to the residues in an amino acid sequence set forth in SEQ ID NO:35.

38 . The method of claim 34 , wherein the modified PH20 polypeptide exhibits increased hyaluronidase activity compared to the hyaluronidase activity of the polypeptide set forth in SEQ ID NO: 3, measured under identical conditions.

39 . The method of claim 34 , wherein the hyaluronidase activity of the modified PH20 polypeptide is at least 120% of the hyaluronidase activity of the PH20 polypeptide of SEQ ID NO:3, measured under identical conditions.

40 . The method of claim 34 , wherein the modified PH20 polypeptide additionally comprises one or more post-translational modifications of the polypeptide selected from among glycosylation, sialylation, albumination, farnesylation, carboxylation, hydroxylation, and phosphorylation.

41 . The method of claim 40 , wherein the post-translational modification is glycosylation.

42 . The method of claim 34 , wherein the pharmaceutical composition further comprises an antibody.