Neutral active soluble truncated PH20 polypeptides and uses thereof

1. A truncated soluble PH20 hyaluronidase, wherein:

the truncated PH20 hyaluronidase is neutral active;

is soluble; and

consists of any sequence of amino acid residues within SEQ NO:107 that terminates at residue 469, 470 or 471 of SEQ ID NO:107.

2. A truncated soluble PH20 hyaluronidase that is selected from among a polypeptide that contains an amino acid substitution or amino acid substitutions in the sequence of amino acids set forth as amino acids 36-469, 36-470 or 36-471 of SEQ ID NO: 107 that has at least 95% sequence identity with the sequence of amino acids set forth as amino acids 36-469, 36-470 or 36-471 of SEQ ID NO: 107, wherein:

the amino acid sequence of the amino acid-substituted polypeptide differs from the sequence of amino acids set forth as amino acids 36-469, 36-470 or 36-471 of SEQ ID NO: 107 only by amino acid substitutions;

the polypeptide is soluble; and

the polypeptide has hyaluronidase activity.

3. The truncated soluble PH20 hyaluronidase of claim 1 that is N-glycosylated.

4. The truncated soluble PH20 hyaluronidase of claim 3 , wherein the N-glycosylated polypeptide comprises an N-acetylglucosamine moiety linked to each of at least three asparagine (N) residues selected from among amino acid residues N82, N166, N235, N254, N368 and N393 of SEQ ID NO:107.

5. The truncated soluble PH20 hyaluronidase of claim 4 , wherein the three asparagine residues are amino acid residues 235, 368 and 393 of SEQ ID NO: 107.

6. The truncated soluble PH20 hyaluronidase of claim 2 that is a polypeptide that contains an amino acid substitution or amino acid substitutions in the sequence of amino acids set forth as amino acids 36-469, 36-470 or 36-471 of SEQ ID NO:107, whereby the amino acid-substituted polypeptide consists of a sequence of amino acids that has at least 98% sequence identity with the corresponding sequence of amino acids set forth as amino acids 36-469, 36-470 or 36-471 of SEQ ID NO:107.

7. A truncated soluble PH20 hyaluronidase that consists of the sequence of amino acids set forth as amino acids 36-469, 36-470 or 36-471 of SEQ ID NO: 107.

8. The truncated soluble PH20 hyaluronidase of claim 1 that is modified by modification selected from among sialation, albumination, farnesylation, carboxylation, hydroxylation and phosphorylation.

9. The truncated soluble PH20 hyaluronidase of claim 1 that is modified by a polymer.

10. The truncated soluble PH20 hyaluronidase of claim 9 , wherein the polymer is dextran or PEG.

11. The truncated soluble PH20 hyaluronidase of claim 1 that is substantially purified.

12. A conjugate, comprising a conjugated moiety linked directly or via a linker to the C-terminus or N-terminus of the truncated soluble PH20 hyaluronidase of claim 1 .

13. The conjugate of claim 12 , wherein the truncated soluble PH20 hyaluronidase is conjugated to a moiety selected from among a multimerization domain, toxin, detectable label or drug.

14. The conjugate of claim 13 , wherein the truncated soluble PH20 hyaluronidase is conjugated to an Fc domain.

15. A composition, comprising the truncated soluble PH20 hyaluronidase polypeptide of claim 1 .

16. A composition, comprising a truncated soluble PH20 hyaluronidase polypeptide of claim 10 .

17. The truncated soluble PH20 hyaluronidase of claim 2 that is N-glycosylated.

18. The truncated soluble PH20 hyaluronidase of claim 17 , wherein the N-glycosylated polypeptide comprises an N-acetylglucosamine moiety linked to each of at least three asparagine (N) residues selected from among amino acid residues N82, N166, N235, N254, N368 and N393 of SEQ ID NO:107.

19. The truncated soluble PH20 hyaluronidase of claim 2 that is modified by a polymer.

20. The truncated soluble PH20 hyaluronidase of claim 19 , wherein the polymer is dextran or PEG.

21. A composition, comprising the truncated soluble PH20 hyaluronidase polypeptide of claim 1 .

22. A composition, comprising the truncated soluble PH20 hyaluronidase polypeptide of claim 7 .