LISTING OF THE CLAIMS
`
`This version of the claims will replace all previous versions.
`
`1. (Original) A modified PH20 polypeptide, comprising one or more amino acid modifications
`
`in an unmodified PH20 polypeptide, wherein:
`
`the unmodified PH20 polypeptide consists of the amino acid sequence selected from among
`
`SEQ ID NOs: 3, 7 and 32-66;
`
`amino acid modifications are selected from among amino acid replacements(s), deletion(s),
`
`and/or insertion(s);
`
`the modified PH20 polypeptide comprises an amino acid replacementat a position
`
`corresponding to residue 324, with reference to amino acid positions set forth in SEQ ID NO:3;
`
`the replacementat the position corresponding to residue 324 is selected from amongA,D,
`
`H, M, N, Rand S;
`
`corresponding aminoacid positions are identified by alignment of the PH20 polypeptide
`
`with the polypeptide having the amino acid sequence of SEQ ID NO:3; and
`
`the modified PH20 polypeptide has at least 91 % sequence identity to a polypeptide having
`
`the amino acid sequenceselected from among SEQ ID NOs: 3, 7 and 32-66.
`
`2. (Original) The modified PH20 polypeptide of claim 1, wherein the modified PH20
`
`polypeptide has at least 95% sequence identity to the amino acid sequence selected from among
`
`SEQ ID NOs: 3, 7, and 32-66.
`
`3. (Original) The modified PH20 polypeptide of claim 1 that has increased
`
`resistance to or stability in denaturing conditions compared to an unmodified PH20 polypeptide that
`
`does not contain the amino acid modification(s).
`
`4. (Original) The modified PH20 polypeptide of claim 1 that exhibits increased hyaluronidase
`
`activity compared to the unmodified PH20 polypeptide not containing the amino acid replacement
`
`at position 324.
`
`5. (Original) The modified PH20 polypeptide of claim 1 that is a soluble PH20 polypeptide.
`
`6. (Original) The modified PH20 polypeptide of claim 1, wherein the replacementat the
`
`position corresponding to residue 324is D.
`
`7. (Original) The modified PH20 polypeptide of claim 1, wherein the replacementat the
`
`position corresponding to residue 324 is Nor R.
`
`8. (Original) The modified PH20 polypeptide of claim 1, wherein the unmodified PH20
`
`polypeptide comprises the amino acid sequence selected from among SEQ ID NOs: 3 and 32-66.
`
`9. (Original) The modified PH20 polypeptide of claim 1, wherein the unmodified PH20
`
`polypeptide consists of the amino acid sequence selected from among SEQ ID NOs: 3 and 32-66.
`
`10. (Original) The modified PH20 polypeptide of claim 6, wherein the unmodified PH20
`
`polypeptide consists of the amino acid sequence selected from among SEQ ID NOs: 3 and 32-66.
`
`DB1i/ 144937442.1
`
`2
`
`

`

`11. (Original) The modified PH20 polypeptide of claim 1, wherein the unmodified PH20
`
`polypeptide consists of the amino acid sequence of SEQ ID NO:35.
`
`12. (Original) The modified PH20 polypeptide of claim 1, wherein the unmodified PH20
`
`polypeptide consists of the amino acid sequence of SEQ ID NO:32.
`
`13. (Original) The modified PH20 polypeptide of claim 6, wherein the unmodified PH20
`
`polypeptide consists of the amino acid sequence of SEQ ID NO:35.
`
`14. (Original) The modified PH20 polypeptide of claim 6, wherein the unmodified PH20
`
`polypeptide consists of the amino acid sequence of SEQ ID NO:32.
`
`15. (Original) The modified PH20 polypeptide of claim 1, comprising a sequence of amino
`
`acids that exhibits at least 91 % sequence identity to the sequence of amino acids set forth in any of
`
`SEQ ID NOs: 3, 32-66, 623, and 624 and that contains an amino acid replacementD at the residue
`
`correspondingto residue 324 with reference to SEQ ID NO:3.
`
`16. (Original) The modified PH20 polypeptide of claim 1 that is C-terminally truncated,
`
`wherebythe polypeptide is soluble.
`
`17. (Original) The modified PH20 polypeptide of claim 1 that comprises one or more
`
`modifications of the polypeptide selected from amongglycosylation, sialylation, aloumination,
`
`famesylation, carboxylation, hydroxylation, and phosphorylation.
`
`18.
`
`19.
`
`(Original) The modified PH20 polypeptide of claim 1 that is glycosylated.
`
`(Original) The modified PH20 polypeptide of claim 18, wherein the polypeptideis a
`
`glycoprotein that comprises an N-acetylglucosamine moietylinked to each of at least three
`
`asparagine (N) residues.
`
`20. (Original) The modified PH20 polypeptide of claim 1 that is conjugated to a polymer.
`
`21. (Original) The modified PH20 polypeptide of claim 20, wherein the polymer is dextran or
`
`polyethylene glycol (PEG).
`
`22. (Original) The modified PH20 polypeptide of claim 1, further comprising a heterologous
`
`signal sequence, wherein the unmodified PH20 polypeptide consists of the amino acid sequence
`
`selected from among SEQ ID NOs: 3 and 32-66.
`
`23. (Original) A chimeric polypeptide, comprising the modified PH20 polypeptide of claim 1.
`
`24. (Original) A pharmaceutical composition, comprising the modified PH20 polypeptide of
`
`claim 1.
`
`25. (Original) The modified PH20 polypeptide of claim 6, wherein:
`
`the unmodified PH20 polypeptide consists of the amino acid sequence of SEQ ID NO:32; and
`
`the amino acid sequence of the modified PH20 polypeptide has at least 95% sequence
`
`identity to the amino acid sequence of SEQ ID NO:32.
`
`26. (Original) The modified PH20 polypeptide of claim 6, wherein:
`
`the unmodified PH20 polypeptide consists of the amino acid sequence of SEQ ID NO:35; and
`
`DB1i/ 144937442.1
`
`3
`
`

`

`the amino acid sequence of the modified PH20 polypeptide has at least 95% sequence
`
`identity to the amino acid sequence of SEQ ID NO:35.
`
`27. (Original) The pharmaceutical composition of claim 24, further comprising a
`
`therapeutically active agent formulated in the same composition or in a separate composition.
`
`28. (Original) The pharmaceutical composition of claim 27, wherein the therapeutically
`
`active agent is a polypeptide, a protein, a nucleic acid, a drug, a small molecule, or an organic
`
`molecule.
`
`29. (Original) The pharmaceutical composition of claim 27, wherein the therapeutically
`
`active agentis selected from among a chemotherapeutic agent, an analgesic agent, an anti-
`
`inflammatory agent, an antimicrobial agent, an amoebicidal agent, a trichomonacidal agent, an anti-
`
`Parkinson agent, an anti-malarial agent, an anticonvulsant agent, an anti-depressant agent, an
`
`antiarthritics agent, an anti-fungal agent, an antihypertensive agent, an antipyretic agent, an anti-
`
`parasite agent, an antihistamine agent, an alpha-adrenergic agonist agent, an alpha blocker agent,
`
`an anesthetic agent, a bronchial dilator agent, a biocide agent, a bactericide agent, a bacteriostat
`
`agent, a beta adrenergic blocker agent, a calcium channel blocker agent, a cardiovascular drug
`
`agent, a contraceptive agent, a decongestant agent, a diuretic agent, a depressant agent, a
`
`diagnostic agent, an electrolyte agent, a hypnotic agent, a hormone agent, a hyperglycemic agent, a
`
`muscle relaxant agent, a muscle contractant agent, an ophthalmic agent, a parasympathomimetic
`
`agent, a psychic energizer agent, a sedative agent, a sympathomimetic agent, a tranquilizer agent, a
`
`urinary agent, a vaginal agent, a viricide agent, a vitamin agent, a non-steroidal anti-inflarmmatory
`
`agent, an angiotensin converting enzyme inhibitor agent, and a sleep inducer.
`
`30. (Original) The pharmaceutical composition of claim 27, wherein the therapeutically
`
`active agent is an antibody.
`
`31. (Withdrawn) A methodfor treating a hyaluronan-associated disease or condition,
`
`comprising administering to a subject a modified PH20 polypeptide ofclaim 1.
`
`32. (Withdrawn) The method of claim 31, wherein the hyaluronan-associated disease or
`
`condition is an inflammatory disease or a tumor or cancer.
`
`33. (Withdrawn) The method of claim 32, wherein the hyaluronan-associated disease or
`
`condition is a solid tumor.
`
`34. (Withdrawn) The modified PH20 polypeptide of claim 1 that is modified by conjugation
`
`to a moiety selected from among a multimerization domain, a toxin, a detectable label, and a drug.
`
`35. (Original) The modified PH20 polypeptide of claim 34, wherein the modified
`
`PH20 polypeptide is conjugated to a multimerization domain that is an Fe domain.
`
`DB1i/ 144937442.1
`
`4
`
`