Hyaluronidase variants with improved stability and pharmaceutical composition comprising the same
AssigneeAlteogen, Inc.
InventorsSoon Jae Park, Hye-Shin Chung, Seung Joo Lee, Kyuwan Kim, Hyung-Nam Song, Sun-Ah You, Chang Woo Lee
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Abstract
Disclosed are novel PH20 variants or fragments thereof with improved thermal stability and enzymatic activity of human hyaluronidase, which is an enzyme that hydrolyzes hyaluronic acid, and more particularly novel PH20 variants or fragments thereof including one or more amino acid residue substitutions in the variant having the amino acid sequence of SEQ ID NO: 3, wherein one or more amino acid residues at the N-terminus and/or the C-terminus are optionally further deleted.
Claims32
A PH20 variant, wherein the amino acid sequence of the PH20 variant is SEQ ID NO:
- 3 with modifications consisting of:
- (a) an amino acid residue substitution of:
- Y357W, M358V, M358R, L362A, W342I, or E343V relative to SEQ ID NO:
- 3;
- (b) an N-terminus deletion of amino acid residues M1 to T35, M1 to L36, M1 to N37, M1 to F38, M1 to R39, or M1 to A40 of SEQ ID NO:
- 3;
- and
- (c) a C-terminus deletion, wherein the C-terminus of the PH20 variant ends with an amino acid residue selected from any one of amino acid residues I465 to S490 of SEQ ID NO:
- 3, and
- wherein the PH20 variant exhibits higher enzymatic activity compared to mature, wild-type human PH20 under the same conditions.
A PH20 variant comprising the amino acid sequence of SEQ ID NO:
- 217, 171, or 207.
A PH20 variant comprising the amino acid sequence of SEQ ID NO:
- 172.
A PH20 variant comprising the amino acid sequence of SEQ ID NO:
- 198 or 173.
A PH20 variant, wherein the amino acid sequence of the PH20 variant is SEQ ID NO:
- 3 with modifications consisting essentially of:
- (a) an amino acid residue substitution of:
- Y357W, M358V, M358R, L362A, W342I, or E343V relative to SEQ ID NO:
- 3;
- (b) an N-terminus deletion of amino acid residues M1 to T35, M1 to L36, M1 to N37, M1 to F38, M1 to R39, or M1 to A40 of SEQ ID NO:
- 3;
- and
- (c) a C-terminus deletion, wherein the C-terminus of the PH20 variant ends with an amino acid residue selected from any one of amino acid residues I465 to S490 of SEQ ID NO:
- 3, and
- wherein the PH20 variant exhibits higher enzymatic activity compared to mature, wild-type human PH20 under the same conditions.
Dependencies are inferred from the claim text.