Granted Patent
B2
US 12,618,055 · App. 17/608,729 · Granted May 5, 2026
Hyaluronidase variants with improved stability and pharmaceutical composition comprising the same
Inventors:
Soon Jae Park (Daejeon, KR); Hye-Shin Chung (Daejeon, KR); Seung Joo Lee (Daejeon, KR); Kyuwan Kim (Daejeon, KR); Hyung-Nam Song (Daejeon, KR); Sun-Ah You (Daejeon, KR); Chang Woo Lee (Daegu, KR)
Assignee:
ALTEOGEN Inc.
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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.
Claims (40)
1 . 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.
2 . The PH20 variant of claim 1 , wherein the amino acid residue substitution is Y357W, M358V, or M358R relative to SEQ ID NO: 3.
3 . The PH20 variant of claim 1 , wherein the amino acid residue substitution is L362A.
4 . The PH20 variant of claim 1 , wherein the amino acid residue substitution is W342I or E343V relative to SEQ ID NO: 3.
5 . The PH20 variant of claim 1 , wherein the amino acid sequence of the PH20 variant consists of the amino acid sequence of SEQ ID NO: 217, 171, or 207.
6 . The PH20 variant of claim 1 , wherein the amino acid sequence of the PH20 variant consists of the amino acid sequence of SEQ ID NO: 172.
7 . The PH20 variant of claim 1 , wherein the amino acid sequence of the PH20 variant consists of the amino acid sequence of SEQ ID NO: 198 or 173.
8 . A pharmaceutical composition comprising the PH20 variant of claim 1 , and one or more selected from the group consisting of diluents, excipients, lubricants, wetting agents, sweeteners, aromatics, emulsifiers, suspensions and preservatives.
9 . The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition is formulated for subcutaneous injection.
10 . The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition further comprises a protein drug and is formulated for subcutaneous injection.
11 . The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition further comprises an anti-cancer drug and is formulated for subcutaneous injection.
12 . A PH20 variant comprising the amino acid sequence of SEQ ID NO: 217, 171, or 207.
13 . A PH20 variant comprising the amino acid sequence of SEQ ID NO: 172.
14 . A PH20 variant comprising the amino acid sequence of SEQ ID NO: 198 or 173.
15 . A pharmaceutical composition comprising the PH20 variant of claim 12 , and one or more selected from the group consisting of diluents, excipients, lubricants, wetting agents, sweeteners, aromatics, emulsifiers, suspensions and preservatives.
16 . The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is formulated for subcutaneous injection.
17 . The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition further comprises a protein drug for treating a disease and is formulated for subcutaneous injection.
18 . The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition further comprises an anti-cancer drug and is formulated for subcutaneous injection.
19 . A pharmaceutical composition comprising the PH20 variant of claim 13 , and one or more selected from the group consisting of diluents, excipients, lubricants, wetting agents, sweeteners, aromatics, emulsifiers, suspensions and preservatives.
20 . The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition is formulated for subcutaneous injection.
21 . The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition further comprises a protein drug for treating a disease and is formulated for subcutaneous injection.
22 . The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition further comprises an anti-cancer drug and is formulated for subcutaneous injection.
23 . A pharmaceutical composition comprising the PH20 variant of claim 14 , and one or more selected from the group consisting of diluents, excipients, lubricants, wetting agents, sweeteners, aromatics, emulsifiers, suspensions and preservatives.
24 . The pharmaceutical composition of claim 23 , wherein the pharmaceutical composition is formulated for subcutaneous injection.
25 . The pharmaceutical composition of claim 23 , wherein the pharmaceutical composition further comprises a protein drug for treating a disease and is formulated for subcutaneous injection.
26 . The pharmaceutical composition of claim 23 , wherein the pharmaceutical composition further comprises an anti-cancer drug and is formulated for subcutaneous injection.
27 . The PH20 variant of claim 1 , wherein: (b) the N-terminus deletion is a deletion of amino acid residues M1 to N37 of SEQ ID NO: 3, or (c) the C-terminus of the PH20 variant ends at F468.
28 . 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.
29 . A pharmaceutical composition comprising the PH20 variant of claim 28 , and one or more selected from the group consisting of diluents, excipients, lubricants, wetting agents, sweeteners, aromatics, emulsifiers, suspensions and preservatives.
30 . The pharmaceutical composition of claim 29 , wherein the pharmaceutical composition is formulated for subcutaneous injection.
31 . The pharmaceutical composition of claim 29 , wherein the pharmaceutical composition further comprises a protein drug for treating a disease and is formulated for subcutaneous injection.
32 . The pharmaceutical composition of claim 29 , wherein the pharmaceutical composition further comprises an anti-cancer drug and is formulated for subcutaneous injection.
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 15, 2025
From: YOU, SUN-AH; LEE, CHANG WOO
To: ALTEOGEN INC.
Reel/Frame 072899/0429 →
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME PREVIOUSLY RECORDED AT REEL: 058068 FRAME: 0966. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT .
Recorded Dec 15, 2021
From: PARK, SOON JAE; CHUNG, HYE-SHIN; LEE, SEUNG JOO; KIM, KYUWAN; SONG, HYUNG-NAM
To: ALTEOGEN INC.
Reel/Frame 058517/0914 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 10, 2021
From: PARK, SOON JAE; CHUNG, HYE-SHIN; LEE, SEUNG JOO; KIM, KYUWAN; SONG, HYUNG-NAM
To: ALTEOGEN, INC.
Reel/Frame 058068/0966 →
Priority Claims (1)
KR 10-2020-0009046
· Jan 23, 2020
· national
Continuity (1)
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