US 12,077,791 B2
PH20 polypeptide variants with a modification at position 309 of the PH20 polypeptide and a method of making thereof
Ge Wei, San Diego, CA (US); H. Michael Shepard, Eugene, OR (US); Qiping Zhao, San Diego, CA (US); and Robert James Connor, Oceanside, CA (US)
Assigned to HALOZYME, INC., San Diego, CA (US)
Filed by HALOZYME, INC., San Diego, CA (US)
Filed on Jun. 22, 2023, as Appl. No. 18/339,829.
Application 15/226,489 is a division of application No. 13/694,731, filed on Dec. 28, 2012, granted, now 9,447,401, issued on Sep. 20, 2016.
Application 16/824,572 is a division of application No. 13/694,731, filed on Dec. 28, 2012, granted, now 9,447,401, issued on Sep. 20, 2016.
Application 16/912,590 is a division of application No. 13/694,731, filed on Dec. 28, 2012, granted, now 9,447,401, issued on Sep. 20, 2016.
Application 18/339,829 is a continuation of application No. 17/327,586, filed on May 21, 2021.
Application 17/327,586 is a continuation of application No. 16/912,590, filed on Jun. 25, 2020, granted, now 11,066,656, issued on Jul. 20, 2021.
Application 17/327,586 is a continuation of application No. 16/824,572, filed on Mar. 19, 2020, granted, now 11,041,149, issued on Jun. 22, 2021.
Application 16/912,590 is a continuation of application No. 15/226,489, filed on Aug. 2, 2016, granted, now 10,865,400, issued on Dec. 15, 2020.
Application 16/824,572 is a continuation of application No. 15/226,489, filed on Aug. 2, 2016, granted, now 10,865,400, issued on Dec. 15, 2020.
Application 17/327,586 is a continuation of application No. 15/226,489, filed on Aug. 2, 2016, granted, now 10,865,400, issued on Dec. 15, 2020.
Application 17/327,586 is a continuation of application No. 13/694,731, filed on Dec. 28, 2012, granted, now 9,447,401, issued on Sep. 20, 2016.
Claims priority of provisional application 61/796,208, filed on Nov. 1, 2012.
Claims priority of provisional application 61/631,313, filed on Dec. 30, 2011.
Prior Publication US 2024/0026327 A1, Jan. 25, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/00 (2006.01); A61K 9/00 (2006.01); A61K 38/00 (2006.01); A61K 38/16 (2006.01); A61K 38/28 (2006.01); A61K 38/43 (2006.01); A61K 38/47 (2006.01); A61K 45/06 (2006.01); A61K 47/10 (2017.01); A61P 35/00 (2006.01); C07K 14/47 (2006.01); C12N 9/26 (2006.01); C12Q 1/34 (2006.01)
CPC C12N 9/2474 (2013.01) [A61K 9/0019 (2013.01); A61K 38/28 (2013.01); A61K 38/47 (2013.01); A61K 45/06 (2013.01); A61K 47/10 (2013.01); A61P 35/00 (2018.01); C07K 14/47 (2013.01); C12Q 1/34 (2013.01); C12Y 302/01035 (2013.01); A61K 38/00 (2013.01); C07K 2319/30 (2013.01); G01N 2333/926 (2013.01); G01N 2333/928 (2013.01); Y02A 50/30 (2018.01)] 10 Claims
 
1. 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 the amino acid sequence of SEQ ID NO: 35 when the sequence of the modified PH20 polypeptide is aligned at positions corresponding to the sequence set forth in the amino acid sequence of SEQ ID NO: 35 to maximize identical residues, and terminal gaps are treated as non-identical; (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 the amino acid sequence of 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 wherein the modified PH20 polypeptide exhibits increased hyaluronidase activity compared to the hyaluronidase activity of the polypeptide of SEQ ID NO: 3, measured under identical conditions.