US 12,240,876 B2
Liver-specific Wnt signal enhancing molecules and uses thereof
Yang Li, Mountain View, CA (US); Zhengjian Zhang, Albany, CA (US); Randall J. Brezski, Alameda, CA (US); Leonard Presta, San Francisco, CA (US); Thomas Lopez, Palo Alto, CA (US); Hui Chen, Foster City, CA (US); Helene Baribault, Redwood City, CA (US); Wen-Chen Yeh, Belmont, CA (US); and Shengjiang Tu, Foster City, CA (US)
Assigned to Surrozen Operating, Inc., South San Francisco, CA (US)
Filed by Surrozen Operating, Inc., South San Francisco, CA (US)
Filed on May 2, 2023, as Appl. No. 18/311,082.
Application 18/311,082 is a continuation of application No. PCT/US2021/059564, filed on Nov. 16, 2021.
Claims priority of provisional application 63/248,157, filed on Sep. 24, 2021.
Claims priority of provisional application 63/182,106, filed on Apr. 30, 2021.
Claims priority of provisional application 63/114,457, filed on Nov. 16, 2020.
Prior Publication US 2023/0374090 A1, Nov. 23, 2023
Int. Cl. C07K 14/47 (2006.01); A61K 38/00 (2006.01); A61P 1/16 (2006.01); C07K 16/24 (2006.01)
CPC C07K 14/4705 (2013.01) [A61P 1/16 (2018.01); C07K 16/24 (2013.01); A61K 38/00 (2013.01); C07K 2317/24 (2013.01); C07K 2317/565 (2013.01); C07K 2319/03 (2013.01)] 10 Claims
 
1. A liver-specific Wingless-related integration site (Wnt) signal enhancing molecule, or a pharmaceutically acceptable salt thereof, comprising:
(a) a first domain comprising two modified human R-spondin 2 polypeptides, wherein the modified R-spondin 2 polypeptides comprise amino acid substitutions at positions F105 and F109 of SEQ ID NO:48, or fragments thereof comprising the furin 1 and furin 2 domains of the modified human R-spondin 2 polypeptides, wherein the first domain specifically binds one or more-transmembrane E3 ubiquitin ligases, wherein the one or more transmembrane E3 ubiquitin ligases are Zinc and Ring Finger 3 (ZNRF3) and Ring Finger Protein 43 (RNF43); and
(b) a second domain comprising an Immunoglobulin G (IgG) antibody comprising two heavy chain polypeptides and two light chain polypeptides, wherein the heavy chain polypeptides comprise a CDRH1 sequence of SYAMS (SEQ ID NO: 34), a CDRH2 sequence of AISGSGGSTYYAESVKG (SEQ ID NO: 63), and a CDRH3 sequence of DFSSRRWYLEY (SEQ ID NO: 36), and the light chain polypeptides comprise a CDRL1 sequence of QGESLRSYYAS (SEQ ID NO: 37), a CDRL2 sequence of YGKSNRPS (SEQ ID NO: 38), and a CDRL3 sequence of CTSLERIGYLSYV (SEQ ID NO: 39), wherein the second domain specifically binds a tissue-specific cell surface molecule, wherein the tissue specific cell surface molecule is an asialoglycoprotein receptor I (ASGRI),
wherein the first modified human R-spondin 2 polypeptides or fragments thereof of the first domain is fused to the N-terminus of the first heavy chain polypeptides of the second domain, and the second modified human R-spondin 2 polypeptide or fragment thereof of the first domain is fused to the N-terminus of the second heavy chain polypeptide of the second domain.