Anti-rspo antibodies and methods of use
AssigneeGenentech, Inc.
InventorsElaine Storm, Frederic J. de Sauvage, Jeremy M. Murray, Cameron L. Noland, Yan Wu, Christine Tan, Jo-Anne Hongo, Yongmei Chen
Life of this patent
Estimating the term…
Abstract
Provided herein are anti-RSPO antibodies, in particular anti-RSPO2 antibodies and/or anti-RSPO3 antibodies, and methods of using the same.
Claims42
An isolated antibody that binds to RSPO2, wherein the antibody inhibits the interaction of RSPO2 with a transmembrane E3 ubiquitinase.
(canceled)
An isolated antibody that binds to RSPO2, wherein the antibody comprises (a) a light chain variable domain (VL) comprising (i) hyper variable region-L1 (HVR-L1) comprising the amino acid sequence of SEQ ID NO:53, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:54, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:55, and (b) a heavy chain variable domain (VH) comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:56, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:57, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:58.
4-5. (canceled)
An isolated antibody that binds to RSPO2, wherein the antibody comprises:
- (a) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:59, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:60, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:61;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:62, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:63, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:64;
- (b) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:65, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:66, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:67;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:68, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:69, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:70;
- or
- (c) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:71, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:72, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:73;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:74, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:75, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:76.
(canceled)
An isolated antibody that binds to RSPO3, wherein the antibody inhibits the interaction of RSPO3 with a transmembrane E3 ubiquitinase.
An isolated antibody that binds to RSPO3, wherein the antibody comprises:
- (a) VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:7;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:8, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:9, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:10;
- (b) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:11, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:12, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:13;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:14, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:15, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:16;
- (c) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:17, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:18, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:19;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:20, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:21, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:22;
- (d) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:23, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:24, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:25;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:26, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:27, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:28;
- (e) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:29, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:30, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:31;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:32, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:33, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:34;
- (f) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:35, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:36, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:37;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:38, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:39, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:40;
- (g) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:41, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:42, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:43;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:44, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:45, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:46
- (h) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:23, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:24, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:25;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:26, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:27, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:188;
- or
- (i) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:23, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:24, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:25;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:26, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:27, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:189.
An isolated antibody that binds to RSPO2 and RSPO3.
13-17. (canceled)
An isolated antibody that binds to RSPO2 and RSPO3, wherein the antibody comprises:
- (a) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:47, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:48, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:49;
- and (b) a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:50, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:51, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:52.
20-23. (canceled)
An isolated antibody that binds to RSPO3, wherein the antibody comprises:
- (a) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:77, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:78, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:79;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:80, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:81, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:82;
- (b) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:83, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:84, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:85;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:86, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:87, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:88;
- or
- (c) a VL comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:77, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:78, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:79;
- and a VH comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:80, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:81, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:216.
An isolated antibody that binds to RSPO3, wherein the antibody binds to a region within amino acids 47-108 (e.g., 49-108) of RSPO3.
44-50. (canceled)
Dependencies are inferred from the claim text.