Alk7 binding proteins and uses thereof

Patent metadata

Field	Value
Publication number	US-2020392233-A1
Application number	US-201816757959-A
Country	US
Kind code	A1
Filing date	Oct 25, 2018
Priority date	Oct 25, 2017
Publication date	Dec 17, 2020
Grant date	—

Abstract

This disclosure provides ALK7-binding proteins such as anti-ALK7 antibodies, and compositions and methods for making the ALK7-binding proteins. In certain embodiments the ALK7-binding proteins inhibit, or antagonize ALK7 activity. In addition, the disclosure provides compositions and methods for diagnosing and treating overweight, obesity, diabetes, overweight, obesity, type 2 diabetes, and their associated conditions; metabolic disorders, and other diseases or conditions that can be treated, prevented or ameliorated by targeting ALK7.

First claim

What is claimed is:

1 . An Activin Receptor-Like Kinase 7 (ALK7)-binding protein that specifically binds at least one primary epitope of an ALK7 protein, wherein the at least one primary epitope is essentially the same as an epitope selected from SEQ ID NOs:310, 313, and 317.

2 . The ALK7-binding protein of claim 1 , further specifically binds at least one conformational epitope of an ALK7 protein, wherein the at least one conformational epitope is essentially the same as an epitope selected from SEQ ID NOs:311, 312, 314, 315, 316, 318, and 319.

3 . (canceled)

4 . The ALK7-binding protein of claim 1 , comprising a set of CDRs: VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, wherein the CDRs are from a heavy chain variable region (VH) and a light chain variable region (VL) pair selected from:
(a) (i) a VH sequence of SEQ ID NO:117, and
(ii) a VL sequence of SEQ ID NO:124;
(b) (i) a VH sequence of SEQ ID NO:105, and
(ii) a VL sequence of SEQ ID NO:110;
(c) (i) a VH sequence of SEQ ID NO:128, and
(ii) a VL sequence of SEQ ID NO:135;
(d) (i) a VH sequence of SEQ ID NO:140, and
(ii) a VL sequence of SEQ ID NO:148;
(e) (i) a VH sequence of SEQ ID NO:91, and
(ii) a VL sequence of SEQ ID NO:98;
(f) (i) a VH sequence of SEQ ID NO:4, and
(ii) a VL sequence of SEQ ID NO:13;
(g) (i) a VH sequence of SEQ ID NO:152, and
(ii) a VL sequence of SEQ ID NO:98;
(h) (i) a VH sequence of SEQ ID NO:159, and
(ii) a VL sequence of SEQ ID NO:110;
(i) (i) a VH sequence of SEQ ID NO:165, and
(ii) a VL sequence of SEQ ID NO:171;
(j) (i) a VH sequence of SEQ ID NO:22, and
(ii) a VL sequence of SEQ ID NO:31;
(k) (i) a VH sequence of SEQ ID NO:40, and
(ii) a VL sequence of SEQ ID NO:49; and
(l) (i) a VH sequence of SEQ ID NO:58, and
(ii) a VL sequence of SEQ ID NO:67,
wherein the protein binds to ALK7.

5 . (canceled)

6 . The ALK7-binding protein of claim 1 , comprising a set of CDRs in which:
(a) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:114;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:115;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:116;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:121;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:122; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:123;
(b) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:102;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:103;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:104;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:107;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:108; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:109;
(c) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:125;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:126;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:127;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:132;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:133; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:134;
(d) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:137;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:138;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:139;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:145;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:146; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:147;
(e) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:88;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:89;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:90;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:95;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:96; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:97;
(g) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:37;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:56;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:90;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:95;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:96; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:97;
(h) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:156;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:157;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:104;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:107;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:108; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:109;
(h) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:1;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:163;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:164;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:167;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:168; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:169;
(i) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:1;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:2;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:3;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:10;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:11; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:12;
(j) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:19;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:20;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:21;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:28;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:29; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:30;
(k) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:37;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:38;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:39;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:46;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:47; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:48; or
(l) (i) VH-CDR1 comprises the amino acid sequence of SEQ ID NO:55;
(ii) VH-CDR2 comprises the amino acid sequence of SEQ ID NO:56;
(iii) VH-CDR3 comprises the amino acid sequence of SEQ ID NO:57;
(iv) VL-CDR1 comprises the amino acid sequence of SEQ ID NO:64;
(v) VL-CDR2 comprises the amino acid sequence of SEQ ID NO:65; and
(vi) VL-CDR3 comprises the amino acid sequence of SEQ ID NO:66,
wherein the protein binds ALK7.

7 . (canceled)

8 . The ALK7-binding protein of claim 1 , wherein the VH and VL pair is selected from:
(a) a VH sequence of SEQ ID NO:117 and a VL sequence of SEQ ID NO:124; (b) a VH sequence of SEQ ID NO:105 and a VL sequence of SEQ ID NO:110; (c) a VH sequence of SEQ ID NO:128 and a VL sequence of SEQ ID NO:135; (d) a VH sequence of SEQ ID NO:140 and a VL sequence of SEQ ID NO:148; (e) a VH sequence of SEQ ID NO:91 and a VL sequence of SEQ ID NO:98; (f) a VH sequence of SEQ ID NO:152 and a VL sequence of SEQ ID NO:98; (g) a VH sequence of SEQ ID NO:159 and a VL sequence of SEQ ID NO:110; (h) a VH sequence of SEQ ID NO:165, and a VL sequence of SEQ ID NO:171; (i) a VH sequence of SEQ ID NO:4 and a VL sequence of SEQ ID NO:13; (j) a VH sequence of SEQ ID NO:22 and a VL sequence of SEQ ID NO:31; (k) a VH sequence of SEQ ID NO:40, and a VL sequence of SEQ ID NO:49; and (l) a VH sequence of SEQ ID NO:58 and a V

Assignees

• Acceleron Pharma Inc
• Adimab Llc

Inventors

• Kumar Ravindra
• Castonguay Roselyne
• Sako Dianne
• Belk Jonathan
• Sharkey Nathan J

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/2863 Primary

  against receptors for growth factors, growth regulators · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title