IP Library Granted Patent US 12,458,693
Granted Patent B2
US 12,458,693 · App. 18/140,121 · Granted Nov 4, 2025

Methods of treating iron overload with a BMP inhibitor

Inventors: Jasbir S. Seehra (Lexington, MA); Jennifer Lachey (Lincoln, MA); Christopher R. Rovaldi (Swampscott, MA); Claudia Ordonez (Lexington, MA)
Assignee: Keros Therapeutics, Inc.
A61K39/3955A61P7/00A61K31/519C07K16/2863C07K16/40
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Quick Facts
Patent No.
US 12,458,693
App. No.
18/140,121
Granted
Nov 4, 2025
Kind
B2
Abstract

The invention features methods of treating iron overload in a subject by administering BMP or hepcidin inhibitors, such as ALK2 inhibitors. The invention also features methods of decreasing iron levels in a subject by administering BMP or hepcidin inhibitors.

Claims (33)

1. A method of treating a subject identified as having iron overload, comprising administering to the subject a therapeutically effective amount of a BMP inhibitor, wherein the BMP inhibitor is an ALK2 antibody or an ALK2 binding fragment thereof comprising:

(a) a light chain CDR1 comprising the amino acid sequence SGSSSNIGSNYVS (SEQ ID NO:1); a light chain CDR2 comprising the amino acid sequence VLIYKNNHRPS (SEQ ID NO:24); a light chain CDR3 comprising the amino acid sequence ASWDHSDRFYV (SEQ ID NO:4); a heavy chain CDR1 comprising the amino acid sequence GGTFSSYGVS (SEQ ID NO:31); a heavy chain CDR2 comprising the amino acid sequence WMGGIIPHFGIANYAQKFQG (SEQ ID NO:36); and a heavy chain CDR3 comprising the amino acid sequence EIGSLDI (SEQ ID NO:13);

(b) a light chain CDR1 comprising the amino acid sequence SGDSIPSFFAS (SEQ ID NO:18); a light chain CDR2 comprising the amino acid sequence LVIYRDSNRPS (SEQ ID NO:25); a light chain CDR3 comprising the amino acid sequence YVTAPWKSIW (SEQ ID NO:5); a heavy chain CDR1 comprising the amino acid sequence GFTFSSHAMS (SEQ ID NO:32); a heavy chain CDR2 comprising the amino acid sequence WVGRIKSKADSGTTDYAAPVKG (SEQ ID NO:37); and a heavy chain CDR3 comprising the amino acid sequence DYGVAFAY (SEQ ID NO:14);

(c) a light chain CDR1 comprising the amino acid sequence SGDNIGTKYAY (SEQ ID NO:19); a light chain CDR2 comprising the amino acid sequence LVIYGDSDRPS (SEQ ID NO:26); a light chain CDR3 comprising the amino acid sequence YSADAQQMKA (SEQ ID NO:6); a heavy chain CDR1 comprising the amino acid sequence GFTFNSSAMS (SEQ ID NO:33); a heavy chain CDR2 comprising the amino acid sequence WVGRIKSKRDGYTTDYAAPVKG (SEQ ID NO:38); and a heavy chain CDR3 comprising the amino acid sequence DYGGLKFDY (SEQ ID NO:15);

(d) a light chain CDR1 comprising the amino acid sequence SGDNLRKYSAH (SEQ ID NO:20); a light chain CDR2 comprising the amino acid sequence LVIYYDNKRPS (SEQ ID NO:27); a light chain CDR3 comprising the amino acid sequence QVYASVHRM (SEQ ID NO:7); a heavy chain CDR1 comprising the amino acid sequence GGTFSSYAIH (SEQ ID NO:34); a heavy chain CDR2 comprising the amino acid sequence WMGRIIPDFGTANYAQKFQG (SEQ ID NO:39); and a heavy chain CDR3 comprising the amino acid sequence GPTQAIHYFAY (SEQ ID NO:16);

(e) a light chain CDR1 comprising the amino acid sequence SGDSLGSKSVH (SEQ ID NO:21); a light chain CDR2 comprising the amino acid sequence LVIYRDSKRPS (SEQ ID NO:28); a light chain CDR3 comprising the amino acid sequence QTYDWSHFGW (SEQ ID NO:8); a heavy chain CDR1 comprising the amino acid sequence GFTFSSAAMH (SEQ ID NO:35); a heavy chain CDR2 comprising the amino acid sequence WVSVISSDGGSTYYADSVKG (SEQ ID NO:12); and a heavy chain CDR3 comprising the amino acid sequence AGFILGSLGVAWMDV (SEQ ID NO:17);

(f) a light chain CDR1 comprising the amino acid sequence RASQGISGNWLT (SEQ ID NO:40); a light chain CDR2 comprising the amino acid sequence LLIYDASNLQS (SEQ ID NO:41); a light chain CDR3 comprising the amino acid sequence HQSYRGPM (SEQ ID NO:42); a heavy chain CDR1 comprising the amino acid sequence GFTFGRFVMH (SEQ ID NO:43); a heavy chain CDR2 comprising the amino acid sequence WVSVIGYSGSSTYYADSVKG (SEQ ID NO:44); and a heavy chain CDR3 comprising the amino acid sequence EPGYYYPSGYYRGPGYWMDV (SEQ ID NO:45);

(g) a light chain CDR1 comprising the amino acid sequence SGDNIRKKYVH (SEQ ID NO:46); a light chain CDR2 comprising the amino acid sequence LVIYRDSNRPS (SEQ ID NO:47); a light chain CDR3 comprising the amino acid sequence SSAGRDNY (SEQ ID NO:48); a heavy chain CDR1 comprising the amino acid sequence GFTFSSSAMH (SEQ ID NO:49); a heavy chain CDR2 comprising the amino acid sequence WVSVIHYDSSETYYADSVKG (SEQ ID NO:50); and a heavy chain CDR3 comprising the amino acid sequence DRYFFDV (SEQ ID NO:51);

(h) a light chain CDR1 comprising the amino acid sequence SGDALRYYIAH (SEQ ID NO:52); a light chain CDR2 comprising the amino acid sequence LVIYYNNNRPS (SEQ ID NO:53); a light chain CDR3 comprising the amino acid sequence QSYGPGSV (SEQ ID NO:54); a heavy chain CDR1 comprising the amino acid sequence GFTFSDYAMH (SEQ ID NO:55); a heavy chain CDR2 comprising the amino acid sequence WVSSIFYSGSNTYYADSVKG (SEQ ID NO:56); and a heavy chain CDR3 comprising the amino acid sequence PKSYASGPFAY (SEQ ID NO:57); or

(i) a light chain CDR1 comprising the amino acid sequence SGSSSNIGQNYVS (SEQ ID NO:58); a light chain CDR2 comprising the amino acid sequence LLIYDNSKRPS (SEQ ID NO:59); a light chain CDR3 comprising the amino acid sequence SSWDLLSKSR (SEQ ID NO:60); a heavy chain CDR1 comprising the amino acid sequence GGTFSTHAIS (SEQ ID NO:61); a heavy chain CDR2 comprising the amino acid sequence WMGLIQPRFGTANYAQKFOR (SEQ ID NO:62); and a heavy chain CDR3 comprising the amino acid sequence DYYGGMAY (SEQ ID NO:63).

2. The method of claim 1 , wherein the subject has hemochromatosis.

3. The method of claim 1 , wherein the iron overload is caused by iron supplementation.

4. The method of claim 1 , wherein the subject has anemia.

5. The method of claim 4 , wherein the anemia is associated with chronic kidney disease.

6. The method of claim 1 , wherein the iron overload is caused by a blood transfusion.

7. The method of claim 1 , wherein the BMP inhibitor is administered in combination with a chelator.

8. The method of claim 7 , wherein the BMP inhibitor and the chelator are administered concurrently.

9. The method of claim 7 , wherein the BMP inhibitor is administered before the chelator.

10. The method of claim 9 , wherein the BMP inhibitor and the chelator are administered within 24 hours of each other.

11. The method of claim 7 , wherein the BMP inhibitor is administered after the chelator.

12. The method of claim 7 , wherein the chelator is deferoxamine, deferasirox, or deferiprone.

13. The method of claim 1 , wherein the subject undergoes phlebotomy.

14. A method of decreasing iron in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a BMP inhibitor, wherein the BMP inhibitor is an ALK2 antibody or an ALK2 binding fragment thereof comprising:

(a) a light chain CDR1 comprising the amino acid sequence SGSSSNIGSNYVS (SEQ ID NO:1); a light chain CDR2 comprising the amino acid sequence VLIYKNNHRPS (SEQ ID NO:24); a light chain CDR3 comprising the amino acid sequence ASWDHSDRFYV (SEQ ID NO:4); a heavy chain CDR1 comprising the amino acid sequence GGTFSSYGVS (SEQ ID NO:31); a heavy chain CDR2 comprising the amino acid sequence WMGGIIPHFGIANYAQKFQG (SEQ ID NO:36); and a heavy chain CDR3 comprising the amino acid sequence EIGSLDI (SEQ ID NO:13);

(b) a light chain CDR1 comprising the amino acid sequence SGDSIPSFFAS (SEQ ID NO:18); a light chain CDR2 comprising the amino acid sequence LVIYRDSNRPS (SEQ ID NO:25); a light chain CDR3 comprising the amino acid sequence YVTAPWKSIW (SEQ ID NO:5); a heavy chain CDR1 comprising the amino acid sequence GFTFSSHAMS (SEQ ID NO:32); a heavy chain CDR2 comprising the amino acid sequence WVGRIKSKADSGTTDYAAPVKG (SEQ ID NO:37); and a heavy chain CDR3 comprising the amino acid sequence DYGVAFAY (SEQ ID NO:14);

(c) a light chain CDR1 comprising the amino acid sequence SGDNIGTKYAY (SEQ ID NO:19); a light chain CDR2 comprising the amino acid sequence LVIYGDSDRPS (SEQ ID NO:26); a light chain CDR3 comprising the amino acid sequence YSADAQQMKA (SEQ ID NO:6); a heavy chain CDR1 comprising the amino acid sequence GFTFNSSAMS (SEQ ID NO:33); a heavy chain CDR2 comprising the amino acid sequence WVGRIKSKRDGYTTDYAAPVKG (SEQ ID NO:38); and a heavy chain CDR3 comprising the amino acid sequence DYGGLKFDY (SEQ ID NO:15);

(d) a light chain CDR1 comprising the amino acid sequence SGDNLRKYSAH (SEQ ID NO:20); a light chain CDR2 comprising the amino acid sequence LVIYYDNKRPS (SEQ ID NO:27); a light chain CDR3 comprising the amino acid sequence QVYASVHRM (SEQ ID NO:7); a heavy chain CDR1 comprising the amino acid sequence GGTFSSYAIH (SEQ ID NO:34); a heavy chain CDR2 comprising the amino acid sequence WMGRIIPDFGTANYAQKFQG (SEQ ID NO:39); and a heavy chain CDR3 comprising the amino acid sequence GPTQAIHYFAY (SEQ ID NO:16);

(e) a light chain CDR1 comprising the amino acid sequence SGDSLGSKSVH (SEQ ID NO:21); a light chain CDR2 comprising the amino acid sequence LVIYRDSKRPS (SEQ ID NO:28); a light chain CDR3 comprising the amino acid sequence QTYDWSHFGW (SEQ ID NO:8); a heavy chain CDR1 comprising the amino acid sequence GFTFSSAAMH (SEQ ID NO:35); a heavy chain CDR2 comprising the amino acid sequence WVSVISSDGGSTYYADSVKG (SEQ ID NO:12); and a heavy chain CDR3 comprising the amino acid sequence AGFILGSLGVAWMDV (SEQ ID NO:17);

(f) a light chain CDR1 comprising the amino acid sequence RASQGISGNWLT (SEQ ID NO:40); a light chain CDR2 comprising the amino acid sequence LLIYDASNLQS (SEQ ID NO:41); a light chain CDR3 comprising the amino acid sequence HQSYRGPM (SEQ ID NO:42); a heavy chain CDR1 comprising the amino acid sequence GFTFGRFVMH (SEQ ID NO:43); a heavy chain CDR2 comprising the amino acid sequence WVSVIGYSGSSTYYADSVKG (SEQ ID NO:44); and a heavy chain CDR3 comprising the amino acid sequence EPGYYYPSGYYRGPGYWMDV (SEQ ID NO:45);

(g) a light chain CDR1 comprising the amino acid sequence SGDNIRKKYVH (SEQ ID NO:46); a light chain CDR2 comprising the amino acid sequence LVIYRDSNRPS (SEQ ID NO:47); a light chain CDR3 comprising the amino acid sequence SSAGRDNY (SEQ ID NO:48); a heavy chain CDR1 comprising the amino acid sequence GFTFSSSAMH (SEQ ID NO:49); a heavy chain CDR2 comprising the amino acid sequence WVSVIHYDSSETYYADSVKG (SEQ ID NO:50); and a heavy chain CDR3 comprising the amino acid sequence DRYFFDV (SEQ ID NO:51);

(h) a light chain CDR1 comprising the amino acid sequence SGDALRYYIAH (SEQ ID NO:52); a light chain CDR2 comprising the amino acid sequence LVIYYNNNRPS (SEQ ID NO:53); a light chain CDR3 comprising the amino acid sequence QSYGPGSV (SEQ ID NO:54); a heavy chain CDR1 comprising the amino acid sequence GFTFSDYAMH (SEQ ID NO:55); a heavy chain CDR2 comprising the amino acid sequence WVSSIFYSGSNTYYADSVKG (SEQ ID NO:56); and a heavy chain CDR3 comprising the amino acid sequence PKSYASGPFAY (SEQ ID NO:57); or

(i) a light chain CDR1 comprising the amino acid sequence SGSSSNIGQNYVS (SEQ ID NO:58); a light chain CDR2 comprising the amino acid sequence LLIYDNSKRPS (SEQ ID NO:59); a light chain CDR3 comprising the amino acid sequence SSWDLLSKSR (SEQ ID NO:60); a heavy chain CDR1 comprising the amino acid sequence GGTFSTHAIS (SEQ ID NO:61); a heavy chain CDR2 comprising the amino acid sequence WMGLIQPRFGTANYAQKFOR (SEQ ID NO:62); and a heavy chain CDR3 comprising the amino acid sequence DYYGGMAY (SEQ ID NO:63).

15. The method of claim 14 , wherein the subject has iron overload.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 8, 2023
From: SEEHRA, JASBIR S.; LACHEY, JENNIFER; ROVALDI, CHRISTOPHER R.; ORDONEZ, CLAUDIA
To: KEROS THERAPEUTICS, INC.
Reel/Frame 064845/0910 →
Continuity (7)
Continuation PCTUS2021057974 · Nov 4, 2021
Provisional Application 63208410 · Jun 8, 2021
Provisional Application 63187386 · May 11, 2021
Provisional Application 63121319 · Dec 4, 2020
Provisional Application 63111471 · Nov 9, 2020
Provisional Application 63109861 · Nov 4, 2020
Related Publication 20230406956A1 · Dec 21, 2023
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