IP Library › Granted Patent US 12,295,973
Granted Patent B2
US 12,295,973 · App. 18/208,490 · Granted May 13, 2025

Luteinizing hormone receptor binding agents and luteinizing hormone agonists to identify, expand, ablate and modify stem cells

Inventors: Jarrod Dudakov (Seattle, WA); Marcel van den Brink (New York, NY); Enrico Velardi (New York, NY); Hans-Peter Kiem (Seattle, WA); Stefan Radtke (Seattle, WA); Scott James (New York, NY)
Assignees: Fred Hutchinson Cancer Center; Memorial Sloan-Kettering Cancer Center
A61K35/28A61K35/12A61K39/461A61K39/4621A61K39/46431A61P35/00C12N5/0647C12N15/86A61K2239/31A61K2239/38
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Quick Facts
Patent No.
US 12,295,973
App. No.
18/208,490
Granted
May 13, 2025
Kind
B2
Abstract

The use of luteinizing hormone receptor (LHR) binding agents and luteinizing hormone (LH) agonists to enrich for primitive hematopoietic stem cell (pHSC) populations, to target pHSC for ablation, and/or to expand pHSC populations are described. The methods can be used to prepare therapeutic hematopoietic stem cell (HSC) populations, to prepare patients for therapeutic HSC transplants, and/or to treat malignancies, such as those associated with hyperproliferative HSC.

Claims (32)

1. A cDNA comprising a sequence as set forth in SEQ ID NO: 19 or SEQ ID NO: 6 or a sequence having at least 90% sequence identity to SEQ ID NO: 19 or SEQ ID NO: 6.

2. The cDNA of claim 1 , wherein the cDNA encodes a luteinizing hormone receptor (LHR) binding agent.

3. The cDNA of claim 2 , wherein the LHR binding agent comprises a luteinizing hormone (LH) alpha subunit and a LH beta subunit.

4. The cDNA of claim 3 , wherein

the LH alpha subunit has the sequence as set forth in SEQ ID NO: 23 or a sequence having at least 90% sequence identity to SEQ ID NO: 23 and the LH beta subunit has the sequence as set forth in SEQ ID NO: 22 or a sequence having at least 90% sequence identity to SEQ ID NO: 22; or

the LH alpha subunit has the sequence as set forth in SEQ ID NO: 11 or a sequence having at least 90% sequence identity to SEQ ID NO: 11 and the LH beta subunit has the sequence as set forth in SEQ ID NO: 9 or a sequence having at least 90% sequence identity to SEQ ID NO: 9.

5. The cDNA of claim 2 , wherein the LHR binding agent has the sequence as set forth in SEQ ID NO: 51 or a sequence having at least 90% sequence identity to SEQ ID NO: 51.

6. The cDNA of claim 2 , wherein the LHR binding agent comprises:

a CDRH1 having the sequence as set forth in SEQ ID NO: 28, a CDRH2 having the sequence as set forth in SEQ ID NO: 29, a CDRH3 having the sequence as set forth in SEQ ID NO: 30, a CDRL1 having the sequence as set forth in SEQ ID NO: 31, a CDRL2 having the sequence DTS, and a CDRL3 having the sequence as set forth in SEQ ID NO: 32;

a CDRH1 having the sequence as set forth in SEQ ID NO: 33, a CDRH2 having the sequence as set forth in SEQ ID NO: 34, a CDRH3 having the sequence as set forth in SEQ ID NO: 35, a CDRL1 having the sequence as set forth in SEQ ID NO: 36, a CDRL2 having the sequence WAS, and a CDRL3 having the sequence as set forth in SEQ ID NO: 37; or

a CDRH1 having the sequence as set forth in SEQ ID NO: 38, a CDRH2 having the sequence as set forth in SEQ ID NO: 39, a CDRH3 having the sequence as set forth in SEQ ID NO: 40, a CDRL1 having the sequence as set forth in SEQ ID NO: 41, a CDRL2 having the sequence NAS, and a CDRL3 having the sequence as set forth in SEQ ID NO: 42.

7. The cDNA of claim 2 , wherein the LHR binding agent comprises

a heavy chain having the sequence as set forth in SEQ ID NO: 43 or a sequence having at least 90% sequence identity to SEQ ID NO: 43 and a light chain having the sequence as set forth in SEQ ID NO: 44 or a sequence having at least 90% sequence identity to SEQ ID NO: 44;

a heavy chain having the sequence as set forth in SEQ ID NO: 45 or a sequence having at least 90% sequence identity to SEQ ID NO: 45 and a light chain having the sequence as set forth in SEQ ID NO: 46 or a sequence having at least 90% sequence identity to SEQ ID NO: 46;

a heavy chain having the sequence as set forth in SEQ ID NO: 47 or a sequence having at least 90% sequence identity to SEQ ID NO: 47 and a light chain having the sequence as set forth in SEQ ID NO: 48 or a sequence having at least 90% sequence identity to SEQ ID NO: 48; or

a heavy chain having the sequence as set forth in SEQ ID NO: 49 or a sequence having at least 90% sequence identity to SEQ ID NO: 49 and a light chain having the sequence as set forth in SEQ ID NO: 50 or a sequence having at least 90% sequence identity to SEQ ID NO: 50.

8. The cDNA of claim 1 , wherein the cDNA encodes the sequence as set forth in SEQ ID NO: 10 or a sequence having at least 90% sequence identity to SEQ ID NO: 10.

9. The cDNA of claim 1 , wherein the cDNA encodes 4-1BB and CD3 zeta.

10. The cDNA of claim 1 , wherein the cDNA encodes a CD28 hinge and a CD28 transmembrane domain.

11. The cDNA of claim 1 , wherein the cDNA encodes

the sequence as set forth in SEQ ID NO: 20 or a sequence having at least 90% sequence identity to SEQ ID NO: 20, or

the sequence as set forth in SEQ ID NO: 7 or a sequence having at least 90% sequence identity to SEQ ID NO: 7.

12. The cDNA of claim 1 , wherein the cDNA encodes the sequence as set forth in SEQ ID NO: 24 or a sequence having at least 90% sequence identity to SEQ ID NO: 24 and SEQ ID NO: 25 or a sequence having at least 90% sequence identity to SEQ ID NO: 25.

13. The cDNA of claim 1 , wherein the cDNA encodes the sequence as set forth in SEQ ID NO: 26 or a sequence having at least 90% sequence identity to SEQ ID NO: 26 and SEQ ID NO: 27 or a sequence having at least 90% sequence identity to SEQ ID NO: 27.

14. The cDNA of claim 1 , wherein the cDNA encodes the sequence as set forth in SEQ ID NO: 15 or a sequence having at least 90% sequence identity to SEQ ID NO: 15 and SEQ ID NO: 16 or a sequence having at least 90% sequence identity to SEQ ID NO: 16.

15. The cDNA of claim 1 , wherein the cDNA encodes

the sequence as set forth in SEQ ID NO: 15 or a sequence having at least 90% sequence identity to SEQ ID NO: 15,

the sequence as set forth in SEQ ID NO: 16 or a sequence having at least 90% sequence identity to SEQ ID NO: 16 and

the sequence as set forth in SEQ ID NO: 17 or a sequence having at least 90% sequence identity to SEQ ID NO: 17.

16. The cDNA of claim 1 , wherein the cDNA is within an immune cell.

17. The cDNA of claim 16 , wherein the immune cell is a hematopoietic stem cell (HSC), a T cell, or a natural killer (NK) cell.

18. The cDNA of claim 17 , wherein the HSC is a primitive HSC (pHSC).

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 5, 2023
From: VAN DEN BRINK, MARCEL; VELARDI, ENRICO
To: MEMORIAL SLOAN-KETTERING CANCER CENTER
Reel/Frame 064157/0772 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 5, 2023
From: DUDAKOV, JARROD; KIEM, HANS-PETER; RADTKE, STEFAN
To: FRED HUTCHINSON CANCER RESEARCH CENTER
Reel/Frame 064157/0781 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 5, 2023
From: JAMES, SCOTT
To: MEMORIAL SLOAN-KETTERING CANCER CENTER
Reel/Frame 064157/0798 →
MERGER AND CHANGE OF NAME Recorded Jul 5, 2023
From: FRED HUTCHINSON CANCER RESEARCH CENTER; SEATTLE CANCER CARE ALLIANCE
To: FRED HUTCHINSON CANCER CENTER
Reel/Frame 064157/0801 →
Continuity (3)
Continuation 16753277
Provisional Application 62566897 · Oct 2, 2017
Related Publication 20240091265A1 · Mar 21, 2024
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