IP Library › Granted Patent US 12,404,342
Granted Patent B2
US 12,404,342 · App. 17/822,638 · Granted Sep 2, 2025

Conjugates for targeted cell surface editing

Inventors: Elliot C. Woods (Burlingame, CA); Han Xiao (East Palo Alto, CA); Carolyn R. Bertozzi (Menlo Park, CA); Melissa Gray (Stanford, CA)
Assignee: The Board of Trustees of the Leland Stanford Junior University
C07K16/32A61P35/00C07K19/00C12N9/2402C12Y302/01018C07K2317/732C07K2319/035C07K2319/33C07K2319/74
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Quick Facts
Patent No.
US 12,404,342
App. No.
17/822,638
Granted
Sep 2, 2025
Kind
B2
Abstract

Provided are conjugates including a targeting moiety that binds to a cell surface molecule of a target cell and a target cell surface-editing enzyme. Also provided are compositions and kits that include the conjugates, as well as methods of using the conjugates. Methods of making conjugates are also provided.

Claims (25)

1. A method of treating cancer in an individual in need thereof, the method comprising administering to the individual a therapeutically effective amount of a conjugate comprising (a) an antibody that binds to a tumor-associated cell surface molecule of a cancer cell and (b) a sialidase conjugated to the antibody, whereupon, after administration to the individual, the sialidase cleaves a sialic acid from the surface of the cancer cell, wherein the sialic acid is a ligand for a sialic acid-binding Ig-like lectin (Siglec) receptor, wherein the sialidase is a prokaryotic sialidase or a eukaryotic sialidase.

2. The method of claim 1 , wherein the conjugate, when administered to the individual, modulates an immune pathway in the individual.

3. The method of claim 1 , wherein the conjugate, when administered to the individual, cleaves all or a portion of the sialic acid from the surface of the cancer cell.

4. The method of claim 1 , wherein the Siglec receptor is an inhibitory immune receptor present on an immune cell selected from the group consisting of: a natural killer (NK) cell, a macrophage, a monocyte, a neutrophil, a dendritic cell, a T cell, a B cell, a mast cell, a basophil, and an eosinophil.

5. The method of claim 1 , wherein the Siglec receptor is Siglec 7.

6. The method of claim 1 , wherein the Siglec receptor is Siglec 9.

7. The method of claim 1 , wherein the sialidase is a bacterial sialidase.

8. The method of claim 7 , wherein the bacterial sialidase is a Salmonella typhimurium sialidase or a Vibrio cholerae sialidase.

9. The method of claim 8 , wherein the sialidase is a Vibrio cholerae sialidase.

10. The method of claim 1 , wherein the sialidase is a mammalian neuraminidase.

11. The method of claim 10 , wherein the mammalian neuraminidase is a human neuraminidase.

12. The method of claim 11 , wherein the sialidase is a human neuraminidase selected from the group consisting of: human neuraminidase 1, human neuraminidase 2, human neuraminidase 3, and human neuraminidase 4.

13. The method of claim 1 , wherein the antibody is an IgG, a single chain Fv (scFv), Fab, (Fab) 2 , or (scFv′) 2 .

14. The method of claim 1 , wherein the antibody comprises a fragment crystallizable (Fc) region.

15. The method of claim 14 , wherein the sialidase is conjugated to the Fc region of the antibody.

16. The method of claim 1 , wherein the sialidase is conjugated to a heavy chain of the antibody.

17. The method of claim 16 , wherein the sialidase is conjugated to the C-terminus of the heavy chain.

18. The method of claim 1 , wherein the sialidase is conjugated to the antibody via a linker.

19. The method of claim 1 , wherein the conjugate is a fusion protein.

20. The method of claim 1 , wherein cleavage of sialic acid on the surface of the cancer cell enhances natural killer (NK) cell activation by increasing natural-killer group 2 member D protein (NKG2D) binding to a NKG2D ligand on the cancer cell surface.

21. The method of claim 1 , wherein the cancer cell is a carcinoma cell.

22. The method of claim 1 , wherein the cancer cell is selected from the group consisting of: a breast cancer cell, an ovarian cancer cell, a gastric cancer cell, and a colon cancer cell.

23. The method of claim 1 , wherein the cell surface molecule is human epidermal growth factor receptor 2 (HER2).

24. The method of claim 1 , wherein the antibody is trastuzumab.

25. The method of claim 1 , wherein the antibody is selected from the group consisting of: cetuximab, daratumumab, girentuximab, panitumumab, ofatumumab, and rituximab.

Assignments (4)
CORRECTIVE ASSIGNMENT TO CORRECT THE APPLICATION NUMBER 17/882,638 PREVIOUSLY RECORDED AT REEL: 061348 FRAME: 0215. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Dec 9, 2022
From: WOODS, ELLIOT C.; XIAO, HAN; GRAY, MELISSA
To: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
Reel/Frame 062116/0620 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 7, 2022
From: BERTOZZI, CAROLYN R.
To: HOWARD HUGHES MEDICAL INSTITUTE
Reel/Frame 061348/0204 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 7, 2022
From: WOODS, ELLIOT C.; XIAO, HAN; GRAY, MELISSA
To: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
Reel/Frame 061348/0215 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 7, 2022
From: HOWARD HUGHES MEDICAL INSTITUTE
To: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
Reel/Frame 061348/0229 →
Continuity (3)
Continuation 16308732
Provisional Application 62357645 · Jul 1, 2016
Related Publication 20230287140A1 · Sep 14, 2023
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