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Last Updated: October 22, 2019

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Claims for Patent: 10,316,094

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Summary for Patent: 10,316,094
Title:Compositions and methods for inducing phagocytosis of MHC class I positive cells and countering anti-CD47/SIRPA resistance
Abstract: Methods and compositions are provided for inducing phagocytosis of a target cell, treating an individual having cancer, treating an individual having an intracellular pathogen infection (e.g., a chronic infection), and/or reducing the number of inflicted cells (e.g., cancer cells, cells infected with an intracellular pathogen, etc.) in an individual. Methods and compositions are also provided for predicting whether an individual is resistant (or susceptible) to treatment with an anti-CD47/SIRPA agent. In some cases, the subject methods and compositions include an anti-MHC Class I/LILRB1 agent. In some cases, the subject methods and compositions include an anti-MHC Class I/LILRB1 agent and an anti-CD47/SIRPA agent (e.g., co-administration of an anti-MHC Class I/LILRB1 agent and an anti-CD47/SIRPA agent). Kits are also provided for practicing the methods of the disclosure.
Inventor(s): Maute; Roy Louis (San Francisco, CA), Weiskopf; Kipp Andrew (Sudbury, MA), Ring; Aaron Michael (New Haven, CT), Weissman; Irving L. (Stanford, CA)
Assignee: The Board of Trustees of the Leland Stanford Junior University (Stanford, CA)
Application Number:15/518,976
Patent Claims:1. A composition for increasing phagocytosis of a target cell, the composition comprising: (a) an antibody that specifically binds to leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) and does not activate signaling through LILRB1 upon binding; and (b) an agent an antibody that binds to the target cell and thereby opsonizes the target cell.

2. The composition of claim 1, wherein the composition further comprises an anti-CD47/signal regulatory protein alpha (SIRPA) agent.

3. The composition according to claim 1, wherein the antibody that binds to the target cell binds to CD20.

4. The composition according to claim 3, wherein the antibody is rituximab.

5. The composition according to claim 1, wherein the antibody that binds to the target cell binds to EGFR.

6. The composition according to claim 5, wherein the antibody is cetuximab.

7. A method of inducing phagocytosis of a target cell, the method comprising: contacting a target cell with a macrophage in the presence of an antibody that specifically binds to leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) and does not activate signaling through LILRB1 upon binding and an antibody that binds to the target cell and thereby opsonizes the target cell, for a period of time sufficient to induce phagocytosis of the target cell by the macrophage.

8. The method according to claim 7, wherein the target cell is a cancer cell.

9. The method according to claim 7, wherein the target cell is a cell infected with an intracellular pathogen.

10. The method according to claim 7, wherein the target cell is a cancer cell of an individual having cancer, or an infected cell of an individual having a chronic intracellular pathogen infection.

11. The method according to claim 7, wherein the contacting is in vitro or ex vivo.

12. The method according to claim 7, wherein the contacting is in vivo.

13. The method according to claim 7, wherein said contacting is in the presence of an antibody that specifically binds to CD47 and blocks interaction of CD47 and SIRP.alpha..

14. The method according to claim 7, wherein the antibody that binds to the target cell binds to CD20.

15. The method according to claim 14, wherein the antibody is rituximab.

16. The method according to claim 7, wherein the antibody that binds to the target cell binds to EGFR.

17. The method according to claim 16, wherein the antibody is cetuximab.

Summary for Patent:   Start Trial

PCT Information
PCT FiledOctober 23, 2015PCT Application Number:PCT/US2015/057233
PCT Publication Date:April 28, 2016PCT Publication Number:WO2016/065329

Details for Patent 10,316,094

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Genentech RITUXAN rituximab VIAL 103705 001 1997-11-26   Start Trial The Board of Trustees of the Leland Stanford Junior University (Stanford, CA) 2034-10-24 RX search
Imclone ERBITUX cetuximab VIAL; INTRAVENOUS 125084 001 2004-06-18   Start Trial The Board of Trustees of the Leland Stanford Junior University (Stanford, CA) 2034-10-24 RX Orphan search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

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