Claims for Patent: 10,106,620

Summary for Patent: 10,106,620

Title:	Blocking CD38 using anti-CD38 F(ab\')2 to protect NK cells
Abstract:	Provided herein are methods of inhibiting growth or proliferation of cells expressing CD38 by contacting the CD38-expressing cells with 1) NK cells bound to an anti-CD38 F(ab\').sub.2 fragment and 2) an anti-CD38 antibody, in either order or simultaneously. Also provided herein are methods of treating or inhibiting a hyperproliferative disorder or an autoimmune disorder in a subject by administering to the subject 1) NK cells bound to an anti-CD38 F(ab\').sub.2 fragment and 2) an anti-CD38 antibody, in either order or simultaneously.
Inventor(s):	Childs; Richard W. (Rockville, MD), Berg; Maria (Bethesda, MD), Espinoza Calderon; Luis (Bethesda, MD), Sasser; Kate (Spring House, PA), Attar; Ricardo (Spring House, PA)
Assignee:	The United States of America, as represented by the Secretary, Department of Health and Human Services (Washington, DC) Janssen Biotech, Inc. (Spring House, PA)
Application Number:	15/319,344
Patent Claims:	1. A method of inhibiting growth or proliferation of CD38-expressing cells, comprising: contacting a population of natural killer (NK) cells with a F(ab').sub.2 fragment of a first anti-CD38 antibody, thereby producing a population of NK cells bound to the F(ab').sub.2 fragment of the first anti-CD38 antibody; and contacting a population of CD38-expressing cells with a second anti-CD38 antibody and the population of NK cells bound to the F(ab').sub.2 fragment of the first anti-CD38 antibody, thereby inhibiting growth or proliferation of the CD38-expressing cells. 2. The method of claim 1, wherein the F(ab').sub.2 fragment of the first anti-CD38 antibody comprises the F(ab').sub.2 fragment of a human anti-CD38 antibody or a humanized anti-CD38 antibody and/or wherein the second anti-CD38 antibody comprises a human anti-CD38 antibody, a humanized anti-CD38 antibody, or a fragment thereof. 3. The method of claim 2, wherein the first anti-CD38 antibody and/or the second anti-CD38 antibody comprise daratumumab or SAR650984. 4. The method of claim 1, wherein the first anti-CD38 antibody and the second anti-CD38 antibody are the same. 5. The method of claim 1, wherein the population of NK cells comprises CD16 positive and/or CD56 positive NK cells. 6. The method of claim 1, wherein contacting the population of NK cells with the F(ab').sub.2 fragment of the first anti-CD38 antibody occurs in vitro or ex vivo and/or contacting the population of CD38-expressing cells with the second anti-CD38 antibody and the population of NK cells bound to the ab').sub.2 fragment of the first anti-CD38 antibody occurs in vivo, in vitro, or ex vivo. 7. The method of claim 6, further comprising expanding the population of NK cells in vitro or ex vivo prior to contacting the population of NK cells with the F(ab').sub.2 fragment of the first anti-CD38 antibody. 8. The method of claim 6, wherein contacting the population of CD38-expressing cells with the second anti-CD38 antibody and the population of NK cells bound to the F(ab').sub.2 fragment of the first anti-CD38 antibody comprises administering the second anti-CD38 antibody and the population of NK cells bound to the F(ab').sub.2 fragment of the first anti-CD38 antibody to a subject with a disorder comprising CD38-expressing cells. 9. The method of claim 8, wherein administering the population of NK cells bound to the F(ab').sub.2 fragment of the first anti-CD38 antibody to the subject occurs before, after, or substantially simultaneously with administering the second anti-CD38 antibody to the subject. 10. The method of claim 1, wherein the CD38-expressing cells comprise CD38-expressing cancer cells or CD38-expressing T-cells, B-cells, NK cells, or plasma cells. 11. The method of claim 10, wherein the CD38-expressing cancer cells comprise solid tumor cells or hematological malignancy cells. 12. The method of claim 11, wherein the hematological malignancy cells comprise multiple myeloma cells, acute lymphocytic leukemia cells, acute myeloid leukemia cells, chronic lymphocytic leukemia cells, chronic myeloid leukemia cells, Hodgkin's lymphoma cells, non-Hodgkin's lymphoma cells, T-LGL leukemia cells, NK cell leukemia cells, or hairy cell leukemia cells. 13. A method of treating or inhibiting a hyperproliferative disorder or an autoimmune disorder in a subject, comprising: administering to the subject an effective amount of a population of natural killer (NK) cells bound to a F(ab').sub.2 fragment of a first anti-CD38 antibody; and administering to the subject an effective amount of a second anti-CD38 antibody, wherein the second anti-CD38 antibody is administered to the subject before, after, or substantially simultaneously with administering the population of natural killer (NK) cells bound to a F(ab').sub.2 fragment of a first anti-CD38 antibody, thereby treating or inhibiting the hyperproliferative disorder. 14. The method of claim 13, wherein the F(ab').sub.2 fragment of the first anti-CD38 antibody comprises the F(ab').sub.2 fragment of a human anti-CD38 antibody or a humanized anti-CD38 antibody and/or wherein the second anti-CD38 antibody comprises a human anti-CD38 antibody, a humanized anti-CD38 antibody, or a fragment thereof. 15. The method of claim 14, wherein the first anti-CD38 antibody and/or the second anti-CD38 antibody comprise daratumumab or SAR650984. 16. The method of claim 13, wherein the first anti-CD38 antibody and the second anti-CD38 antibody are the same. 17. The method of claim 13, wherein the population of NK cells comprises CD16 positive and/or CD56 positive NK cells. 18. The method of claim 13, wherein the population of NK cells bound to the F(ab').sub.2 fragment of the first anti-CD38 antibody is produced in vitro or ex vivo by contacting a population of natural killer (NK) cells with the F(ab').sub.2 fragment of the first anti-CD38 antibody. 19. The method of claim 18, further comprising expanding the population of NK cells in vitro or ex vivo prior to contacting the population of NK cells with the F(ab').sub.2 fragment of the first anti-CD38 antibody. 20. The method of claim 13, wherein the population of NK cells comprises autologous NK cells or allogeneic NK cells. 21. The method of claim 13, wherein the hyperproliferative disorder comprises a solid tumor or a hematological malignancy. 22. The method of claim 21, wherein the hematological malignancy comprises multiple myeloma, acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkin's lymphoma, or non-Hodgkin's lymphoma. 23. The method of claim 21, wherein the cells of the solid tumor or the hematological malignancy express CD38. 24. A method of treating or inhibiting a hyperproliferative disorder in a subject comprising: contacting a population of NK cells isolated from the subject with a F(ab').sub.2 fragment of a first anti-CD38 antibody to produce a population of NK cells bound to the F(ab').sub.2 fragment of the first anti-CD38 antibody; administering to the subject a therapeutically effective amount of a second anti-CD38 antibody or fragment thereof; and administering to the subject the population of NK cells bound to the F(ab').sub.2 fragment of the first anti-CD38 antibody, thereby treating or inhibiting the hyperproliferative disorder. 25. A pharmaceutical composition comprising a population of natural killer (NK) cells bound to a F(ab').sub.2 fragment of an anti-CD38 antibody and a pharmaceutically acceptable carrier. 26. The pharmaceutical composition of claim 25, wherein the F(ab').sub.2 fragment of the anti-CD38 antibody comprises a F(ab').sub.2 fragment of a human anti-CD38 antibody or a humanized anti-CD38 antibody. 27. The pharmaceutical composition of claim 25, wherein the anti-CD38 antibody comprises daratumumab or SAR650984.

Details for Patent 10,106,620

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	DARZALEX	daratumumab	Injection	761036	11/16/2015		2034-06-16