Claims for Patent: 10,766,965

Summary for Patent: 10,766,965

Title:	Anti-CD38 antibodies for treatment of light chain amyloidosis and other CD38-positive hematological malignancies
Abstract:	The present invention relates to methods of treatment of light chain amyloidosis and other CD38-positive hematological malignancies with anti-CD38 antibodies.
Inventor(s):	Chaulagain; Chakra (Broward, FL), Comenzo; Raymond (Boston, MA), Doshi; Parul (Spring House, PA), Ma; Xun (Boston, MA), Sasser; Amy (Spring House, PA)
Assignee:	JANSSEN BIOTECH, INC. (Horsham, PA) TUFTS MEDICAL CENTER, INC. (Boston, MA)
Application Number:	15/160,476
Patent Claims:	1. A method of treating a patient having relapsed or refractory light chain amyloidosis (AL), comprising administering to the patient in need thereof an anti-CD38 antibody which is an IgG1 isotype comprising a heavy chain variable region (VH) sequence of SEQ ID NO: 4 and a light chain variable region (VL) sequence of SEQ ID NO: 5 for a time sufficient to treat relapsed or refractory AL. 2. The method of claim 1, wherein the patient has been treated with a proteasome inhibitor, cyclophosphamide and/or a corticosteroid. 3. The method of claim 2, wherein the proteasome inhibitor is bortezomib. 4. The method of claim 2, wherein the corticosteroid is dexamethasone. 5. The method of claim 1, wherein the anti-CD38 antibody is administered in combination with a second therapeutic agent. 6. The method of claim 2, wherein the anti-CD38 antibody is administered in combination with a second therapeutic agent. 7. The method of claim 5, wherein the second therapeutic agent is a proteasome inhibitor, cyclophosphamide or a corticosteroid. 8. The method of claim 7, wherein the proteasome inhibitor is bortezomib or ixazomib. 9. The method of claim 7, wherein the corticosteroid is dexamethasone. 10. The method of claim 5, wherein the second therapeutic agent is bortezomib, ixazomib, carfilzomib, panobinostat, cyclophosphamide, melphalan, thalidomide, lenalidomide, pomalidomide, dexamethasone or interferon alpha. 11. The method of claim 1, wherein the anti-CD38 antibody is administered in combination with a proteasome inhibitor, cyclophosphamide and a corticosteroid. 12. The method of claim 11, wherein the proteasome inhibitor is bortezomib. 13. The method of claim 11, wherein the proteasome inhibitor is ixazomib. 14. The method of claim 11, wherein the corticosteroid is dexamethasone. 15. The method of claim 11, wherein the proteasome inhibitor is bortezomib and the corticosteroid is dexamethasone. 16. The method of claim 11, wherein the proteasome inhibitor is ixazomib and the corticosteroid is dexamethasone. 17. The method of claim 5, wherein the anti-CD38 antibody and the second therapeutic agent are administered simultaneously, sequentially or separately. 18. The method of claim 11, wherein the proteasome inhibitor, cyclophosphamide and the corticosteroid are administered simultaneously, sequentially or separately. 19. The method of claim 1, wherein the patient is further treated with radiotherapy. 20. The method of claim 1, wherein the anti-CD38 antibody does not mediate killing of CD34-positive hematopoietic progenitor cells by complement dependent cytotoxicity (CDC). 21. The method of claim 1, wherein the anti-CD38 antibody induces killing of CD38 positive plasma cells by antibody-dependent cell-mediated cytotoxicity (ADCC), antibody dependent cellular phagocytosis (ADCP), complement dependent cytotoxicity (CDC), apoptosis, or modulation of CD38 enzymatic activity. 22. The method of claim 1, wherein the anti-CD38 antibody comprises a heavy chain comprising an amino acid sequence that is 95%, 96%, 97%, 98%, 99%, or 100% identical to that of SEQ ID NO: 12 and a light chain comprising an amino an amino acid sequence that is 95%, 96%, 97%, 98%, 99%, or 100% identical to that of SEQ ID NO: 13. 23. The method of claim 22, wherein the anti-CD38 antibody comprises the heavy chain of SEQ ID NO: 12 and the light chain of SEQ ID NO: 13. 24. The method of claim 1, wherein the anti-CD38 antibody is human. 25. The method of claim 1, wherein the anti-CD38 antibody is administered intravenously. 26. The method of claim 1, further comprising performing hematopoietic stem cell transplantation (HSCT) after administering the effective amount of anti-CD38 antibody to the patient having relapsed or refractory AL. 27. The method of claim 26, wherein the HSCT is allogeneic, autologous or syngeneic. 28. The method of claim 26, wherein the HSCT comprises transplantation of blood stem cells derived from bone marrow, blood or amniotic fluid. 29. The method of claim 26, wherein the patient has completed chemotherapy and/or radiation therapy prior to HSCT. 30. The method of claim 1, wherein the anti-CD38 antibody is administered in a pharmaceutical composition comprising the anti-CD38 antibody and a hyaluronidase. 31. A method of induction of selective killing of CD38.sup.+ hematological cancer cells and preservation of CD38.sup.+CD34.sup.+ hematopoietic stem cells in a patient with relapsed or refractory light chain amyloidosis (AL), comprising: contacting CD38.sup.+ cells of the patient with an anti-CD38 antibody which is an IgG1 isotype comprising a heavy chain variable region (VH) sequence of SEQ ID NO: 4 and a light chain variable region (VL) sequence of SEQ ID NO: 5; wherein CD38.sup.+ hematological cancer cells within the patient are killed and CD38.sup.+CD34.sup.+ hematopoietic stem cells within the patient are preserved. 32. A method of performing a hematopoietic stem cell transplant (HSCT) in a patient with relapsed or refractory light chain amyloidosis (AL), comprising: introducing hematopoietic stem cells into the patient; and administering to the patient an anti-CD38 antibody after introduction of the hematopoietic stem cells, the anti-CD38 antibody comprising a heavy chain variable region (VH) sequence of SEQ ID NO: 4 and a light chain variable region (VL) sequence of SEQ ID NO: 5, wherein the anti-CD38 antibody is an IgG1 isotype and induces killing of CD38.sup.+ hematological cancer cells, and wherein CD38.sup.+CD34.sup.+ hematopoietic stem cells within the transplant survive. 33. A method of performing a hematopoietic stem cell transplant (HSCT) in a patient with relapsed or refractory light chain amyloidosis (AL), comprising: administering to the patient an anti-CD38 antibody which is an IgG1 isotype comprising a heavy chain variable region (VH) sequence of SEQ ID NO: 4 and a light chain variable region (VL) sequence of SEQ ID NO: 5; and introducing hematopoietic stem cells into the patient after administration of the anti-CD38 antibody, wherein the anti-CD38 antibody induces killing of CD38.sup.+ hematological cancer cells, and wherein CD38.sup.+CD34.sup.+ hematopoietic stem cells within the transplant survive.

Details for Patent 10,766,965

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	May 05, 2004		2040-10-06
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	December 02, 2004		2040-10-06
Amphastar Pharmaceuticals, Inc.	AMPHADASE	hyaluronidase	Injection	021665	October 26, 2004		2040-10-06