Anti-CD38 antibodies for treatment of light chain amyloidosis and other CD38-positive hematological malignancies

Patent metadata

Field	Value
Publication number	US-12091466-B2
Application number	US-202016986214-A
Country	US
Kind code	B2
Filing date	Aug 5, 2020
Priority date	May 20, 2015
Publication date	Sep 17, 2024
Grant date	Sep 17, 2024

Abstract

The present invention relates to methods of treatment of light chain amyloidosis and other CD38-positive hematological malignancies with anti-CD38 antibodies.

First claim

What is claimed is:

1. A method of treating light chain amyloidosis (AL) in a newly diagnosed AL patient, comprising administering to the patient a pharmaceutical composition comprising an anti-CD38 antibody and a hyaluronidase for a time sufficient to treat the AL, wherein:
a) the anti-CD38 antibody is of 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;
b) the hyaluronidase is rHuPH20 recombinant hyaluronidase; and
c) the pharmaceutical composition is administered in combination with cyclophosphamide, bortezomib and dexamethasone (CyBorD).

2. The method of claim 1 , wherein the anti-CD38 antibody and CyBorD are administered simultaneously.

3. The method of claim 1 , wherein the anti-CD38 antibody and CyBorD are administered sequentially or separately.

4. The method of claim 1 , wherein the cyclophosphamide, the bortezomib and the dexamethasone are administered simultaneously.

5. The method of claim 1 , wherein the cyclophosphamide, the bortezomib and the dexamethasone are administered sequentially or separately.

6. The method of claim 1 , wherein the patient is undergoing hematopoietic stem cell transplantation (HSCT).

7. The method of claim 6 , wherein the HSCT is allogeneic.

8. The method of claim 6 , wherein the HSCT is autologous or syngeneic.

9. The method of claim 6 , wherein the HSCT comprises transplantation of blood stem cells derived from bone marrow, blood or amniotic fluid.

10. The method of claim 6 , wherein the anti-CD38 antibody is administered prior to HSCT.

11. The method of claim 6 , wherein the anti-CD38 antibody is administered during or after HSCT.

12. The method of claim 6 , wherein the patient has completed chemotherapy and/or radiation therapy prior to HSCT.

13. The method of claim 1 , wherein the patient is further treated with radiotherapy.

14. 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).

15. 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.

16. The method of claim 1 , wherein the anti-CD38 antibody binds at least to the region SKRNIQFSCKNIYR (SEQ ID NO: 2) and the region EKVQTLEAWVIHGG (SEQ ID NO: 3) of human CD38 SEQ ID NO: 1.

17. 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 acid sequence that is 95%, 96%, 97%, 98%, 99% or 100% identical to that of SEQ ID NO: 13.

18. The method of claim 1 , wherein the anti-CD38 antibody comprises the heavy chain of SEQ ID NO: 12 and the light chain of SEQ ID NO: 13.

Assignees

• Janssen Biotech Inc
• Tufts Medical Ct Inc

Inventors

• Chaulagain Chakra
• Comenzo Raymond
• Doshi Parul
• Ma Xun
• Sasser Amy

Classifications

• C12Y302/01035

  Hyaluronoglucosaminidase (3.2.1.35), i.e. hyaluronidase · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title