Combination of an anti-CD19 antibody and a Bruton's tyrosine kinase inhibitor and uses thereof
The present disclosure describes a pharmaceutical combination of an anti-CD19 antibody and a Bruton's tyrosine kinase (BTK) inhibitor for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and/or acute lymphoblastic leukemia.
1. A synergistic combination for treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and/or acute lymphoblastic leukemia, said composition comprising an antibody specific for CD19 wherein said antibody comprises an HCDR1 region of sequence SYVMH (SEQ ID NO: 1), an HCDR2 region of sequence NPYNDG (SEQ ID NO: 2), an HCDR3 region of sequence GTYYYGTRVFDY (SEQ ID NO: 3), an LCDR1 region of sequence RSSKSLQNVNGNTYLY (SEQ ID NO: 4), an LCDR2 region of sequence RMSNLNS (SEQ ID NO: 5), and an LCDR3 region of sequence MQHLEYPIT (SEQ ID NO: 6) and Ibrutinib.
2. A combination according to claim 1 , wherein the antibody comprises a variable heavy chain of the sequence EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGYINPY NDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGTYYYGTRVFDYWG QGTLVTVSS (SEQ ID NO: 10) and a variable light chain of the sequence DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQLLIYR MSNLNSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYPITFGAGTKLEIK (SEQ ID NO: 11).
3. A combination according to claim 1 , wherein the antibody comprises a heavy chain constant domain of the sequence
(SEQ ID NO: 12)
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP
KSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGK
EYKCKVSNKALPAPEEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTC
LVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRW
QQGNVFSCSVMHEALHNHYTQKSLSLSPGK.
4. A combination according to claim 1 , wherein the antibody comprises a light chain constant domain of the sequence
(SEQ ID NO: 13)
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
SFNRGEC.
5. A method for treatment of chronic lymphocytic leukemia, acute lymphoblastic leukemia or non-Hodgkin's lymphoma in a patient, said method comprising administering the combination of claim 1 to the patient.
6. The method according to claim 5 for use in the treatment of non-Hodgkin's lymphoma, wherein the non-Hodgkin's lymphoma is selected from the group consisting of follicular lymphoma, small lymphocytic lymphoma, mucosa-associated lymphoid tissue, marginal zone, diffuse large B cell, Burkitt's, and mantle cell.
7. The method according to claim 6 , wherein the non-Hodgkin's lymphoma is follicular lymphoma.
8. The method according to claim 6 , wherein the non-Hodgkin's lymphoma is small lymphocytic lymphoma.
9. The method according to claim 6 , wherein the non-Hodgkin's lymphoma is mucosa-associated lymphoid tissue.
10. The method according to claim 6 , wherein the non-Hodgkin's lymphoma is diffuse large B cell lymphoma.
11. The method according to claim 6 , wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma.
12. The method according to claim 6 , wherein the non-Hodgkin's lymphoma is mantle cell lymphoma.
13. The method according to claim 5 , wherein the antibody specific for CD19 and the Ibrutinib of said combination are administered separately.
14. The method of claim 5 , wherein the Ibrutinib of said combination is administered prior to administration of the antibody specific for CD19.
15. The method of claim 5 , wherein the antibody specific for CD19 and the Ibrutinib of said combination are administered simultaneously.
16. The method of claim 5 , wherein the antibody specific for CD19 and the Ibrutinib of said combination are administered at a time where both drugs are active in the patient at the same time.