COMBINATION OF AN ANTI-CD19 ANTIBODY AND A BRUTON'S TYROSINE KINASE INHIBITOR AND USES THEREOF
The present disclsoure describes a pharmaceutical combination of an anti-CD19 antibody and a Bruton's tyrosine kinase (BTK) inhibitor and its use for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and/or acute lymphoblastic leukemia.
1 . A synergistic combination 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 a Bruton's tyrosine kinase (BTK) inhibitor for use in the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and/or acute lymphoblastic leukemia.
2 - 18 . (canceled)
19 . A method for treatment of chronic lymphocytic leukemia, acute lymphoblastic leukemia or non-Hodgkin's lymphoma in a patient, said method comprising administering to the patient 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 a Bruton's tyrosine kinase (BTK) inhibitor.
20 . The method according to claim 19 , 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.
21 . The method according to claim 19 , wherein the non-Hodgkin's lymphoma is follicular lymphoma.
22 . The method according to claim 19 , wherein the non-Hodgkin's lymphoma is small lymphocytic lymphoma.
23 . The method according to claim 19 , wherein the non-Hodgkin's lymphoma is mucosa-associated lymphoid tissue.
24 . The method according to claim 19 , wherein the non-Hodgkin's lymphoma is diffuse large B cell lymphoma.
25 . The method according to claim 19 , wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma.
26 . The method according to claim 19 , wherein the non-Hodgkin's lymphoma is mantle cell lymphoma.
27 . The method according to claim 19 , wherein the antibody specific for CD19 and the Bruton's tyrosine kinase (BTK) inhibitor of said combination are administered separately.
28 . The method according to claim 19 , wherein the Bruton's tyrosine kinase (BTK) inhibitor of said combination is administered prior to administration of the antibody specific for CD19.
29 . The method according to claim 19 , wherein the antibody specific for CD19 and the Bruton's tyrosine kinase (BTK) inhibitor of said combination are administered simultaneously.
30 . The method according to claim 19 , wherein the antibody specific for CD19 and the Bruton's tyrosine kinase (BTK) inhibitor of said combination are administered at a time where both drugs are active in the patient at the same time.
31 . The method according to claim 19 , 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).
32 . The method according to claim 19 , wherein the antibody comprises a heavy chain constant domain of the sequence
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFP PKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT VVHQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL HNHYTQKSLSLSPGK (SEQ ID NO: 12).
33 . The method according to claim 31 , wherein the antibody comprises a heavy chain constant domain of the sequence
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFP PKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT VVHQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL HNHYTQKSLSLSPGK (SEQ ID NO: 12).
34 . The method according to claim 19 , wherein the antibody comprises a light chain constant domain of the sequence
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC. (SEQ ID NO: 13).
35 . The method according to claim 31 , wherein the antibody comprises a light chain constant domain of the sequence
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC. (SEQ ID NO: 13).
36 . The method according to claim 32 , wherein the antibody comprises a light chain constant domain of the sequence
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC. (SEQ ID NO: 13).
37 . The method according to claim 33 , wherein the antibody comprises a light chain constant domain of the sequence
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC. (SEQ ID NO: 13).