Treatment Paradigm for an Anti-CD19 Antibody Therapy

1 - 23 . (canceled)

24 : A method of treating a cancer in a human subject in need thereof, the method comprising administering to the human subject an anti-CD19 antibody, wherein the anti-CD19 antibody is administered at a dose of at least 24 mg/kg.

25 : The method of claim 24 , wherein the anti-CD19 antibody comprises a heavy chain variable region comprising an HCDR1 region comprising the sequence SYVMH (SEQ ID NO: 1), an HCDR2 region comprising the sequence NPYNDG (SEQ ID NO: 2), and an HCDR3 region comprising the sequence GTYYYGTRVFDY (SEQ ID NO: 3) and a light chain variable region comprising the sequence LCDR1 region comprising the sequence RSSKSLQNVNGNTYLY (SEQ ID NO: 4), an LCDR2 region comprising the sequence RMSNLNS (SEQ ID NO: 5), and an LCDR3 region comprising the sequence MQHLEYPIT (SEQ ID NO: 6).

26 : The method of claim 24 , wherein the anti-CD19 antibody comprises a heavy chain variable region comprising an HCDR1 region of SYVMH (SEQ ID NO: 1), an HCDR2 region of NPYNDG (SEQ ID NO: 2), and an HCDR3 region of GTYYYGTRVFDY (SEQ ID NO: 3) and a light chain variable region comprising an LCDR1 region of RSSKSLQNVNGNTYLY (SEQ ID NO: 4), an LCDR2 region of RMSNLNS (SEQ ID NO: 5), and an LCDR3 region of MQHLEYPIT (SEQ ID NO: 6).

27 : The method of claim 24 , wherein the anti-CD19 antibody comprises a heavy chain variable region of

(SEQ ID NO: 7)

EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIG

YINPYNDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCAR

GTYYYGTRVFDYWGQGTLVTVSS

and a light chain variable region of

(SEQ ID NO: 8)

DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSP

QLLIYRMSNLNSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLE

YPITFGAGTKLEIK.

28 : The method of claim 24 , wherein the anti-CD19 antibody comprises an Fc domain comprising an amino acid substitution at position S239 and/or 1332, wherein the numbering is according to the EU index as in Kabat.

29 : The method of claim 24 , wherein the anti-CD19 antibody comprises an Fc domain comprising an S239D amino acid substitution and an I332E amino acid substitution, wherein the numbering is according to the EU index as in Kabat.

30 : The method of claim 24 , wherein the anti-CD19 antibody comprises a heavy chain constant region of

(SEQ ID NO: 9)

ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSG

VHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV

EPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTCVVV

DVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDW

LNGKEYKCKVSNKALPAPEEKTISKTKGQPREPQVYTLPPSREEMTKNQ

VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

and a light chain constant region of

(SEQ ID NO: 10)

RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGEC.

31 : The method of claim 24 , wherein the anti-CD19 antibody comprises a heavy chain region of

(SEQ ID NO: 11)

EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIG

YINPYNDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCAR

GTYYYGTRVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS

LGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVF

LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK

PREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKALPAPEEKTISKT

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT

QKSLSLSPGK

and a light chain region of

(SEQ ID NO: 12)

DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSP

QLLIYRMSNLNSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLE

YPITFGAGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR

EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKV

YACEVTHQGLSSPVTKSFNRGEC.

32 : The method of claim 24 , wherein the anti-CD19 antibody is administered intravenously, by intravenous infusion or subcutaneously.

33 : The method claim 24 , wherein said dose reduces the dosing frequency from once weekly to at least once every two weeks.

34 : The method of claim 24 , wherein the cancer is a hematological malignancy.

35 : The method of claim 24 , wherein the cancer is a lymphoma or a leukemia.

36 : The method claim 24 , wherein the cancer is non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) or acute lymphoblastic leukemia (ALL).

37 : The method of claim 24 , wherein the cancer is Diffuse large B-cell lymphoma (DLBCL) or relapsed or refractory Diffuse large B-cell lymphoma (r/r DLBCL).

38 : The method of claim 24 , wherein the anti-CD19 antibody is administered once a week, once every two weeks or once every four weeks.

39 : The method of claim 24 , wherein the anti-CD19 antibody is administered at a dose in the range of between 24 mg/kg to 30 mg/kg.

40 : The method of any claim 24 , wherein the anti-CD19 antibody is administered at a dose of 24 mg/kg.

41 : The method of claim 24 , wherein the anti-CD19 antibody is administered at a dose of 30 mg/kg.

42 : The method of claim 24 , wherein the anti-CD19 antibody is administered in 28-day cycles, wherein on: a) days 1, 4 and 9 of the first cycle, a dose of 12 mg/kg is administered and on day 15 of the first cycle a dose of at least 24 mg/kg is administered; b) days 1 and 15 of cycles 2-3, a dose of at least 24 mg/kg is administered; and c) day 1 of further subsequent cycles, a dose of at least 24 mg/kg is administered.

43 : The method of claim 24 , wherein the anti-CD19 antibody is administered in 28-day cycles, wherein on: a) days 1, 4 and 9 of the first cycle, a dose of 12 mg/kg is administered and on day 15 of the first cycle a dose in the range of between 24 mg/kg to 30 mg/kg is administered; b) days 1 and 15 of cycles 2-3, a dose in the range of between 24 mg/kg to 30 mg/kg is administered; and c) day 1 of further subsequent cycles, a dose in the range of between 24 mg/kg to 30 mg/kg is administered.

44 : The method of claim 24 , wherein the anti-CD19 antibody is administered in 28-day cycles, wherein on: a) days 1, 4 and 9 of the first cycle, a dose of 12 mg/kg is administered and on day 15 of the first cycle a dose of 24 mg/kg is administered; b) days 1 and 15 of cycles 2-3, a dose of 24 mg/kg is administered; and c) day 1 of further subsequent cycles, a dose of 24 mg/kg is administered.

45 : The method of claim 24 , wherein the anti-CD19 antibody is administered in 28-day cycles, wherein on: a) days 1, 4 and 9 of the first cycle, a dose of 12 mg/kg is administered and on day 15 of the first cycle a dose of 30 mg/kg is administered; b) days 1 and 15 of cycles 2-3, a dose of 30 mg/kg is administered; and c) day 1 of further subsequent cycles, a dose of 30 mg/kg is administered.

46 : The method of claim 24 , wherein the anti-CD19 antibody is administered in combination with lenalidomide.