JPWO2019186273A5 - - Google Patents

Claims (17)

A therapeutic agent for relapsed / refractory multiple myeloma, which comprises an isolated human anti-CD38 antibody, wherein the anti-CD38 antibody comprises the amino acid of CDR1, SEQ ID NO: 4 having the amino acid sequence of SEQ ID NO: 3. A variable weight (VH) chain region containing CDR2 having a sequence and CDR3 having an amino acid sequence of SEQ ID NO: 5, CDR1 having an amino acid sequence of SEQ ID NO: 6, CDR2 having an amino acid sequence of SEQ ID NO: 7, and SEQ ID NO: 8 An agent comprising a variable light (VL) chain region comprising CDR3 having the amino acid sequence of, wherein the agent is subcutaneously administered to a subject at a dosage of 45 to 1,800 milligrams as the antibody . The agent according to claim 1, wherein the administration of the anti-CD38 antibody does not cause hemolytic anemia or thrombocytopenia. Administration of the anti-CD38 antibody is selected from the group consisting of anemia, hemolytic anemia, thrombocytopenia, fatigue, infusion-related reactions (IRR), leukopenia, and lymphopenia, grade 3 or 4. The agent according to claim 1 or 2 , which results in an incidence of less than 30% of one or more treatment-related adverse events (TRAEs) or therapeutically manifested adverse events (TEAEs). The anti-CD38 antibody is depleted of less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1% of RBC. The agent according to any one of claims 1 to 3 . The anti-CD38 antibody is depleted of less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1% of platelets. The agent according to any one of claims 1 to 4 . The agent according to any one of claims 1 to 5 , wherein the VH chain region has the amino acid sequence of SEQ ID NO: 9, and the VL chain region has the amino acid sequence of SEQ ID NO: 10. The agent according to any one of claims 1 to 6 , wherein the anti-CD38 antibody comprises a heavy chain amino acid sequence of SEQ ID NO: 11 and a light chain amino acid sequence of SEQ ID NO: 12. The antibody is 135 to 1,800 mg, 600 to 1,800 mg, 1,200 to 1,800 mg, 45 to 1,200 mg, 45 to 600 mg, 45 to 135 mg, 135 to 1,200 mg. , 135-600 mg, or 1,200-1,800 mg, according to any one of claims 1-7 . The agent according to any one of claims 1 to 8 , which is in the form of a pharmaceutically acceptable composition. The agent according to any one of claims 1 to 9 , wherein the dosage is a one-week dosage. A unit dosage form comprising an isolated antibody comprising a heavy chain variable region comprising SEQ ID NO: 9 and a light chain variable region comprising SEQ ID NO: 10, wherein the isolated antibody binds to CD38. And, without binding to human erythrocytes, the unit dosage form is formulated for subcutaneous administration at a dosage of 45 to 1,800 milligrams of the antibody, and the unit dosage form is recurrent / refractory multiple occurrences. The unit dosage form formulated for subcutaneous administration of the antibody in the treatment of sex myeloma. The unit dosage form is 135 to 1,800 mg, 600 to 1,800 mg, 1,200 to 1,800 mg, 45 to 1,200 mg, 45 to 600 mg, 45 to 135 mg, 135 of the antibody. 11. The unit dosage form of claim 11, formulated for subcutaneous administration at a dosage of ~ 1,200 milligrams, 135-600 milligrams, or 1,200-1,800 milligrams. The unit dosage form of claim 11 or 12, wherein the isolated antibody comprises a heavy chain comprising SEQ ID NO: 11 and a light chain comprising SEQ ID NO: 12. The unit dosage form according to claim 11 or 12, wherein the anti-CD38 antibody does not cause hemolytic anemia or thrombocytopenia. The anti-CD38 antibody is depleted of less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1% of RBC. The unit dosage form according to any one of claims 11 to 14, which results in the above-mentioned. The anti-CD38 antibody is depleted of less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1% of platelets. The unit dosage form according to any one of claims 11 to 15, which results in the above-mentioned. The unit dosage form according to any one of claims 11 to 16, wherein the dosage is a one-week dosage.