Biopharmacuetical Compositions and Related Methods
The invention described herein provides compositions comprising anti-BCMA antigen binding proteins and related methods for treating BCMA mediated diseases or disorders.
1 .- 56 . (canceled)
57 . A composition comprising anti-BCMA antibodies, wherein the anti-BCMA antibodies comprise a belantamab variant, wherein the belantamab variant comprises one or more of:
a. deamidation of a residue selected from the group consisting of N388 and N393 of SEQ ID NO:9;
b. oxidation at a residue selected from the group consisting of M34, M256, and M432 of SEQ ID NO:9;
c. an amino acid change of aspartic acid (D) to asparagine (N) at residue 103 of SEQ ID NO:9;
d. C-terminal lysine cleavage; or
e. N-terminal conversion of glutamine to pyroglutamic acid.
58 . The composition of claim 57 , wherein 0.1-40% of antibodies in the composition comprise the oxidation.
59 . The composition of claim 57 , wherein 0.1-25% of the antibodies comprise the amino acid change.
60 . The composition of claim 58 , wherein the oxidation is at residue M34 of SEQ ID NO:9.
61 . The composition of claim 59 , wherein the anti-BCMA antibodies comprise an anti-BCMA antibody comprising (i) a heavy chain amino acid sequence that is at least about 90% identical to the heavy chain amino acid sequence of SEQ ID NO:9 and (ii) the light chain amino acid sequence of SEQ ID NO:10.
62 . The composition of claim 60 , wherein the anti-BCMA antibodies comprise an anti-BCMA antibody comprising (i) a heavy chain amino acid sequence that is at least about 90% identical to the heavy chain amino acid sequence of SEQ ID NO:9 and (ii) the light chain amino acid sequence of SEQ ID NO:10.
63 . The composition according to claim 57 , wherein 0.1-100% of the belantamab variant in the composition comprises oxidation at residue M256.
64 . The composition according to claim 57 , wherein 0.1-100% of the belantamab variant in the composition comprises oxidation at residue M432.
65 . The composition according to claim 57 , wherein 0.1-100% of the belantamab variant in the composition comprises at least one selected from the group consisting of:
a. deamidation of a residue selected from the group consisting of N388 and N393 of SEQ ID NO:9;
b. oxidation at a residue selected from the group consisting of M34, M256, and M432 of SEQ ID NO:9;
c. an amino acid change of aspartic acid (D) to asparagine (N) at residue 103 of SEQ ID NO:9;
d. C-terminal lysine cleavage; or
e. N-terminal conversion of glutamine to pyroglutamic acid.
66 . The composition according to claim 57 , wherein the composition comprises any percentage of glycoforms G0, G1, G2, G0-GlcNac or G0-2GlcNac.
67 . The composition according to claim 57 , which comprises belantamab.
68 . The composition according to claim 57 , which comprises belantamab mafodotin.
69 . The composition according to claim 57 , wherein an anti-BCMA antibody is conjugated to a cytotoxic agent to form an antibody-drug-conjugate.
70 . The composition of claim 69 , wherein percent DL2 is at least about 30%, about 15% to about 27%, or about 15% to about 32%; percent DL4a is at least about 30%, about 35% to about 38%, or about 30% to about 40%; percent DL4b is at least about 5%, about 7% to about 9%, or about 5% to about 10%; percent DL6 is at least about 10%, about 14% to about 20%, or about 10% to about 20%; and/or DL8 is at least about 1%, about 6.0% to about 12.0%, or about 4% to about 15%.
71 . The composition of claim 69 , wherein the average DAR is about 3.4 to about 4.6.
72 . The composition of claim 69 , wherein percent DL0 is less than or equal to about 10% or about 5%.
73 . A pharmaceutical composition comprising the composition of claim 57 and at least one pharmaceutically acceptable excipient.
74 . A formulation comprising the pharmaceutical composition of claim 73 comprising an anti-BCMA antigen binding protein at about 20 mg/mL to about 60 mg/mL, citrate buffer at about 10 mM to about 30 mM, trehalose at about 120 mM to about 240 mM, EDTA at about 0.01 mM to about 0.1 mM, polysorbate 20 or polysorbate 80 at about 0.01% to about 0.05%, at a pH of about 5.9 to about 6.5.
75 . The formulation of claim 74 , comprising about 20 mg/mL, about 25 mg/mL, about 50 mg/mL, or about 60 mg/mL belantamab mafodotin, 25 mM citrate buffer, 200 mM trehalose, 0.05 mM disodium EDTA, 0.02% polysorbate 20 or polysorbate 80, at a pH of about 5.9 to about 6.5.
76 . A method of treating cancer in a subject in need thereof, the method comprising:
administering to the subject a therapeutically effective amount of the composition of claim 57 .