Anti-CD19 antibody formulations
The present disclosure describes a pharmaceutical formulation of an anti-CD19 antibody.
1 . A solution comprising:
an anti-CD19 antibody in a concentration of 20 mg/ml to 125 mg/ml, wherein the anti-CD19 antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1 region of sequence SYVMH (SEQ ID NO: 1), an HCDR2 region of sequence NPYNDG (SEQ ID NO:2), and an HCDR3 region of sequence GTYYYGTRVFDY (SEQ ID NO:3), and wherein the light chain variable region comprises 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);
a buffer;
polysorbate in a concentration of 0.005% (w/v) to 0.06% (w/v); and
a) trehalose in a concentration of 180 mM to 240 mM; or
b) mannitol in a concentration of 180 mM to 240 mM and sucrose in a concentration of 10 mM to 50 mM.
2 . The solution of claim 1 , wherein the buffer has a pH range of 5.6 to 7.0.
3 . The solution of claim 1 , wherein the buffer has a pH range of 6.
4 . The solution of claim 1 , wherein the buffer is a citrate buffer or a phosphate buffer.
5 . The solution of claim 4 , wherein the citrate buffer or the phosphate buffer is in a concentration of between 20 and 50 mM.
6 . The solution of claim 4 , wherein the citrate buffer or the phosphate buffer is in a concentration of 25 mM.
7 . The solution of claim 1 comprising trehalose in a concentration of 200 mM.
8 . The solution of claim 1 comprising mannitol in a concentration of 219 mM and sucrose in a concentration of 29 mM.
9 . The solution of claim 1 , wherein the polysorbate is polysorbate 20.
10 . The solution of claim 1 comprising polysorbate in a concentration of 0.02% (w/v).
11 . The solution of claim 1 comprising said anti-CD19 antibody in an amount of 40 mg/ml, citrate buffer in a concentration of 25 mM, trehalose in a concentration of 200 mM, and polysorbate in a concentration of 0.02% (w/v), wherein the polysorbate is polysorbate 20, and wherein said solution has a pH of 6.0.
12 . The solution of claim 1 comprising the anti-CD19 antibody in a concentration of 40 mg/mL, a citrate buffer in a concentration of 25 mM, mannitol in a concentration of 219 mM, sucrose in a concentration of 29 mM, and polysorbate in a concentration of 0.02% (w/v), wherein the polysorbate is polysorbate 20, and wherein said solution has a pH of 6.0.
13 . The solution of claim 1 , wherein said anti-CD19 antibody comprises a heavy chain constant domain of the sequence ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG PDVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQF NSTFRVVSVLTVVHQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:8) and a light chain constant domain of the sequence RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQ DSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:9).
14 . The solution of claim 13 , wherein the heavy chain variable region comprises the sequence EVOLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHVWRQAPGKGLEWIGYINPYNDGT KYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGTYYYGTRVFDYWGQGTL VTVSS (SEQ ID NO: 10) and the light chain variable region comprises the sequence DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQLLIYRMSNL NSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYPITFGAGTKLEIK (SEQ ID NO: 11).
15 . The solution of claim 1 , wherein the heavy chain variable region comprises the sequence EVOLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHVWRQAPGKGLEWIGYINPYNDGT KYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGTYYYGTRVFDYWGQGTL VTVSS (SEQ ID NO: 10) and the light chain variable region comprises the sequence DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQLLIYRMSNL NSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYPITFGAGTKLEIK (SEQ ID NO: 11).
16 . The solution of claim 11 , wherein the heavy chain variable region comprises the sequence EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHVWRQAPGKGLEWIGYINPYNDGT KYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGTYYYGTRVFDYWGQGTL VTVSS (SEQ ID NO: 10) and the light chain variable region comprises the sequence DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQLLIYRMSNL NSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYPITFGAGTKLEIK (SEQ ID NO: 11).
17 . The solution of claim 16 , wherein said anti-CD19 antibody comprises a heavy chain constant domain of the sequence ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG PDVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQF NSTFRVVSVLTVVHQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:8) and a light chain constant domain of the sequence RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQ DSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:9).