Anti-CD19 antibody formulations
The present disclosure describes a pharmaceutical formulation of an anti-CD19 antibody.
1. A lyophilized pharmaceutical formulation comprising an anti-CD19 antibody,
wherein the lyophilized pharmaceutical formulation is stable at 2-8° C. for at least 24 months,
wherein the formulation prior to lyophilization comprises a buffer with a pH range of about 5.6 to about 7.0 in a concentration of between 10 and 75 mM,
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; and
the anti-CD19 antibody in a concentration of 20 mg/ml to 125 mg/ml,
wherein the anti-CD19 antibody comprises a 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
wherein the anti-CD19 antibody comprises a heavy chain constant domain of the sequence ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVV HQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGK (SEQ ID NO:8) and a light chain constant domain of the sequence RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:9).
2. The formulation of claim 1 , wherein the formulation prior to lyophilization comprises the anti-CD19 antibody in a concentration of 40 mg/ml.
3. The formulation of claim 1 , wherein the buffer is a citrate buffer or a phosphate buffer.
4. The formulation of claim 3 , wherein the formulation prior to lyophilization comprises the citrate buffer or the phosphate buffer in a concentration of between 20 and 50 mM.
5. The formulation of claim 3 , wherein the formulation prior to lyophilization comprises the citrate buffer or the phosphate buffer in a concentration of 25 mM.
6. The formulation of claim 1 , wherein the formulation prior to lyophilization comprises trehalose in a concentration of 200 mM.
7. The formulation of claim 1 , wherein the formulation prior to lyophilization comprises mannitol in a concentration of 219 mM and sucrose in a concentration of 29 mM.
8. The formulation of claim 1 , wherein the polysorbate is polysorbate 20.
9. The formulation of claim 1 , wherein the formulation prior to lyophilization comprises polysorbate in a concentration of 0.02% (w/v).
10. The formulation of claim 1 , wherein the anti-CD19 antibody comprises a variable heavy chain of the sequence EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGYINPYNDGTKYNEKF QGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGTYYYGTRVFDYWGQGTLVTVSS (SEQ ID NO:10) and a variable light chain of the sequence DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQLLIYRMSNLNSGVP DRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYPITFGAGTKLEIK (SEQ ID NO:11).
11. The formulation of claim 1 , wherein the formulation prior to lyophilization comprises the anti-CD19 antibody in a concentration of 40 mg/mL, a citrate buffer in a concentration of 25 mM, trehalose in a concentration of 200 mM, polysorbate in a concentration of 0.02% (w/v), and has a pH of 6.0.
12. The formulation of claim 1 , wherein the formulation prior to lyophilization comprises 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, polysorbate in a concentration of 0.02% (w/v), and has a pH of 6.0.