Therapeutic antibody formulation

Abstract

Stable aqueous pharmaceutical formulations for therapeutic antibodies and methods of using such stable aqueous pharmaceutical formulations.

1 - 9 . (canceled) 
     
     
         10 . A method of treating RA, Ps, GenPs, Pruritus, AS, PA, PPP, HS or MM comprising administering to a patient in need thereof an effective amount of a bufferless aqueous pharmaceutical formulation comprising:
 (i) an anti-IL-17A antibody at a concentration of 80 mg/mL+/−10%;   (ii) sucrose in a concentration of 234 mM+/−10%; and   (iii) a surfactant in a concentration of between 0.005% w/v+/−10% to 0.05% w/v+/−10%,   wherein, the pharmaceutical formulation is an aqueous solution at a pH between 5.2 to 6.5 and the anti-IL17A antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the LCVR comprises complementarity determining regions (CDRs) LCDR1, LCDR2, and LCDR3 and the HCVR comprises CDRs HCDR1, HCDR2, and HCDR3, wherein:   LCDR1 comprises the amino acid sequence of SEQ ID NO. 1,   LCDR2 comprises the amino acid sequence of SEQ ID NO. 2,   LCDR3 comprises the amino acid sequence of SEQ ID NO. 3,   HCDR1 comprises the amino acid sequence of SEQ ID NO. 4,   HCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and   HCDR3 comprises the amino acid sequence of SEQ ID NO. 6.   
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 10 , comprising:
 administering subcutaneously, to the patient, an initial dose of the pharmaceutical formulation, on day 0, followed by administering subcutaneously the pharmaceutical formulation to the patient at every four week interval thereafter,   wherein the initial dose of the pharmaceutical formulation comprises the anti-IL17A antibody at a concentration of about 160 mg, and the pharmaceutical formulation administered to the patient at every four week interval after the initial dose comprises the anti-IL17A antibody at a concentration of about 80 mg/mL.   
     
     
         13 . The method of  claim 12 , wherein the initial dose of the pharmaceutical formulation, comprising the anti-IL-17A antibody at a concentration of about 160 mg, comprises two doses of the pharmaceutical formulation wherein each of the two doses comprises about 80 mg of the anti-IL17A antibody. 
     
     
         14 . The method of  claim 10 , comprising:
 administering subcutaneously, to the patient, an initial dose of the pharmaceutical formulation, on day 0, followed by administering subcutaneously the pharmaceutical formulation to the patient at every two week interval thereafter,   wherein the initial dose of the pharmaceutical formulation comprises the anti-IL17A antibody at a concentration of about 160 mg, and the pharmaceutical formulation administered to the patient at every two week interval after the initial dose comprises the anti-IL17A antibody at a concentration of about 80 mg/mL.   
     
     
         15 . The method of  claim 14 , wherein the initial dose of the pharmaceutical formulation, comprising the anti-IL-17A antibody at a concentration of about 160 mg, comprises two doses of the pharmaceutical formulation wherein each of the two doses comprises about 80 mg of the anti-IL17A antibody. 
     
     
         16 . The method of  claim 10 , comprising:
 administering subcutaneously, to the patient, an initial dose of the pharmaceutical formulation, on day 0, followed by administering subcutaneously the pharmaceutical formulation to the patient on each of days 14, 28, 42, 56, 70 and 84, and followed by administering subcutaneously the pharmaceutical formulation to the patient at every four week interval thereafter,   wherein the initial dose of the pharmaceutical formulation comprises the anti-IL17A antibody at a concentration of about 160 mg and,   wherein the pharmaceutical formulation, administered to the patient at each of days 14, 28, 42, 56, 70 and 84, and every four week interval thereafter, comprises the anti-IL17A antibody at a concentration of about 80 mg/mL.   
     
     
         17 . The method of  claim 16 , wherein the initial dose of the pharmaceutical formulation, comprising the anti-IL-17A antibody at a concentration of about 160 mg, comprises two doses of the pharmaceutical formulation wherein each of the two doses comprises about 80 mg of the anti-IL17A antibody. 
     
     
         18 . A method of reducing injection-associated pain experienced by a patient at the time of, or shortly after, SQ, IP and/or IM administration of an aqueous pharmaceutical formulation comprising an anti-IL17A antibody, the method comprising administering to a patient a bufferless aqueous pharmaceutical formulation comprising:
 (i) an anti-IL-17A antibody at a concentration of 80 mg/mL+/−10%;   (ii) sucrose in a concentration of 234 mM+/−10%; and   (iii) a surfactant in a concentration of between 0.005% w/v+/−10% to 0.05% w/v+/−10%,   wherein, the pharmaceutical formulation is an aqueous solution at a pH between 5.2 to 6.5 and the anti-IL17A antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the LCVR comprises complementarity determining regions (CDRs) LCDR1, LCDR2, and LCDR3 and the HCVR comprises CDRs HCDR1, HCDR2, and HCDR3, wherein:   LCDR1 comprises the amino acid sequence of SEQ ID NO. 1,   LCDR2 comprises the amino acid sequence of SEQ ID NO. 2,   LCDR3 comprises the amino acid sequence of SEQ ID NO. 3,   HCDR1 comprises the amino acid sequence of SEQ ID NO. 4,   HCDR2 comprises the amino acid sequence of SEQ ID NO. 5, and   HCDR3 comprises the amino acid sequence of SEQ ID NO. 6,   wherein, said step of administering provides a therapeutically favorable level of injection-associated pain.   
     
     
         19 . The method of  claim 18 , wherein the therapeutically favorable level of injection-associated pain comprises a VAS score of less than 30 mm or less than 20 mm. 
     
     
         20 . The method of  claim 18 , wherein the pharmaceutical formulation of claim  1  is substantially free of an ionic tonicity excipient and is substantially free of L-amino acid excipients and the surfactant of the pharmaceutical formulation is polysorbate 80, and wherein the LCVR comprises the amino acid sequence of SEQ ID NO. 7 and the HCVR comprises the amino acid sequence of SEQ ID NO. 8. 
     
     
         21 . The method of  claim 10 , wherein the surfactant is polysorbate 20 or polysorbate 80. 
     
     
         22 . The method of  claim 21 , wherein the surfactant is polysorbate 80. 
     
     
         23 . The method of  claim 10 , wherein the pharmaceutical formulation is substantially free of ionic tonicity excipient. 
     
     
         24 . The method of  claim 10 , wherein the pharmaceutical formulation is substantially free of L-amino acid excipients. 
     
     
         25 . The method of  claim 10 , wherein the LCVR comprises the amino acid sequence of SEQ ID NO. 7 and the HCVR comprises the amino acid sequence of SEQ ID NO. 8. 
     
     
         26 . The method of  claim 10 , wherein anti-IL17A antibody comprises a light chain (LC) and a heavy chain (HC), wherein the LC comprises the amino acid sequence of SEQ ID NO. 9 and the HC comprises the amino acid sequence of SEQ ID NO. 10. 
     
     
         27 . The method of  claim 26 , wherein the anti-IL17A antibody is ixekizumab. 
     
     
         28 . The method of  claim 10 , wherein the surfactant is polysorbate 80, the pharmaceutical formulation is substantially free of ionic tonicity excipient and is substantially free of L-amino acid excipients, and wherein the LCVR comprises the amino acid sequence of SEQ ID NO. 7 and the HCVR comprises the amino acid sequence of SEQ ID NO. 8.