COMPOSITIONS AND METHODS FOR TREATING SYNUCLEINOPATHIES
The present invention relates to stable and low viscosity liquid pharmaceutical compositions comprising antibodies binding to human alpha synuclein and to methods for use of antibodies binding to human alpha synuclein for treating synucleinopathies or prodromal synucleinopathy, incl. suitable doses and/or dosing regimens. These antibodies for use in treatment of synucleinopathies or prodromal synucleinopathy may be formulated in the stable and low viscosity liquid pharmaceutical compositions of the invention.
1 - 26 . (canceled)
27 . A liquid pharmaceutical composition comprising a full length IgG1 monoclonal anti-alpha synuclein antibody in a concentration of 25-225 mg/mL, wherein said antibody comprises:
a. a Heavy Chain CDR1 having the amino acid sequence of SEQ ID NO:1;
b. a Heavy Chain CDR2 having the amino acid sequence of SEQ ID NO:34;
c. a Heavy Chain CDR3 having the amino acid sequence of SEQ ID NO:3;
d. a Light Chain CDR1 having the amino acid sequence of SEQ ID NO:4;
e. a Light Chain CDR2 having the amino acid sequence of SEQ ID NO:5; and
f. a Light Chain CDR3 having the amino acid sequence of SEQ ID NO:6;
and wherein the composition further comprises histidine buffer, a pharmaceutically acceptable tonicity agent, a pharmaceutically acceptable surfactant and wherein the pH of the composition is between 5.5 to 6.5.
28 . The liquid pharmaceutical composition of claim 27 , wherein the tonicity agent is selected from Mannitol, Sorbitol, Lactose, Dextrose, Trehalose, Sodium Chloride (NaCl), Potassium Chloride (KCl), Glycerol or Glycerine.
29 . The liquid pharmaceutical composition according to claim 27 , wherein the tonicity agent is Sodium Chloride (NaCl).
30 . The liquid pharmaceutical composition according to claim 27 , wherein the tonicity agent is Sodium Chloride (NaCl) in a concentration of about 100 mM.
31 . The liquid pharmaceutical composition according to claim 27 , wherein the surfactant is selected from Polysorbate 20, Polysorbate 80, Poloxamer 188 or Triton X-100.
32 . The liquid pharmaceutical composition according to claim 27 , wherein the surfactant is Polysorbate 80 in an amount of about 0.02%.
33 . The liquid pharmaceutical composition according to claim 27 , wherein the concentration of the histidine buffer is about 25 mM.
34 . The liquid pharmaceutical composition according to claim 27 , wherein the pHis 6.0.
35 . The liquid pharmaceutical composition according to claim 27 , wherein the monoclonal anti-alpha synuclein antibody concentration is about 30-220 mg/mL.
36 . The liquid pharmaceutical composition according to claim 27 , wherein the monoclonal anti-alpha synuclein antibody concentration is about 45-55 mg/mL.
37 - 38 . (canceled)
39 . The liquid pharmaceutical composition according to claim 27 , wherein the composition further comprises at least one bulking agent selected from Sucrose, Trehalose, Glucose, Lactose, Sorbitol, Mannitol, Glycerol, Arginine, Aspartic Acid, Glutamic acid, Glutamate, Lysine, Glycine, Histidine, Methionine, Alanine, Gelatin, PVP, PLGA, PEG, dextran, cyclodextrin and derivatives, starch derivatives, HSA or BSA.
40 . The liquid pharmaceutical composition according to claim 39 , wherein the bulking agent is Arginine, Glutamate, Sucrose, Glycine or Sorbitol in a concentration of 100-200 mM.
41 . (canceled)
42 . The liquid pharmaceutical composition according to claim 27 , comprising 53±5 mg/mL of the monoclonal anti-alpha synuclein antibody, 1.40 mg/mL L-Histidine, 3.34 mg/mL L-Histidine monohydrochloride, 34.16 mg/mL Sucrose, 5.83 mg/mL sodium chloride (NaCl), 0.20 mg/mL polysorbate 80 at pH 6.0.
43 . (canceled)
44 . The liquid pharmaceutical composition according to claim 27 , comprising 53 mg/mL of the monoclonal anti-alpha synuclein antibody, 25 mM histidine buffer, 100 mM Sucrose, 100 mM sodium chloride (NaCl) or having amounts of each constituent within +/−20% of said values and 0.02% polysorbate 80 or having a concentration within +/−30% of said concentration, and having a pH of 6.0 or within +/−20% of said value.
45 . (canceled)
46 . The liquid pharmaceutical composition according to claim 27 , wherein said liquid pharmaceutical composition is a stable liquid pharmaceutical composition.
47 . The liquid pharmaceutical composition according to claim 27 , wherein said liquid pharmaceutical composition is a stable for at least 12 months when stored at 5° C.±3° C.
48 . The liquid pharmaceutical composition according to claim 27 , wherein said liquid pharmaceutical composition is a stable for at least 24 months when stored at 5° C.±3° C.
49 . The liquid pharmaceutical composition according to claim 27 , wherein said liquid pharmaceutical composition is a stable for at least 36 months when stored at 5° C.±3° C.
50 . The liquid pharmaceutical composition according to claim 27 , wherein said liquid pharmaceutical composition is a low viscosity liquid pharmaceutical composition.
51 . The liquid pharmaceutical composition according to claim 27 , wherein said liquid pharmaceutical composition is a low viscosity liquid pharmaceutical composition having a viscosity below 20 cP.
52 . The liquid pharmaceutical composition according to claim 27 , wherein said liquid pharmaceutical composition is a low viscosity liquid pharmaceutical composition having a viscosity below 10 cP.
53 . (canceled)
54 . The liquid pharmaceutical composition according to claim 27 , wherein said antibody comprises a heavy chain consisting of a variable domain of SEQ ID NO:31 and a light chain consisting of a variable domain of SEQ ID NO:8.
55 . The liquid pharmaceutical composition according to claim 27 , wherein said antibody comprises a constant heavy chain domain as defined in SEQ ID NO:18 and a kappa light chain constant domain as defined in SEQ ID NO:17.