Patent application EP20163014A (EP), filed 2020-03-13
Publication number: EP3714902A1
Title: STABILIZATION OF PHARMACEUTICAL COMPOSITIONS COMPRISING POLYSORBATE
Abstract: The present invention relates to stabilized pharmaceutical compositions comprising an improved histidine-based buffer system that reduces the degradation of polysorbates.
IPC codes: A61K  31/    00            A I
A61K  39/    00            A I
A61K  47/    18            A I
A61K  47/    26            A I
A61K   9/    00            A I
A61K   9/    08            A I
Claims: number: 1
text: A stabilized pharmaceutical composition comprising an active agent, polysorbate, and a histidine buffer consisting of histidine and a histidine buffer salt, wherein the histidine buffer salt is selected from the group consisting of histidine malate, histidine maleate, histidine fumarate, histidine tartrate, histidine citrate, histidine phosphate, histidine lactate, and mixtures thereof.
number: 2
text: The stabilized pharmaceutical composition of claim 1, wherein the polysorbate is selected from the group consisting of polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, polysorbate 81, polysorbate 85, polysorbate 120, and mixtures thereof.
number: 3
text: The stabilized pharmaceutical composition of claims 1 or 2, comprising the polysorbate in a concentration of from about 0.0001% (w/v) to about 1.0% (w/v), preferably in a concentration of from about 0.01% (w/v) to about 0.25% (w/v).
number: 4
text: The stabilized pharmaceutical composition of any one of the preceding claims, comprising the histidine buffer salt in a concentration of from about 1 mM to about 200 mM, preferably in a concentration of from about 5 mM to about 100 mM, more preferably from about 10 mM to about 50 mM, most preferably in a concentration of about 20 mM.
number: 5
text: The stabilized pharmaceutical composition of any one of the preceding claims, wherein the pH of the composition is from about pH 4.0 to about pH 8.5, preferably from about pH 5.5 to about pH 7.0.
number: 6
text: The stabilized pharmaceutical composition of any one of the preceding claims, wherein the composition comprises a therapeutically effective amount of the active agent.
number: 7
text: The stabilized pharmaceutical composition of any one of the preceding claims, wherein the active agent is a protein, preferably a monoclonal or a polyclonal antibody, or an antigen-binding fragment thereof.
number: 8
text: The stabilized pharmaceutical composition of any one of the preceding claims, wherein the buffering salt is not histidine chloride or histidine acetate.
number: 9
text: The stabilized pharmaceutical composition of any one of the preceding claims, wherein the composition is a liquid composition or a lyophilized composition, preferably a liquid composition.
number: 10
text: The stabilized pharmaceutical composition of any one of the preceding claims, for intravenous, subcutaneous or intramuscular administration, preferably for intravenous or subcutaneous administration.
number: 11
text: The pharmaceutical composition of any one of the preceding claims, wherein the polysorbate degradation is reduced relative to the same composition comprising histidine chloride as the histidine buffer salt.
number: 12
text: The pharmaceutical composition of claim 11, wherein the polysorbate ester hydrolysis is reduced relative to the same composition comprising histidine chloride as the histidine buffer salt.
number: 13
text: A method for preparing a stabilized pharmaceutical composition, which comprises including a histidine buffer consisting of histidine and a histidine buffer salt into a pharmaceutical composition comprising an active agent and polysorbate, wherein the histidine buffer salt is selected from the group consisting of histidine malate, histidine maleate, histidine fumarate, histidine tartrate, histidine citrate, histidine phosphate, histidine lactate, and mixtures thereof.
number: 14
text: Use of a histidine buffer salt selected from the group consisting of histidine malate, histidine maleate, histidine fumarate, histidine tartrate, histidine citrate, histidine phosphate, histidine lactate, and mixtures thereof, for stabilizing polysorbate in a pharmaceutical composition comprising a histidine buffer consisting of histidine and a histidine buffer salt, preferably in a liquid pharmaceutical composition.
Office action: search_report, dated 2020-09-30
Rejection reasons: novelty_epc_54
Prior art cited: ref_id: - "Remington 's Pharmaceutical Sciences", 1980
ref_type: npl
severity: background
ref_id: - HEWITT, D. ET AL., J. CHROMATOGR. A, vol. 1218, 2011, pages 2138 - 2145
ref_type: npl
severity: background
ref_id: WO2019106206A1
ref_type: patent
severity: background
ref_id: EP3156071A1
ref_type: patent
severity: background
ref_id: EP3607969A1
ref_type: patent
severity: background
ref_id: WO2018060210A1
ref_type: patent
severity: background
ref_id: EP3156071
ref_type: patent
severity: novelty_destroying
ref_id: WO2018060210
ref_type: patent
severity: novelty_destroying
ref_id: WO2019106206
ref_type: patent
severity: novelty_destroying
ref_id: EP3607969
ref_type: patent
severity: novelty_destroying
Final disposition: pending (2020-09-30)