AR083338A1 - STABILIZED FORMULATIONS CONTAINING ANTI-RECEIVER ANTIBODIES OF INTERLEUCINE-4 (IL-4R) - Google Patents

STABILIZED FORMULATIONS CONTAINING ANTI-RECEIVER ANTIBODIES OF INTERLEUCINE-4 (IL-4R)

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Publication number
AR083338A1
AR083338A1 ARP110103663A AR083338A1 AR 083338 A1 AR083338 A1 AR 083338A1 AR P110103663 A ARP110103663 A AR P110103663A AR 083338 A1 AR083338 A1 AR 083338A1
Authority
AR
Argentina
Prior art keywords
seq
pharmaceutical formulation
liquid pharmaceutical
buffer
concentration
Prior art date
Application number
Other languages
Spanish (es)
Original Assignee
Regeneron Pharma
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Regeneron Pharma filed Critical Regeneron Pharma
Publication of AR083338A1 publication Critical patent/AR083338A1/en

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Abstract

La presente proporciona formulaciones farmacéuticas que comprenden un anticuerpo humano que se une específicamente al receptor de interleucina-4 humano (hlL-4R). Las formulaciones pueden contener, además de un anticuerpo anti-hlL-4R, al menos un aminoácido, al menos un carbohidrato, o al menos un tensoactivo no iónico. Las formulaciones farmacéuticas de la presente exhiben un grado sustancial de estabilidad del anticuerpo después del almacenamiento durante varios meses.Reivindicación 1: Una formulación farmacéutica líquida que comprende: (i) un anticuerpo humano que se une específicamente al receptor de interleucina-4 a humano (hlL-4Ra); (ii) un tampón a un pH de 5,9 ± 0,5 unidades de pH; (iii) un codisolvente orgánico; (iv) un estabilizador térmico; y (v) un agente reductor de la viscosidad. Reivindicación 2: La formulación farmacéutica líquida de la reivindicación 1, en la que el anticuerpo está a una concentración de 150 mg/ml ± 50 mg/ml. Reivindicación 4: La formulación farmacéutica líquida de cualquiera de las reivindicaciones 1 - 3, en la que el tampón comprende un primer tampón que tiene un intervalo de pH efectivo de 3,6 - 5,6 y un segundo tampón que tiene un intervalo de pH efectivo de 5,5 - 7,4. Reivindicación 6: La formulación farmacéutica líquida de la reivindicación 5, en la que el primer tampón es acetato y el segundo tampón es histidina. Reivindicación 8: La formulación farmacéutica líquida de cualquiera de las reivindicaciones 1 - 7, en la que el codisolvente orgánico se selecciona del grupo que consiste en polisorbato 20, poloxámero 181 y polietilen glicol 3350. Reivindicación 9: La formulación farmacéutica líquida de cualquiera de las reivindicaciones 1 - 8, en la que el codisolvente orgánico está a una concentración de alrededor del 0,085% a alrededor del 1,15% p/v. Reivindicación 10: La formulación farmacéutica líquida de cualquiera de las reivindicaciones 1 - 9, en la que el codisolvente orgánico es polisorbato 20 a una concentración del 0,2% ± 0,03% p/v. Reivindicación 11: La formulación farmacéutica líquida de cualquiera de las reivindicaciones 1 - 10, en la que el estabilizador térmico se selecciona del grupo que consiste en sacarosa, manitol y trehalosa. Reivindicación 12: La formulación farmacéutica líquida de cualquiera de las reivindicaciones 1 - 11, en la que el estabilizador térmico está a una concentración de alrededor del 3,5% a alrededor del 11% p/v. Reivindicación 14: La formulación farmacéutica líquida de cualquiera de las reivindicaciones 1 - 13, en la que el agente reductor de la viscosidad está a una concentración que es menor de alrededor de 100 mM. Reivindicación 15: La formulación farmacéutica líquida de cualquiera de las reivindicaciones 1 - 14, en la que el agente reductor de la viscosidad es arginina a una concentración de 25 mM ± 3,75 mM ó 50 mM ± 7,5 mM. Reivindicación 26: La formulación farmacéutica líquida de la reivindicación 1, en la que dicho anticuerpo humano que se une específicamente a hlL-4R comprende una región variable de la cadena pesada (HCVR) y una región variable de la cadena ligera (LCVR), en la que (a) la HCVR comprende las regiones determinantes de la complementariedad de la cadena pesada HCDR1, HCDR2 y HCDR3 que comprenden la secuencia de aminoácidos de (i) SEQ ID Nº 2, SEQ ID Nº 3 y SEQ ID Nº 4, respectivamente, (ii) SEQ ID Nº 10, SEQ ID Nº 11 y SEQ ID Nº 12, respectivamente, o (iii) SEQ ID Nº 18, SEQ ID Nº 19 y SEQ ID Nº 20, respectivamente; y (b) la LCVR comprende las regiones determinantes de la complementariedad de la cadena ligera LCDR1, LCDR2 y LCDR3 que comprenden la secuencia de aminoácidos de (i) SEQ ID Nº 6, SEQ ID Nº 7 y SEQ ID Nº 8, respectivamente, (ii) SEQ ID Nº 14, SEQ ID Nº 15 y SEQ ID Nº 16, respectivamente, o (iii) SEQ ID Nº 22, SEQ ID Nº 23 y SEQ ID Nº 24, respectivamente.The present provides pharmaceutical formulations comprising a human antibody that specifically binds to the human interleukin-4 receptor (hlL-4R). The formulations may contain, in addition to an anti-hlL-4R antibody, at least one amino acid, at least one carbohydrate, or at least one non-ionic surfactant. The pharmaceutical formulations herein exhibit a substantial degree of antibody stability after storage for several months. Claim 1: A liquid pharmaceutical formulation comprising: (i) a human antibody that specifically binds to the human interleukin-4 receptor ( hlL-4Ra); (ii) a buffer at a pH of 5.9 ± 0.5 pH units; (iii) an organic co-solvent; (iv) a thermal stabilizer; and (v) a viscosity reducing agent. Claim 2: The liquid pharmaceutical formulation of claim 1, wherein the antibody is at a concentration of 150 mg / ml ± 50 mg / ml. Claim 4: The liquid pharmaceutical formulation of any one of claims 1-3, wherein the buffer comprises a first buffer having an effective pH range of 3.6-5.6 and a second buffer having a pH range cash of 5.5 - 7.4. Claim 6: The liquid pharmaceutical formulation of claim 5, wherein the first buffer is acetate and the second buffer is histidine. Claim 8: The liquid pharmaceutical formulation of any one of claims 1-7, wherein the organic cosolvent is selected from the group consisting of polysorbate 20, poloxamer 181 and polyethylene glycol 3350. Claim 9: The liquid pharmaceutical formulation of any of the claims 1-8, wherein the organic cosolvent is at a concentration of about 0.085% to about 1.15% w / v. Claim 10: The liquid pharmaceutical formulation of any one of claims 1-9, wherein the organic co-solvent is polysorbate 20 at a concentration of 0.2% ± 0.03% w / v. Claim 11: The liquid pharmaceutical formulation of any one of claims 1-10, wherein the thermal stabilizer is selected from the group consisting of sucrose, mannitol and trehalose. Claim 12: The liquid pharmaceutical formulation of any one of claims 1-11, wherein the thermal stabilizer is at a concentration of about 3.5% to about 11% w / v. Claim 14: The liquid pharmaceutical formulation of any of claims 1-13, wherein the viscosity reducing agent is at a concentration that is less than about 100 mM. Claim 15: The liquid pharmaceutical formulation of any one of claims 1-14, wherein the viscosity reducing agent is arginine at a concentration of 25 mM ± 3.75 mM or 50 mM ± 7.5 mM. Claim 26: The liquid pharmaceutical formulation of claim 1, wherein said human antibody that specifically binds hlL-4R comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR), in which (a) the HCVR comprises the regions determining the complementarity of the HCDR1, HCDR2 and HCDR3 heavy chain comprising the amino acid sequence of (i) SEQ ID No. 2, SEQ ID No. 3 and SEQ ID No. 4, respectively, (ii) SEQ ID No. 10, SEQ ID No. 11 and SEQ ID No. 12, respectively, or (iii) SEQ ID No. 18, SEQ ID No. 19 and SEQ ID No. 20, respectively; and (b) the LCVR comprises the regions determining the complementarity of the light chain LCDR1, LCDR2 and LCDR3 comprising the amino acid sequence of (i) SEQ ID No. 6, SEQ ID No. 7 and SEQ ID No. 8, respectively, ( ii) SEQ ID No. 14, SEQ ID No. 15 and SEQ ID No. 16, respectively, or (iii) SEQ ID No. 22, SEQ ID No. 23 and SEQ ID No. 24, respectively.

ARP110103663 2010-10-06 2011-10-03 STABILIZED FORMULATIONS CONTAINING ANTI-RECEIVER ANTIBODIES OF INTERLEUCINE-4 (IL-4R) AR083338A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US39028310P 2010-10-06 2010-10-06

Publications (1)

Publication Number Publication Date
AR083338A1 true AR083338A1 (en) 2013-02-21

Family

ID=45995014

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP110103663 AR083338A1 (en) 2010-10-06 2011-10-03 STABILIZED FORMULATIONS CONTAINING ANTI-RECEIVER ANTIBODIES OF INTERLEUCINE-4 (IL-4R)

Country Status (13)

Country Link
AR (1) AR083338A1 (en)
DK (2) DK2624865T3 (en)
ES (2) ES2820246T3 (en)
HK (1) HK1258305A1 (en)
HR (1) HRP20181822T1 (en)
HU (1) HUE052089T2 (en)
LT (1) LT2624865T (en)
PT (1) PT3354280T (en)
RS (1) RS57850B1 (en)
SI (1) SI2624865T1 (en)
TW (7) TWI568445B (en)
UA (1) UA111731C2 (en)
UY (1) UY33652A (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2690675C2 (en) 2012-08-21 2019-06-05 Санофи Байотекнолоджи Methods for treatment or prevention of asthma by administering il-4r antagonist
LT3010539T (en) * 2013-06-21 2019-10-10 Sanofi Biotechnology Methods for treating nasal polyposis by administering an il-4r antagonist
CA2915839A1 (en) * 2013-06-21 2014-12-24 Leda MANNENT Methods for treating nasal polyposis by administering an il-4r antagonist
CA2967602A1 (en) 2014-11-14 2016-05-19 Sanofi Biotechnology Methods for treating chronic sinusitis with nasal polyps by administering an il-4r antagonist
JP7315545B2 (en) 2017-10-30 2023-07-26 サノフィ・バイオテクノロジー Methods for treating or preventing asthma by administering an IL-4R antagonist

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7608693B2 (en) * 2006-10-02 2009-10-27 Regeneron Pharmaceuticals, Inc. High affinity human antibodies to human IL-4 receptor
ES2332082B1 (en) * 2008-07-24 2010-10-26 Consejo Superior De Investigaciones Cientificas (Csic) 45% PATTERN ALIGNMENT SYSTEM IN A SUBSTRATE BY LITOGRAPHY BY ESTENCIL.
WO2010029664A1 (en) * 2008-09-10 2010-03-18 日本エクスラン工業株式会社 Crosslinked acrylate-based fibers and the production thereof
PE20120359A1 (en) * 2009-03-06 2012-04-13 Genentech Inc FORMULATION WITH ANTIBODY

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Publication number Publication date
TWI679988B (en) 2019-12-21
TW202320851A (en) 2023-06-01
HRP20181822T1 (en) 2018-12-28
ES2687813T3 (en) 2018-10-29
UA111731C2 (en) 2016-06-10
TWI568445B (en) 2017-02-01
LT2624865T (en) 2018-10-25
TW201221141A (en) 2012-06-01
PT3354280T (en) 2020-09-01
TWI498121B (en) 2015-09-01
UY33652A (en) 2012-04-30
TW201542229A (en) 2015-11-16
TWI782325B (en) 2022-11-01
RS57850B1 (en) 2018-12-31
ES2820246T3 (en) 2021-04-20
TWI718890B (en) 2021-02-11
TW202102262A (en) 2021-01-16
DK2624865T3 (en) 2018-10-22
SI2624865T1 (en) 2018-10-30
TW202026011A (en) 2020-07-16
DK3354280T3 (en) 2020-09-28
HK1258305A1 (en) 2019-11-08
TW201924718A (en) 2019-07-01
HUE052089T2 (en) 2021-04-28
TW201716086A (en) 2017-05-16
TWI690329B (en) 2020-04-11

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