JPWO2019182901A5 - - Google Patents

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JPWO2019182901A5
JPWO2019182901A5 JP2020542113A JP2020542113A JPWO2019182901A5 JP WO2019182901 A5 JPWO2019182901 A5 JP WO2019182901A5 JP 2020542113 A JP2020542113 A JP 2020542113A JP 2020542113 A JP2020542113 A JP 2020542113A JP WO2019182901 A5 JPWO2019182901 A5 JP WO2019182901A5
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protein drug
sample
drug sample
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JP7315565B2 (en
JP2021516334A (en
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一実施形態では、サンプル濃度について確立されたアッセイ範囲は0.4mg/ml~0.6mg/mlであり、分析されている約7μg/ml~11μg/mlの最終濃度に対応しており、この最終濃度がマイクロチップキャピラリー電気泳動システム上でMCE分析にかけられて、電気泳動図が作成される。この方法は、汚染物質または不純物に対応する、電気泳動図中のピークを特定することによって、完結する。
[本発明1001]
155~175mMの2-ヨードアセトアミドと、
0.50~1.5%のドデシル硫酸リチウムと、
75~95mMのリン酸ナトリウムと
を含み、
7未満のpHを有する、
水性電気泳動サンプル緩衝液。
[本発明1002]
pHが6である、本発明1001の水性緩衝液。
[本発明1003]
166mMの2-ヨードアセトアミドと、0.81%のドデシル硫酸リチウムと、81mMのリン酸ナトリウムとを含む、本発明1001または1002の水性緩衝液。
[本発明1004]
166mMの2-ヨードアセトアミドと、
0.81%のドデシル硫酸リチウムと、
81mMのリン酸ナトリウムと
から成り、
6.0のpHを有する、
水性電気泳動サンプル緩衝液。
[本発明1005]
0.50~1.5%のドデシル硫酸リチウムと、
45~75mMのリン酸ナトリウムと、
還元剤と
を含み、
8より大きいpHを有する、
水性電気泳動サンプル緩衝液。
[本発明1006]
pHが9である、本発明1005の水性緩衝液。
[本発明1007]
135~155mMのジチオスレイトールを含む、本発明1005または1006の水性緩衝液。
[本発明1008]
0.69%のドデシル硫酸リチウムと、69mMのリン酸ナトリウムと、142mMのジチオスレイトールとを含む、本発明1005~1007のいずれかの水性緩衝液。
[本発明1009]
0.69%のドデシル硫酸リチウムと、
69mMのリン酸ナトリウムと、
142mMのジチオスレイトールと
から成り、
9.0のpHを有する、
水性電気泳動サンプル緩衝液。
[本発明1010]
タンパク質薬物サンプル中の汚染物質または不純物を同定する方法であって、
前記タンパク質薬物サンプルを本発明1001~1004のいずれかの緩衝液に添加して、緩衝化されたタンパク質薬物サンプルを形成するステップと、
前記緩衝化されたタンパク質薬物サンプルを、65~85℃に5~15分間、加熱して、変性した緩衝化されたタンパク質薬物サンプルを形成するステップと、
前記変性した緩衝化されたタンパク質薬物サンプルに検出可能な標識を添加し、30~40℃で20~40分間、加熱して、変性した標識されたタンパク質薬物サンプルを形成するステップと、
前記変性した標識されたタンパク質薬物サンプルを希釈し、MCEにかけて、マイクロチップキャピラリー電気泳動システム上で、希釈されたタンパク質薬物サンプルを分離し、電気泳動図を作成するステップと、
汚染物質または不純物に対応する、前記電気泳動図におけるピークを同定するステップと
を含む、方法。
[本発明1011]
前記緩衝化されたタンパク質薬物サンプルを、70℃で10分間、加熱する、本発明1010の方法。
[本発明1012]
前記標識されたタンパク質薬物サンプルを、35℃で30分間、加熱する、本発明1010または1011の方法。
[本発明1013]
前記希釈されたタンパク質薬物サンプルが9mg/mlである、本発明1010~1012のいずれかの方法。
[本発明1014]
タンパク質薬物サンプル中の汚染物質または不純物を同定する方法であって、
前記タンパク質サンプルを本発明1005~1009のいずれかの緩衝液に添加して、緩衝化されたタンパク質薬物サンプルを形成するステップと、
前記緩衝化されたタンパク質薬物サンプルを65~85℃に5~15分間、加熱して、変性したタンパク質薬物サンプルを形成するステップと、
前記変性したタンパク質薬物サンプルに、検出可能な標識を添加し、30~40℃で20~40分間、加熱して、変性した標識されたタンパク質薬物サンプルを形成するステップと、
前記変性した標識されたタンパク質薬物サンプルを希釈し、マイクロチップキャピラリー電気泳動システム上でMCE分析にかけて、電気泳動図を作成するステップと、
汚染物質または不純物に対応する、前記電気泳動図におけるピークを同定するステップと
を含む、方法。
[本発明1015]
前記緩衝化されたタンパク質薬物サンプルを、70℃で10分間、加熱する、本発明1014の方法。
[本発明1016]
前記サンプルを、35℃で30分間、加熱する、本発明1014または1015の方法。
[本発明1017]
前記希釈されたタンパク質薬物サンプルが9μg/mlである、本発明1014~1016のいずれかの方法。
[本発明1018]
前記検出可能な標識がDY-631 N-ヒドロキシスクシンイミジルエステルである、本発明1010~1017のいずれかの方法。
[本発明1019]
本発明1001~1009のいずれかの緩衝液と、前記緩衝液中での電気泳動のためにサンプルを調製するための書面による指示書とを含む、キット。
[本発明1020]
55~75mMの2-ヨードアセトアミドと、
0.1~1.0%のドデシル硫酸リチウムと、
5~115mMの塩化ナトリウムと、
5~85mMのHEPESと
を含み、
9未満のpHを有する、
水性電気泳動サンプル緩衝液。
[本発明1021]
66.4mMの2-ヨードアセトアミドと、
0.32%のドデシル硫酸リチウムと、
48.6mMのNaClと、
16.2mMのHEPESと
を含み、
9未満のpHを有する、
水性電気泳動サンプル緩衝液。
[本発明1022]
pHが8である、本発明1020または1021の水性緩衝液。
[本発明1023]
0.05~0.75%のドデシル硫酸リチウムと、
5mM~115mMのNaClと、
5mM~85mMのHEPESと、
35~50mMのジチオスレイトールと
を含み、
7より大きいpHを有する、
水性電気泳動サンプル緩衝液。
[本発明1024]
0.28%のドデシル硫酸リチウムと、
41.5mMのNaClと、
13.8mMのHEPESと、
42.5mMのジチオスレイトールと
を含み、
7より大きいpHを有する、
水性電気泳動サンプル緩衝液。
[本発明1025]
pHが8である、本発明1023または1024の水性緩衝液。
In one embodiment, the established assay range for sample concentration is 0.4 mg / ml to 0.6 mg / ml, corresponding to the final concentration of about 7 μg / ml to 11 μg / ml being analyzed. The final concentration is subjected to MCE analysis on a microchip capillary electrophoresis system to produce an electrophoretogram. This method is completed by identifying peaks in the electrophoretogram that correspond to contaminants or impurities.
[Invention 1001]
With 155-175 mM 2-iodoacetamide,
With 0.50 to 1.5% lithium dodecyl sulfate,
With 75-95 mM sodium phosphate
Including
Has a pH of less than 7,
Aqueous electrophoresis sample buffer.
[Invention 1002]
The aqueous buffer of the present invention 1001 having a pH of 6.
[Invention 1003]
The 1001 or 1002 aqueous buffer of the invention comprising 166 mM 2-iodoacetamide, 0.81% lithium dodecyl sulfate and 81 mM sodium phosphate.
[Invention 1004]
With 166 mM 2-iodoacetamide,
With 0.81% lithium dodecyl sulfate,
With 81 mM sodium phosphate
Consists of
Has a pH of 6.0,
Aqueous electrophoresis sample buffer.
[Invention 1005]
With 0.50 to 1.5% lithium dodecyl sulfate,
45-75 mM sodium phosphate and
With a reducing agent
Including
Has a pH greater than 8,
Aqueous electrophoresis sample buffer.
[Invention 1006]
The aqueous buffer of the present invention 1005 having a pH of 9.
[Invention 1007]
Aqueous buffer of the present invention 1005 or 1006 containing 135-155 mM dithiothreitol.
[Invention 1008]
The aqueous buffer of any of 1005-1007 of the present invention comprising 0.69% lithium dodecyl sulfate, 69 mM sodium phosphate and 142 mM dithiothreitol.
[Invention 1009]
With 0.69% lithium dodecyl sulfate,
69 mM sodium phosphate and
With 142 mM dithiothreitol
Consists of
Has a pH of 9.0,
Aqueous electrophoresis sample buffer.
[Invention 1010]
A method for identifying contaminants or impurities in protein drug samples,
A step of adding the protein drug sample to any of the buffers of the present invention 1001 to 1004 to form a buffered protein drug sample.
The step of heating the buffered protein drug sample to 65-85 ° C. for 5-15 minutes to form a denatured buffered protein drug sample.
A step of adding a detectable label to the denatured buffered protein drug sample and heating at 30-40 ° C. for 20-40 minutes to form a denatured labeled protein drug sample.
A step of diluting the denatured labeled protein drug sample, subjecting it to MCE, separating the diluted protein drug sample on a microchip capillary electrophoresis system, and creating an electrophoretogram.
Steps to identify peaks in the electrophoretogram corresponding to contaminants or impurities
Including, how.
[Invention 1011]
The method of the invention 1010, wherein the buffered protein drug sample is heated at 70 ° C. for 10 minutes.
[Invention 1012]
The method of the invention 1010 or 1011, wherein the labeled protein drug sample is heated at 35 ° C. for 30 minutes.
[Invention 1013]
The method of any of 1010-1012 of the present invention, wherein the diluted protein drug sample is 9 mg / ml.
[Invention 1014]
A method for identifying contaminants or impurities in protein drug samples,
A step of adding the protein sample to any of the buffers of the present invention 1005 to 1009 to form a buffered protein drug sample.
A step of heating the buffered protein drug sample to 65-85 ° C. for 5-15 minutes to form a denatured protein drug sample.
A step of adding a detectable label to the denatured protein drug sample and heating at 30-40 ° C. for 20-40 minutes to form a denatured labeled protein drug sample.
A step of diluting the denatured labeled protein drug sample and subjecting it to MCE analysis on a microchip capillary electrophoresis system to create an electrophoretogram.
Steps to identify peaks in the electrophoretogram corresponding to contaminants or impurities
Including, how.
[Invention 1015]
The method of the invention 1014, wherein the buffered protein drug sample is heated at 70 ° C. for 10 minutes.
[Invention 1016]
The method of the invention 1014 or 1015, wherein the sample is heated at 35 ° C. for 30 minutes.
[Invention 1017]
The method of any of 1014-1016 of the present invention, wherein the diluted protein drug sample is 9 μg / ml.
[Invention 1018]
The method of any of 1010-1017 of the present invention, wherein the detectable label is DY-631 N-hydroxysuccinimidyl ester.
[Invention 1019]
A kit comprising any of the buffers 1001-1009 of the present invention and written instructions for preparing a sample for electrophoresis in said buffer.
[Invention 1020]
55-75 mM 2-iodoacetamide,
With 0.1-1.0% lithium dodecyl sulfate,
5 to 115 mM sodium chloride and
With 5 to 85 mM HEPES
Including
Has a pH of less than 9,
Aqueous electrophoresis sample buffer.
[Invention 1021]
66.4 mM 2-iodoacetamide and
With 0.32% lithium dodecyl sulfate,
48.6 mM NaCl and
With 16.2 mM HEPES
Including
Has a pH of less than 9,
Aqueous electrophoresis sample buffer.
[Invention 1022]
Aqueous buffer of the invention 1020 or 1021 having a pH of 8.
[Invention 1023]
With 0.05 to 0.75% lithium dodecyl sulfate,
5 mM to 115 mM NaCl and
With 5 mM to 85 mM HEPES,
With 35-50 mM dithiothreitol
Including
Has a pH greater than 7,
Aqueous electrophoresis sample buffer.
[Invention 1024]
With 0.28% lithium dodecyl sulfate,
41.5 mM NaCl and
13.8 mM HEPES and
With 42.5 mM dithiothreitol
Including
Has a pH greater than 7,
Aqueous electrophoresis sample buffer.
[Invention 1025]
Aqueous buffer of the present invention 1023 or 1024 having a pH of 8.

Claims (17)

155~175mMの2-ヨードアセトアミドと、
0.50~1.5%のドデシル硫酸リチウムと、
75~95mMのリン酸ナトリウムと
を含み、
7未満のpHを有する、
水性電気泳動サンプル緩衝液。
With 155 to 175 mM 2-iodoacetamide,
With 0.50 to 1.5% lithium dodecyl sulfate,
Contains 75-95 mM sodium phosphate and
Has a pH of less than 7,
Aqueous electrophoresis sample buffer.
pHが6である、請求項1に記載の水性電気泳動サンプル緩衝液。 The aqueous electrophoresis sample buffer according to claim 1, which has a pH of 6. 166mMの2-ヨードアセトアミドと、0.81%のドデシル硫酸リチウムと、81mMのリン酸ナトリウムとを含む、請求項1記載の水性電気泳動サンプル緩衝液。 The aqueous electrophoresis sample buffer according to claim 1 , which comprises 166 mM 2-iodoacetamide, 0.81% lithium dodecyl sulfate, and 81 mM sodium phosphate. 166mMの2-ヨードアセトアミドと、
0.81%のドデシル硫酸リチウムと、
81mMのリン酸ナトリウムと
から成り、
6.0のpHを有する、
水性電気泳動サンプル緩衝液。
With 166 mM 2-iodoacetamide,
With 0.81% lithium dodecyl sulfate,
Consists of 81 mM sodium phosphate
Has a pH of 6.0,
Aqueous electrophoresis sample buffer.
タンパク質薬物サンプル中の汚染物質または不純物を同定する方法であって、
前記タンパク質薬物サンプルを、155~175mMの2-ヨードアセトアミドと0.50~1.5%のドデシル硫酸リチウムと75~95mMのリン酸ナトリウムを含み、7未満のpHを有する、水性電気泳動サンプル緩衝液に添加して、緩衝化されたタンパク質薬物サンプルを形成するステップと、
前記緩衝化されたタンパク質薬物サンプルを、65~85℃に5~15分間、加熱して、変性した緩衝化されたタンパク質薬物サンプルを形成するステップと、
前記変性した緩衝化されたタンパク質薬物サンプルに検出可能な標識を添加し、30~40℃で20~40分間、加熱して、変性した標識されたタンパク質薬物サンプルを形成するステップと、
前記変性した標識されたタンパク質薬物サンプルを希釈し、マイクロチップキャピラリー電気泳動にかけて、マイクロチップキャピラリー電気泳動システム上で、希釈された変性した標識されたタンパク質薬物サンプルを分離し、電気泳動図を作成するステップと、
汚染物質または不純物に対応する、前記電気泳動図におけるピークを同定するステップと
を含む、方法。
A method for identifying contaminants or impurities in protein drug samples,
The protein drug sample contains an aqueous electrophoresis sample buffer containing 155 to 175 mM 2-iodoacetamide, 0.50 to 1.5% lithium dodecyl sulfate and 75 to 95 mM sodium phosphate and having a pH of less than 7. Steps to add to the solution to form a buffered protein drug sample,
The step of heating the buffered protein drug sample to 65-85 ° C. for 5-15 minutes to form a denatured buffered protein drug sample.
A step of adding a detectable label to the denatured buffered protein drug sample and heating at 30-40 ° C. for 20-40 minutes to form a denatured labeled protein drug sample.
The denatured labeled protein drug sample is diluted and subjected to microchip capillary electrophoresis to separate the diluted denatured labeled protein drug sample on a microchip capillary electrophoresis system and create an electrophoretogram. Steps and
A method comprising the step of identifying a peak in the electrophoretogram corresponding to a contaminant or impurity.
前記緩衝化されたタンパク質薬物サンプルを、70℃で10分間、加熱する、請求項5に記載の方法。 The method of claim 5, wherein the buffered protein drug sample is heated at 70 ° C. for 10 minutes. 前記変性した緩衝化されたタンパク質薬物サンプルを、35℃で30分間、加熱する、請求項5に記載の方法。 5. The method of claim 5, wherein the denatured buffered protein drug sample is heated at 35 ° C. for 30 minutes. 前記希釈されたタンパク質薬物サンプルが9μg/mlである、請求項のいずれか一項に記載の方法。 The method of any one of claims 5 , wherein the diluted protein drug sample is 9 μg / ml. 前記検出可能な標識がDY-631 N-ヒドロキシスクシンイミジルエステルである、請求項5に記載の方法 The method of claim 5, wherein the detectable label is DY-631 N-hydroxysuccinimidyl ester . タンパク質薬物サンプル中の汚染物質または不純物を同定する方法であって、
前記タンパク質サンプルを、0.50~1.5%のドデシル硫酸リチウムと45~75mMのリン酸ナトリウムと還元剤とを含み、8より大きいpHを有する、水性電気泳動サンプル緩衝液に添加して、緩衝化されたタンパク質薬物サンプルを形成するステップと、
前記緩衝化されたタンパク質薬物サンプルを65~85℃に5~15分間、加熱して、変性したタンパク質薬物サンプルを形成するステップと、
前記変性したタンパク質薬物サンプルに、検出可能な標識を添加し、30~40℃で20~40分間、加熱して、変性した標識されたタンパク質薬物サンプルを形成するステップと、
前記変性した標識されたタンパク質薬物サンプルを希釈し、マイクロチップキャピラリー電気泳動システム上でマイクロチップキャピラリー電気泳動分析にかけて、電気泳動図を作成するステップと、
汚染物質または不純物に対応する、前記電気泳動図におけるピークを同定するステップと
を含む、方法。
A method for identifying contaminants or impurities in protein drug samples,
The protein sample was added to an aqueous electrophoresis sample buffer containing 0.50 to 1.5% lithium dodecyl sulfate, 45 to 75 mM sodium phosphate and a reducing agent and having a pH greater than 8 . Steps to form a buffered protein drug sample,
A step of heating the buffered protein drug sample to 65-85 ° C. for 5-15 minutes to form a denatured protein drug sample.
A step of adding a detectable label to the denatured protein drug sample and heating at 30-40 ° C. for 20-40 minutes to form a denatured labeled protein drug sample.
A step of diluting the denatured labeled protein drug sample and subjecting it to microchip capillary electrophoresis analysis on a microchip capillary electrophoresis system to create an electrophoretic diagram.
A method comprising the step of identifying a peak in the electrophoretogram corresponding to a contaminant or impurity.
前記緩衝化されたタンパク質薬物サンプルを、70℃で10分間、加熱する、請求項10に記載の方法。 10. The method of claim 10 , wherein the buffered protein drug sample is heated at 70 ° C. for 10 minutes. 前記変性したタンパク質薬物サンプルを、35℃で30分間、加熱する、請求項10に記載の方法。 10. The method of claim 10 , wherein the denatured protein drug sample is heated at 35 ° C. for 30 minutes. 前記希釈されたタンパク質薬物サンプルが9μg/mlである、請求項10に記載の方法。 10. The method of claim 10 , wherein the diluted protein drug sample is 9 μg / ml. 155~175mMの2-ヨードアセトアミドと0.50~1.5%のドデシル硫酸リチウムと75~95mMのリン酸ナトリウムを含み、7未満のpHを有する、水性電気泳動サンプル緩衝液と、前記緩衝液中での電気泳動のためにサンプルを調製するための書面による指示書とを含む、キット。 An aqueous electrophoresis sample buffer and said buffer containing 155 to 175 mM 2-iodoacetamide, 0.50 to 1.5% lithium dodecyl sulfate and 75 to 95 mM sodium phosphate and having a pH of less than 7. A kit containing written instructions and instructions for preparing a sample for electrophoresis in. 55~75mMの2-ヨードアセトアミドと、
0.1~1.0%のドデシル硫酸リチウムと、
5~115mMの塩化ナトリウムと、
5~85mMのHEPESと
を含み、
9未満のpHを有する、
水性電気泳動サンプル緩衝液。
55-75 mM 2-iodoacetamide and
With 0.1-1.0% lithium dodecyl sulfate,
5 to 115 mM sodium chloride and
Including 5 to 85 mM HEPES
Has a pH of less than 9,
Aqueous electrophoresis sample buffer.
66.4mMの2-ヨードアセトアミドと、
0.32%のドデシル硫酸リチウムと、
48.6mMのNaClと、
16.2mMのHEPESと
を含み、
9未満のpHを有する、
水性電気泳動サンプル緩衝液。
66.4 mM 2-iodoacetamide and
With 0.32% lithium dodecyl sulfate,
48.6 mM NaCl and
Including 16.2 mM HEPES
Has a pH of less than 9,
Aqueous electrophoresis sample buffer.
pHが8である、請求項16に記載の水性電気泳動サンプル緩衝液。 The aqueous electrophoresis sample buffer of claim 16 , wherein the pH is 8.
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US201862644933P 2018-03-19 2018-03-19
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JPWO2019182901A5 true JPWO2019182901A5 (en) 2022-03-18
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Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3089655A1 (en) 2018-03-19 2019-09-26 Regeneron Pharmaceuticals, Inc. Microchip capillary electrophoresis assays and reagents
JP7342279B2 (en) * 2020-01-21 2023-09-11 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Deglycosylation method for electrophoresis of glycosylated proteins
TW202233827A (en) 2021-01-20 2022-09-01 美商再生元醫藥公司 Methods of improving protein titer in cell culture
CN113189184B (en) * 2021-04-28 2022-09-09 浙江大学 Capillary gel electrophoresis sample buffer solution containing cysteine
EP4348234A1 (en) * 2021-06-01 2024-04-10 Regeneron Pharmaceuticals, Inc. Micropchip capillary electrophoresis assays and reagents
AU2022348521A1 (en) 2021-09-20 2024-04-04 Regeneron Pharmaceuticals, Inc. Methods of controlling antibody heterogeneity
CA3236367A1 (en) 2021-10-26 2023-05-04 Michelle Lafond Systems and methods for generating laboratory water and distributing laboratory water at different temperatures

Family Cites Families (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6818745B1 (en) * 1998-05-18 2004-11-16 University College London Polypeptide hormone phosphatonin
US7087411B2 (en) 1999-06-08 2006-08-08 Regeneron Pharmaceuticals, Inc. Fusion protein capable of binding VEGF
EP1506399A2 (en) 2001-05-21 2005-02-16 Aclara BioSciences, Inc. Methods and compositions for analyzing proteins
JP2003114216A (en) * 2001-10-05 2003-04-18 Advance Co Ltd Electrophoretic device
PL375045A1 (en) * 2002-02-21 2005-11-14 Wyeth Gasp1: a follistatin domain containing protein
US6927004B2 (en) 2002-03-08 2005-08-09 Asml Netherlands B.V. Mask for use in lithography, method of making a mask, lithographic apparatus, and device manufacturing method
DE10258150A1 (en) 2002-12-10 2004-07-08 Dyomics Gmbh Hydrophilic markers based on benzopyrylo-polymethines
AU2003903317A0 (en) * 2003-06-27 2003-07-10 Proteome Systems Intellectual Property Pty Ltd Method of isolating a protein
EP2306192B1 (en) * 2003-12-05 2015-10-14 The Cleveland Clinic Foundation Risk Markers For Cardiovascular Disease
US7378396B2 (en) 2004-08-11 2008-05-27 The Cleveland Clinic Foundation Therapeutic agents and methods for cardiovascular disease
ES2398076T3 (en) 2006-06-02 2013-03-13 Regeneron Pharmaceuticals, Inc. High affinity antibodies against the human IL-6 receptor
US7608693B2 (en) 2006-10-02 2009-10-27 Regeneron Pharmaceuticals, Inc. High affinity human antibodies to human IL-4 receptor
PL2614832T3 (en) * 2007-02-12 2017-01-31 A1M Pharma Ab Diagnosis and treatment of preeclampsia
EP2158328B1 (en) * 2007-05-18 2014-01-01 Life Technologies Corporation Rapid protein labeling and analysis
PL2178916T3 (en) 2007-07-31 2015-08-31 Regeneron Pharma Human antibodies to human cd20 and method of using thereof
US8309088B2 (en) 2007-08-10 2012-11-13 Regeneron Pharmaceuticals, Inc. Method of treating osteoarthritis with an antibody to NGF
NZ592436A (en) * 2008-11-06 2012-10-26 Glenmark Pharmaceuticals Sa Treatment with anti-alpha2 integrin antibodies
JO3672B1 (en) 2008-12-15 2020-08-27 Regeneron Pharma High Affinity Human Antibodies to PCSK9
EP2975051B1 (en) 2009-06-26 2021-04-14 Regeneron Pharmaceuticals, Inc. Readily isolated bispecific antibodies with native immunoglobulin format
US8778685B2 (en) * 2009-08-25 2014-07-15 Life Technologies Corporation Quantitative fluorescent protein standards
JO3417B1 (en) 2010-01-08 2019-10-20 Regeneron Pharma Stabilized formulations containing anti-interleukin-6 receptor (il-6r) antibodies
JO3340B1 (en) 2010-05-26 2019-03-13 Regeneron Pharma Antibodies to human gdf8
JOP20190250A1 (en) 2010-07-14 2017-06-16 Regeneron Pharma Stabilized formulations containing anti-ngf antibodies
AR083044A1 (en) 2010-09-27 2013-01-30 Regeneron Pharma ANTI-CD48 ANTIBODIES AND USES OF THE SAME
CN106267189B (en) 2010-10-06 2021-02-26 瑞泽恩制药公司 Stable formulations containing anti-interleukin-4 receptor (IL-4R) antibodies
JO3756B1 (en) 2010-11-23 2021-01-31 Regeneron Pharma Human antibodies to the glucagon receptor
AR087329A1 (en) 2011-06-17 2014-03-19 Regeneron Pharma HUMAN ANTIBODIES AGAINST PROTEIN 3 OF HUMAN ANGIOPOIETIN TYPE
LT2780368T (en) 2011-11-14 2018-03-12 Regeneron Pharmaceuticals, Inc. Compositions and methods for increasing muscle mass and muscle strength by specifically antagonizing gdf8 and/or activin a
EP2807190B1 (en) 2012-01-23 2018-12-26 Regeneron Pharmaceuticals, Inc. Stabilized formulations containing anti-ang2 antibodies
JO3820B1 (en) 2012-05-03 2021-01-31 Regeneron Pharma Human antibodies to fel d1 and methods of use thereof
TW201843172A (en) 2012-06-25 2018-12-16 美商再生元醫藥公司 Anti-egfr antibodies and uses thereof
EA028244B1 (en) 2012-08-13 2017-10-31 Ридженерон Фармасьютикалз, Инк. ANTI-PCSK9 ANTIBODIES WITH pH-DEPENDENT BINDING CHARACTERISTICS
JOP20200236A1 (en) 2012-09-21 2017-06-16 Regeneron Pharma Anti-cd3 antibodies, bispecific antigen-binding molecules that bind cd3 and cd20, and uses thereof
WO2014055936A1 (en) * 2012-10-04 2014-04-10 Integenx Inc. Preservation of biological materials in non-aqueous fluid media
US10357538B2 (en) * 2012-12-24 2019-07-23 Northern Sydney Local Health District Vaccines for the treatment of cancer and compositions for enhancing vaccine efficacy
JO3405B1 (en) 2013-01-09 2019-10-20 Regeneron Pharma ANTI-PDGFR-beta ANTIBODIES AND USES THEREOF
EP2948177A1 (en) 2013-01-22 2015-12-02 AbbVie Inc. Methods for optimizing domain stability of binding proteins
JO3532B1 (en) 2013-03-13 2020-07-05 Regeneron Pharma Anti-il-33 antibodies and uses thereof
TWI659968B (en) 2013-03-14 2019-05-21 再生元醫藥公司 Human antibodies to respiratory syncytial virus f protein and methods of use thereof
US9637535B2 (en) 2013-03-15 2017-05-02 Regeneron Pharmaceuticals, Inc. IL-33 antagonists and uses thereof
TWI641620B (en) 2013-08-21 2018-11-21 再生元醫藥公司 Anti-prlr antibodies and uses thereof
TWI681969B (en) 2014-01-23 2020-01-11 美商再生元醫藥公司 Human antibodies to pd-1
TWI680138B (en) 2014-01-23 2019-12-21 美商再生元醫藥公司 Human antibodies to pd-l1
JP6632984B2 (en) 2014-03-11 2020-01-22 リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. Anti-EGFRvIII antibodies and uses thereof
TWI701042B (en) 2014-03-19 2020-08-11 美商再生元醫藥公司 Methods and antibody compositions for tumor treatment
EP3636073B1 (en) 2014-05-05 2023-11-15 Regeneron Pharmaceuticals, Inc. Humanized c5 and c3 animals
JO3701B1 (en) 2014-05-23 2021-01-31 Regeneron Pharma Human antibodies to middle east respiratory syndrome – coronavirus spike protein
EA201790377A1 (en) 2014-09-16 2017-08-31 Регенерон Фармасьютикалз, Инк. ANTIBODIES TO GLUCAGON AND THEIR APPLICATIONS
TWI710573B (en) 2015-01-26 2020-11-21 美商再生元醫藥公司 Human antibodies to ebola virus glycoprotein
CA3089655A1 (en) 2018-03-19 2019-09-26 Regeneron Pharmaceuticals, Inc. Microchip capillary electrophoresis assays and reagents

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