CN102066420A - 1d05 pcsk9拮抗剂 - Google Patents
1d05 pcsk9拮抗剂 Download PDFInfo
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- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
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- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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Abstract
Description
序号: | 说明 |
SEQ ID NO:1 | 轻链(“LC”);1D05 |
SEQ ID NO:2 | 轻链(“LC”)核酸;1D05 |
SEQ ID NO:3 | VL CDR1;1D05 |
SEQ ID NO:4 | VL CDR1核酸;1D05 |
SEQ ID NO:5 | VL CDR2;1D05 |
SEQ ID NO:6 | VL CDR2核酸;1D05 |
SEQ ID NO:7 | VL CDR3;1D05 |
SEQ ID NO:8 | VL CDR3核酸;1D05 |
SEQ ID NO:9 | 包含连接子和标签的Fd链;1D05 |
SEQ ID NO:10 | Fd链核酸;1D05 |
SEQ ID NO:11 | VH;1D05 |
SEQ ID NO:12 | VH核酸;1D05 |
SEQ ID NO:13 | VH CDR1;1D05 |
SEQ ID NO:14 | VH CDR1;核酸;1D05 |
SEQ ID NO:15 | VH CDR2;1D05 |
SEQ ID NO:16 | VH CDR2核酸;1D05 |
SEQ ID NO:17 | VH CDR3;1D05 |
SEQ ID NO:18 | VH CDR3核酸;1D05 |
SEQ ID NO:19 | 加工位点的片段 |
SEQ ID NO:20 | 加工位点的片段 |
SEQ ID NO:21 | IgG1的恒定区结构域 |
SEQ ID NO:22 | IgG2的恒定区结构域 |
SEQ ID NO:23 | IgG4的恒定区结构域 |
SEQ ID NO:24 | IgG2m4的恒定区结构域 |
SEQ ID NO: | 说明 |
SEQ ID NO:25 | 1D05IgG2m4重链(“HC”) |
SEQ ID NO:26 | 1D05IgG轻(κ)链 |
SEQ ID NO:27 | VL;1D05 |
SEQ ID NO:28 | VL核酸;1D05 |
SEQ ID NO:29 | 1D05IgG2m4HC核酸 |
SEQ ID NO:30 | 1D05IgG LC核酸 |
SEQ ID NO:31 | 1D05IgG2m4HC质粒 |
SEQ ID NO:32 | 1D05IgG LC质粒 |
SEQ ID NO:33 | 引物 |
SEQ ID NO:34 | 引物 |
SEQ ID NO:35 | 引物 |
SEQ ID NO:36 | 引物 |
SEQ ID NO:37 | 1D05表位结构域 |
SEQ ID NO:38 | 附图中的PCSK9序列的一部分 |
SEQ ID NO:39 | 人类表位区域 |
SEQ ID NO:40 | 共有序列 |
SEQ ID NO:41 | 小鼠表位区域 |
SEQ ID NO:42 | 次级足迹表位 |
SEQ ID NO:43 | 1D05变体VH CDR1序列 |
SEQ ID NO:44 | 1D05变体VH CDR2序列 |
SEQ ID NO:45 | 1D05变体VH CDR3序列 |
SEQ ID NO:46 | 1D05变体VL CDR1序列 |
SEQ ID NO:47 | 1D05变体VL CDR2序列 |
SEQ ID NO:48 | 1D05变体VL CDR3序列 |
SEQ ID NO:49 | VL;1D05变体序列 |
SEQ ID NO:50 | VH;1D05变体序列 |
突变体 | 增加/减少 | LDL-C(mg/dI) | EC-50(nM)Exopolar |
S127R | 增加 | 277 | 14 |
D374Y | 增加 | 388 | 1.3 |
野生型 | 140 | 51 | |
R46L | 减少 | 116 | 78 |
测定的m/z | 预期的MW | 肽 | 切割的氨基酸 |
1969.1 | 1969.1 | 153-168 | Asp169 |
2222.0 | 2222.0 | 31-49 | Asp49 |
4412.9 | 4411.2 | 698-737 | Asp698 |
hPCSK9v5His | mPCSK9v5His | |
ka(1/Ms) | 6.6E+04±6.1E+03 | 1.41E+05±1.2E+04 |
kd(1/s) | 4.8E-05±7.4E-06 | 7.18E-05±2.9E-06 |
KA(1/M) | 1.5E+09±3.0E+08 | 2.0E+09±1.5E+08 |
KD(M) | 7.4E-10±1.6E-10 | 5.1E-10±3.8E-11 |
Ab ID | 突变的链 | 包含VH | KD(nM) |
H32Y | 重链 | SEQ ID NO:51 | 2.01 |
M48AQ | 重链 | SEQ ID NO:52 | 2.06 |
M48L | 重链 | SEQ ID NO:53 | 1.52 |
H99Y | 重链 | SEQ ID NO:54 | 1.45 |
M48L/M109L/M115L | 重链 | SEQ ID NO:55 | 1.13 |
M48V | 重链 | SEQ ID NO:56 | 1.95 |
N50D | 轻链 | SEQ ID NO:57 | 3.42 |
N50Q | 轻链 | SEQ ID NO:58 | 0.615 |
N50T | 轻链 | SEQ ID NO:59 | 2.13 |
N50Y | 轻链 | SEQ ID NO:60 | 2.58 |
Claims (41)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US6394908P | 2008-02-07 | 2008-02-07 | |
US61/063949 | 2008-02-07 | ||
US6657708P | 2008-02-21 | 2008-02-21 | |
US61/066577 | 2008-02-21 | ||
PCT/US2009/033341 WO2009100297A1 (en) | 2008-02-07 | 2009-02-06 | 1d05 pcsk9 antagonists |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410267367.XA Division CN104017081A (zh) | 2008-02-07 | 2009-02-06 | 1d05 pcsk9拮抗剂 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102066420A true CN102066420A (zh) | 2011-05-18 |
CN102066420B CN102066420B (zh) | 2014-07-23 |
Family
ID=40467022
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200980104498.3A Expired - Fee Related CN102066420B (zh) | 2008-02-07 | 2009-02-06 | 1d05 pcsk9拮抗剂 |
CN201410267367.XA Pending CN104017081A (zh) | 2008-02-07 | 2009-02-06 | 1d05 pcsk9拮抗剂 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410267367.XA Pending CN104017081A (zh) | 2008-02-07 | 2009-02-06 | 1d05 pcsk9拮抗剂 |
Country Status (11)
Country | Link |
---|---|
US (3) | US8188234B2 (zh) |
EP (1) | EP2245071A1 (zh) |
JP (2) | JP5775308B2 (zh) |
CN (2) | CN102066420B (zh) |
AR (1) | AR070316A1 (zh) |
AU (1) | AU2009212262B2 (zh) |
CA (1) | CA2711794A1 (zh) |
CL (1) | CL2009000260A1 (zh) |
PA (1) | PA8815301A1 (zh) |
TW (1) | TW200938552A (zh) |
WO (1) | WO2009100297A1 (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105085684A (zh) * | 2014-05-14 | 2015-11-25 | 上海亨臻实业有限公司 | Pcsk9靶向重组疫苗设计及其应用 |
CN105801701A (zh) * | 2016-03-31 | 2016-07-27 | 北京中科励骏生物医学科技有限公司 | 一种pcsk9抗体的重链和轻链可变区及其应用 |
TWI615158B (zh) * | 2012-11-06 | 2018-02-21 | 拜耳製藥股份有限公司 | 多肽之調配物 |
CN107840892A (zh) * | 2016-09-20 | 2018-03-27 | 上海药明生物技术有限公司 | 新型抗‑pcsk9抗体 |
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JOP20080381B1 (ar) | 2007-08-23 | 2023-03-28 | Amgen Inc | بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9) |
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US8206943B1 (en) | 2008-06-30 | 2012-06-26 | Schering Corporation | Assay for PCSK9 inhibitors |
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US8357371B2 (en) | 2008-12-15 | 2013-01-22 | Regeneron Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia using antibodies to PCSK9 |
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CN105085684A (zh) * | 2014-05-14 | 2015-11-25 | 上海亨臻实业有限公司 | Pcsk9靶向重组疫苗设计及其应用 |
CN105085684B (zh) * | 2014-05-14 | 2020-04-17 | 上海亨臻实业有限公司 | Pcsk9靶向重组疫苗设计及其应用 |
CN105801701A (zh) * | 2016-03-31 | 2016-07-27 | 北京中科励骏生物医学科技有限公司 | 一种pcsk9抗体的重链和轻链可变区及其应用 |
CN105801701B (zh) * | 2016-03-31 | 2019-03-29 | 河北仁博科技有限公司 | 一种pcsk9抗体的重链和轻链可变区及其应用 |
CN107840892A (zh) * | 2016-09-20 | 2018-03-27 | 上海药明生物技术有限公司 | 新型抗‑pcsk9抗体 |
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US8697070B2 (en) | 2014-04-15 |
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PA8815301A1 (es) | 2009-09-17 |
CA2711794A1 (en) | 2009-08-13 |
JP5775308B2 (ja) | 2015-09-09 |
US8188234B2 (en) | 2012-05-29 |
TW200938552A (en) | 2009-09-16 |
EP2245071A1 (en) | 2010-11-03 |
CN102066420B (zh) | 2014-07-23 |
JP2011511637A (ja) | 2011-04-14 |
CN104017081A (zh) | 2014-09-03 |
WO2009100297A1 (en) | 2009-08-13 |
CL2009000260A1 (es) | 2009-06-26 |
US20120301461A1 (en) | 2012-11-29 |
US20090246192A1 (en) | 2009-10-01 |
US20140220027A1 (en) | 2014-08-07 |
AR070316A1 (es) | 2010-03-31 |
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