fibronectin-based scaffold domain proteins that bind to pcsk9

专利摘要:
  PROTEINS WITH "SCAFFOLD" DOMAIN BASED ON FIBRONECTIN THAT CONNECT TO PCSK9, ITS USE AS WELL AS A PHARMACEUTICAL COMPOSITION UNDERSTANDING THE SAME.The present invention relates to fibronectin-based scaffold domain proteins that bind to PCSK9. The invention also relates to the use of innovative proteins in therapeutic applications to treat atherosclerosis, hypercholesterolemia and other cholesterol-related diseases. The invention further relates to cells comprising such proteins, polynucleotides that encode such proteins or fragments thereof and to vectors comprising polynucleotides that encode the innovative protein.
公开号:BR112012026216A2
申请号:R112012026216-5
申请日:2011-04-13
公开日:2020-09-01
发明作者:Ray Camphausen；Katie A. Russo；Ching-Hsiung Frederick Lo；Bowman Miao；Rex A. Parker；Doree F. Sitkoff；Sharon T. Cload；Jonathan H. Davis；Fabienne M. Denhez；Amna Saeed-Kothe；Dasa Lipovsek；Chee Meng Low；Tracy S. Mitchell；Ginger C. Rakestraw
申请人:Bristol-Myers Squibb Company；
IPC主号:

专利说明:

Invention Patent Descriptive Report for "SCAFFOLD DOMAIN PROTEINS" BASED ON FIBRONECTIN THAT CONNECT TO PCSK9, ITS USE AS WELL AS PHARMACEUTICAL COMPOSITION UNDERSTANDING THE SAME ". 5 SEQUENCE LISTING This application contains a Sequence Listing which was sent in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on April 13, 2011, is called 11594 PCT.ST25.txt and has a size of 1,382 KB.
FIELD OF THE INVENTION The present invention relates to proteins with fibronectin-based "scaf fold" domain that bind to the subtilisin kinase type 9 pro-protein convertase (Proprotein Convertase Subtilisin Kexin type 9 - PCSK9). The invention also relates to the use of innovative proteins in therapeutic applications to treat atherosclerosis, hypercholesterolemia and other cholesterol-related diseases. The invention also relates to cells comprising such proteins, polynucleotides that encode such proteins or fragments thereof and vectors comprising polynucleotides that encode innovative proteins.
INTRODUCTION Atherosclerosis is a disease of the arteries responsible for coronary heart disease (Coronary Heart Disease - CHD) that is responsible for many deaths in industrialized countries. (Lusis (2000)). Several risk factors for CHD have now been well established: dyslipidemia, hypertension, diabetes, smoking, poor diet, inactivity and stress. The most clinically relevant and common dyslipidemia are characterized by an increase in low density lipoprotein and very low density lipoproteins (Low Density Lipoprotein and Very Low Density Lipoproteins - LDL and VLDL) with hypercholesterolemia in the absence or presence of hypertriglyceridemia ( Fredrickson et al. (1967)). An isolated elevation of LDL cholesterol is one of the most common risk factors for CHD. PCSK9 (also referred to as HCHOLA3, NARC-1 or FH3) is a protease that belongs to the proteinase K subfamily of the secretory subtilase family (Naureckiene et al., Arch.

权利要求:
Claims (12)
[1]
1. Isolated polypeptide, characterized by the fact that it comprises a tenth domain of fibronectin type III (10Fn3), where 10 Fn3 has a loop selected from loops BC, DE and FG, and where loop 5 BC comprises SEQ ID NO: 14, the DE loop comprises SEQ ID NO: 25 and the FG loop comprises SEQ ID NO: 37, and in which the polypeptide binds to PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9).
[2]
2. Isolated polypeptide, characterized by the fact that it comprises a tenth domain of fibronectin type III (10Fn3), in which 10 10 Fn3 has a loop selected from loops BC, DE and FG, and in which loop BC comprises SEQ ID NO: 112, the DE loop comprises SEQ ID NO: 138 and the FG loop comprises SEQ ID NO: 156, and the polypeptide binds to PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9).
[3]
Isolated polypeptide according to claim 1 or 2, 15 characterized by the fact that it binds to PCSK9 with a KD of less than 500 nM.
[4]
4. Isolated polypeptide according to claim 1 or 2, characterized in that it further comprises one or more pharmacokinetic portions (PK) selected from the group consisting of polyethylene 20 glycol, sialic acid, Fc, Fc fragment, transferrin, albumin serum, a protein that binds to serum albumin and a protein that binds to serum immunoglobulin.
[5]
5. Isolated polypeptide, characterized by the fact that 10 comprises an Fn3 domain, comprises SEQ ID NO: 82 and in which the polypeptide binds to PCSK9.
[6]
6. Isolated polypeptide, characterized by the fact that 10 comprises an Fn3 domain, comprises SEQ ID NO: 209 and in which the polypeptide binds to PCSK9.
[7]
An isolated polypeptide according to claim 5 or 6, 30 characterized by the fact that it binds to PCSK9 with a KD of less than 500 nM.
[8]
An isolated polypeptide according to claim 5 or 6,
characterized by the fact that it also comprises one or more pharmacokinetic portions (PK) selected from the group consisting of polyethylene glycol, sialic acid, Fc, Fc fragment, transferrin, serum albumin, a protein that binds to serum albumin and a protein from binding to serum immunoglobulin.
[9]
9. Use of a polypeptide as defined in any of claims 1-8, characterized by the fact that it is for the preparation of a drug for the treatment of a patient, in which the patient has or is at risk of having a related disease cholesterol. 10
[10]
10. Use according to claim 10, characterized by the fact that the cholesterol-related disease is hypercholesterolemia or atherosclerosis.
[11]
11. Pharmaceutically acceptable composition, characterized in that it comprises the polypeptide as defined in any one of claims 1 to 8.
[12]
Pharmaceutical composition, characterized in that it comprises a therapeutically effective amount of a polypeptide as defined in any one of claims 1-8 and a pharmaceutically acceptable carrier.

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法律状态:
2020-09-15| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2020-11-17| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |

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2021-11-23| B350| Update of information on the portal [chapter 15.35 patent gazette]|

优先权:

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申请号 | 申请日 | 专利标题

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US32356210P| true| 2010-04-13|2010-04-13|

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US61/323,562|2010-04-13|

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US33073110P| true| 2010-05-03|2010-05-03|

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US61/330,731|2010-05-03|

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PCT/US2011/032231|WO2011130354A1|2010-04-13|2011-04-13|Fibronectin based scaffold domain proteins that bind pcsk9|

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