Use of a pcsk9 inhibitor to treat hyperlipidemia

A technology for inhibitors and hypercholesterolemia, applied in the field of PCSK9 inhibitors to treat patients with hyperlipidemia who are not receiving statin therapy, and can solve problems such as statin intolerance, non-compliance, and poor control

Inactive Publication Date: 2016-07-27
SANOFI BIOTECH SAS +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Specifically, treatment with statins, which lower LDL-C by inhibiting cholesterol synthesis and upregulating hepatic LDL receptors, may have little effect in patients with absent or defective LDL receptors
Additionally, many patients are statin non-responsive, poorly controlled on statin therapy, cannot tolerate statins, and / or do not adhere to their prescribed therapeutic statin regimen because of statin-related side effects

Method used

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  • Use of a pcsk9 inhibitor to treat hyperlipidemia
  • Use of a pcsk9 inhibitor to treat hyperlipidemia
  • Use of a pcsk9 inhibitor to treat hyperlipidemia

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0116] Production of Human Antibodies

[0117] Methods for producing human antibodies in transgenic mice are known in the art. Any such known method may be used in the context of the present invention to prepare human antibodies that specifically bind human PCSK9.

[0118] Use VELOCIMMUNE TM technology (see, eg, US6,596,541, Regeneron Pharmaceuticals) or any other known technique for generating monoclonal antibodies, initially isolate a high affinity chimeric antibody against PCSK9 having human variable regions and mouse constant regions. The technique involves generating a transgenic mouse having a genome comprising human heavy and light chain variable regions operably linked to endogenous mouse constant region loci such that the mouse produces genes comprising human variable regions in response to antigenic stimuli. and mouse constant region antibodies. The DNA encoding the variable regions of the heavy and light chains of the antibody is isolated and operably linked to ...

Embodiment 1

[0168] Example 1. Generation of human antibodies against human PCSK9

[0169] Human anti-PCSK9 antibodies were generated as described in US Patent No. 8,062,640. An exemplary PCSK9 inhibitor used in the following examples is a human anti-PCSK9 antibody designated "mAb316P", also known as "REGN727" or "alirocumab". mAb316P has the following amino acid sequence characteristics: a heavy chain comprising SEQ ID NO:5 and a light chain comprising SEQ ID NO:9; a heavy chain variable region (HCVR) comprising SEQ ID NO:1 and a light chain variable domain (LCVR) comprising SEQ ID NO:6 ); heavy chain complementarity determining region 1 (HCDR1) comprising SEQ ID NO:2, HCDR2 comprising SEQ ID NO:3, HCDR3 comprising SEQ ID NO:4, light chain complementarity determining region 1 (LCDR1) comprising SEQ ID NO:7, comprising SEQ ID NO:8 LCDR2 and LCDR3 comprising SEQ ID NO:10.

Embodiment 2

[0170] Example 2: Monotherapy with an anti-PCSK9 antibody ("mAb316P") versus ezetimibe in patients with hypercholesterolemia: results of a 24-week, double-blind, randomized phase 3 clinical trial

[0171] background

[0172] Hypercholesterolemia, especially increased levels of low-density lipoprotein cholesterol (LDL-C), constitutes a major risk for the development of atherosclerosis and CHD, the leading causes of death and disability in the Western world . LDL-C has been identified as a major target of cholesterol-lowering therapy and is recognized as a valid surrogate endpoint. Multiple studies have demonstrated that lowering LDL-C levels reduces CHD risk primarily through 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoA) inhibition with statins, with a relationship between LDL-C levels and CHD events There is a strong direct relationship; for every 1 mmol / L (approximately 40 mg / dL) reduction in LDL-C, there is a 22% reduction in cardiovascular disease (CVD) mortality and...

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Abstract

The present invention provides methods for treating hyperlipidemia in patients who are not on statin therapy. The methods of the present invention comprise administering to a patient a pharmaceutical composition comprising a PCSK9 inhibitor. In certain embodiments, the PCSK9 inhibitor is an anti-PCSK9 antibody such as the exemplary antibody referred to herein as mAb316P.

Description

field of invention [0001] The present invention relates to the field of therapeutic treatment of diseases and conditions associated with elevated lipid and lipoprotein levels. More specifically, the present invention relates to the use of PCSK9 inhibitors for the treatment of hyperlipidemic patients not on statin therapy, including statin non-responsive patients, patients poorly controlled on statin therapy, statin intolerant patients or patients with a history of adverse reactions to statin therapy. Background technique [0002] Hypercholesterolemia, particularly increased levels of low-density lipoprotein (LDL) cholesterol (LDL-C), constitutes a major risk for the development of atherosclerosis and coronary heart disease (CHD) (Sharrett et al., 2001, Circulation 104:1108- 1113). Low-density lipoprotein cholesterol has been identified as a major target of cholesterol-lowering therapy and is accepted as a valid surrogate treatment endpoint. Several studies have demonstrat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/40A61K39/395A61P3/06
CPCA61K2039/505A61K2039/545C07K16/40A61P3/06A61P43/00A61K39/3955A61K45/06A61K2300/00C07K2317/21C07K2317/76
Inventor M·巴卡拉-迪内L·贝萨克U·乔杜里C·哈诺廷R·C·波迪W·J·萨希拉D·A·施韦默尔吉普
Owner SANOFI BIOTECH SAS
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