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b‑lymphocyte targeting agents for use in methods of treatment of disease

A technology of lymphocytes and cells, applied in the direction of disease diagnosis, allergic diseases, cardiovascular system diseases, etc.

Inactive Publication Date: 2017-10-24
夏里特柏林大学医学院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Problems underlying the present invention are solved by B-lymphocyte targeting agents for use in methods of treatment of cardiac insufficiency

Method used

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  • b‑lymphocyte targeting agents for use in methods of treatment of disease
  • b‑lymphocyte targeting agents for use in methods of treatment of disease
  • b‑lymphocyte targeting agents for use in methods of treatment of disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0107] Example 1: Detection of B-lymphocytes in patients with cardiac insufficiency

[0108] Endomyocardial biopsies were taken from the RV septum, frozen in liquid nitrogen and stored at -80°C. Embed the sample in Tissue Tec (SLEE, Mainz, Germany) and immediately snap-frozen in liquid nitrogen-cooled methylbutane. Embedded samples were serially cut into 5 μm thick cryosections and placed on slides precoated with 10% poly-L-lysine. After fixation in cold acetone for 10 min followed by air drying, cryosections were 2 o 2 A solution in phosphate-buffered saline was incubated for 20 minutes to inhibit endogenous peroxidase activity.

[0109] For immunohistostaining, CD20 monoclonal mouse antibody clone 8J662 (Fa. Biomol, Hamburg, Germany) was used for 45 min in a humidified chamber. In the humidified chamber, the EnVision TM Peroxidase-conjugated rabbit anti-mouse antibody (DakoCytomation, Hamburg, Germany) was used as secondary antibody for 30 min. Immunohistological sta...

Embodiment 2

[0112] Example 2: Treatment of Male Inflammatory Dilated Cardiomyopathy (DCMi) Patients

[0113] A 76-year-old male patient with a 3-year history of cardiac insufficiency (caused by DCMi) was treated with Rituxan using the manufacturer's recommended dosing regimen (end-stage DCM, severe DCMi; mild cardiac inflammation, absence of cardiac virus, cardiac biopsy sample Medium is CD20 positive, NYHA III, EF 20%; LVEDD71mm). Symptoms and LV function (EF 29%) had improved 24 hours after the first single dose of Rituxan and remained stable after the second Rituxan administration as per protocol. Stress echocardiography showed an improvement in LV functional reserve as well, compared with the examination performed before the application of Rituxan.

Embodiment 3

[0114] Example 3: Treatment of Female Patients with Inflammatory Dilated Cardiomyopathy (DCMi)

[0115] The patient was a 73-year-old woman with a 5-year history of heart failure symptoms caused by severe dilated cardiomyopathy (EF 24%) despite use of heart failure medications and biventricular ICD stimulation (NYHA class III) keep showing up.

[0116] With heart failure drugs and 375mg / m 2 Rituxan (rituximab) for body surface area treated this female patient in two phases.

[0117] Echocardiography showed a significant increase in left ventricular ejection fraction (LVEF) after the first dose of Rituxan and a further increase after the second dose of Rituxan ( image 3 A). At the same time, the left ventricular end diastolic diameter (LVEDD) decreased ( image 3 B). In Table 1 the individual measured values ​​are listed.

[0118] After treatment with Rituxan, BNP levels were significantly reduced ( Figure 4 A).

[0119] Rituxan treatment also improved patients' perfo...

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Abstract

The present invention is related to a B-lymphocyte targeting agent for use in a method for the treatment or diagnosis of cardiac insufficiency. Furthermore, it is related to a composition comprising such B-lymphocyte targeting agent and methods for determining whether a patient suffering from cardiac insufficiency is amenable to the use of the B-lymphocyte targeting agent for its treatment.

Description

technical field [0001] The present invention relates to B-lymphocyte targeting agents for use in methods of treatment or diagnosis of cardiac insufficiency. In addition, the present invention relates to a composition comprising the B-lymphocyte targeting agent, and a method for determining whether a patient with cardiac insufficiency is suitable for treating the disease with the B-lymphocyte targeting agent. Background technique [0002] Cardiac insufficiency or heart failure is a disease characterized by a physiological state in which cardiac output does not meet the body's needs. [0003] Common causes of heart failure include myocardial infarction and other forms of ischemic heart disease, hypertension, valvular heart disease, and cardiomyopathy. Cardiomyopathy is a disease of the heart muscle that is defined by central hemodynamics and gross pathology and has been divided into 5 major forms: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive ca...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00C07K16/28A61K39/395G01N33/68
CPCA61K39/39541A61K47/6849A61K49/0002A61K49/0004A61P9/00A61P9/04A61P9/10A61P37/02A61P43/00C07K16/2803C07K16/2896G01N33/56972G01N2800/325G01N2800/52
Inventor 卡斯滕·乔普H-P·舒尔特海斯菲利斯塔斯·艾雪汉斯-迪特尔·沃尔克佩特拉·赖因克
Owner 夏里特柏林大学医学院