Antibodies Against Phosphorylcholine In Combination Therapy with Biologic Agents

a technology of phosphorylcholine and biologic agents, which is applied in the direction of drug compositions, immunological disorders, metabolism disorders, etc., can solve the problems of increased risk of cvdsup>16-18 etc., to achieve anti-inflammatory properties, low levels of anti-pc, and lack of response

Inactive Publication Date: 2013-01-03
MEDIRISTA BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009]In summary, low levels of anti-PC predict a lack of response to treatment with biologics in RA. It has previously been demonstrated that anti-PC have anti-inflammatory properties by inhibiting effects of inflammatory phospholipids like PAF20. This finding indicates that treatment to inhibit such inflammatory reactions promoted by inflammatory phospholipids could potentiate the effect of biologics.

Problems solved by technology

Further, low anti-PC levels are independently associated with increased risk of CVD16-18.

Method used

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  • Antibodies Against Phosphorylcholine In Combination Therapy with Biologic Agents
  • Antibodies Against Phosphorylcholine In Combination Therapy with Biologic Agents
  • Antibodies Against Phosphorylcholine In Combination Therapy with Biologic Agents

Examples

Experimental program
Comparison scheme
Effect test

example 2

Inhibition of Lysophosphatidylcholine Induced Cell Death by Anti-PC IgM

[0117]Peripheral blood mononuclear cells (PBMC) in 96 well plates (with 300,000 cells / well) were incubated with lysophosphatidylcholine (LPC) for 2 h, and cell death was assessed by measuring lactate dehydrogenase (LDH) activity in the supernatant. Antibodies against phosphorylcholine (anti-PC IgM) or control antibodies which did not bind PC, were preincubated with LPC 90 minutes before starting the treatment. The results were expressed as units per liter of LDH. As can be seen from FIG. 3, anti-PC IgM reduced cell death more than total IgM and flowthrough IgM.

[0118]PBMC (3,000,000 cells / well) were incubated with LPC for 18 h, and cell death was assessed by measuring the decrease in mitochondrial dependent reduction of MTT to formazin. Anti-PC, total IgM and IgM which did not bind PC (flow through) were preincubated with LPC 90 minutes before starting the treatment. The results were expressed as percentage of via...

example 3

Protective Effect of Combination of High Anti-PC with High Anti-MDA-LDL or High Anti-OxLDL

ELSA-study

Materials and Methods

Subjects

[0119]Serum samples were obtained from 226 subjects with established hypertension (diastolic pressure >95 mm Hg) prior to their entry into the Swedish component of the European Lacidipine Study on Atherosclerosis (ELSA)44, 45. Samples were collected following a 4-week washout period without medication to minimize the effects of treatment on the measured parameters. Blood pressure, cholesterol and triglyceride levels were determined as described previously44, 45 One hundred and fifteen of the subjects were subsequently assigned to treatment with the β-blocker atenolol, and 111 of the subjects were assigned to treatment with the calcium antagonist lacidipine.

[0120]Carotid ultrasound determinations were performed and analysed as detailed elsewhere19,44,45. A total of 226 patients had valid ultrasound measurements at baseline and after 4 years of follow up. Br...

example 4

Increased Risk of CVD from Combination of Low IgM Anti-PC with Low Anti-OxCL or Low Anti-OxPS

Study of 60-Year Olds

[0127]Objective.

[0128]We here determine the role of IgM antibodies against phosphorylcholine (anti-PC) in combination with antibodies against oxidized cardiolipin (anti-OxCL) or antibodies against oxidized phosphatidylserine (anti-OxPS) in prediction of cardiovascular disease (CVD).

[0129]Methods.

[0130]From a screening of 4232 subjects, 60-years old (2039 men and 2193 women), 211 incident cases of CVD (myocardial infarction, ischemic stroke, or hospitalized angina pectoris) and 633 age- and sex-matched controls were identified through a 5-7 year follow-up18,46,47. Serum levels of antibodies was determined by ELISA. Cardiolipin and phosphatidylserine was oxidized in aqueous solutions containing 1.5 mmol / L tert-butylhydroperoxide and CuSO4 in 20 μmol / L.

[0131]Results.

[0132]In women, there were no significant associations between anti-PC and CVD. Among men, individuals with a...

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Abstract

Antibodies against PC, PC conjugate or bioactive components and/or fragments thereof for use in combination therapy with one or more biologic agents and/or stem cells are disclosed, as well as compositions comprising the antibodies in combination with one or more biologic agents and/or stem cells. Also disclosed are PC conjugates, PC or bioactive components and/or parts/fragments thereof for use in activation immunotherapy prior to or in combination with treatment with biologic agents and/or stem cells for curing, treating, preventing, and/or reducing the risk of developing auto-immune diseases, chronic inflammatory diseases, and cancer diseases, as well as compositions comprising them in combination with biologic agents and/or stem cells.

Description

FIELD OF THE INVENTION[0001]This invention relates to antibodies against PC, PC conjugate or bioactive components and / or fragments thereof for use in combination therapy with one or more biologic agents and / or stem cells in a mammal, as well as to compositions comprising the antibodies in combination with one or more biologic agents and / or stem cells. It also relates to PC conjugates, PC or bioactive components and / or parts / fragments thereof for use in activation immunotherapy in a mammal prior to or in combination with the treatment of a mammal with biologic agents and / or stem cells for curing, treating, preventing, and / or reducing the risk of developing autoimmune diseases, chronic inflammatory diseases, and cancer diseases, as well as compositions comprising them in combination with biologic agents and / or stem cells. It also relates to the use of antibodies against phosphorylcholine (PC), PC conjugate or bioactive components and / or fragments thereof in combination therapy with on...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K16/18C07F9/09A61K39/00A61P37/06A61P29/00A61P35/00A61P9/00A61P9/10A61P3/10A61P25/28A61P19/02A61P17/06A61P17/00A61P25/00A61P21/04A61P1/00A61P21/00A61P13/12A61P37/04A61K39/395
CPCC07K16/241A61K2039/505C07K16/2887A61P1/00A61P3/10A61P9/00A61P9/10A61P13/12A61P17/00A61P17/06A61P19/02A61P21/00A61P21/04A61P25/00A61P25/28A61P29/00A61P35/00A61P37/04A61P37/06A61K35/28A61K39/39533C07K14/525C07K16/18C07K2317/21C07K2317/24C07K2319/30
Inventor FROSTEGARD, JOHAN
Owner MEDIRISTA BIOTECH
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