Antibodies Against Phosphorylcholine In Combination Therapy with Biologic Agents

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.

1 . 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. 
     
     
         2 . Antibodies according to  claim 1  for curing, treating, preventing, and/or reducing the risk of developing autoimmune diseases, chronic inflammatory diseases, or cancerous diseases in a mammal. 
     
     
         3 . Antibodies against PC, PC conjugate or bioactive components and/or fragments thereof for immunization, treating, preventing, and/or reducing the risk of developing autoimmune diseases, chronic inflammatory diseases, and cancerous diseases in a mammal, said mammal being in therapy with one or more biologic agents and/or stem cells. 
     
     
         4 . A composition comprising antibodies according to  claim 1 ,  2  or  3 , in combination with one or more biologic agents and/or stem cells. 
     
     
         5 . A composition according to  claim 4  for use as a medicament. 
     
     
         6 . A composition according to  claim 5  for curing, treating, preventing, and/or reducing the risk of developing autoimmune diseases, chronic inflammatory diseases, or cancerous diseases in a mammal. 
     
     
         7 . Antibodies against PC, PC conjugate or bioactive components and/or fragments thereof according to  claim 1 ,  2  or  3  or a composition according to  claim 4 ,  5  or  6  wherein said antibodies against PC, PC conjugate or bioactive components and/or fragments thereof is selected from the group comprising a monoclonal, polyclonal or chimeric antibody of isotype IgA, IgD, IgE, IgG, IgM, optionally in combination with any suitable excipients or adjuvants. 
     
     
         8 . Antibodies against PC, PC conjugate or bioactive components and/or fragments thereof according to  claim 1 ,  2 ,  3  or  7  or a composition according to  claim 4 ,  5 ,  6  or  7  wherein said mammal is selected from the group comprising rabbits, dogs, cats, horses and humans. 
     
     
         9 . Antibodies against PC, PC conjugate or bioactive components and/or fragments thereof according to  claim 1 ,  2 ,  3 ,  7  or  8  or a composition according to  claim 4 ,  5 ,  6 ,  7  or  8  wherein said biologic agents are selected from the group comprising tumor necrosis factor alpha (TNFa) blockers, such as, but not limited to, etanercept, infliximab, adalimumab, certolizumab pegol, golimumab, Interleukin 1 (IL-1) blockers, such as, but not limited to, anakinra, monoclonal antibodies against B cells, such as, but not limited to, rituximab, T cell costimulation blocker, such as, but not limited to, abatacept, Interleukin 6 (IL-6) blockers, such as, but not limited to, tocilizumab, or other antibodies, such as, but not limited to, antibodies against oxidized phospholipids and/or oxidized lipoproteins and/or fragments or derivatives thereof, such as, but not limited to, antibodies against apoB100 and/or fragments or derivatives thereof, anti-MDA-LDL, anti-OxLDL, anti-oxCL or anti-oxPS. 
     
     
         10 . Antibodies against PC, PC conjugate or bioactive components and/or fragments thereof according to  claim 2 ,  3 ,  7 ,  8  or  9  or a composition according to  claim 6 ,  7 ,  8  or  9  wherein said autoimmune diseases, chronic inflammatory diseases, and cancer diseases are selected from the group comprising cardiovascular disease (CVD), such as atherosclerosis, atheromatous plaque rupture, myocardial infarction, acute coronary syndrome, stroke, transient ischemic attack (TIA), claudication, angina pectoris, diabetes mellitus type 1 and 2, Alzheimer's disease, dementia in general, rheumatic diseases, acute and/or chronic inflammatory conditions, rheumatoid arthritis, psoriasis, psoriatic arthritis, spondylopathies, such as ankylosing spondylitis, Reiter's Syndrome, systemic lupus erythematosus, dermatomyositis, Sjogren's syndrome, multiple sclerosis, myasthenia gravis, encephalitis, inflammatory bowel disease, arthritis, idiopathic inflammatory myopathies (IIM), dermatomyositis (DM), polymyositis (PM), inclusion body myositis, vasculitis (including Wegeners granulomatosus, Takayasu arteritis, temporal arteritis), polymyalgia rheumatica, bowel disease including Crohn's disease and colitis of different kinds, nephritis, or cancer diseases such as but not limited to non-Hodgkin's lymphoma, colorectal cancer, head and neck cancer and breast cancer and/or other cancer diseases where immunomodulation is used as treatment. 
     
     
         11 . Antibodies against PC, PC conjugate or bioactive components and/or fragments thereof according to  claim 1 ,  2 ,  3 ,  7 ,  8 ,  9  or  10  or a composition according to  claim 4 ,  5 ,  6 ,  7 ,  8 ,  9  or  10  for use in preventing the rupture of atheromatous plaques. 
     
     
         12 . Antibodies against PC, PC conjugate or bioactive components and/or fragments according to  claim 1 ,  2 ,  3 ,  7 ,  8 ,  9  or  10  or a composition according to  claim 4 ,  5 ,  6 ,  7 ,  8 ,  9  or  10  for use in preventing or treating cancer. 
     
     
         13 . 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. 
     
     
         14 . PC conjugates, PC or bioactive components and/or fragments according to  claim 13  wherein said mammal is selected from the group comprising rabbits, dogs, cats, horses and humans. 
     
     
         15 . PC conjugate, PC or bioactive components and/or fragments according to  claim 13  or  14  wherein said biologic agents are selected from the group comprising tumor necrosis factor alpha (TNFa) blockers, such as, but not limited to, etanercept, infliximab, adalimumab, certolizumab pegol, golimumab, Interleukin 1 (IL-1) blockers, such as, but not limited to, anakinra, monoclonal antibodies against B cells, such as, but not limited to, rituximab, T cell costimulation blocker, such as, but not limited to, abatacept, Interleukin 6 (IL-6) blockers, such as, but not limited to, tocilizumab, or other antibodies, such as, but not limited to, antibodies against oxidized phospholipids and/or oxidized lipoproteins and/or fragments or derivatives thereof, such as, but not limited to, antibodies against apoB100 and/or fragments or derivatives thereof, anti-MDA-LDL, anti-OxLDL, anti-oxCL or anti-oxPS. 
     
     
         16 . PC conjugates, PC or bioactive components and/or parts/fragments thereof according to  claim 13 ,  14  or  15  wherein said autoimmune diseases, and chronic inflammatory diseases, and cancer diseases are selected from the group comprising cardiovascular disease (CVD), such as atherosclerosis, atheromatous plaque rupture, myocardial infarction, acute coronary syndrome, stroke, transient ischemic attack (TIA), claudication, angina pectoris, diabetes mellitus type 1 and 2, Alzheimer's disease, dementia in general, rheumatic diseases, acute and/or chronic inflammatory conditions, rheumatoid arthritis, psoriasis, psoriatic arthritis, spondylopathies, such as ankylosing spondylitis, Reiter's Syndrome, systemic lupus erythematosus, dermatomyositis, Sjogren's syndrome, multiple sclerosis, myasthenia gravis, encephalitis, inflammatory bowel disease, arthritis, idiopathic inflammatory myopathies (IIM), dermatomyositis (DM), polymyositis (PM), inclusion body myositis, vasculitis (including Wegeners granulomatosus, Takayasu arteritis, temporal arteritis), polymyalgia rheumatica, bowel disease including Crohn's disease and colitis of different kinds, nephritis, or cancer diseases such as but not limited to non-Hodgkin's lymphoma, colorectal cancer, head and neck cancer and breast cancer and/or other cancer diseases where immunomodulation is used as treatment. 
     
     
         17 . PC conjugates, PC or bioactive components and/or parts/fragments thereof according to  claim 13 ,  14 ,  15  or  16  for use in preventing the rupture of atheromatous plaques. 
     
     
         18 . PC conjugates, PC or bioactive components and/or parts/fragments thereof according to  claim 13 ,  14 ,  15  or  16  for use in preventing or treating cancer. 
     
     
         19 . Use of antibodies against phosphorylcholine (PC), PC conjugate or bioactive components and/or fragments thereof in the preparation of a medicament for use in combination therapy with one or more biologic agents and/or stem cells in a mammal. 
     
     
         20 . Use of antibodies against PC, PC conjugate or bioactive components and/or fragments thereof in combination therapy with one or more biologic agents and/or stem cells for curing, treating, preventing, and/or reducing the risk of developing autoimmune diseases, chronic inflammatory diseases, or cancerous diseases in a mammal. 
     
     
         21 . Use of antibodies against PC, PC conjugate or bioactive components and/or fragments thereof for immunization, treating, preventing, and/or reducing the risk of developing autoimmune diseases, chronic inflammatory diseases, and cancerous diseases in a mammal, said mammal being in therapy with one or more biologic agents and/or stem cells. 
     
     
         22 . Use according to  claim 19 ,  20  or  21  wherein said antibodies against PC, PC conjugate or bioactive components and/or fragments thereof is selected from the group comprising a monoclonal, polyclonal or chimeric antibody of isotype IgA, IgD, IgE, IgG, IgM, optionally in combination with any suitable excipients or adjuvants. 
     
     
         23 . Use according to  claim 19 ,  20 ,  21  or  22  wherein said mammal is selected from the group comprising rabbits, dogs, cats, horses and humans. 
     
     
         24 . Use according to  claim 19 ,  20 ,  21 ,  22  or  23  wherein said biologic agents are selected from the group comprising tumor necrosis factor alpha (TNFa) blockers, such as, but not limited to, etanercept, infliximab, adalimumab, certolizumab pegol, golimumab, Interleukin 1 (IL-1) blockers, such as, but not limited to, anakinra, monoclonal antibodies against B cells, such as, but not limited to, rituximab, T cell costimulation blocker, such as, but not limited to, abatacept, Interleukin 6 (IL-6) blockers, such as, but not limited to, tocilizumab, or other antibodies, such as, but not limited to, antibodies against oxidized phospholipids and/or oxidized lipoproteins and/or fragments or derivatives thereof, such as, but not limited to, antibodies against apoB100 and/or fragments or derivatives thereof, anti-MDA-LDL, anti-OxLDL, anti-oxCL or anti-oxPS. 
     
     
         25 . Use according to  claim 19 ,  20 ,  21 ,  22 ,  23  or  24  wherein said autoimmune diseases, chronic inflammatory diseases, and cancer diseases are selected from the group comprising cardiovascular disease (CVD), such as atherosclerosis, atheromatous plaque rupture, myocardial infarction, acute coronary syndrome, stroke, transient ischemic attack (TIA), claudication, angina pectoris, diabetes mellitus type 1 and 2, Alzheimer's disease, dementia in general, rheumatic diseases, acute and/or chronic inflammatory conditions, rheumatoid arthritis, psoriasis, psoriatic arthritis, spondylopathies, such as ankylosing spondylitis, Reiter's Syndrome, systemic lupus erythematosus, dermatomyositis, Sjogren's syndrome, multiple sclerosis, myasthenia gravis, encephalitis, inflammatory bowel disease, arthritis, idiopathic inflammatory myopathies (IIM), dermatomyositis (DM), polymyositis (PM), inclusion body myositis, vasculitis (including Wegeners granulomatosus, Takayasu arteritis, temporal arteritis), polymyalgia rheumatica, bowel disease including Crohn's disease and colitis of different kinds, nephritis, or cancer diseases such as but not limited to non-Hodgkin's lymphoma, colorectal cancer, head and neck cancer and breast cancer and/or other cancer diseases where immunomodulation is used as treatment. 
     
     
         26 . Use of antibodies against phosphorylcholine (PC), PC conjugate or bioactive components and/or fragments thereof in preventing the rupture of atheromatous plaques. 
     
     
         27 . Use of antibodies against phosphorylcholine (PC), PC conjugate or bioactive components and/or fragments thereof in preventing or treating cancer. 
     
     
         28 . Use of PC conjugates, PC or bioactive components and/or parts/fragments thereof 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. 
     
     
         29 . Use according to  claim 28  wherein said mammal is selected from the group comprising rabbits, dogs, cats, horses and humans. 
     
     
         30 . Use according to  claim 28  or  29  wherein said biologic agents are selected from the group comprising tumor necrosis factor alpha (TNFa) blockers, such as, but not limited to, etanercept, infliximab, adalimumab, certolizumab pegol, golimumab, Interleukin 1 (IL-1) blockers, such as, but not limited to, anakinra, monoclonal antibodies against B cells, such as, but not limited to, rituximab, T cell costimulation blocker, such as, but not limited to, abatacept, Interleukin 6 (IL-6) blockers, such as, but not limited to, tocilizumab, or other antibodies, such as, but not limited to, antibodies against oxidized phospholipids and/or oxidized lipoproteins and/or fragments or derivatives thereof, such as, but not limited to, antibodies against apoB100 and/or fragments or derivatives thereof, anti-MDA-LDL, anti-OxLDL, anti-oxCL or anti-oxPS. 
     
     
         31 . Use according to  claim 28 ,  29  or  30  wherein said said autoimmune diseases, and chronic inflammatory diseases, and cancer diseases are selected from the group comprising cardiovascular disease (CVD), such as atherosclerosis, atheromatous plaque rupture, myocardial infarction, acute coronary syndrome, stroke, transient ischemic attack (TIA), claudication, angina pectoris, diabetes mellitus type 1 and 2, Alzheimer's disease, dementia in general, rheumatic diseases, acute and/or chronic inflammatory conditions, rheumatoid arthritis, psoriasis, psoriatic arthritis, spondylopathies, such as ankylosing spondylitis, Reiter's Syndrome, systemic lupus erythematosus, dermatomyositis, Sjogren's syndrome, multiple sclerosis, myasthenia gravis, encephalitis, inflammatory bowel disease, arthritis, idiopathic inflammatory myopathies (IIM), dermatomyositis (DM), polymyositis (PM), inclusion body myositis, vasculitis (including Wegeners granulomatosus, Takayasu arteritis, temporal arteritis), polymyalgia rheumatica, bowel disease including Crohn's disease and colitis of different kinds, nephritis, or cancer diseases such as but not limited to non-Hodgkin's lymphoma, colorectal cancer, head and neck cancer and breast cancer and/or other cancer diseases where immunomodulation is used as treatment. 
     
     
         32 . Use of PC conjugates, PC or bioactive components and/or parts/fragments thereof in preventing the rupture of atheromatous plaques. 
     
     
         33 . Use of PC conjugates, PC or bioactive components and/or parts/fragments thereof in preventing or treating cancer. 
     
     
         34 . A composition comprising phosphorylcholine (PC), PC conjugate and/or bioactive components and/or fragments thereof in combination with biologic agents and/or stem cells. 
     
     
         35 . Antibodies against PC, PC conjugate or bioactive components and/or fragments thereof according to  claim 1 ,  2 ,  3 ,  7 ,  8 ,  9 ,  10 ,  11  or  12  or a composition according to  claim 4 ,  5 ,  6 ,  7 ,  8 ,  9 ,  10 ,  11  or  12  wherein said biologic agents comprise one or more antibodies selected from the list consisting of antibodies against apoB100 and/or fragments or derivatives thereof, anti-MDA-LDL, anti-OxLDL, anti-oxCL and anti-oxPS. 
     
     
         36 . PC conjugates, PC or bioactive components and/or parts/fragments thereof according to  claim 13 ,  14 ,  15 ,  16 ,  17  or  18  wherein said biologic agents comprise one or more antibodies selected from the list consisting of antibodies against apoB100 and/or fragments or derivatives thereof, anti-MDA-LDL, anti-OxLDL, anti-oxCL and anti-oxPS. 
     
     
         37 . Use according to  claim 19 ,  20 ,  21 ,  22 ,  23 ,  24 ,  25 ,  28 ,  29 ,  30  or  31  wherein said biologic agents comprise one or more antibodies selected from the list consisting of antibodies against apoB100 and/or fragments or derivatives thereof, anti-MDA-LDL, anti-OxLDL, anti-oxCL and anti-oxPS. 
     
     
         38 . A composition according to  claim 34  wherein said biologic agents comprise one or more antibodies selected from the list consisting of antibodies against apoB100 and/or fragments or derivatives thereof, anti-MDA-LDL, anti-OxLDL, anti-oxCL and anti-oxPS.