| Sonstiges: |
- Nachgewiesen in: USPTO Patent Applications
- Sprachen: English
- Document Number: 20050153329
- Publication Date: July 14, 2005
- Appl. No: 10/997985
- Application Filed: November 29, 2004
- Claim: 1. Method for analysing the amount of tumour derived substances, including receptor-bound immune complexes and proteolytic fragments of tumour tissue substances, wherein said tumor derived substances is a fragment of extracellular matrix, including collagen, fibronectin, and laminin, or a fragment of blood proteins, including albumin, immunoglobulin, and fibrinogen isolated from tumour tissue, blood or urine from cancer patients, characterised in that they have an activity at a molecular weight of 3 to 30 kDa, that they have a capacity to bind to tumour or immune cell receptors and induce the production of cytokines determined in cultures of normal peripheral blood mononuclear cells, whereby the amount of such dys-regulatory mechanism substances is determined by utilising binding substances including antibodies directed to these substances or probes complementary to their DNA and/or RNA in a tissue sample, whereby the prognosis of a subject suffering from cancer can be determined and/or the therapeutic efficacy of any anti-cancer treatment can be predicted and monitored.
- Claim: 2. Method according to claim 1, for diagnosis of concomitant immunity phenomena by analysing the presence of dysregulatory factors of claim 1.
- Claim: 3. Method according to claim 1, wherein tissue is whole blood, serum, plasma, lymphatic fluid, saliva, urine, faeces, ascites, pleural effusion, pus, as well as any tissue, including inflammatory cells.
- Claim: 4. Method according to claim 1, wherein any compound having the ability of inhibiting the production, activation or activity of enzymes generating fragments of intra-tumoural tissue are determined.
- Claim: 5. Method according to claim 1, wherein any fragment or new epitopes generated by the activity of intratumoural enzymes is determined in any tissue from a cancer patient.
- Claim: 6. Method according to claim 3, wherein the activity of any compound having the ability of inhibiting the production, activation or activity of enzymes generating fragments is monitored by determining these fragments or new epitopes exposed by the enzymatic activity in any tissue from a cancer patient.
- Claim: 7. Method according to claim 6, wherein the inhibiting compound is a matrix metalloproteinase inhibitor.
- Claim: 8. Method according to claim 1, wherein any compound blocking production or biological activity of a factor inducing pathological production of any dys-regulatory mechanism of immunoregulatory substances, including one or more cytokines, including IL-1β, IL-1Ra, IL-6, IL-10, IL-17, TNF-α, and others including enzymes, production, is determined.
- Claim: 9. Method according to claim 1, wherein the amount of any inducing factor or mRNA thereof inducing the production of immunoregulatory substances, including one or more cytokines including IL-1β, IL-1Ra, IL-6, IL-10, IL-17, TNF-α and others, found in tissue, is determined by determining the production of immunoregulatory substances, including cytokines, including IL-1Ra, IL-6, IL-1β and/or TNF-α and others produced by PBMC after exposure to these factors.
- Claim: 10. Method according to claim 1, wherein samples are obtained in a way, including tubes and syringes, not binding or inactivating immunoregulatory substances, including inducing factors.
- Claim: 11. Method according to claim 1, wherein the amount of any inducing factor inducing the production of immunoregulatory substances, including one or more cytokines including IL-1β, IL-1Ra, IL-6, IL-10, IL-17, TNF-α, and others, is determined directly.
- Claim: 12. Method according to claim 1, wherein the amount of any urine present inducing factor inducing the production of immunoregulatory substances, including IL-1β, IL-1Ra, IL-6, IL-10, IL-17, TNF-α, and others, is determined by using an urine dip stick containing binding substance/s binding said inducing factor and/or colour developing reagents to said inducing factor.
- Claim: 13. Method according to claim 1, wherein the amount of cell bound immune complexes, CBIC, is determined.
- Claim: 14. Method according to claim 1, wherein peripheral blood mononuclear cells PBMC being positive for any immunoglobulin staining are determined.
- Claim: 15. Method according to claim 1, wherein IL-1Ra is determined.
- Claim: 16. Method according to claim 1, wherein down-regulation of CD28 on CD4+ and/or CD8+ lymphocytes is determined.
- Claim: 17. Method according to claim 1, wherein down-regulation of CD80 and/or CD86 is determined.
- Claim: 18. Method according to claim 1, wherein determination of any other modulation of other immunoregulatory substances is made.
- Claim: 19. Method according to claim 18, wherein the assay utilises any tissue and the determinations are made using any immuno-cyto-histochemical method, as electrophoresis, chromatography, any immunoassay including, ELISA, Elispot, RIA and others any blotting technique, including Western blotting, Southern blotting and others, any bioassay, any tissue culture technique, RT-PCR, flow cytometry, cytometric bead array, DNA microarray and/or proteomics.
- Claim: 20. Method according to claim 1, wherein dys-regulatory mechanism substances in tissue from cancer patients, which substances suppress the immune mediated systemic protection resulting in establishment of micrometastases, are identified.
- Claim: 21. Method according to claim 1 for diagnosing of presence/absence of cancer by identifying pathological immunoregulatory substances in cancer and diagnosis of cancer related/tumour derived tissue factor of importance for a cancer patient's performance status, immune mediated anti-tumour reactivity, systemic protection of metastatic disease of a patient suffering from cancer and response to treatment including immuno-, chemo-, bio- and radiotherapy.
- Claim: 22. Method according to claim 21, wherein said factor is present in tumour tissue and body fluids.
- Claim: 23. Method according to claim 21, wherein said factor has the ability of inducing cytokines or other immunoregulatory substances.
- Claim: 24. Method according to claim 21, wherein said factor directly or indirectly has the ability of inducing production of proteolytic enzymes by tumour cells or inflammatory cells.
- Claim: 25. The use of at least one regulatory mechanism controlling factor of at least tumour derived substances, including receptor-bound immune complexes and proteolytic fragments of tumour tissue substances, wherein said tumor derived substances is a fragment of extracellular matrix, including collagen, fibronectin, and laminin, or a fragment of blood proteins, including albumin, immunoglobulin, and fibrinogen isolated from tumour tissue, blood or urine from cancer patients, characterised in that they have an ctivity at a molecular weight of 3 to 30 kDa, that they have a capacity to bind to tumour or immune cell receptors and induce the production of cytokines determined in cultures of normal peripheral blood mononuclear cells, for the production of a pharmaceutical preparation to be used for therapeutic control and for minimisation of pathological production of immunosuppresive immunoregulatory substances, including IL-1β, IL-1Ra, IL-6, IL-10, IL-17, and/or TNF-α, and others, including enzymes or to stimulate production of immunosupportive immunoregulatory substances in a patient suffering from a cancer and to enhance the efficacy and/or possibility of therapeutic treatment of cancer or modulation of dys-regulatory factors to enhance performance status.
- Claim: 26. Use according to claim 25, wherein a FcR modulating agent is used in the manufacture of a pharmaceutical preparation for controlling immunoregulatory substances, including one or more cytokines, including IL-1β, IL-1Ra, IL-6, IL-10, IL-17, and/or TNF-α, and others, production in a patient suffering from cancer by therapeutically modulating FcR activity, such as blocking FcR/FcγR activity or cross-linking FcR/FcγR activity.
- Claim: 27. Use according to claim 25, wherein at least one immunoglobulin, FcR antibodies or fragments of antibodies or synthetic constructs including peptides directed to FcR is used in the manufacture of a pharmaceutical preparation for blocking or cross-linking FcR cross-linking.
- Claim: 28. Use according to claim 26, wherein an agent modulating FcγR I, FcγR II and/or FcγR III used to stimulate IL-2 stimulation of clonal expansion of lymphocytes is used in the manufacture of a pharmaceutical preparation.
- Claim: 29. Use according to claim 26, wherein at least one FcR-modulating soluble receptor, fragment, peptide or synthetic construct directed to the Fc-part of immunoglobulins is used in the manufacture of a pharmaceutical preparation.
- Claim: 30. Use according to claim 26, wherein at least one FcR-modulating enzyme inhibitor is used in the manufacture of a pharmaceutical preparation.
- Claim: 31. Use according to claim 26, wherein at least one FcR-inhibiting matrix metalloproteinase inhibitor is used in the manufacture of a pharmaceutical preparation.
- Claim: 32. Use according to claim 25, wherein any compound including any enzymes, blocking production or biological activity of any factor inducing pathological production of one or more cytokines is used in the manufacture of a pharmaceutical preparation for blocking a factor inducing pathological production of such cytokines.
- Claim: 33. Use according to claim 25, wherein a compound having the ability of inhibiting the activation and/or activity of enzymes generating immunomodulatory fragments is used in the manufacture of a pharmaceutical preparation for inhibiting the activation or activity of enzymes generating immunomodulatory fragments.
- Claim: 34. Use according to claim 25, wherein antibodies directed to enzymes generating immuno-modulatory fragments are used in the manufacture of a pharmaceutical preparation.
- Claim: 35. Use according to claim 25, wherein at least one monoclonal antibody, anti-integrin antibody, peptide and/or synthetic construct thereol is used inl tile manufacture of a pharmaceutical preparation.
- Claim: 36. A pharmaceutical composition comprising a regulatory mechanism controlling factor tumour derived substances, including receptor-bound immune complexes and proteolytic fragments of tumour tissue substances, wherein said tumor derived substances is a fragment of extracellular matrix, including collagen, fibronectin, and laminin, or a fragment of blood proteins, including albumin, immunoglobulin, and fibrinogen isolated from tumour tissue, blood or urine from cancer patients, characterised in that they have an-ctivity at a molecular weight of 3 to 30 kDa, that they have a capacity to bind to tumour or immune cell receptors and induce the production of cytokines determined in cultures of normal peripheral blood mononuclear cells or cell lines, to be used for therapeutically control and minimise pathological production of immunosuppresive immunoregulatory substances including one or more cytokine, or to stimulate production of an immunosupportive immunoregulatory substance in a patient suffering from a cancer to enhance the efficacy and/or possibility of therapeutic treatment of cancer, optionally in combination with therapeutically inert additive to enhance performance status.
- Claim: 37. Pharmaceutical composition according to claim 36, wherein a FcR modulating agent is present in a pharmaceutical preparation for controlling immunoregulatory substances, including one or more cytokine production in a patient suffering from cancer by therapeutically modulating FcR activity.
- Claim: 38. Pharmaceutical composition according to claim 37, wherein a FcR modulating agent is used in tihe manufacture of a pharmaceutical preparation for controlling immunoregulatory substances, including one or more cytokines, including IL-1β, IL-1Ra, IL-6, IL-10, IL-17, TNF-α, and others, including enzymes, production in a patient suffering from cancer is modulated by therapeutically blocking FcR/FcγR activity.
- Claim: 39. Pharmaceutical composition according to claim 37, wherein at least one immunoglobulin, FcR antibodies or fragments of antibodies or synthetic constructs including peptides directed to FcR is used in the manufacture of a pharmaceutical preparation for blocking or cross-linking FcR activity.
- Claim: 40. Pharmaceutical composition according to claim 39, wherein an agent modulating FcγR I, FcγR II and/or FcγR III is present to stimulate IL-2 stimulation of clonal expansion of lymphocytes.
- Claim: 41. Pharmaceutical composition according to claim 39, wherein anti-FcγR I antibodies is present in a pharmaceutical preparation for blocking of FcγR.
- Claim: 42. Pharmaceutical composition according to claim 39, wherein any compound blocking production or biological activity of any factor inducing pathological production of one or more cytokines is used in the manufacture of a pharmaceutical preparation for blocking a factor inducing pathological production of such cytokines.
- Claim: 43. Pharmaceutical composition according to claim 36, wherein a compound having the ability of inhibiting the production, activation of enzymes generating immunomodulatory fragments is present in the pharmaceutical preparation for inhibiting the activation of enzymes generating immunomodulatory fragments.
- Claim: 44. Pharmaceutical composition according to claim 36, wherein a compound blocking a factor inducing pathological production of immunoregulatory substances, including one or more cytokine production is present in the pharmaceutical preparation for blocking a factor inducing pathological production of such immunoregulatory substances.
- Claim: 45. Pharmaceutical composition according to claim 36, wherein antibodies directed to enzymes generating immuno-modulatory fragments are present.
- Claim: 46. Pharmaceutical composition according to claim 36, wherein at least one monoclonal antibody, anti-integrin antibody, peptide and/or synthetic construct thereof, is used.
- Claim: 47. Cancer related/tumour derived tissue factor of importance for a cancer patient's performance status, immune mediated anti-tumour reactivity, systemic protection of metastatic disease of a patient suffering from cancer and response to treatment including immuno-, chemo-, bio- and radiotherapy.
- Claim: 48. Factor according to claim 47, wherein said factor is present in tumour tissue and body fluids.
- Claim: 49. Factor according to claim 47, wherein said factor has the ability of inducing cytokines or other immunoregulatory substances.
- Claim: 50. Factor accordinrg to claim 47, wherein said factor directly or indirectly has the ability of inducing production of proteolytic enzymes by tumour cells or inflammatory cells.
- Claim: 51. Factor according to claim 47, wherein said factor is a fragment of extra cellular matrix, including collagen, fibronectin and laminin.
- Claim: 52. Factor according to claim 47, wherein said factor is a fragment of at least one serum protein.
- Claim: 53. Factor according to claim 52, wherein said factor is a fragment of serum albumin.
- Claim: 54. Factor according to claim 47, wherein said factor is a fragment of at least one immunoglobulin.
- Claim: 55. Factor according to claim 47, wherein said factor is a fragment of fibrinogen.
- Claim: 56. Method for increasing efficacy and/or possibility of therapeutic treatment of cancer, wherein, tumour derived substances, including receptor-bound immune complexes and proteolytic fragments of tumour tissue substances, wherein said tumor derived substances is a fragment of extracellular matrix, including collagen, fibronectin, and laminin, or a fragment of blood proteins, including albumin, immunoglobulin, and fibrinogen isolated from tumour tissue, blood or urine from cancer patients, characterised in that they have an activity at a molecular weight of 3 to 30 kDa, that they have a capacity to bind to tumour or immune cell receptors and induce the production of cytokines determined in cultures of normal peripiheral blood mononuclear cells or cell lines, whereby the amount of such dys-regulatory mechanism substances is therapeutically controlled to minimise pathological production or biological activity of such immunoregulatory substances being immunosuppresive, or to stimulate the production of such immunoregulatory substances being immunosupportive to enhance the performance status of the patient and/or to enhance the therapeutic control of a malignant tumour in a subject suffering from a cancer.
- Claim: 57. Method according to claim 56, wherein the cytokines IL-1β, IL-1Ra, IL-6, IL-10, IL-17, TNF-α, and others, are therapeutically controlled.
- Claim: 58. Method according to claim 56, wherein any dys-regulatory mechanism of immunoregulatory substances, including one or more cytokines, including IL-1β, IL-1Ra, IL-6, IL-10, IL-17, TNF-α and others, production in a patient suffering from cancer is modulated by therapeutically treating the patient to provide a FcR modulation by administering a therapeutically effective amount of a FcR modulating agent, such as a FcR/FcγR blocking agent or a FcR/FcγR cross-linking agent.
- Claim: 59. Method according to claims claim 58, wherein blocking or cross-linking of FcR is carried out using a therapeutically active amount of at least one immunoglobulin, FcR antibodies or fragments of antibodies or synthetic constructs including peptides directed to FcR.
- Claim: 60. Method according to claim 56, wherein a compound having the ability of inhibiting the production, activation or activity of enzymes generating immunomodulatory fragments is administered in a therapeutically effective amount.
- Claim: 61. Method according to claim 60, wherein the inhibiting compound is a monoclonal antibody, an anti-integrin antibody, peptides and/or synthetic constructs.
- Claim: 62. Method according to claim 58, wherein the modulating substance is an enzyme inhibitor.
- Claim: 63. Method according to one or more of the preceding claims claim 58, wherein the inhibiting compound is a matrix metalloproteinase inhibitor.
- Claim: 64. Method according to claim 57, wherein any compound blocking the factor inducing IL-6 production is administered in a therapeutically effective amount.
- Claim: 65. Method according to claim 57, wherein any compound blocking the factor inducing IL-1β production is administered in a therapeutically effective amount.
- Claim: 66. Method according to claim 57, wherein any compound blocking the factor inducing IL-10 production is administered in a therapeutically effective amount.
- Claim: 67. Method according to claim 57, wherein any compound blocking the factor inducing TNF-α production is administered in a therapeutically effective amount.
- Claim: 68. Method according to claim 57, wherein any compound blocking the factor inducing IL-1Ra production is administered in a therapeutically effective amount.
- Claim: 69. Method according to claim 57, wherein monoclonal antibodies directed to enzymes generating immuno-modulatory fragments are administered in a therapeutically effective amount.
- Claim: 70. Method according to claim 57, wherein at least one anti-integrin antibody, peptide or construct is administered in a therapeutically effective amount.
- Claim: 71. Method according to claim 56, for treating cancer by administering a therapeutically active amount of compound to a person suffering from a cancer, which compound inhibits the production and/or biological activity of at least one factor of importance for the performance status of a patient suffering from cancer, immune mediated anti-tumour reactivity of a patient suffering from cancer, systemic protection of metastatic disease of a patient suffering from cancer and response to treatment including immuno-, chemo-, bio- and radiotherapy of a patient suffering from cancer.
- Claim: 72. Method according to claim 71, wherein the fragment to be inhibited is extra cellular matrix derived fragment matrix, including fragments of collagen, fibronectin and laminin.
- Claim: 73. Method according to claim 71, wherein the fragment to be inhibited is a serum protein fragment.
- Claim: 74. Method according to claim 73, wherein the fragment to be inhibited is a serum albumin derived fragment.
- Claim: 75. Method according to claim 71, wherein the fragment to be inhibited is an immunoglobulin derived fragment.
- Claim: 76. Method according to claim 71, wherein the fragment to be inhibited is a fibrinogen derived fragment.
- Claim: 77. Method according to claim 71, wherein a matrix metalloprotease inhibitor having the ability of inhibiting the proteolytic effect of matrix metalloproteases in forming a tissue factor of cancer.
- Claim: 78. Method according to claim 77, wherein the inhibitor has the ability of inhibiting the proteolytic effect of one or more of the matrix metalloproteases, including the group of MMP-1, MMP -2, MMP -3, MMP-7, MMP-13.
- Current U.S. Class: 435006/000
|
