ErbB antagonists for pain therapy

Abstract

The present application describes the use of ErbB antagonist, especially ErbB2 antibodies such as rhuMAb 2C4, for treating pain.

1 . A method of treating pain in a patient comprising administering an ErbB antagonist to the patient in a dose confirmed to reduce or eliminate the pain or the analgesia requirement of the patient.  
     
     
         2 . The method of  claim 1  wherein pain is measured by a pain score or quality of life score reflective of pain.  
     
     
         3 . The method of  claim 2  wherein pain is measured by the McGill Pain Index on a six point scale of 0 to 5.  
     
     
         4 . The method of  claim 2  wherein pain is measured using a visual analog scale of 0-100 reflective of the subjective feeling of pain of the patient.  
     
     
         5 . The method of  claim 1  wherein analgesia requirement is measured using an analgesia score.  
     
     
         6 . The method of  claim 5  wherein one dose of a non-steroidal analgesic agent corresponds to an analgesia score of 1, and one 10 mg dose of morphine, or an equivalent dose of another opiate analgesic agent corresponds to an analgesia score of 2.  
     
     
         7 . The method of  claim 1  wherein pain is monitored daily.  
     
     
         8 . The method of  claim 1  wherein analgesia requirement is monitored daily.  
     
     
         9 . The method of  claim 1  wherein the antagonist is an antibody that binds an ErbB.  
     
     
         10 . The method of  claim 9  wherein the antibody blocks ligand activation of an ErbB.  
     
     
         11 . The method of  claim 9  wherein the antibody blocks formation of an ErbB heterodimer.  
     
     
         12 . The method of  claim 9  wherein the antibody blocks binding of monoclonal antibody 2C4 to ErbB2.  
     
     
         13 . The method of  claim 9  wherein the antibody has a biological characteristic of monoclonal antibody 2C4.  
     
     
         14 . The method of  claim 9  wherein the antibody comprises monoclonal antibody 2C4 or humanized 2C4.  
     
     
         15 . The method of  claim 9  wherein the antibody is an antibody fragment.  
     
     
         16 . The method of  claim 15  wherein the antibody fragment is a Fab fragment.  
     
     
         17 . The method of  claim 9  wherein the antibody is not conjugated with a cytotoxic agent.  
     
     
         18 . The method of  claim 9  wherein the antibody is conjugated with a cytotoxic agent.  
     
     
         19 . The method of  claim 15  wherein the antibody fragment is not conjugated with a cytotoxic agent.  
     
     
         20 . The method of  claim 15  wherein the antibody fragment is conjugated with a cytotoxic agent.  
     
     
         21 . The method of  claim 1  wherein the pain is chronic pain.  
     
     
         22 . The method of  claim 21  wherein the chronic pain is selected from the group consisting of nociceptive pain, neuropathic pain and psychogenic pain.  
     
     
         23 . The method of  claim 22  wherein the pain is nociceptive pain.  
     
     
         24 . The method of  claim 1  wherein the pain is cancer related pain.  
     
     
         25 . The method of  claim 24  wherein the cancer expresses an ErbB receptor.  
     
     
         26 . The method of  claim 25  wherein the ErbB receptor is ErbB2 or EGFR.  
     
     
         27 . The method of  claim 24  wherein the cancer is metastatic cancer.  
     
     
         28 . The method of  claim 27  wherein the pain is associated with cancer metastasis.  
     
     
         29 . The method of  claim 26  wherein the cancer is prostate cancer.  
     
     
         30 . The method of  claim 29  wherein the metastasis is bone metastasis.  
     
     
         31 . The method of  claim 24  wherein the cancer is selected from the group consisting of breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, squamous cell cancer, lung cancer, cancer of the peritoneum, hepatocellular cancer, gastric cancer, glioblastoma, cervical cancer, liver cancer, bladder cancer, hepatoma, colon cancer, rectal cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, and head and neck cancer.  
     
     
         32 . The method of  claim 31  wherein the cancer is prostate cancer.  
     
     
         33 . The method of  claim 32  wherein the cancer is androgen independent prostate cancer.  
     
     
         34 . The method of  claim 24  wherein the cancer is not in remission or continues to grow during treatment.  
     
     
         35 . The method of  claim 1  wherein the pain is non-cancer related.  
     
     
         36 . The method of  claim 1  wherein the patient is not suffering from malignancy.  
     
     
         37 . A method for treating cancer-related pain in a patient diagnosed with cancer, comprising administering an effective amount of an ErbB antagonist to the patient, wherein the cancer is not in remission or continues to grow during said treatment.  
     
     
         38 . The method of  claim 37  wherein the cancer is not in remission during said treatment.  
     
     
         39 . The method of  claim 37  wherein the cancer continues to grow during said treatment.  
     
     
         40 . The method of  claim 37  wherein the cancer is selected from the group consisting of breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, squamous cell cancer, lung cancer, cancer of the peritoneum, hepatocellular cancer, gastric cancer, glioblastoma, cervical cancer, liver cancer, bladder cancer, hepatoma, colon cancer, rectal cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, and head and neck cancer.  
     
     
         41 . The method of  claim 37  wherein the cancer is metastatic cancer.  
     
     
         42 . The method of  claim 41  wherein the metastasis is soft tissue metastasis.  
     
     
         43 . The method of  claim 41  wherein the metastasis includes bone metastasis.  
     
     
         44 . The method of  claim 40  wherein the cancer is prostate cancer.  
     
     
         45 . The method of  claim 44  wherein the cancer is androgen independent prostate cancer.  
     
     
         46 . The method of  claim 44  wherein the patient's PSA shows no reduction during treatment.  
     
     
         47 . The method of  claim 44  wherein the patient's PSA becomes elevated during treatment.  
     
     
         48 . The method of  claim 37  wherein the antagonist is an antibody that binds an ErbB.  
     
     
         49 . The method of  claim 48  wherein the antibody blocks ligand activation of an ErbB.  
     
     
         50 . The method of  claim 48  wherein the antibody blocks formation of an ErbB heterodimer.  
     
     
         51 . The method of  claim 48  wherein the antibody blocks binding of monoclonal antibody 2C4 to ErbB2.  
     
     
         52 . The method of  claim 48  wherein the antibody has a biological characteristic of monoclonal antibody 2C4.  
     
     
         53 . The method of  claim 48  wherein the antibody comprises monoclonal antibody 2C4 or humanized 2C4.  
     
     
         54 . The method of  claim 48  wherein the antibody is an antibody fragment.  
     
     
         55 . The method of  claim 54  wherein the antibody fragment is a Fab fragment.  
     
     
         56 . The method of  claim 48  wherein the antibody is not conjugated with a cytotoxic agent.  
     
     
         57 . The method of  claim 48  wherein the antibody is conjugated with a cytotoxic agent.  
     
     
         58 . The method of  claim 54  wherein the antibody fragment is not conjugated with a cytotoxic agent.  
     
     
         59 . The method of  claim 54  wherein the antibody fragment is conjugated with a cytotoxic agent.  
     
     
         60 . A method for treating non-cancer related pain in a patient comprising administering an effective amount of an ErbB antagonist to the patient.  
     
     
         61 . The method of  claim 60  wherein the antagonist is an anti-ErbB antibody.  
     
     
         62 . The method of  claim 61  wherein the antibody blocks ligand activation of an ErbB.  
     
     
         63 . The method of  claim 61  wherein the antibody blocks formation of an ErbB heterodimer.  
     
     
         64 . The method of  claim 61  wherein the antibody blocks binding of monoclonal antibody 2C4 to ErbB2.  
     
     
         65 . The method of  claim 61  wherein the antibody has a biological characteristic of monoclonal antibody 2C4.  
     
     
         66 . The method of  claim 61  wherein the antibody comprises monoclonal antibody 2C4 or humanized 2C4.  
     
     
         67 . The method of  claim 61  wherein the antibody is an antibody fragment.  
     
     
         68 . The method of  claim 67  wherein the antibody fragment is a Fab fragment.  
     
     
         69 . A kit comprising an effective amount of an ErbB antagonist, and instructions to administer said antagonist for the treatment of pain.  
     
     
         70 . The kit of  claim 69  wherein the antagonist is an antibody that binds an ErbB.  
     
     
         71 . The kit of  claim 70  wherein the antibody blocks ligand activation of an ErbB.  
     
     
         72 . The kit of  claim 70  wherein the antibody blocks formation of an ErbB heterodimer.  
     
     
         73 . The kit of  claim 70  wherein the antibody blocks binding of monoclonal antibody 2C4 to ErbB2.  
     
     
         74 . The kit of  claim 70  wherein the antibody has a biological characteristic of monoclonal antibody 2C4.  
     
     
         75 . The kit of  claim 70  wherein the antibody comprises monoclonal antibody 2C4 or humanized 2C4.  
     
     
         76 . The kit of  claim 70  wherein the antibody is an antibody fragment.  
     
     
         77 . The kit of  claim 76  wherein the antibody fragment is a Fab fragment.  
     
     
         78 . The kit of  claim 69  wherein the pain is cancer-related.  
     
     
         79 . The kit of  claim 69  wherein the pain is non-cancer related.  
     
     
         80 . The kit of  claim 69  wherein the pain is chronic pain.