Biological materials and uses thereof

Abstract

The present invention concerns a peptide molecule or a nucleic acid molecule, for use in medicine and, in particular, for use in preventing or treating a non-cancerous condition or relieving pain in a patient. The invention also relates to a pharmaceutical composition comprising the peptide or nucleic acid molecule of the invention and methods of treatment thereof.

1 . An isolated or recombinant peptide molecule comprising or consisting of a polypeptide sequence selected from the group: 
       
         
           
                 
                 
               
                     
                   (i) 
                 
                     
                   MSKLIEYDETARRAMEVGMDKLADTVRVT; 
                 
                     
                     
                 
                     
                   (ii) 
                 
                     
                   LGPRGRHVVLAKAFGGPTVTN; 
                 
                     
                     
                 
                     
                   (iii) 
                 
                     
                   DGVTVAREIELEDPFEDLGAQLVKSVATKTNDV; 
                 
                     
                     
                 
                     
                   (iv) 
                 
                     
                   AGDGTTTATILAQALIKGGLRLVAAGVN; 
                 
                     
                     
                 
                     
                   (v) 
                 
                     
                   PIALGVGIGKAADAVSEALLASATP; 
                 
                     
                     
                 
                     
                   (vi) 
                 
                     
                   EEGIVPGGGASLIHQARKALTELRASL; 
                 
                     
                     
                 
                     
                   (vii) 
                 
                     
                   TGDEVLGVDVFSEALAAPLFWIAANAGL; 
                 
                     
                     
                 
                     
                   (viii) 
                 
                     
                   DGSVVVNKVSELPAGHGLNVNTLSYGDLAAD; 
                 
                     
                     
                 
                     
                   (ix) 
                 
                     
                   GVIDPVKVTRSAVLNASSVARMVLTTETVVV; 
                 
                     
                     
                 
                     
                   (x) 
                 
                     
                   LTTETVVVDKPAKAEDHDHHHGHAH; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         (xi) a polypeptide sequence which has more than 66% or 70% or 75% or 80% or 85% or 90% or 95% identity to a polypeptide sequence defined in any of (i) to (x) and has a function equivalent to a polypeptide sequence defined in any of (i) to (x); and 
         (xii) a fragment of a polypeptide sequence defined in any of (i) to (xi) which has a function equivalent to a polypeptide sequence defined in any of (i) to (xi). 
       
     
     
         2 . An isolated or recombinant nucleic acid molecule comprising or consisting of a polynucleotide sequence selected from the group:
 (a) a polynucleotide sequence which encodes a polypeptide sequence selected from the group consisting of:   
       
         
           
                 
                 
               
                     
                   (i) 
                 
                     
                   MSKLIEYDETARRAMEVGMDKLADTVRVT; 
                 
                     
                     
                 
                     
                   (ii) 
                 
                     
                   LGPRGRHVVLAKAFGGPTVTN; 
                 
                     
                     
                 
                     
                   (iii) 
                 
                     
                   DGVTVAREIELEDPFEDLGAQLVKSVATKTNDV; 
                 
                     
                     
                 
                     
                   (iv) 
                 
                     
                   AGDGTTTATILAQALIKGGLRLVAAGVN; 
                 
                     
                     
                 
                     
                   (v) 
                 
                     
                   PIALGVGIGKAADAVSEALLASATP; 
                 
                     
                     
                 
                     
                   (vi) 
                 
                     
                   EEGIVPGGGASLIHQARKALTELRASL; 
                 
                     
                     
                 
                     
                   (vii) 
                 
                     
                   TGDEVLGVDVFSEALAAPLFWIAANAGL; 
                 
                     
                     
                 
                     
                   (viii) 
                 
                     
                   DGSVVVNKVSELPAGHGLNVNTLSYGDLAAD; 
                 
                     
                     
                 
                     
                   (ix) 
                 
                     
                   GVIDPVKVTRSAVLNASSVARMVLTTETVVV; 
                 
                     
                     
                 
                     
                   (x) 
                 
                     
                   LTTETVVVDKPAKAEDHDHHHGHAH ; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         (b) a polynucleotide sequence which has more than 66% or 70% or 75% or 80% or 85% or 90% or 95% identity to a polynucleotide sequence defined in (a); or a polynucleotide sequence which hybridizes to a polynucleotide sequence defined in (a) under conditions of 2×SSC, 65° C. which encodes a polypeptide sequence having a function equivalent to a polypeptide sequence defined in any of (i) to (x); and 
         (c) a fragment of a polynucleotide sequence defined in (a) or (b) which encodes a polypeptide sequence having a function equivalent to a polypeptide sequence defined in any of (i) to (x). 
       
     
     
         3 . A peptide molecule as defined in  claim 1  for use in medicine. 
     
     
         4 . A nucleic acid molecule as defined in  claim 2  for use in medicine. 
     
     
         5 . A peptide molecule as defined in  claim 1  for use in preventing and/or treating a non-cancerous condition or a cancerous condition. 
     
     
         6 . A nucleic acid molecule as defined in  claim 2  for use in preventing and/or treating a non-cancerous condition or a cancerous condition. 
     
     
         7 . Use of a peptide molecule as defined in  claim 1  or a nucleic acid molecule as defined in  claim 2  in the manufacture of a medicament for preventing and/or treating a non-cancerous condition or a cancerous condition. 
     
     
         8 . A pharmaceutical composition comprising or consisting of a peptide molecule as defined in  claim 1 , and a pharmaceutically-acceptable excipient. 
     
     
         9 . A pharmaceutical composition comprising or consisting of a nucleic acid molecule as defined in  claim 2 , and a pharmaceutically-acceptable excipient. 
     
     
         10 . The pharmaceutical composition according to  claim 8  or  9  which is for use in preventing or treating a non-cancerous condition or a cancerous condition. 
     
     
         11 . A method of preventing and/or treating a non-cancerous condition or a cancerous condition in a patient comprising the step of administering to a patient in need thereof an effective amount of a peptide molecule as defined in  claim 1  or a pharmaceutical composition as defined in  claim 8  or  10 . 
     
     
         12 . A method of preventing and/or treating a non-cancerous condition or a cancerous condition in a patient comprising the step of administering to a patient in need thereof an effective amount of a nucleic acid molecule as defined in  claim 2  or a pharmaceutical composition as defined in  claim 9  or  10 . 
     
     
         13 . A peptide molecule according to  claim 5  or a nucleic acid molecule according to  claim 6  or a use according to  claim 7  or a pharmaceutical composition according to  claim 10  or a method according to  claim 11  or  12  wherein the non-cancerous condition is selected from the group comprising or consisting of: autoimmune disorders, such as haemolytic anaemia, thrombocytopenia, thyroiditis, pernicious anaemia, Addison's disease, autoimmune diabetes, myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus, atherosclerosis, and autoimmune encephalitis; allergic conditions such as eczema, dermatitis, allergic rhinitis, allergic conjunctivitis; allergic airways diseases; hyper-eosinophilic syndrome; contact dermatitis, food allergy; and respiratory diseases characterized by eosinophilic airway inflammation and airway hyper-responsiveness, such as allergic asthma, intrinsic asthma, allergic bronchopulmonary aspergillosis, eosinophilic pneumonia, allergic bronchitis bronchiectasis, occupational asthma, reactive airway disease syndrome, interstitial lung disease, hyper-eosinophilic syndrome, parasitic lung disease. 
     
     
         14 . A peptide molecule according to  claim 5  or a nucleic acid molecule according to  claim 6  or a use according to  claim 7  or a pharmaceutical composition according to  claim 10  or a method according to  claim 11  or  12  wherein the non-cancerous condition is asthma. 
     
     
         15 . A peptide molecule according to  claim 5  or a nucleic acid molecule according to  claim 6  or a use according to  claim 7  or a pharmaceutical composition according to  claim 10  or a method according to  claim 11  or  12  wherein the non-cancerous condition is arthritis. 
     
     
         16 . A peptide molecule according to  claim 5  or a nucleic acid molecule according to  claim 6  or a use according to  claim 7  or a pharmaceutical composition according to  claim 10  or a method according to  claim 11  or  12  wherein the non-cancerous condition is selected from the group comprising or consisting of: solid phase tumors/malignancies, locally advanced tumors, human soft tissue sarcomas, metastatic cancer, including lymphatic metastases, blood cell malignancies including multiple myeloma, acute and chronic leukemias, and lymphomas, head and neck cancers including mouth cancer, larynx cancer and thyroid cancer, lung cancers including small cell carcinoma and non-small cell cancers, breast cancers including small cell carcinoma and ductal carcinoma, gastrointestinal cancers including esophageal cancer, stomach cancer, colon cancer, colorectal cancer and polyps associated with colorectal neoplasia, pancreatic cancers, liver cancer, urologic cancers including bladder cancer and prostate cancer, malignancies of the female genital tract including ovarian carcinoma, uterine (including endometrial) cancers, and solid tumor in the ovarian follicle, kidney cancers including renal cell carcinoma, brain cancers including intrinsic brain tumors, neuroblastoma, astrocytic brain tumors, gliomas, metastatic tumor cell invasion in the central nervous system, bone cancers including osteomas, skin cancers including malignant melanoma, tumor progression of human skin keratinocytes, squamous cell carcinoma, basal cell carcinoma, hemangiopericytoma and Karposi's sarcoma 
     
     
         17 . A peptide molecule as defined in  claim 1  for use in the relief of pain. 
     
     
         18 . A nucleic acid molecule as defined in  claim 2  for use in the relief of pain. 
     
     
         19 . The pharmaceutical composition according to  claim 8  or  9  which is for use in the relief of pain. 
     
     
         20 . Use of a peptide molecule as defined in  claim 1  or a nucleic acid molecule as defined in  claim 2  in the manufacture of a medicament for the relief of pain. 
     
     
         21 . The use according to  claim 20  wherein the medicament further comprises at least one additive for assisting or augmenting the action of the peptide molecule or nucleic acid molecule. 
     
     
         22 . The use according to  claim 21  wherein the additive is selected from at least one of paracetamol, aspirin, ibuprofen, other non-steroidal anti-inflammatory drugs (NSAIDS), cylooxygenase-2-selective inhibitors (CSIs), opiates. 
     
     
         23 . The use according to any of  claims 20  to  22  wherein the medicament provides prolonged or sustained pain relief. 
     
     
         24 . The use according to any of  claims 20  to  23  wherein the daily dosage level will be from 0.0001 to 100,000 mg, administered in single or divided doses. 
     
     
         25 . The use according to  claim 24  wherein the daily dosage level is 0.0001 to 1000 mg. 
     
     
         26 . The use according to  claim 24  or  25  wherein the time between dose administration to the patient is between six and twelve hours. 
     
     
         27 . The use according to  claim 24  or  25  wherein the time between dose administration to the patient is between nine and twelve hours after the previous dose 
     
     
         28 . The use according to  claim 24  or  25  wherein the time between dose administration to the patient is between twelve hours and twelve days. 
     
     
         29 . The use according to  claim 24  or  25  wherein the time between dose administration to the patient is between twelve days and six months. 
     
     
         30 . The use according to any of  claims 20  to  29  wherein the medicament is used to relieve pain in a human or animal patient. 
     
     
         31 . The pharmaceutical composition according to any one of  claims 8  to  10  or  18  or the medicament as defined in any of  claim 7  or  20  to  30  wherein the pharmaceutical composition or medicament is formulated to permit administration by at least one route selected from the group comprising or consisting of: intranasal; oral; parenteral; topical; ophthalmic; suppository; pessary; or inhalation routes. 
     
     
         32 . A peptide molecule according to  claim 16  or a nucleic acid molecule according to  claim 17  or a pharmaceutical composition according to  claim 29  or a use as defined in any of  claim 7  or  20  to  30  wherein pain is selected from the group comprising or consisting of: backache; headache; toothache; earache; arthritis; gout; soft tissue trauma; ligament and/or tendon traumatic damage; broken bones; cancer; post-operative pain; menstrual pain; obstetric pain; renal tract pain; visceral pain; burns; abscesses; and other infections. 
     
     
         33 . A method of relieving pain in a patient comprising the step of administering to a patient in need thereof an effective amount of a peptide molecule as defined in  claim 1  or a pharmaceutical composition according to any one of  claims 8  to  10 ,  20  or  31 . 
     
     
         34 . A method of relieving pain in a patient comprising the step of administering to a patient in need thereof an effective amount of a nucleic molecule as defined in  claim 2  or a pharmaceutical composition according to any one of  claims 8  to  10 ,  20  or  31 . 
     
     
         35 . Use of a peptide molecule as defined in  claim 1  or a nucleic acid molecule as defined in  claim 2  as an adjuvant. 
     
     
         36 . An adjuvant system comprising (i) a peptide molecule as defined in  claim 1  or a nucleic acid molecule as defined in  claim 2  and (ii) an antigen. 
     
     
         37 . The adjuvant system according to  claim 36  wherein the antigen is selected from the group comprising or consisting of: anthrax antigen; cholera antigen; diphtheria antigen; haemophilus influenza b (Hib) antigen; hepatitis A antigen; hepatitis B antigen; influenza antigen; Japanese encephalitis antigen; measles, mumps and rubella (MMR) antigen; meningococcal antigen; pertussis antigen; pneumococcal antigen; poliomyelitis antigen; rabies antigen; rubella antigen; smallpox and/or vaccinia antigen; tetanus antigen; tick-borne encephalitis antigen; tuberculosis antigen; typhoid antigen; varicella/herpes zoster antigen; yellow fever antigen; and veterinary vaccine antigen. 
     
     
         38 . A method of stimulating cytokine production in a cell comprising the step of administering a peptide molecule as defined in  claim 1  or a nucleic acid molecule as defined in  claim 2 . 
     
     
         39 . The method according to  claim 38  wherein cytokine production is increased at least 10-fold relative to normal levels. 
     
     
         40 . The method according to  claim 38  or  39  wherein the cytokine is selected from the group comprising or consisting of: IL-1β; IL-2; IL-6; IL-8; IL-10; IL-12; TNF-α; Interferon-γ; GM-CSF. 
     
     
         41 . A method of assessing the presence and/or amount in a sample of a peptide molecule according to  claim 1  or a nucleic acid molecule according to  claim 2  comprising or consisting of the steps of:
 i) providing a test sample; 
 ii) contacting the test sample with a cell; 
 iii) measuring and/or detecting the level of production of one or more cytokine by the cell; 
 iv) comparing the level of production of one or more cytokine in (iii) with the level of production of the one or more cytokine in a control sample 
 
       wherein a higher level of production of one or more cytokine induced by the test sample compared to the control sample indicates the presence and/or amount in the test sample of a peptide molecule according to  claim 1  or a nucleic acid molecule according to  claim 2 . 
     
     
         42 . A peptide molecule or a nucleic acid molecule substantially as described herein with reference to the accompanying description and drawings. 
     
     
         43 . A pharmaceutical composition, use or method substantially as described herein with reference to the accompanying description and drawings.