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(19) & (11) EP 2 188 016 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 38/31 (2006.01) A61P 11/00 (2006.01) 01.08.2012 Bulletin 2012/31 A61P 31/06 (2006.01) A61P 31/04 (2006.01) A61P 7/00 (2006.01) A61P 9/00 (2006.01) (2006.01) (2006.01) (21) Application number: 08802149.8 A61P 13/00 A61P 15/00 A61P 17/00 (2006.01) A61P 19/00 (2006.01) (22) Date of filing: 09.09.2008 (86) International application number: PCT/EP2008/007598 (87) International publication number: WO 2009/033722 (19.03.2009 Gazette 2009/12) (54) USE OF OCTREOTIDE AS A THERAPEUTIC AGENT VERWENDUNG VON OCTREOTID ALS THERAPEUTISCHES MITTEL UTILISATION D’ OCTREOTIDE COMME AGENT THÉRAPEUTIQUE (84) Designated Contracting States: (74) Representative: Arth, Hans-Lothar AT BE BG CH CY CZ DE DK EE ES FI FR GB GR ABK Patent Attorneys HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT Jasminweg 9 RO SE SI SK TR 14052 Berlin (DE) (30) Priority: 11.09.2007 EP 07017752 (56) References cited: EP-A- 0 222 578 (43) Date of publication of application: 26.05.2010 Bulletin 2010/21 • WOOD A J J: "Drug therapy" THE NEW ENGLAND JOURNAL OF MEDICINE, vol. 334, no. 4, 1996, (73) Proprietor: Mondobiotech Laboratories AG pages 246-254, XP002522071 9490 Vaduz (LI) • CORLETO V D ET AL: "Long-term octreotide treatment of metastatic carcinoid tumor" (72) Inventors: ANNALS OF ONCOLOGY, vol. 11, 2000, pages • BEVEC, Dorian 491-493, XP002522070 82110 Germering (DE) • MATON P. N.: "Expanding use of octreotide" • CAVALLI, Fabio BAILLIERE’SCLINICAL GASTROENTEROLOGY, CH-6925 Gentilino (CH) vol. 8, no. 2, 1994, pages 321-337, XP002522069 • CAVALLI, Vera • ROEHR CH C ET AL: "Somatostatin or octreotide CH-6925 Gentilino (CH) as treatment options for chylothorax in young • BACHER, Gerald children: a systemic review" INTENSIVE CARE 82110 Germering (DE) MED, vol. 32, 2006, pages 650-657, XP002522072 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 188 016 B1 Printed by Jouve, 75001 PARIS (FR) EP 2 188 016 B1 Description [0001] The present invention is directed to the use of the peptide compound D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-L- threoninol(Octreotide) as a therapeutic agent for the prophylaxis and/or treatment of Mycobacterium tuberculosis infection 5 or Streptococcus pneumoniae infection and infectious diseases caused by Mycobacterium tuberculosis infection selected from infectious diseases in the lung, of the central nervous system, in the lymphatic system, in the circulatory system, in the genitourinary system, of the bones, joints, and skin. Background of the invention 10 [0002] The identification of a therapeutic compound effective for the prophylaxis and/or treatment of a disease can be based on the activity of the compound in a biological assay. A biological assay that mimics a disease causative mechanism can be used to test the therapeutic activity of a candidate peptide. [0003] The causative mechanism of many diseases is the over activity of a biological pathway. A peptide that can 15 reduce the activity of the biological pathway can be effective in the prophylaxis and/or treatment of the disease caused by the over activity of the biological pathway. Similarly the causative mechanism of many diseases is the over production of a biological molecule. A peptide that can reduce the production of the biological molecule or block the activity of the over produced biological molecule can be effective in the prophylaxis and/or treatment of the disease caused by the over production of the biological molecule. 20 [0004] Conversely, the causative mechanism of many diseases is the under activity of a biological pathway. A peptide that can increase the activity of the biological pathway can be effective in the prophylaxis and/or treatment of the disease caused by the under activity of the biological pathway. Also similarly the causative mechanism of many diseases is the under production of a biological molecule. A peptide that can increase the production of the biological molecule or mimic the biological activity of the under produced biological molecule can be effective in the prophylaxis and/or treatment of 25 the disease caused by the under production of the biological molecule. Octreotide, a somatostatin analogue inhibits the release of growth hormone, glucagon and insulin. Scientific publications described different established and probable indications for the use of Octreotide in the treatment of diseases of the gastrointestinal system, like the use in the control of bleeding from esophage-varices and the reduction of fluid production by pancreatic fistulas and pseudocysts (Wood A.J.J. et al., The New England J of Medicine; 1996: 334; 246-254 and Maton P.N. et al., Bailliere’s Clinical Gastroenter- 30 ology: 1994; 8; 321-337).. Octreotide has further been used for the control of hormone secretion in patints with growth hormone-secreting pituitary tumors and for treatment of other tumors (Wood A.J.J. et al., The New England J of Medicine; 1996; 334;246-254 and Corleto V.D. et al., Annals of Oncology: 2000; 11; 491-493). The European patent EP 0222578 A2 describes the use of cyclic somatostatin analogues, as cyclic Octreotide, in the treatment of immediate hypersensitivity diseases, like asthma or urticaria. 35 [0005] It is the object of the present invention to provide a compound for the prophylaxis and/or treatment of Myco- bacterium tuberculosis infection or Streptococcus pneumoniae infection and infectious diseases caused by Mycobac- terium tuberculosis infection selected from infectious diseases in the lung, of the central nervous system, in the lymphatic system, in the circulatory system, in the genitourinary system, of the bones, joints, and skin. [0006] The object of the present invention is solved by the teaching of the independent claims. Further advantageous 40 features, aspects and details of the invention are evident from the dependent claims, the description, and the examples of the present application. Description of the invention 45 [0007] The present invention relates to the use of the peptide D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-L-threoninol (Oc- treotide), for the manufacture of a pharmaceutical composition for the prophylaxis and/or treatment of Mycobacterium tuberculosis infection or Streptococcus pneumoniae infection and infectious diseases caused by Mycobacterium tuber- culosis infection selected from infectious diseases in the lung, of the central nervous system, in the lymphatic system, in the circulatory system, in the genitourinary system, of the bones, joints, and skin. 50 [0008] Also disclosed are pharmaceutical formulations preferably in form of a lyophilisate or liquid buffer solution or artifical mother milk formulation containing the peptide. The peptide is useful for prophylaxis and/or treatment of Myco- bacterium tuberculosis infection or Streptococcus pneumoniae infection and infectious diseases caused by Mycobac- terium tuberculosis infection selected from infectious diseases in the lung, of the central nervous system, in the lymphatic system, in the circulatory system, in the genitourinary system, of the bones, joints, and skin. 55 Cancer, tumors, proliferative diseases, malignancies and their metastases [0009] The term "cancer" as used herein refers also to tumors, proliferative diseases, malignancies and their metas- 2 EP 2 188 016 B1 tases. Examples for cancer diseases are adenocarcinoma, choroidal melanoma, acute leukemia, acoustic neurinoma, ampullary carcinoma, anal carcinoma, astrocytoma, basal cell carcinoma, pancreatic cancer, desmoid tumor, bladder cancer, bronchial carcinoma, non-small cell lung cancer (NSCLC), breast cancer, Burkitt’s lymphoma, corpus cancer, CUP-syndrome (carcinoma of unknown primary), colorectal cancer, small intestine cancer, small intestinal tumors, 5 ovarian cancer, endometrial carcinoma, ependymoma, epithelial cancer types, Ewing’s tumors, gastrointestinal tumors, gastric cancer, gallbladder cancer, gall bladder carcinomas, uterine cancer, cervical cancer, cervix, glioblastomas, gyne- cologic tumors, ear, nose and throat tumors, hematologic neoplasias, hairy cell leukemia, urethral cancer, skin cancer, skin testis cancer, brain tumors (gliomas), brain metastases, testicle cancer, hypophysis tumor, carcinoids, Kaposi’s sarcoma, laryngeal cancer, germ cell tumor, bone cancer, colorectal carcinoma, head and neck tumors (tumors of the 10 ear, nose and throat area), colon carcinoma, craniopharyngiomas, oral cancer (cancer in the mouth area and on lips), cancer of the central nervous system, liver cancer, liver metastases, leukemia, eyelid tumor, lung cancer, lymph node cancer [0010] (Hodgkin’s/Non-Hodgkin’s), lymphomas, stomach cancer, malignant melanoma, malignant neoplasia, malig- nant tumors gastrointestinal tract, breast carcinoma, rectal cancer, medulloblastomas, melanoma, meningiomas, Hodg- 15 kin’s disease, mycosis fungoides, nasal cancer, neurinoma, neuroblastoma, kidney cancer, renal cell carcinomas, non- Hodgkin’s lymphomas, oligodendroglioma, esophageal carcinoma, osteolytic carcinomas and osteoplastic carcinomas, osteosarcomas, ovarial carcinoma, pancreatic carcinoma, penile cancer, plasmocytoma, squamous
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  • Diseases of the Digestive System (KOO-K93)

    Diseases of the Digestive System (KOO-K93)

    CHAPTER XI Diseases of the digestive system (KOO-K93) Diseases of oral cavity, salivary glands and jaws (KOO-K14) lijell Diseases of pulp and periapical tissues 1m Dentofacial anomalies [including malocclusion] Excludes: hemifacial atrophy or hypertrophy (Q67.4) K07 .0 Major anomalies of jaw size Hyperplasia, hypoplasia: • mandibular • maxillary Macrognathism (mandibular)(maxillary) Micrognathism (mandibular)( maxillary) Excludes: acromegaly (E22.0) Robin's syndrome (087.07) K07 .1 Anomalies of jaw-cranial base relationship Asymmetry of jaw Prognathism (mandibular)( maxillary) Retrognathism (mandibular)(maxillary) K07.2 Anomalies of dental arch relationship Cross bite (anterior)(posterior) Dis to-occlusion Mesio-occlusion Midline deviation of dental arch Openbite (anterior )(posterior) Overbite (excessive): • deep • horizontal • vertical Overjet Posterior lingual occlusion of mandibular teeth 289 ICO-N A K07.3 Anomalies of tooth position Crowding Diastema Displacement of tooth or teeth Rotation Spacing, abnormal Transposition Impacted or embedded teeth with abnormal position of such teeth or adjacent teeth K07.4 Malocclusion, unspecified K07.5 Dentofacial functional abnormalities Abnormal jaw closure Malocclusion due to: • abnormal swallowing • mouth breathing • tongue, lip or finger habits K07.6 Temporomandibular joint disorders Costen's complex or syndrome Derangement of temporomandibular joint Snapping jaw Temporomandibular joint-pain-dysfunction syndrome Excludes: current temporomandibular joint: • dislocation (S03.0) • strain (S03.4) K07.8 Other dentofacial anomalies K07.9 Dentofacial anomaly, unspecified 1m Stomatitis and related lesions K12.0 Recurrent oral aphthae Aphthous stomatitis (major)(minor) Bednar's aphthae Periadenitis mucosa necrotica recurrens Recurrent aphthous ulcer Stomatitis herpetiformis 290 DISEASES OF THE DIGESTIVE SYSTEM Diseases of oesophagus, stomach and duodenum (K20-K31) Ill Oesophagitis Abscess of oesophagus Oesophagitis: • NOS • chemical • peptic Use additional external cause code (Chapter XX), if desired, to identify cause.