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(12) Patent Application Publication (10) Pub. No.: US 2008/0193414 A1 Proudfoot Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2008/0193414 A1 Proudfoot Et Al US 2008O193414A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0193414 A1 Proudfoot et al. (43) Pub. Date: Aug. 14, 2008 (54) USE OF AN IMMUNOGLOBULIN (30) Foreign Application Priority Data DOMAN-CONTAINING CELL SURFACE RECOGNITION MOLECULE FOR TREATING May 6, 2005 (EP) .................................. 05103791.9 DISEASES Publication Classification (76) Inventors: Amanda Proudfoot, Chens Sur (51) Int. Cl. Leman (FR); Bruno Antonsson, A638/17 (2006.01) Billiat (FR); Linda Kontula, A638/2 (2006.01) Geneva (CH); Francis Vilbois, A63L/7088 (2006.01) Minzier (FR) A6IR 39/44 (2006.01) A6IR 48/00 (2006.01) Correspondence Address: A6IP3L/2 (2006.01) SALWANCHIK LLOYD & SALWANCHIK A6IP3L/00 (2006.01) A PROFESSIONAL ASSOCATION A6IP33/00 (2006.01) PO BOX 142950 A6IP37/00 (2006.01) A6IP35/00 (2006.01) GAINESVILLE, FL 32614-2950 (US) A6IP 9/00 (2006.01) (21) Appl. No.: 11/913,620 A6IP 7/00 (2006.01) (52) U.S. Cl. ................ 424/85.6; 514/12: 514/13: 514/8: (22) PCT Filed: May 4, 2006 514/11: 514/44; 424/178.1; 424/85.4; 424/93.2 (57) ABSTRACT (86). PCT No.: PCT/EPO6/62O63 The invention relates to the use of INSP052 for treatment and/or prevention of infectious disease, properdin-related S371 (c)(1), disease, MBL2-related disease, MASP1-related disease, (2), (4) Date: Nov. 5, 2007 MASP2-related disease, Antithrombin III-related disease, Complement factor H-related disease and/or Albumin-related Related U.S. Application Data disease. Combinations of INSP052 with an interferon, a TNF (60) Provisional application No. 60/681,651, filed on May antagonist or a further anti-infectious or anti-blood clotting 17, 2005. agent are also within the present invention. US 2008/O 1934.14 A1 Aug. 14, 2008 USE OF AN IMMUNOGLOBULIN MASP1-related disease, MASP2-related disease, Antithrom DOMAN-CONTAINING CELL SURFACE bin III-related disease, Complement factor H-related disease RECOGNITION MOLECULE FOR TREATING and/or Albumin-related disease, wherein said polypeptide is DISEASES selected from the group consisting of: 0007) a) A polypeptide consisting of SEQID NO: 16, or FIELD OF THE INVENTION 0008 b) A polypeptide comprising any of SEQID NO: 0001. The invention relates to the use of INSP052 for the 2, SEQID NO: 4, SEQID NO: 6, SEQID NO: 8, SEQ treatment and/or prevention of infectious disease, properdin ID NO: 10, SEQ ID NO: 12, SEQID NO: 14, SEQ ID related disease, MBL2-related disease, MASP1-related dis NO:16, SEQID NO: 18, SEQID NO:20, SEQID NO: ease, MASP2-related disease, Antithrombin III-related dis 22, SEQID NO: 24, SEQID NO:26, SEQID NO: 27, ease, Complement factor H-related disease and/or Albumin SEQID NO:28, SEQID NO:29, SEQID NO:30, SEQ related disease. ID NO:31, SEQID NO:32 or SEQ ID NO:33, or 0009 c) A soluble form consisting of any of SEQ ID BACKGROUND OF THE INVENTION NO:20, SEQID NO:22, SEQID NO:27, SEQID NO: 0002. The protein INSP052 was disclosed in WO2003/ 28, SEQID NO: 29, SEQID NO:30, SEQID NO:31, 093316 and International Application No. PCT/GB2004/ SEQID NO:32 or SEQ ID NO:33, or 004772 as an immunoglobulin domain-containing cell Sur 0.010 d) A mature form consisting of any of SEQ ID face recognition molecule, and more particularly, as a NO: 22, SEQID NO: 24 or SEQID NO: 26, or cytokine antagonist. 0.011 e) A histidine tag form consisting of SEQID NO: 29, or SUMMARY OF THE INVENTION 0012 f) A glycosylated form of any of the polypeptides of (a) to (e), wherein the polypeptide is glycosylated at 0003. The invention is based on the unexpected finding that INSP052 interacts with proteins of the complement path one or more sites, or way, namely properdin, mannose-binding lectin C (MBL-C), 0013 g) A mutein of any of the polypeptides of(a) to (f), MASP1, MASP2, antithrombin III, complement factor Hand wherein the amino acid sequence has at least 40% or albumin. 50% or 60% or 70% or 80% or 90% identity to at least 0004. It is therefore a first object of the invention to use one of the corresponding sequences in (a) to (f), and INSP052 for the preparation of a medicament for the treat retaining INSP052 biological activity, or ment and/or prevention of infectious disease, properdin-re 0.014 h) A mutein of any of the polypeptides of (a) to (f) lated disease, MBL2-related disease, MASP1-related dis wherein any changes in the amino acid sequence are ease, MASP2-related disease, Antithrombin III-related conservative amino acid substitutions to the amino acid disease, Complement factor H-related disease and/or Albu sequences in (a) to (f), and retaining INSP052 biological min-related disease. It is a second object of the invention to activity, or use a cell expressing INSP052, or an expression vector com 0.015 i) A salt or an isoform, fusion protein, functional prising the coding sequence of INSP052, for the preparation derivative, active fraction or circularly permutated of a medicament for the treatment and/or prevention of infec derivative of any of the polypeptides of (a) to (h). tious disease, properdin-related disease, MBL2-related dis 0016. In a second aspect, the invention relates to the use of ease, MASP1-related disease, MASP2-related disease, Anti an INSP052 nucleic acid molecule for the preparation of a thrombin III-related disease, Complement factor H-related medicament for the treatment and/or prevention of infectious disease and/or Albumin-related disease. The present inven disease, properdin-related disease, MBL2-related disease, tion is also directed towards the use of INSP052 for the MASP1-related disease, MASP2-related disease, Antithrom preparation of a pharmaceutical composition for the treat bin III-related disease, Complement factor H-related disease ment and/or prevention of infectious disease, properdin-re and/or Albumin-related disease, wherein said nucleic acid is lated disease, MBL2-related disease, MASP1-related dis selected from the group consisting of: ease, MASP2-related disease, Antithrombin III-related 0017 a) A nucleic acid sequence as set forth in any of disease, Complement factor H-related disease and/or Albu SEQ ID NO: 1, SEQID NO:3, SEQID NO:5, SEQID min-related disease. NO:7, SEQID NO:9, SEQID NO:11, SEQID NO:13, SEQID NO:15, SEQID NO: 17, SEQID NO: 19, SEQ DESCRIPTION OF THE INVENTION ID NO: 21, SEQID NO: 23, or SEQ ID NO: 25, or 0005. The invention is based on the unexpected finding 0.018 b) A nucleic acid sequence which hybridizes to that INSP052 interacts with proteins of the complement path the complement of the nucleic acid sequence of (a) way, namely properdin, mannose-binding lectin C (MBL-C), under moderately stringent conditions or under highly MASP1, MASP2, antithrombin III, complement factor Hand stringent conditions, or albumin. These Surprising properties presently characterized 0.019 c) A nucleic acid sequence of any of (a) or (b) of the polynucleotides or the corresponding polypeptides of wherein said nucleic acid sequence encodes an amino WO2003/093316 and International Application No. PCT/ acid sequence having conservative amino acid Substitu GB2004/004772 make them particularly suitable for the tions to the amino acid sequences in any of SEQID NO: preparation of a medicament or of a pharmaceutical compo 2, SEQID NO: 4, SEQID NO: 6, SEQID NO: 8, SEQ sition. ID NO: 10, SEQ ID NO: 12, SEQID NO: 14, SEQ ID 0006. In a first aspect, the invention therefore relates to the NO:16, SEQID NO: 18, SEQID NO:20, SEQID NO: use of an INSP052 polypeptide for the preparation of a medi 22, SEQID NO: 24, SEQID NO:26, SEQID NO: 27, cament for the treatment and/or prevention of infectious dis SEQID NO:28, SEQID NO:29, SEQID NO:30, SEQ ease, properdin-related disease, MBL2-related disease, ID NO:31, SEQID NO:32 or SEQ ID NO:33. US 2008/O 1934.14 A1 Aug. 14, 2008 0020. In a third aspect, the invention relates to the use of an 22, SEQID NO: 24, SEQID NO:26, SEQID NO: 27, INSP052 polypeptide for the preparation of a pharmaceutical SEQID NO:28, SEQID NO:29, SEQID NO:30, SEQ composition for the treatment and/or prevention of infectious ID NO:31, SEQID NO:32 or SEQ ID NO:33. disease, properdin-related disease, MBL2-related disease, 0034 Preferably, a soluble INSP052 is used for the prepa MASP1-related disease, MASP2-related disease, Antithrom ration of a medicament or of a pharmaceutical composition. bin III-related disease, Complement factor H-related disease and/or Albumin-related disease, wherein said polypeptide is 0035. The term “soluble INSP052” or “sINSP052 herein selected from the group consisting of: refers to an INSP052 polypeptide which is not membrane 0021 a) A polypeptide consisting of SEQID NO: 16, or bound or to an INSP052 polypeptide which doesn't contain 0022 b) A polypeptide comprising any of SEQID NO: one or more transmembrane domains. 2, SEQID NO: 4, SEQID NO: 6, SEQID NO: 8, SEQ 0036. It will be appreciated by the person skilled in the art ID NO: 10, SEQ ID NO: 12, SEQID NO: 14, SEQ ID that in accordance with the present invention, a Substance NO:16, SEQID NO: 18, SEQID NO:20, SEQID NO: which stimulates release or potentiates the activity of endog 22, SEQID NO: 24, SEQID NO: 26, SEQID NO:27, enous INSP052 can equally be used for treatment and/or SEQID NO: 28, SEQID NO:29, SEQID NO:30, SEQ prevention of infectious disease, properdin-related disease, ID NO:31, SEQID NO:32 or SEQ ID NO:33, or MBL2-related disease, MASP1-related disease, MASP2-re 0023 c) A soluble form consisting of any of SEQ ID lated disease, Antithrombin III-related disease, Complement NO:20, SEQID NO:22, SEQID NO:27, SEQID NO: factor H-related disease and/or Albumin-related disease.
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