WO2000029588A1 - Traitement d'infections au moyen de proteines de fusion lysozyme - Google Patents

Traitement d'infections au moyen de proteines de fusion lysozyme Download PDF

Info

Publication number
WO2000029588A1
WO2000029588A1 PCT/US1999/027403 US9927403W WO0029588A1 WO 2000029588 A1 WO2000029588 A1 WO 2000029588A1 US 9927403 W US9927403 W US 9927403W WO 0029588 A1 WO0029588 A1 WO 0029588A1
Authority
WO
WIPO (PCT)
Prior art keywords
lysozyme
seq
composition
mice
bacterial
Prior art date
Application number
PCT/US1999/027403
Other languages
English (en)
Inventor
Timothy Edward Weaver
Henry Toyin Akinbi
Original Assignee
Children's Hospital Medical Center
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US09/193,877 external-priority patent/US5993809A/en
Application filed by Children's Hospital Medical Center filed Critical Children's Hospital Medical Center
Priority to EP99967112A priority Critical patent/EP1129201A1/fr
Priority to AU23459/00A priority patent/AU759743B2/en
Priority to CA002349837A priority patent/CA2349837A1/fr
Priority to JP2000582571A priority patent/JP2002530083A/ja
Priority to BR9915218-5A priority patent/BR9915218A/pt
Publication of WO2000029588A1 publication Critical patent/WO2000029588A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2462—Lysozyme (3.2.1.17)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention relates to prophylactic and therapeutic uses of
  • the respiratory tract such as cystic fibrosis or the gastrointestinal tract such as
  • bacterial infections may have severe
  • colonization of the lungs indicates that their systemic immunity is essentially
  • the respiratory and gastrointestinal tracts are frequent sites of
  • the normal respiratory tract has
  • immunoglobulins IgA and IgM secretory immunoglobulins IgA and IgM, the proteins lactoferrin, betalysin and
  • fibronectin fibronectin, complement components and the enzyme lysozyme.
  • lysozyme is the best established antimicrobial substance
  • Human lysozyme is a naturally occurring enzyme that is known
  • Lysozyme is a small ( 1 5
  • Lysozyme can
  • Lysozyme produced by
  • polymorphonuclear leukocytes such as neutrophils, inhibits chemotaxis of
  • Lysozyme is also probably
  • Pulmonary surfactant a complex mixture of phospholipids and
  • Surfactant protein-B is one of the protein
  • This invention is directed to a composition for the prophylaxis or
  • composition for treating a bacterial infection in a mammal.
  • SP-B lysozyme/surfactant protein-B
  • composition prevents or treats a respiratory infection such as occurs frequently in individuals with cystic fibrosis, or may
  • Pseudomonas aeruginosa which is the major airway pathogen in patients with
  • cystic fibrosis Furthermore, the elevated lysozyme activity in bronchoalveolar
  • lavage fluid resulting from administration of lysozyme is not associated with
  • the invention is also directed to a method of preventing or
  • composition in a dosing regimen sufficient to prevent or treat the infection.
  • the route of administration may be parenteral, for example by inhalation, or
  • the invention is still further directed to a fusion protein SEQ ID NO: 1
  • the invention is still further directed to a fusion protein SEQ ID NO: 1
  • the invention is additionally directed to a method of treating a
  • the fusion protein may be administered by aerosol installation
  • the invention is also directed to a method of preventing or
  • the invention is additionally directed to a composition
  • a composition comprising
  • FIG. 1 is a histogram showing bacterial clearance from lungs of
  • transgenic lysozyme/surfactant protein-B fusion protein
  • FIG. 2A is a photograph showing expression of recombinant
  • FIG 2B is a photograph showing
  • mouse line probed with rat cDNA mouse line probed with rat cDNA.
  • FIG. 3 is a photograph showing analysis of lysozyme protein
  • FIG. 4 is a histogram of lysozyme activity in bronchoalveolar
  • FIG. 5A is a photograph showing lysozyme cellular localization in
  • FIG. 5B is a photograph showing lysozyme cellular
  • FIG. 6A is a photograph showing lung structure in transgenic mice
  • FIG. 6B is a photograph showing lung
  • FIG. 7 is a histogram illustrating the cellular composition of BAL
  • FIG 8 is a histogram showing clearance of Group B Streptococcus
  • FIG 9 is a histogram showing clearance of Pseudomonas
  • aeruginosa from the lungs at twenty-four hours post infection.
  • Rat lysozyme is a hydrophobic peptide of 1 48 amino acids SEQ ID NO:
  • Human lysozyme SEQ ID NO:5 also has 1 48 amino acids and has
  • Surfactant protein-B is a hydrophobic peptide of 79 amino
  • Human SP-B is synthesized by alveolar type II epithelial cells as a
  • propeptide of 1 77 amino acids propeptide of 1 77 amino acids, and a carboxy terminal (C-terminal)
  • propeptide of 102 amino acids The C-terminal propeptide has been shown to function in maintenance of the size of lamellar bodies which store SP-B and in
  • oligonucleotide primers based on the published sequence of the rat enzyme by
  • SP-B cDNA has previously been described (Glasser, S.W., et al. cDNA and deduced amino acid sequence of human pulmonary surfactant-associated
  • proteolipid SPL (Phe). Proc. Natl. Acad. Sci. USA 84:4007-401 1 , 1 987).
  • the synthesized cDNAs were either generated into a chimeric
  • SP-B human surfactant protein B
  • this chimeric molecule was a fusion protein of residues 1 -1 48 of rat lysozyme
  • transgenic mice expressing a transgene construct encoding the fusion protein
  • SP-C protein C
  • mice was restricted to the distal respiratory epithelium. Expression of the chimeric protein SEQ ID NO:3 was confirmed.
  • transgene product was detected in both lung homogenates and in
  • BAL bronchoalveolar lavage
  • chimeric protein SEQ ID NO:3 was not associated with altered lung structure
  • transgenic mouse lines were generated in which rat lysozyme SEQ ID NO: 1
  • SP-C human surfactant protein C
  • PBS sterile phosphate buffered saline
  • tuberculin syringes fitted with 27 gauge needles in preparation for the
  • mice Five to six week old mice maintained in clean rooms were used
  • mice were anesthetized with a mixture of
  • the two halves of the thyroid muscles were apposed at
  • mice were harvested, weighed, homogenized in PBS and plated on BAP
  • CFU/g gram of lung tissue
  • transgenic mice was even less than the number of bacteria that had been
  • transgenic mice had significantly enhanced
  • mice had 1 .99 ⁇ 1 .4 x 10 4 CFU/g of tissue, while BAP inoculated with
  • lung tissue from wild type (control) mice had 25.49 ⁇ 1 2.43 x 1 0 4 CFU/g
  • mice had 9.9 ⁇ 6.43 x 10 4 CFU/g tissue, while BAP
  • transgenic mice facilitated bacterial clearance from the airway.
  • mice carrying the lysozyme/surfactant protein-B fusion protein show that in mice carrying the lysozyme/surfactant protein-B fusion protein
  • mice which expressed a lysozyme/surfactant protein B fusion protein SEQ ID NO: 1
  • lysozyme transgene was assessed by Northern blot analysis of 2 ⁇ g of total
  • FIG. 2A complementary DNA (cDNA) (FIG. 2A) and rat cDNA (FIG. 2B) .
  • cDNA complementary DNA
  • FIG. 2B rat cDNA
  • mouse cDNA probe because of cross hybridization between rat lysozyme and mouse
  • FIG. 2A both the larger endogenous mouse lysozyme mRNA and rat
  • mice lysozyme mRNA were detected.
  • the mouse lysozyme mRNA was used as an
  • FIG. 3 shows
  • mice from transgenic line 3.5 had
  • lysozyme was used to generate a standard curve.
  • mice from transgenic line 3.5 had a 1 7.5-fold
  • transgenic line 3.5 versus transgenic line 2.6.
  • transgenic line 2.6 As predicted from Western
  • FIG. 5B wild type control littermates
  • Lysozyme was detected in Type II cells in wild type and
  • transgenic mice with more intense staining in Type II cells from transgenic
  • mice Transgenic mice, in addition, have expression in bronchiolar epithelial cells.
  • transgenic mice and wild type littermate controls were compared following an
  • mice intratracheal injection of 1 0 6 colony forming units (CFU) of GBS. All mice
  • transgenic line 2.6 (4.2 ⁇ 0.8 x 10 6 CFU/g lung tissue versus 7.1 ⁇ 0.6
  • mice received intratracheal injections with 1 0 7 CFU of Pseudomonas
  • FIG. 9 shows CFU/g lung tissue ⁇ SEM. Bacterial clearance was
  • the lysozyme/SP-B fusion protein SEQ ID NO:3 or SEQ ID NO:6
  • lysozyme SEQ ID NO: 1 of the invention may be used to treat
  • Cystic fibrosis is a systemic disease in which mucus secretion is
  • lysozyme or the lysozyme/surfactant protein-B fusion protein in vivo offers a
  • the method and composition of the invention may range from total prevention,
  • the lysozyme/SP-B fusion protein SEQ ID NO:3 or
  • SEQ ID NO:6 or recombinant lysozyme SEQ ID NO: 1 may be used to protect
  • Staphylococcus aureus Streptococcus species
  • Streptococcus Streptococcus
  • the invention may be used to combat gastrointestinal
  • the lysozyme/surfactant protein-B fusion protein SEQ ID NO:3 or
  • SEQ ID NO:6 may be administered by an enteral route to target the
  • enterocolitica Campy/obacter fetus, ssp. jej ' uni, and Helicobacter pylori.
  • lysozyme/SP-B may be formulated for oral administered as a solid or liquid in
  • saposin A structurally related saposin protein family
  • saposin B structurally related saposin protein family
  • saposin C saposin C
  • saposin D NK lysin
  • pore forming peptide of amoebapore A etc. could be generated.
  • Various modes of administration besides inhalation could be generated.
  • fusion protein SEQ ID NO:3 or SEQ ID NO:

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Communicable Diseases (AREA)
  • Pulmonology (AREA)
  • Oncology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne une méthode et une composition destinées au traitement prophylactique et curatif d'infections bactériennes, en particulier au niveau des voies respiratoires. Une protéine de fusion de lysozyme et du propeptide C-terminal de la protéine tensioactive B (SP-B) avec les dix acides aminés précédents du peptide SP-B mature, ou le lysozyme recombinant seul, est administré à un patient via un support acceptable au plan pharmaceutique. La protéine de fusion seule ou le lysoszyme recombinant peut être sélectionné de manière à pouvoir être administré sur un site d'infection cible, tel que les poumons ou l'appareil gastro-intestinal. Ce procédé et cette composition permettent d'éviter certains problèmes associés à des traitements antibiotiques classiques, tels que la perte d'efficacité ou le développement de souches bactériennes résistant aux antibiotiques.
PCT/US1999/027403 1998-11-18 1999-11-18 Traitement d'infections au moyen de proteines de fusion lysozyme WO2000029588A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP99967112A EP1129201A1 (fr) 1998-11-18 1999-11-18 Traitement d'infections au moyen de proteines de fusion lysozyme
AU23459/00A AU759743B2 (en) 1998-11-18 1999-11-18 Lysozyme fusion proteins in infections
CA002349837A CA2349837A1 (fr) 1998-11-18 1999-11-18 Traitement d'infections au moyen de proteines de fusion lysozyme
JP2000582571A JP2002530083A (ja) 1998-11-18 1999-11-18 感染におけるリゾチーム融合タンパク質
BR9915218-5A BR9915218A (pt) 1998-11-18 1999-11-18 Composição proteìna de fusão, lisozima recombinante e método de profilaxia ou tratamento terapêutico de infecção bacteriana em mamìfero

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US09/193,877 US5993809A (en) 1998-11-18 1998-11-18 Lysozyme fusion proteins in infections
US44074299A 1999-11-16 1999-11-16
US09/440,742 1999-11-16
US09/193,877 1999-11-16

Publications (1)

Publication Number Publication Date
WO2000029588A1 true WO2000029588A1 (fr) 2000-05-25

Family

ID=26889453

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/027403 WO2000029588A1 (fr) 1998-11-18 1999-11-18 Traitement d'infections au moyen de proteines de fusion lysozyme

Country Status (6)

Country Link
EP (1) EP1129201A1 (fr)
JP (1) JP2002530083A (fr)
AU (1) AU759743B2 (fr)
BR (1) BR9915218A (fr)
CA (1) CA2349837A1 (fr)
WO (1) WO2000029588A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001000855A1 (fr) * 1999-06-23 2001-01-04 Ppl Therapeutics (Scotland) Ltd. Proteines de fusion incorporant un lysozyme
WO2005059142A1 (fr) * 2003-12-18 2005-06-30 Werner Seeger Nouveaux activateurs chimeres du plasminogene et leur utilisation a des fins pharmaceutiques
WO2005108563A2 (fr) * 2004-04-19 2005-11-17 University Of Chicago Proteine hydrolysant le peptidoglycane encodée par bacteriophage n4
WO2006081429A1 (fr) * 2005-01-27 2006-08-03 Novartis Vaccines And Diagnostics Inc. Methode de caracterisation de l'efficacite d'un agent ciblant un defaut de fibrose cystique primaire
CN103635584A (zh) * 2011-04-12 2014-03-12 冈戈根股份有限公司 嵌合抗菌多肽
CN104817616A (zh) * 2014-01-30 2015-08-05 陈光健 寡肽cd02及其制备方法和应用
CN104817618A (zh) * 2014-01-30 2015-08-05 陈光健 寡肽cd01及其制备方法和应用

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114149986B (zh) * 2022-02-08 2022-05-06 中国科学院天津工业生物技术研究所 一种地衣芽孢杆菌溶菌酶突变体及其在虹鳟鱼保鲜中的应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0222366A2 (fr) * 1985-11-12 1987-05-20 BOEHRINGER INGELHEIM INTERNATIONAL GmbH Procédé pour la préparation du lysozyme humain
EP0343406A2 (fr) * 1988-05-27 1989-11-29 Medichemie Ag Utilisation de lysozyme pour la préparation d'un agent pour le traitement de la membrane muqueuse nasale
WO1990007469A1 (fr) * 1988-12-29 1990-07-12 Benson Bradley J Administration par voie pulmonaire de substances pharmaceutiquement actives

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0222366A2 (fr) * 1985-11-12 1987-05-20 BOEHRINGER INGELHEIM INTERNATIONAL GmbH Procédé pour la préparation du lysozyme humain
EP0343406A2 (fr) * 1988-05-27 1989-11-29 Medichemie Ag Utilisation de lysozyme pour la préparation d'un agent pour le traitement de la membrane muqueuse nasale
WO1990007469A1 (fr) * 1988-12-29 1990-07-12 Benson Bradley J Administration par voie pulmonaire de substances pharmaceutiquement actives

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
AKINBI H.T. ET AL.: "Rescue of SP-B knockout mice with a truncated SP-B protein.", J. BIOL. CHEM., vol. 272, no. 5, 11 April 1997 (1997-04-11), pages 9640 - 9647, XP002133931 *
CLANCY R. ET AL.: "Acute on chronic bronchitis: a model of mucosal immunology", IMMUN. CELL BIOL., vol. 73, 1995, pages 414 - 417, XP000891413 *
GRIESE M. ET AL.: "Nebulization of a bovine surfactant in cystic fibrosis", EUR. RESP. J., vol. 10, 1997, pages 1989 - 1894, XP000891398 *
WHITE T.J. ET AL.: "Primary structure of rat lysozyme.", BIOCHEMISTRY, vol. 16, 1977, pages 1430 - 1436, XP002134002 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7045677B2 (en) 1999-06-23 2006-05-16 Pharming Intellectual Property Bv Fusion proteins incorporating lysozyme
WO2001000855A1 (fr) * 1999-06-23 2001-01-04 Ppl Therapeutics (Scotland) Ltd. Proteines de fusion incorporant un lysozyme
AU2003290092B2 (en) * 2003-12-18 2009-11-19 Justus-Liebig-Universitat Giessen Novel chimeric plasminogen activators and their pharmaceutical use
WO2005059142A1 (fr) * 2003-12-18 2005-06-30 Werner Seeger Nouveaux activateurs chimeres du plasminogene et leur utilisation a des fins pharmaceutiques
US8124588B2 (en) 2003-12-18 2012-02-28 Justus Liebig Universität Giessen Chimeric plasminogen activators and their pharmaceutical use
WO2005108563A2 (fr) * 2004-04-19 2005-11-17 University Of Chicago Proteine hydrolysant le peptidoglycane encodée par bacteriophage n4
WO2005108563A3 (fr) * 2004-04-19 2006-12-07 Univ Chicago Proteine hydrolysant le peptidoglycane encodée par bacteriophage n4
US7485284B2 (en) 2005-01-27 2009-02-03 Novartis Vaccines And Diagnostic, Inc. Method for characterizing the efficacy of an agent targeting a primary cystic fibrosis defect
WO2006081429A1 (fr) * 2005-01-27 2006-08-03 Novartis Vaccines And Diagnostics Inc. Methode de caracterisation de l'efficacite d'un agent ciblant un defaut de fibrose cystique primaire
CN103635584A (zh) * 2011-04-12 2014-03-12 冈戈根股份有限公司 嵌合抗菌多肽
CN103635584B (zh) * 2011-04-12 2017-10-27 冈戈根股份有限公司 嵌合抗菌多肽
CN104817616A (zh) * 2014-01-30 2015-08-05 陈光健 寡肽cd02及其制备方法和应用
CN104817618A (zh) * 2014-01-30 2015-08-05 陈光健 寡肽cd01及其制备方法和应用

Also Published As

Publication number Publication date
BR9915218A (pt) 2001-07-31
CA2349837A1 (fr) 2000-05-25
EP1129201A1 (fr) 2001-09-05
JP2002530083A (ja) 2002-09-17
AU2345900A (en) 2000-06-05
AU759743B2 (en) 2003-05-01

Similar Documents

Publication Publication Date Title
US5993809A (en) Lysozyme fusion proteins in infections
Porter et al. Broad-spectrum antimicrobial activity of human intestinal defensin 5
EP0721501B1 (fr) Composition pharmaceutique comportant la phosphatase ou son derive
EP0375724B1 (fr) Fragments de proteines bactericides/augmentant la permeabilite, biologiquement actifs
US6287811B1 (en) Biologically active bactericidal/permeability-increasing protein fragments
US6896884B2 (en) Human chitinase, its recombinant production, its use for decomposing chitin, its use in therapy or prophylaxis against infection diseases
WO2003045976A2 (fr) Utilisation de proteines et peptides antimicrobiens dans le traitement de l'otite moyenne et de la sinusite paranasale
US7985729B2 (en) Use of antimicrobial proteins and peptides for the treatment of otitis media and paranasal sinusitis
JP2002515893A (ja) ヒトラクトフェリンおよびその改変体の有用な特性
AU759743B2 (en) Lysozyme fusion proteins in infections
US5939279A (en) Inhibition of bacterial binding by high-mannose oligosaccharides
US20020173460A1 (en) Use of recombinant human uteroglobin in treatment of inflammatory and fibrotic conditions
US5043156A (en) Method of treating infectious diseases with granulocyte colony-stimulating factor
US20060194732A1 (en) Recombinant SP-A for the treatment or prevention of pulmonary infection and inflammation
Balfour-Lynn The protease-antiprotease battle in the cystic fibrosis lung
JP7423523B2 (ja) ディフェンシンによる移植片対宿主病の予防と治療
SK169798A3 (en) Chitinase materials and methods
CA2328134A1 (fr) Induction de proteines et de peptides antibiotiques au moyen de la proteine scd14/lait
US20020107174A1 (en) Composition comprising endotoxin neutralizing protein and derivatives and uses thereof
US5770561A (en) Method for potentiating BPI protein product bactericidal activity by administration of LBP protein products
US6132775A (en) Therapeutic uses of biologically active bactericidal/permeability-increasing protein fragments
KR20210148320A (ko) 사람 혈청의 존재하에 슈도모나스 아에루기노사에 대해 살균 활성을 갖는 리신 및 이의 유도체
Rae The effect of Mannheimia haemolytica pneumonia on antimicrobial peptide expression in ruminant lung
Sakurai et al. Effect of Macrolide Antibiotics on Biological Activities Induced by Clostridium perfringens Alpha-Toxin

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
ENP Entry into the national phase

Ref document number: 2349837

Country of ref document: CA

Ref country code: CA

Ref document number: 2349837

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 1999967112

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 23459/00

Country of ref document: AU

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 582571

Kind code of ref document: A

Format of ref document f/p: F

WWP Wipo information: published in national office

Ref document number: 1999967112

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWG Wipo information: grant in national office

Ref document number: 23459/00

Country of ref document: AU

WWW Wipo information: withdrawn in national office

Ref document number: 1999967112

Country of ref document: EP