AU2009246543B2 - Recombinant human CC10 and compositions thereof for use in the treatment of nasal rhinitis - Google Patents

Recombinant human CC10 and compositions thereof for use in the treatment of nasal rhinitis Download PDF

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Publication number
AU2009246543B2
AU2009246543B2 AU2009246543A AU2009246543A AU2009246543B2 AU 2009246543 B2 AU2009246543 B2 AU 2009246543B2 AU 2009246543 A AU2009246543 A AU 2009246543A AU 2009246543 A AU2009246543 A AU 2009246543A AU 2009246543 B2 AU2009246543 B2 AU 2009246543B2
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AU
Australia
Prior art keywords
nasal
administered
pharmaceutical composition
patient
rhcc10
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Legal status (The legal status 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 status listed.)
Ceased
Application number
AU2009246543A
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English (en)
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AU2009246543A1 (en
Inventor
Aprile L. Pilon
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Clarassance Inc
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Clarassance Inc
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Application filed by Clarassance Inc filed Critical Clarassance Inc
Publication of AU2009246543A1 publication Critical patent/AU2009246543A1/en
Priority to AU2015204387A priority Critical patent/AU2015204387A1/en
Application granted granted Critical
Publication of AU2009246543B2 publication Critical patent/AU2009246543B2/en
Ceased legal-status Critical Current
Anticipated expiration legal-status Critical

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Otolaryngology (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Pulmonology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Inorganic Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
AU2009246543A 2008-05-13 2009-05-12 Recombinant human CC10 and compositions thereof for use in the treatment of nasal rhinitis Ceased AU2009246543B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2015204387A AU2015204387A1 (en) 2008-05-13 2015-07-17 Recombinant human cc10 and compositions thereof for use in the treatment of nasal rhinitis

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US5286108P 2008-05-13 2008-05-13
US61/052,861 2008-05-13
PCT/US2009/043613 WO2009140269A2 (en) 2008-05-13 2009-05-12 Recombinant human cc10 and compositions thereof for use in the treatment of nasal rhinitis

Related Child Applications (1)

Application Number Title Priority Date Filing Date
AU2015204387A Division AU2015204387A1 (en) 2008-05-13 2015-07-17 Recombinant human cc10 and compositions thereof for use in the treatment of nasal rhinitis

Publications (2)

Publication Number Publication Date
AU2009246543A1 AU2009246543A1 (en) 2009-11-19
AU2009246543B2 true AU2009246543B2 (en) 2015-08-06

Family

ID=41319290

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2009246543A Ceased AU2009246543B2 (en) 2008-05-13 2009-05-12 Recombinant human CC10 and compositions thereof for use in the treatment of nasal rhinitis

Country Status (12)

Country Link
US (3) US20110240012A1 (https=)
EP (2) EP3085382A1 (https=)
JP (1) JP5773437B2 (https=)
KR (1) KR20110014199A (https=)
CN (1) CN102292099A (https=)
AU (1) AU2009246543B2 (https=)
BR (1) BRPI0911945A2 (https=)
CA (1) CA2724277A1 (https=)
IL (1) IL208940A0 (https=)
MX (1) MX2010012234A (https=)
NZ (2) NZ600803A (https=)
WO (1) WO2009140269A2 (https=)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060281681A1 (en) 1997-05-28 2006-12-14 Pilon Aprile L Methods and compositions for the reduction of neutrophil influx and for the treatment of bronchpulmonary dysplasia, respiratory distress syndrome, chronic lung disease, pulmonary fibrosis, asthma and chronic obstructive pulmonary disease
NZ600803A (en) 2008-05-13 2013-12-20 Clarassance Inc Recombinant human cc10 and compositions thereof for use in the treatment of nasal rhinitis
US9168285B2 (en) 2009-10-15 2015-10-27 Therabron Therapeutics, Inc. Recombinant human CC10 protein for treatment of influenza and ebola
MX2012004409A (es) * 2009-10-15 2012-08-23 Clarassance Inc Proteina recombinante de humano cc10 para el tratamiento de la influenza.
WO2012170842A2 (en) 2011-06-09 2012-12-13 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Peptide for protection of allergic respiratory disorders
WO2014106021A1 (en) 2012-12-27 2014-07-03 Massachusetts Eye & Ear Infirmary Treatment of rhinosinusitis with p-glycoprotein inhibitors
PE20200404A1 (es) * 2013-03-15 2020-02-26 Janssen Pharmaceutica Nv Composicion farmaceutica de clorhidrato de s-ketamina
WO2016205430A1 (en) * 2015-06-15 2016-12-22 Therabron Therapeutics, Inc. Recombinant human cc10 protein facilitates repair and protects against damage to the respiratory epithelium due to exposure to both cigarette and other smoke
WO2017123933A1 (en) 2016-01-15 2017-07-20 Massachusetts Eye And Ear Infirmary Secreted p-glycoprotein is a non-invasive biomarker of chronic rhinosinusitis
EP3930808A4 (en) * 2019-02-27 2022-12-14 Oticara, Inc. METHODS OF TREATMENT OF NASAL, SINONASAL AND NASOPHARYNGEAL TISSUE INFECTION AND/OR INFLAMMATION
MX2021010683A (es) 2019-03-05 2021-12-10 Janssen Pharmaceuticals Inc Esketamina para el tratamiento de la depresión.
US12295933B2 (en) 2019-03-25 2025-05-13 Massachusetts Eye And Ear Infirmary Methods and compositions to treat and diagnose diseases or pathologies associated with inflammation of the sinuses and nasal cavity

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003057257A1 (en) * 2002-01-02 2003-07-17 The Johns Hopkins University Cc10 inhibits th2 cytokines and eotaxins involved in allergic diseases
US20060025348A1 (en) * 1997-05-28 2006-02-02 Pilon Aprile L Methods and compositions for the treatment of fibrotic conditions & impaired lung function & to enhance lymphocyte production

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4691009A (en) 1984-12-26 1987-09-01 Repligen Corporation Hybrid proteins produced by an ultrahigh prokaryotic expression system
WO1987002367A2 (en) 1985-10-18 1987-04-23 The Upjohn Company Cyclic hydrocarbons with an aminoalkyl sidechain
US4820514A (en) 1985-12-30 1989-04-11 Texas A&M University System Low dosage of interferon to enhance vaccine efficiency
JP2656944B2 (ja) 1987-04-30 1997-09-24 クーパー ラボラトリーズ タンパク質性治療剤のエアロゾール化
US5266562A (en) 1987-11-19 1993-11-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Anti-inflammatory agents
US5354269A (en) 1991-12-20 1994-10-11 Fibrogenex, Inc. Method for treating cancer resections
US5491130A (en) 1992-11-10 1996-02-13 The United States Of America As Represented By The Department Of Health And Human Services Peptide inhibitors of fibronectin and related collagen-binding proteins
US5482930A (en) 1993-06-09 1996-01-09 The Regents Of The University Of California Anti-inflammatory composition and method with des-Tyr dynorphin and analogues
US5470885A (en) 1993-09-29 1995-11-28 The Research Foundation Of The State University Of New York Fluorocarbons as anti-inflammatory agents
FR2724665B1 (fr) 1994-09-16 1996-12-20 Rhone Poulenc Rorer Sa Procede de production de proteines recombinantes, plasmides et cellules modifiees
US5696092A (en) 1995-03-07 1997-12-09 George Washington University Methods and compositions for inhibiting metastasis of epithelial cell-derived cancers
US5935860A (en) 1995-03-07 1999-08-10 The George Washington University Use of uteroglobin expression as a molecular marker for prostatic intraepithelial neoplasia
WO1997001627A1 (en) 1995-06-27 1997-01-16 Igen International, Inc. High-level expression and efficient recovery of ubiquitin fusion proteins from escherichia coli
US5817750A (en) 1995-08-28 1998-10-06 La Jolla Cancer Research Foundation Structural mimics of RGD-binding sites
CA2248136A1 (en) 1996-03-21 1997-09-25 Human Genome Sciences, Inc. Human endometrial specific steroid-binding factor i, ii and iii
AU5253998A (en) 1996-11-13 1998-06-03 Board Of Regents, The University Of Texas System Diminishing viral gene expression by promoter replacement
US6255281B1 (en) 1997-05-28 2001-07-03 Claragen, Inc. And U.S. Government Use of recombinant human uteroglobin in treatment of inflammatory and fibrotic conditions
US20030008816A1 (en) 1997-05-28 2003-01-09 Pilon Aprile L. Methods and compositions for the treatment of fibrotic conditions & impaired lung function & to enhance lymphocyte production
US20030207795A1 (en) 1997-05-28 2003-11-06 Pilon Aprile L. Methods for the production of purified recombinant human uteroglobin for the treatment of inflammatory and fibrotic conditions
US20040047857A1 (en) 1997-05-28 2004-03-11 Pilon Aprile L. Methods and compositions for the treatment of fibrotic conditions & impaired lung function & to enhance lymphocyte production
US7122344B2 (en) 1997-05-28 2006-10-17 Claragen, Inc. Methods for the production of purified recombinant human uteroglobin for the treatment of inflammatory and fibrotic conditions
US20050261180A1 (en) 1997-05-28 2005-11-24 Pilon Aprile L Use of recombinant human uteroglobin in treatment of inflammatory and fibrotic conditions
US20020169108A1 (en) 1997-05-28 2002-11-14 Pilon Aprile L. Methods and compositions for the treatment of fibrotic conditions & impaired lung function & to enhance lymphocyte production
US20060281681A1 (en) 1997-05-28 2006-12-14 Pilon Aprile L Methods and compositions for the reduction of neutrophil influx and for the treatment of bronchpulmonary dysplasia, respiratory distress syndrome, chronic lung disease, pulmonary fibrosis, asthma and chronic obstructive pulmonary disease
US20020160948A1 (en) 1998-07-21 2002-10-31 Aprile Pilon Recombinant human uteroglobin in treatment of inflammatory and fibrotic conditions
DE69939165D1 (de) 1998-04-16 2008-09-04 Encysive Pharmaceuticals Inc N,n-disubstituierte amide welche die bindung von integrinen an ihre rezeptoren hemmen
AU5836700A (en) 1999-06-01 2000-12-18 Patrick T. Prendergast Peptides for therapeutic use
JP2003512856A (ja) 1999-11-04 2003-04-08 ヒューマン ジノーム サイエンシーズ， インコーポレイテッド ウテログロビン様ポリヌクレオチド、ポリペプチド、および抗体
WO2001079285A1 (en) 2000-04-14 2001-10-25 Claragen, Inc. Methods and compositions for the treatment of fibrotic conditions and impaired lung function and to enhance lymphocyte production
US20020025510A1 (en) 2000-07-26 2002-02-28 Strongin Alex Y. Screening methods based on superactivated alpha V beta 3 integrin
US20090227025A1 (en) 2003-06-06 2009-09-10 The Board Of Regents Of The University Of Texas System Ex vivo human lung/immune system model using tissue engineering for studying microbial pathogens with lung tropism
KR101380200B1 (ko) * 2004-08-12 2014-04-01 헬신 세라퓨틱스 (유.에스.) 인크. 성장 호르몬 분비촉진제를 이용하여 위장관계의 운동성을촉진하는 방법
WO2008066644A1 (en) * 2006-11-02 2008-06-05 Riolan Technologies, Inc. Methods of treating epiphora
EP1935242A1 (en) * 2006-12-21 2008-06-25 Philip Morris Products S.A. Transgenic animal model
US20090253174A1 (en) 2008-04-08 2009-10-08 Zach Serber Expression of Heterologous Sequences
NZ600803A (en) 2008-05-13 2013-12-20 Clarassance Inc Recombinant human cc10 and compositions thereof for use in the treatment of nasal rhinitis
MX2012004409A (es) 2009-10-15 2012-08-23 Clarassance Inc Proteina recombinante de humano cc10 para el tratamiento de la influenza.

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060025348A1 (en) * 1997-05-28 2006-02-02 Pilon Aprile L Methods and compositions for the treatment of fibrotic conditions & impaired lung function & to enhance lymphocyte production
WO2003057257A1 (en) * 2002-01-02 2003-07-17 The Johns Hopkins University Cc10 inhibits th2 cytokines and eotaxins involved in allergic diseases

Also Published As

Publication number Publication date
IL208940A0 (en) 2011-01-31
NZ588895A (en) 2012-07-27
US20180125931A1 (en) 2018-05-10
JP5773437B2 (ja) 2015-09-02
EP2303308A2 (en) 2011-04-06
US20160158315A1 (en) 2016-06-09
NZ600803A (en) 2013-12-20
CA2724277A1 (en) 2009-11-19
EP3085382A1 (en) 2016-10-26
US20110240012A1 (en) 2011-10-06
EP2303308A4 (en) 2012-11-07
JP2011520894A (ja) 2011-07-21
KR20110014199A (ko) 2011-02-10
WO2009140269A2 (en) 2009-11-19
CN102292099A (zh) 2011-12-21
US9844580B2 (en) 2017-12-19
WO2009140269A3 (en) 2011-10-27
BRPI0911945A2 (pt) 2015-10-13
MX2010012234A (es) 2011-03-03
AU2009246543A1 (en) 2009-11-19

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