IP Library Granted Patent US 9,301,994
Granted Patent B2
US 9,301,994 · App. 13/010,670 · Granted Apr 5, 2016

LIGHT inhibitors for asthma, lung and airway inflammation, respiratory, interstitial, pulmonary and fibrotic disease treatment

Inventors: Michael Croft (San Diego, CA); Taylor Doherty (San Diego, CA); Shahram Salek-Ardakani (San Diego, CA)
Assignee: La Jolla Institute for Allergy and Immunology
A61K38/191A61K31/00
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Quick Facts
Patent No.
US 9,301,994
App. No.
13/010,670
Granted
Apr 5, 2016
Kind
B2
Abstract

Methods of treating inflammatory conditions, disease and disorders are provided. Method include, for example, contacting or administering a sufficient amount of a LIGHT inhibitor to a subject to treat the inflammatory condition, disease or disorder.

Claims (23)

1. A method for reducing or inhibiting lung airway remodeling or fibrosis in a subject with asthma, comprising administering a sufficient amount of an inhibitor of LIGHT (p30 polypeptide) comprising: a LTβR (lymphotoxin beta receptor) polypeptide subsequence, a soluble LTβR, a dominant-negative variant of LTβR, or a chimeric polypeptide comprising an LTβR polypeptide, LTβR polypeptide subsequence, soluble LTβR or dominant-negative variant of LTβR to the subject with asthma to reduce or inhibit lung airway remodeling or fibrosis.

2. A method for treating lung airway remodeling or fibrosis in a subject with asthma, comprising administering a sufficient amount of an inhibitor of LIGHT (p30 polypeptide) comprising: a LTβR (lymphotoxin beta receptor) polypeptide subsequence, a soluble LTβR, a dominant-negative variant of LTβR, or a chimeric polypeptide comprising an LTβR polypeptide, LTβR polypeptide subsequence, soluble LTβR or dominant-negative variant of LTβR to the subject with asthma to treat lung airway remodeling or fibrosis.

3. The method of claim 1 , wherein the subject has allergic asthma.

4. A method for reducing or inhibiting lung airway remodeling or fibrosis in a subject with: Extrinsic bronchial asthma;

Hypersensitivity pneumonitis; Allergic bronchopulmonaryaspergillosis; or Chronic eosinophilic pneumonia comprising administering a sufficient amount of an inhibitor of LIGHT (p30 polypeptide) comprising: a LTβR (lymphotoxin beta receptor) polypeptide subsequence, a soluble LTβR, a dominant-negative variant of LTβR, or a chimeric polypeptide comprising an LT βR polypeptide LTβR polypeptide subsequence soluble LTβR or dominant-negative variant of LTβR to the subject to treat lung airway remodeling or fibrosis.

5. A method for reducing or inhibiting lung airway remodeling or fibrosis in a subject with: Asbestosis,

Bronchiolitis, Bronchitis, Silicosis, Sarcoidosis, Idiopathic pulmonary fibrosis, Chronic Obstructive Pulmonary Disease (COPD); Interstitial Lung Disease; or Cystic Fibrosis comprising administering a sufficient amount of an inhibitor of LIGHT (p30 polypeptide) comprising: a LTI 3 R (lymphotoxin beta receptor) polypeptide subsequence, a soluble LTβR, a dominant-negative variant of LTβR, or a chimeric polypeptide comprising an LTβR polypeptide, LTβR polypeptide subsequence, soluble LTβR or dominant-negative variant of LTβR to the subject to treat lung airway remodeling or fibrosis.

6. The method of claim 1 , wherein the subject has non-allergic asthma.

7. The method of claim 1 , 4 or 5 , wherein the method reduces, decreases, inhibits, delays, eliminates or prevents the probability, severity, frequency, or duration of one or more symptoms associated with or caused by the lung airway remodeling or fibrosis.

8. The method of claim 1 , 4 or 5 , wherein one or more symptoms of the lung airway-remodeling or fibrosis is reduced, inhibited, abrogated, eliminated or reversed.

9. The method of claim 8 , wherein the symptom comprises shortness of breath (dyspnea), wheezing, stridor, coughing, rapid breathing (tachypnea), prolonged expiration, runny nose, rhonchous lung, over-inflation of the chest or chest-tightness, decreased lung capacity, an acute asthmatic episode, or lung, airway or respiratory mucosum inflammation or tissue damage.

10. The method of claim 8 , wherein the symptom comprises infiltration of eosinophils in lung, lung draining lymph nodes or airway, leukocyte infiltration of lung draining lymph nodes or airway, hyperplasia of mucus secreting epithelium, inflammatory lesion of lung, goblet cell hyperplasia, or increased Th2 cytokine production.

11. The method of claim 10 , wherein the Th2 cytokine is an interleukin (IL).

12. The method of claim 11 , wherein the interleukin (IL) is IL-4, IL-5, IL-9, IL-13, IL-16, IL-17 or IL-25.

13. The method of claim 1 , 4 or 5 , wherein the method reduces or inhibits progression, severity, frequency, duration or probability of a symptom of the lung airway remodeling or fibrosis.

14. The method of claim 1 , wherein the lung airway remodeling or fibrosis is caused by an allergen.

15. The method of claim 1 , 4 or 5 , wherein the lung airway remodeling or fibrosis is chronic or acute.

16. The method of claim 1 , 2 , 4 or 5 , wherein the subject is a mammal.

17. The method of claim 1 , 2 , 4 or 5 , wherein the subject is a human.

18. The method of claim 1 , 2 , 4 or 5 , wherein the method reduces or decreases undesirable or abnormal eosinophil migration, chemotaxis or generation.

19. The method of claim 1 , 2 , 4 or 5 , wherein the LTβR polypeptide subsequence, soluble LTβR, dominant-negative variant of LTβR, or chimeric polypeptide comprising an LTβR polypeptide, LTβR polypeptide subsequence, soluble LTβR or dominant-negative variant of LTβR is administered via inhalation.

20. The method of claim 1 , 2 , 4 or 5 , wherein the LTβR polypeptide subsequence, soluble LTZβR, dominant-negative variant of LTβR, or chimeric polypeptide comprising an LTβR polypeptide, LTβR polypeptide subsequence, soluble LTβR or dominant-negative variant of LTβR is formulated into an aerosol.

21. The method of claim 1 , 2 , 4 or 5 , wherein the LTβR polypeptide subsequence, soluble LTβR, dominant-negative variant of LTβR, or chimeric polypeptide comprising an LTβR polypeptide, LTβR polypeptide subsequence, soluble LTβR or dominant-negative variant of LTβR is delivered to the lung airways.

Assignments (2)
CONFIRMATORY LICENSE Recorded Jul 25, 2011
From: LA JOLLA INSTITUTE FOR ALLERGY/IMMUNOLOGY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 026642/0199 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 20, 2011
From: CROFT, MICHAEL; DOHERTY, TAYLOR; SALEK-ARDAKANI, SHAHRAM
To: LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY
Reel/Frame 025672/0392 →
Continuity (3)
Division 12233428 · Sep 18, 2008
Provisional Application 60973383 · Sep 18, 2007
Related Publication 20110150785A1 · Jun 23, 2011