Inhibition of factor B, the alternative complement pathway and methods related thereto
Disclosed are novel inhibitors of the alternative complement pathway and particularly, novel anti-factor B antibodies. Also disclosed is the use of such inhibitors to reduce or prevent airway hyperresponsiveness and/or airway inflammation by selectively inhibiting the alternative complement pathway, thereby treating diseases in which such conditions play a role. Also disclosed is the use of such inhibitors to reduce or prevent other diseases and conditions, including ischemia-reperfusion injury, by inhibition of the alternative complement pathway.
1. A method to reduce airway hyperresponsiveness (“AHR”) or airway inflammation in a human having AHR associated with inflammation or airway inflammation, said method comprising administering to said human an isolated antibody or antigen-binding fragment thereof that selectively binds to factor B, wherein the antibody or antigen binding fragment thereof prevents formation of a C3bBb complex, and wherein the antibody or antigen-binding fragment thereof selectively binds to factor B at the same epitope as the anti-factor B monoclonal antibody 1379 (produced by ATCC Deposit No. PTA-6230).
2. The method of claim 1 , wherein the antibody or antigen binding fragment thereof is administered by a route selected from the group consisting of oral, nasal, topical, inhaled, intratracheal, transdermal, rectal and parenteral routes.
3. The method of claim 2 , wherein the antibody or antigen binding fragment thereof is administered to the human in an amount effective to measurably reduce airway hyperresponsiveness in the human as compared to prior to administration of the antibody or antigen binding fragment thereof.
4. The method of claim 2 , wherein the antibody or antigen binding fragment thereof is administered to the human in an amount effective to measurably reduce airway hyperresponsiveness in the human as compared to a level of airway hyperresponsiveness in a population of humans having inflammation wherein the antibody or antigen binding fragment thereof was not administered.
5. The method of claim 2 , wherein administration of the antibody or antigen binding fragment thereof decreases the human's responsiveness to methacholine or to histamine.
6. The method of claim 2 , wherein the antibody or antigen binding fragment thereof is administered with a pharmaceutically acceptable carrier selected from the group consisting of: a dry, dispersible powder; anhydrous ethanol; small capsules; liposomes; a nebulized spray; and an injectable excipient.
7. The method of claim 2 , wherein the antibody or antigen binding fragment thereof is administered in a carrier or device selected from the group consisting of: anhydrous ethanol; a dry powder inhalation system; ultrasonic inhalation system; a pressurized metered dose inhaler; and a metered solution device.
8. The method of claim 2 , wherein said antibody or antigen binding fragment thereof is administered to said human in conjunction with an agent selected from the group consisting of: corticosteroids, β-agonists (long or short acting), leukotriene modifiers, antihistamines, phosphodiesterase inhibitors, sodium cromoglycate, Nedocromil, theophylline, cytokine antagonists, cytokine receptor antagonists, anti-IgE, and inhibitors of T cell function.
9. The method of claim 2 , wherein said airway hyperresponsiveness or airway inflammation is associated with a disease selected from the group consisting of asthma, chronic obstructive pulmonary disease (“COPD”), allergic bronchopulmonary aspergillosis, hypersensitivity pneumonia, eosinophilic pneumonia, emphysema, bronchitis, allergic bronchitis bronchiectasis, cystic fibrosis, tuberculosis, hypersensitivity pneumonitis, occupational asthma, sarcoid, reactive airway disease syndrome, interstitial lung disease, hyper-eosinophilic syndrome, rhinitis, sinusitis, exercise-induced asthma, pollution-induced asthma, cough variant asthma, parasitic lung disease, respiratory syncytial virus (“RSV”) infection, parainfluenza virus (“PIV”) infection, rhinovirus (“RV”) infection and adenovirus infection.
10. The method of claim 2 , wherein the airway hyperresponsiveness is associated with allergic inflammation.
11. The method of claim 2 , wherein the airway hyperresponsiveness or airway inflammation is associated with asthma.
12. The method of claim 2 , wherein the airway hyperresponsiveness or airway inflammation is associated with COPD.
13. The method of claim 1 , wherein the isolated antibody is a monoclonal antibody.
14. The method of claim 1 , wherein the antigen-binding fragment is an Fab.
15. The method of claim 1 , wherein the isolated antibody or antigen-binding fragment thereof is a humanized antibody or antigen-binding fragment thereof.