Targeting sites of damaged lung tissue
The present invention relates to methods and compositions for targeting damaged lung tissue. Compositions provided feature a targeting moiety coupled to one or more other moieties, including, for example, a cross-linkable moiety, an imaging moiety, and/or one or more other targeting moieties. The methods and compositions of the invention find use, for example, in detecting and treating a pulmonary condition such as emphysema.
1 . A method of reducing lung volume comprising:
administering to a subject a composition comprising a first targeting moiety and a second targeting moiety wherein said targeting moieties are coupled and wherein said targeting moieties target damaged lung tissue; and
allowing said targeting moieties to target different sites of damaged lung tissue, thereby reducing lung volume.
2 . The method as recited in claim 1 wherein said lung tissue comprises epithelial lining fluid.
3 . The method as recited in claim 1 wherein said different sites comprise different sites within an enlarged air space.
4 . The method as recited in claim 1 wherein said first targeting moiety targets a first damage-correlated moiety and said second targeting moiety targets a second damage-correlated moiety, said first and second damage-correlated moieties occurring at said different sites.
5 . The method as recited in claim 4 wherein said first and second damage-correlated moieties are the same.
6 . The method as recited in claim 4 wherein said first and second damage-correlated moieties are different.
7 . The method as recited in claim 1 wherein said targeting moieties are coupled via a chemical linker.
8 . The method as recited in claim 7 wherein said chemical linker comprises two functional groups.
9 . The method as recited in claim 8 wherein at least one of said functional groups is a hydroxyl group, a carboxyl group, an ester group, an amine group or a lysine group.
10 . The method as recited in claim 8 wherein at least one of said functional groups is a cyano group, a thol group, a cysteine group, a carbonyl group, an aldehyde group or a ketone group.
11 . The method as recited in claim 1 wherein said targeting moieties are coupled as a fusion polypeptide.
12 . The method as recited in claim 1 wherein said targeting moieties are coupled via a protein.
13 . The method as recited in claim 1 wherein said targeting moieties are coupled via an antibody.
14 . The method as recited in claim 1 wherein said method is performed without prior identification of said damaged lung tissue.
15 . The method as recited in claim 1 wherein said method does not damage epithelial cells within lung tissue.
16 . The method as recited in claim 1 wherein said method damages epithelial cells within lung tissue by use of a sclerosing agent.
17 . The method as recited in claim 16 wherein said sclerosing agent is at least one compound selected from doxycycline, bleomycin, minocycline, doxorubicin, cisplatin+cytarabine, mitoxantrone, Corynebacterium Parvum , streptokinase, and urokinase.
18 . The method as recited in claim 1 wherein said composition does not comprise a polysaccharide or a carbohydrate moiety.
19 . The method as recited in claim 1 wherein said composition does not comprise a mutant plasminogen activator-inhibitor type 1.
20 . The method as recited in claim 1 wherein said first and/or second targeting moiety targets a damage-correlated moiety.
21 . The method as recited in claim 20 wherein said damage-correlated moiety comprises a cell surface marker.
22 . The method as recited in claim 20 wherein said damage-correlated moiety comprises an ECM component.
23 . The method as recited in claim 1 wherein said first and/or second targeting moiety targets elastase.
24 . The method as recited in claim 1 wherein said first and/or second targeting moiety targets neutrophil elastase.
25 . The method as recited in claim 1 wherein said first and/or second targeting moiety comprises a protease inhibitor moiety.
26 . The method as recited in claim 1 wherein said first and/or second targeting moiety comprises an alpha-1 antitrypsin moiety.
27 . The method as recited in claim 26 wherein said alpha-1 antitrypsin moiety is a recombinant alpha-1 antitrypsin moiety.
28 . The method as recited in claim 1 wherein said first and/or second targeting moiety comprises an elafin moiety.
29 . The method as recited in claim 28 wherein said elafin moiety is a recombinant elafin moiety.
30 . The method as recited in claim 1 wherein said first and/or second targeting moiety comprises a serpin moiety.
31 . The method as recited in claim 30 wherein said serpin moiety is a recombinant serpin moiety.
32 . The method as recited in claim 30 wherein said serpin moiety is a secretory leukoprotease inhibitor (SLP 1 ) moiety.
33 . The method as recited in claim 32 wherein said secretory leukoprotease inhibitor (SLP1) moiety is a recombinant secretory leukoprotease inhibitor (SLP1) moiety.
34 . The method as recited in claim 1 wherein said first and/or second targeting moiety targets at least one matrix metalloproteinase selected from MMP-1, MMP-2, MMP-3, MMP-4, MMP-5, MMP-6, MMP-7, MMP-8, and MMP-9.
35 . The method as recited in claim 34 wherein said composition does not comprise a hyaluronic acid or a salt thereof.
36 . The method as recited in claim 1 wherein said first and/or second targeting moiety targets desmosine and/or isodesmosine.
37 . The method as recited in claim 1 wherein said first and/or second targeting moiety targets CD8 and/or CD4.
38 . The method as recited in claim 1 wherein said first and/or second targeting moiety targets a smoke-related moiety.
39 . The method as recited in claim 1 wherein said composition is less than 10 microns.
40 . The method as recited in claim 1 wherein said composition is less than 5 microns.
41 . The method as recited in claim 1 wherein said composition is less than 1 micron.
42 . The method as recited in claim 1 wherein said administering is carried out via inhalation.
43 . The method as recited in claim 42 wherein said inhalation is carried out via the mouth.
44 . The method as recited in claim 1 wherein said administering is carried out via trans-thoracic administration.
45 . The method as recited in claim 1 , further comprising administering a growth factor.
46 . The method as recited in claim 1 , further comprising administering an anti-surfactant.
47 . The method as recited in claim 1 , further comprising administering an antibiotic.
48 . The method as recited in claim 1 , further comprising collapsing a first portion or all of the lung of said subject.
49 . The method as recited in claim 48 wherein said collapsing comprises use of negative pressure from within the lung of said subject.
50 . The method as recited in claim 48 wherein said collapsing comprises use of positive pressure from without the lung of said subject.
51 . The method as recited in claim 48 , further comprising re-inflating a second portion of the lung of said subject wherein said second portion does not comprise said damaged lung tissue.
52 . The method as recited in claim 1 wherein said composition further comprises a cross-linkable moiety coupled to said first and/or second targeting moieties.
53 . The method as recited in claim 52 , further comprising cross-linking said damaged lung tissue.
54 . The method as recited in claim 1 wherein said composition further comprises an imaging moiety coupled to said first and/or second targeting moieties.
55 . The method as recited in claim 54 , further comprising imaging said damaged lung tissue.
56 . The method as recited in claim 1 , further comprising administering a washing moiety.
57 . A method of treating a pulmonary condition comprising:
administering to a subject a composition comprising a first targeting moiety and a second targeting moiety wherein said targeting moieties are coupled and wherein said targeting moieties target damaged lung tissue; and
allowing said targeting moieties to target different sites of damaged lung tissue, thereby treating said pulmonary condition.
58 . The method as recited in claim 57 wherein said lung tissue comprises epithelial lining fluid.
59 . The method as recited in claim 57 wherein said pulmonary condition is emphysema.
60 . The method as recited in claim 57 wherein said pulmonary condition is COPD.