Use of avian antibodies

Details Use of avian antibodies Use of avian antibodies

1999-09-20

2003-03-25

Minnifield, Nita (Department: 1645)

Drug, bio-affecting and body treating compositions

Immunoglobulin, antiserum, antibody, or antibody fragment,...

Monoclonal antibody or fragment thereof

C424S130100, C424S137100, C424S170100, C424S157100, C424S134100, C424S164100, C435S253300, C514S851000, C530S389500, C530S387100, C530S389100, C530S423000, C530S388200, C530S388400, C426S047000, C426S055000, C426S037000

Reexamination Certificate

active

06537550

ABSTRACT:

The present application is the national stage under 35 U.S.C. 371 of PCT/SE98/00526, filed Mar. 20, 1998, which claims priority from Swedish application 9701026-8, filed Mar. 20, 1997.
TECHNICAL FIELD
The present invention relates to the use of avian antibodies against infectious antigen for treatment and/or prevention of respiratory tract infections, The antibodies are administered through local application at the oral cavity, and/or pharynx,
BACKGROUND OF THE INVENTION AND PRIOR ART
It is well known that domestic avian species, e.g. hens, produce high titres of antibodies in their eggs against factors against which they have been immunised (4), In several trials avian antibodies have been used to prevent or treat bacterial or viral infections in the digestive tract of different animals with promising results (12-17), but there is no evidence in the scientific literature that avian antibodies, or antibodies of any other origin, have been used in preventing or treating respiratory tract infections, neither in mammals nor humans. Traditionally respiratory tract infections are treated with conventional therapy, such as antibiotic treatment. The reason for not using antibodies is that no possible way of administering the antibodies, when treating respiratory tract infections, has been seen. Most surprisingly, the present inventors found that the administration of antibodies through local application at the oral cavity and/or pharynx could be used to treat respiratory tract infections.
SUMMARY OF THE INVENTION
The present invention suggests, for the first time, use of avian antibodies and/or antigen binding fragments thereof, for the production of a drug for preventing and/or treating respiratory tract infections.
Most surprisingly, the present invention suggests, for the first time, that avian antibodies can be used to prevent and/or treat respiratory tract infections when administered through local application at the oral cavity and/or pharynx, preferably by gargling and/or swallowing. The present inventors have verified this by clinical studies on humans.
The present invention relates to treatment of respiratory tract infections—i.e. infections in the nasal cavity, paranasal sinuses the lymphatic ring in the oropharynx, larinx, trachea, bronchi, bronchioli and/or alveoli, i.e. all the way down the respiratory tree—caused by e.g. Pseudomonads and/or related microorganisms.
Treatment and/or prevention of respiratory tract infections according to the invention are particularly appropriate for those individuals having increased susceptibility to infections or increased risk of catching infections, since the treatment is mild and not accompanied by undesirable side effects.
DETAILED DESCRIPTION OF THE INVENTION
To test the use of antibodies for treating respiratory tract infections the present inventors choose the group of patients suffering from cystic fibrosis (CF). These patients have increased susceptibility to infections with reoccurring or chronic respiratory tract infections of
Pseudomonas aeruginosa
. Cystic fibrosis patients have hitherto had to rely on conventional therapy, such as antibiotic treatment which is sometimes not successful and accompanied by undesired side effects.
Chronic colonisation with
Pseudomonas aeruginosa
in the respiratory tract of patients with cystic fibrosis (CF) is a principal cause of the high morbidity and mortality in this disease. It is very difficult to get rid of
Pseudomonas aeruginosa
once it has been isolated from the sputum of CF-patients. Only a temporary eradication of this pathogen can be achieved by vigorous antibiotic treatment during very early phases of colonization—and the bacteria will return very soon (1-3). The best results hitherto have been reported from the CF-center in Copenhagen (2) where 14 CF-patients were treated daily with oral ciprofloxacin and inhalation of colistin for 3 weeks at their first
Pseudomonas aeruginosa
-positive culture. After treatment, these CF-patients were observed for up to 27 months (totally 214 months; mean 15.3 months). During this time 2 of the patients became chronically colonized with
Pseudomonas aeruginosa
(defined as six consecutive sputum cultures positive for the bacteria) and there were 49 sputum cultures positive for
Pseudomonas aeruginosa
out of 214 (=23%). From another Copenhagen study it is reported that
Pseudomonas aeruginosa
reoccured in sputum cultures already 4 months after a course of anti-pseudomonas chemotherapy in 98.3% of the CF-patients (3).
Each egg from a hen contains more than 100 mg antibodies. These antibodies are produced by hens and transported to their eggs where they are found in high concentrations. High titres of specific antibodies against bacteria were achieved by repeated immunization of hens with killed specific bacteria or fragments thereof, Specific antibodies against
Pseudomonas aeruginosa
have been produced by repeated immunizations of hens with killed
Pseudomonas aeruginosa
. Eggs from these hens have been used to make a solution with high specific antibody concentration.
An antibody consists of two parts; a Fab fragment which is the part of the antibody that binds to the antigen and a Fc fragment that lack antigen binding properties, The basis of oral administration of immunoglobulins has been attributed to interference with bacterial adherence and neutralization of toxins produced by the pathogens. The protective effect should therefore be conferred by either the whole IgY molecule or the antigen binding fragment thereof since both are capable of above functions. In fact this was demonstrated by the work of Ahren and Svennerholm (5) who observed that Fab fragments of anti-CFA/I reduced fluid secretion (diarrhoea) almost as effectively as non-cleaved immunoglobulin fraction of the serum. Fab fragments from chicken IgY will thus have similar protective functions against bacterial infections as the whole IgY molecule.
In contrast to antibodies from mammals (eg bovine), the antibodies from eggs (6) do not activate the human complement system (7). This is a tremendous advantage since activated complement factors are very effective mediators of inflammatory reactions. In addition, antibodies from eggs do not react with rheumafactors (8), human Fc-receptors (9), bacterial Fc-receptors (10) or human anti-mouse IgG-antibodies (11), which make them very safe to use.
The following examples are provided to further illustrate the invention without being limiting.


REFERENCES:
patent: 4714612 (1987-12-01), Nakamura et al.
patent: 4994269 (1991-02-01), Collins et al.
patent: 5215746 (1993-06-01), Stolle et al.
patent: 5240704 (1993-08-01), Tsurumizu et al.
patent: 5290540 (1994-03-01), Prince et al.
patent: 5420253 (1995-05-01), Emery et al.
patent: 5505945 (1996-04-01), Gristina et al.
patent: 5530102 (1996-06-01), Gristina et al.
patent: 5601823 (1997-02-01), Williams
patent: 5681565 (1997-10-01), Gristina et al.
patent: 5707627 (1998-01-01), Gristina et al.
patent: 5718899 (1998-02-01), Gristina et al.
patent: 5759544 (1998-06-01), Harada et al.
patent: 5817312 (1998-10-01), Gristina et al.
patent: 5922344 (1999-07-01), Hilty et al.
patent: 0 225 254 (1987-06-01), None
patent: 0 503 293 (1992-09-01), None
patent: 360028937 (1985-02-01), None
patent: 01226828 (1988-03-01), None
patent: 406009356 (1994-01-01), None
patent: 9-20684 (1997-01-01), None
patent: 9020684 (1997-01-01), None
patent: 409002926 (1997-01-01), None
patent: 409052822 (1997-02-01), None
patent: 94 13264 (1994-06-01), None
patent: WO94/13264 (1994-06-01), None
patent: WO 9631186 (1996-10-01), None
Zrein et al. Arch. Virol. 90: 197-206, 1986.*
Ma et al. Arch. Oral. Biol. 35: Suppl. 115S-122S, 1990.*
Sugita-Konishi et al. Biosci. Biotech. Biochem. 60(5): 886-888, 1996.*
Yokoyama et al. Infect. Immun. 60: 998-1007, abstract, 1992.*
Larsson et al., “Chicken Anti-Protein G for the Detection of Small Amounts of Protein G”,Hybridoma, vol. 12, No. 1, pp. 143-147, (1993).
Larsson et al., “Chicken Antibodies: A Tool to Avoid Interference by Human Anti-Mouse in ELISA After In vivo Trea

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