Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Reexamination Certificate
2000-07-05
2004-02-03
Navarro, Mark (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
C424S197110, C424S009200, C424S184100, C424S234100, C435S072000, C435S097000, C435S170000, C435S197000
Reexamination Certificate
active
06685949
ABSTRACT:
BACKGROUND OF THE INVENTION
Moraxella
(
Branhamella
)
catarrhalis
is a pathogenic bacterium, recognized as the third most common causative agent of otitis media and sinusitis in children, after
Streptococcus pneumoniae
and
Haemophilus influenzae
(Bluestone, C. D., 1986, Drugs 31(Suppl 3):132-41; Catlin, B. W., 1990, Clin. Microbiol. Rev. 3:293-320; Doem, G. V., 1986, Diagn. Microbiol. Infect. Dis. 4:191-201; Enright, M. C. & H. McKenzie, 1997, J. Med. Microbiol. 46:360-71; Faden, H., et al., 1994, J. Infect. Dis. 169:1312-1317). This Gram-negative diplococcus also causes respiratory tract infections in adults (Boyle, F. M., et al., 1991, Med. J. Aust. 154:592-596; Sarubbi, F. A., et al., 1990, Am. J. Med. 88:9S-14S), especially those who are immunocompromised or have chronic obstructive pulmonary diseases (Enright, M. C. & H. McKenzie, 1997, J. Med. Microbiol. 46:360-371). The incidence of disease caused by
M. catarrhalis
appears to be increasing (McLeod, D. T., et al., 1986, Br. Med. J. 292:1103-1105; Fung, C.P., et al., 1992, J. Antimicrob. Chemother. 30:47-55). Currently, there is no vaccine for
M. catarrhalis
-mediated diseases.
Although protective antigens of
M. catarrhalis
have not been clearly defined, development of serum antibodies against
M. catarrhalis
appears to be important in immunity against
M. catarrhalis
. For example, normal adults with immunity resulting from natural colonization or infection have a lower carriage rate (1 to 6%) than children (50 to 78%) and elderly persons (>26%), and suffer fewer infections (Ejlertsen T. et al., 1994, J. Infect. 29:23-31; Faden H. et al., 1994, J. Infect. Dis. 169:1312-1317; Eliasson, I., 1986, Drugs 31 (Suppl 3):7-10; Vaneechoutte, M., et al., 1990., J. Clin. Microbiol. 28:2674-2680). Children develop serum antibodies to
M. catarrhalis
gradually during the first four years of life, which seems to correlate with a decrease in the incidence of bacteremia and otitis media caused by
M. catarrhalis
(CDR Weekly Reports, 1992-1995, Communicable Disease Surveillance Centre, London; Goldblatt D., et al., 1990, J. Infect. Dis. 162:1128-1135; Vaneechoutte, M., et al., 1990., J Clin Microbiol 28:2674-2680; Bluestone, C. D., 1986, Drugs 31 (Suppl 3):132-141). Antibodies to
M. catarrhalis
have also been detected in acute and in convalescent sera of adult patients (Christensen, J. J., et al., 1990, Clin. Diagn. Lab. Immunol. 3:717-721; Rahman, M., et al., 1997, APMIS 105:213-220). Most convalescent sera demonstrate bactericidal activity against the corresponding
M. catarrhalis
isolate (Chapman, A. J. Jr., et al., 1985, J. Infect. Dis. 151:878-882). These results indicate that serum antibodies are likely to =be involved in protection against infections with
M. catarrhalis.
Efforts to date to study
M. catarrhalis
as an important pathogen have generally focused on describing surface antigens, such as outer membrane proteins (OMP) (Bhushan, R., et al., 1994, J. Bacteriol. 176:6636-6643; Campagnari, A. A., et al., 1994, Infect. Immun. 62:4909-4914; Helminen, M. E., et al., 1993, Infect. Immun. 61:2003-2010; Helminen, M. E., et al., 1994, J. Infect. Dis. 170:867-872; Murphy, T. F., et al., 1993, Mol. Microbiol. 10:87-97). Two outer membrane proteins that have been extensively studied are a high-molecular-weight protein (UspA) and a major outer membrane protein (CD). Both of these proteins are relatively conserved among different strains of
M. catarrhalis
and are able to generate bactericidal antibodies (Helminen, M. E., et al., 1994, J. Infect. Dis. 170:867-872; Murphy, T. F., et al., 1993, Mol. Microbiol. 10:87-97; Yang, Y. P., et al., 1997, FEMS Immunol. Med. Microbiol. 17:187-199). In addition, passive immunization with monoclonal antibodies to UspA, or immunization with UspA, has resulted in enhanced pulmonary clearance of
M. catarrhalis
strains in a murine model (Helminen, M. E., et al., 1994, J. Infect. Dis. 170:867-872; Chen, D., et al., 1996, Infect. Immun. 64:1900-1905). Genes encoding CD protein have been cloned and sequenced (Murphy et al., 1993, Molec. Microbiol. 10(1):87).
Other outer membrane proteins that have been purified and characterized include protein E (OMP E) (Bhushan et al., 1994, J. Bacteriol., 176(21):6636), protein B1 (Ducey et al., 1996, Abstracts, Gen. Mtg. Am. Soc. Microbiol., 96(0):186), and protein COPB (Aebi et al., 1996, Abstracts, Intersci. Conf. Antimicrobial Agents & Chemotherapy 36:158). Other surface antigens include fimbriae, which have not been found in all isolates (Marrs, C. F. & S. Weir, 1990, Am. J. Med. 88 (suppl 5A):36S-40S), and a capsular polysaccharide, whose existence is controversial (Ahmed, K., et al., 1991, Microbiol. Immunol. 35:361-366). Lipooligosaccharide-associated high molecular weight outer membrane protein has also been identified (Klingman & Murphy, 1992, Abstr. Gen Mtg. Am. Soc. Microbiol.).
Lipooligosaccharide (LOS), a major surface component of
M. catarrhalis
, is a virulence factor for the pathogenesis of the bacterial infections (Doyle, W. J., 1989, Pediatr. Infect. Dis. J. 81(Suppl): S45-S47; Fomsgaard, J. S., et al., 1991, Infect. Immun. 59:3346-3349). The LOS may be important for development of immunoprotection because (1) serum antibodies to LOS have been detected in patients with
M. catarrhalis
infections, (2) the convalescent-phase IgG anti-LOS from patients has demonstrated bactericidal activity against
M. catarrhalis
strains, and (3) LOS appears to have a conserved structure based on its serological properties in humans (Rahman, M., et al., 1995, Eur. J. Clin. Microbiol. Infect. Dis. 14:297-304; Tanaka, H., et al., 1992, J. Jpn. Assoc. Infect. Dis. 66: 709-715). Similarly, serum bactericidal LPS or PS antibodies specific to other microorganisms (e.g.,
H. influenzae
type b,
Neisseria meningitidis, Vibrio cholerae, Shigella sonnei
) confer immunity to those pathogens in humans (Robbins, J.B., et al., 1995, J. Infect. Dis. 171:1387-1398; Cohen, D., et al., 1997, Lancet 349:155-159).
Three major antigenic types (A, B and C) of LOS account for about 95% of
M. catarrhalis
strains (i.e., 61% A; 29% B; and 5% C in one study) (Vaneechoutte, M., et al., 1990, J. Clin. Microbiol. 28:182-187). Studies have shown that these LOSs contain an oligosaccharide linked to lipid A, without an 0-specific polysaccharide, and the oligosaccharides from the three serotypes are branched with a common inner core (Edebrink, P., et al., 1994, Carbohydr. Res. 257:269-284; Edebrink, P., et al., 1995, Carbohydr. Res. 266:237-261; Edebrink, P., et al., 1996, Carbohydr. Res. 295:127-146).
Lipopolysaccharide (LPS) and LOS from a variety of microorganisms are generally toxic in vivo to mammals. Many approaches have been used to detoxify LPS or LOS, or to obtain nontoxic polysaccharides from LPS or oligosaccharides from LOS. For example, mild-acid treatment of LPS or LOS has been used to cleave the lipid A portion from the LOS molecule at the Kdo-glucosamine linkage (Gu, X. X., & C. M. Tsai, 1993, Infect. Immun. 61:1873-1880). Another method is mild-alkali treatment of LOS, removes ester-linked fatty acids while preserving amide-linked fatty acids of lipid A (Gupta, R. K., et al., 1992, Infect. Immun. 60:3201-3208; Gu et al., 1996, Infect. & Imm. 64(10):4047).
Development of vaccines against
M. catarrhalis
and other microorganisms has been attempted using a variety of approaches (Karma et al., 1995, Intl. J. Ped. Otorhinolaryngol. 32 (SUPPL.): S127-S134). Vaccines against
M. catarrhalis
based on outer membrane proteins E and CD, derived peptides and oligopeptides, or nucleotides encoding these proteins have been disclosed in U.S. Pat. No. 5,607,846 and U.S. Pat. No. 5,556,755. Conjugate vaccines made up of a carbohydrate-containing antigen bound to an immunomodulating cytokine, lymphokine, hormone or growth factor have been disclosed in U.S. Pat. No. 5,334,379. Canadian Pat. No. 2,162,193 discloses that a purified bacterial lactoferrin receptor protein may be used as a vaccine against pathogens that produce a lactoferrin receptor protein, including
Gu Xin-Xing
Robbins John B.
Knobbe Martens Olson & Bear LLP
Navarro Mark
Shahnan-Shah Khatol S
The United States of America as represented by the Department of
LandOfFree
Lipooligosaccharide based vaccine for prevention of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Lipooligosaccharide based vaccine for prevention of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Lipooligosaccharide based vaccine for prevention of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3307801