Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Reexamination Certificate
1999-05-24
2003-10-28
Swartz, Rodney P. (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
C424S093440, C424S165100, C424S237100, C530S350000, C536S023700
Reexamination Certificate
active
06638516
ABSTRACT:
DESCRIPTION OF DEPOSITED BIOLOGICAL MATERIALS
The
Streptococcus pneumoniae
strain designated Rx1 has been deposited pursuant to, and in satisfaction of, the requirements of the Budapest Treaty on the International Recognition of The Deposit of Microorganisms for The Purposes of Patent Procedure, with the American Type Culture Collection (ATCC), now at 10801 University Boulevard, Manassas, Va. 20110-2209, under ATCC Accession No. 55834, on Oct. 3, 1996.
BACKGROUND OF THE INVENTION
Streptococcus pneumoniae is an important cause of otitis media, meningitis, bacteremia and pneumonia, and a leading cause of fatal infections in the elderly and persons with underlying medical conditions such as pulmonary disease, liver disease, alcoholism, sickle cell anemia, cerebrospinal fluid leaks, acquired immune deficiency syndrome (AIDS), and patients undergoing immunosuppressive therapy. It is also a leading cause of morbidity in young children. Pneumococcal infections cause approximately 40,000 deaths in the U.S. each year. The most severe pneumococcal infections involve invasive meningitis and bacteremia infections, of which there are 3,000 and 50,000 cases annually, respectively.
Despite the use of antibiotics and vaccines, the prevalence of pneumococcal infections has declined little over the last twenty-five years; the case-fatality rate for bacteremia is reported to be 15-20% in the general population, 30-40% in the elderly, and 36% in inner-city African Americans. Less severe forms of pneumococcal disease are pneumonia, of which there are 500,000 cases annually in the U.S., and otitis media in children, of which there are an estimated 7,000,000 of such cases each year are caused by pneumococcus. Strains of drug-resistant
S. pneumoniae
are becoming ever more common in the U.S. and worldwide. In some areas, as many as 30% of pneumococcal isolates are resistant to penicillin. The increase in antimicrobial resistant pneumococcus further emphasizes the need for preventing pneumococcal infections.
Pneumococcus asymptomatically colonizes the upper respiratory tract of normal individuals; disease often results from the spread of organisms from the nasopharynx to other tissues during opportunistic events. The incidence of carriage in humans varies with age and circumstances. Carrier rates in children are typically higher than those of adults. Studies have demonstrated that 38 to 60% of preschool children, 29 to 35% of grammar school children and 9 to 25% of junior high school children are carriers of pneumococcus. Among adults, the rate of carriage drops to 6% for those without children at home, and to 18 to 29% for those with children at home. It is not surprising that the higher rate of carriage in children than in adults parallels the incidence of pneumococcal disease in these populations.
An attractive goal for streptococcal vaccination is to reduce carriage in the vaccinated populations and subsequently reduce the incidence of pneumococcal disease. There is speculation that a reduction in pneumococcal carriage rates by vaccination could reduce the incidence of the disease in non-vaccinated individuals as well as vaccinated individuals. This “herd immunity” induced by vaccination against upper respiratory bacterial pathogens has been observed using the
Haemophilus influenzae
type b conjugate vaccines (Takala, A. K., et al., J. Infect. Dis. 1991; 164: 982-986; Takala, A. K., et al., Pediatr. Infect. Dis. J., 1993; 12: 593-599; Ward, J., et al., Vaccines, S. A. Plotkin and E. A. Mortimer, eds., 1994, pp. 337-386; Murphy, T. V., et al., J. Pediatr., 1993; 122; 517-523; and Mohle-Boetani, J. C., et al., Pediatr. Infect. Dis. J., 1993; 12: 589-593).
It is generally accepted that immunity to
Streptococcus pneumoniae
can be mediated by specific antibodies against the polysaccharide capsule of the pneumococcus. However, neonates and young children fail to make adequate immune response against most capsular polysaccharide antigens and can have repeated infections involving the same capsular serotype. One approach to immunizing infants against a number of encapsulated bacteria is to conjugate the capsular polysaccharide antigens to protein to make them immunogenic. This approach has been successful, for example, with
Haemophilus influenzae
b (see U.S. Pat. No. 4,496,538 to Gordon and U.S. Pat. No. 4,673,574 to Anderson).
However, there are over ninety known capsular serotypes of
S. pneumoniae
, of which twenty-three account for about 95% of the disease. For a pneumococcal polysaccharide-protein conjugate to be successful, the capsular types responsible for most pneumococcal infections would have to be made adequately immunogenic. This approach may be difficult, because the twenty-three polysaccharides included in the presently-available vaccine are not all adequately immunogenic, even in adults.
Protection mediated by anti-capsular polysaccharide antibody responses are restricted to the polysaccharide type. Different polysaccharide types differentially facilitate virulence in humans and other species. Pneumococcal vaccines have been developed by combining 23 different capsular polysaccharides that are the prevalent types of human pneumococcal disease. These 23 polsaccharide types have been used in a licensed pneumococcal vaccine since 1983 (D. S. Fedson and M. Musher,
Vaccines
, S. A. Plotkin and J. E. A. Montimer, eds., 1994, pp. 517-564). The licensed 23-valent polysaccharide vaccine has a reported efficacy of approximately 60% in preventing bacterermia caused by vaccine type pneumococci in healthy adults.
However, the efficacy of the vaccine has been controversial, and at times, the justification for the recommended use of the vaccine questioned. It has been speculated that the efficacy of this vaccine is negatively affected by having to combine 23 different antigens. Having a large number of antigens combined in a single formulation may negatively affect the antibody responses to individual types within this mixture because of antigenic competition. The efficacy is also affected by the fact that the 23 serotypes encompass all serological types associated with human infections and carriage.
An alternative approach for protecting children, and also the elderly, from pneumococcal infection would be to identify protein antigens that could elicit protective immune responses. Such proteins may serve as a vaccine by themselves, may be used in conjunction with successful polysaccharide-protein conjugates, or as carriers for polysaccharides.
McDaniel et al. (I), J. Exp. Med. 160:386-397, 1984, relates to the production of monoclonal antibodies that recognize cell surface polypeptide(s) on
S. pneumoniae
and protection of mice from infection with certain strains of encapsulated pneumococci by such antibodies.
This surface protein antigen has been termed “pneumococcal surface protein A”, or “PspA” for short.
McDaniel et al. (II), Microbial Pathogenesis 1:519-531, 1986, relates to studies on the characterization of the PspA. Considerable diversity in the PspA molecule in different strains was found, as were differences in the epitopes recognized by different antibodies.
McDaniel et al. (III), J. Exp. Med. 165:381-394, 1987, relates to immunization of X-linked immunodeficient (XID) mice with non-encapsulated pneumococci expressing PspA protects mice from subsequent fatal infection with pneumococci, but immunization with isogenic pneumococci which do not express PspA does not confer protection.
McDaniel et al. (IV), Infect. Irnmun., 59:222-228, 1991, relates to immunization of mice with a recombinant full length fragment of PspA that is able to elicit protection against pneumococcal strains of capsular types 6A and 3.
Crain et al, Infect.Immun., 56:3293-3299, 1990, relates to a rabbit antiserum that detects PspA in 100% (n=95) of clinical and laboratory isolates of strains of
S. pneumoniae
. When reacted with seven monoclonal antibodies to PspA, fifty-seven
S. pneumoniae
isolates exhibited thirty-one different patterns of reactivity.
U.S. Pat. No. 5,476,929, relates to vaccines comprisi
Becker Robert S.
Briles David E.
Hollingshead Susan
Nixon & Peabody LLP
Swartz Rodney P.
The UAB Research Foundation
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