Anti-bacterial antibodies and methods of use

Details Anti-bacterial antibodies and methods of use Anti-bacterial antibodies and methods of use

2001-09-27

2002-11-05

Scheiner, Laurie (Department: 1648)

Chemistry: molecular biology and microbiology

Animal cell, per se ; composition thereof; process of...

Animal cell, per se, expressing immunoglobulin, antibody, or...

C435S007330, C435S007340, C435S332000, C436S507000, C424S164100, C424S165100

Reexamination Certificate

active

06475788

ABSTRACT:

BACKGROUND OF THE INVENTION
The invention relates to the field of antibodies, immunology, infectious diseases, and medicine.
Pathogenic bacteria are a substantial cause of sickness and death in both humans and animals. Prominent among these is
Staphylococcus aureus
(
S. aureus
). Infection with these gram-positive cocci often results in the development of a superficial abscess. Other cases of
S. aureus
infection are more serious. For example, intrusion of
S. aureus
into the lymphatics and blood, can lead to a systemic infection which, in turn, can cause complications such as endocarditis, arthritis, osteomyelitis, pneumonia, septic shock and even death.
Streptococci also cause a large number of infections in humans and animals. Although many infections with streptococci are mild in nature, others can result in profound illness. Diseases associated with streptococcal infection include superficial cutaneous infections, pharyngitis, toinsilitis, impetigo, erysipelas, scarlet fever, urinary tract infections, endocarditis, acute rheumatic fever, acute glomerulonephritis, necrotizing fasciitis, and bacteremia. Severe cases of streptococcal infection can also lead to septic shock and death.
For most of this century, standard treatment for bacterial infections has been antibiotic therapy. Unfortunately, over the last several decades, several pathogenic strains of bacteria have developed resistance to various antibiotics. Worse, some of these strains have acquired resistance to multiple antibiotics. The advent of methicillin-resistant
S. aureus
in the last decade is perhaps the most significant example of this phenomenon. Vancomycin has thus become the antibiotic of choice for treating methicillin-resistant
S. aureus
infections. Recently,
S. aureus
strains displaying intermediate resistance to vancomycin have emerged. MMWR, 46:813-815, 1997.
SUMMARY OF THE INVENTION
The invention relates to antibodies that are capable of binding to a bacterial antigen, but lack the ability to be bound by bacterial Fc-binding proteins (e.g., staphylococcal Protein A, streptococcal Protein G, streptococcal protein H, etc.). Preparations of such antibodies should be effective for treating infections caused by bacteria that express Fc-binding proteins.
Effective antibody-mediated clearance of a bacterial infection generally requires the participation of two portions of an antibody molecule. The antigen-binding portion (e.g., the variable region of the Fab portion) of an antibody molecule serves to direct the antibody to a bacterial cell by physically engaging an antigen on that bacterial cell surface. The effector portion (e.g., the constant region or Fc region) of an antibody bound on the bacterial cell surface attracts effector molecules (e.g., complement or Fc receptors) that directly or indirectly kill the bacterium. Thus, an antibody bound to a bacterium typically has its antigen-binding portion directed toward the bacterial surface and its effector portion directed away from the bacterial cell surface. This orientation is thought to allow the effector portion of an antibody to physically interact with effector molecules and thereby facilitate the immune system-mediated clearance of bacteria. In bacteria expressing bacterial Fc-binding proteins, however, bacteria-specific antibodies may be bound to the bacterial cell surface in an opposite orientation (i.e., with the effector portion directed towards the bacterial cell surface and the antigen-binding portion directed away from the bacterial cell surface). In the latter orientation, the effector portion of an antibody is sterically-obscured by the bacterial Fc-binding protein and thus not readily able to bind effector molecules. In this manner, bacterial Fc-binding proteins may help the bacteria evade clearance by the immune system.
Accordingly, the present invention features a composition containing a purified polyclonal antibody enriched for immunoglobulins having both an antigen-binding portion specific for a bacterial antigen (e.g., a
S. aureus
antigen) and a constant region that does not bind a bacterial Fc-binding protein. The invention also features a composition containing a purified monoclonal antibody having both an antigen-binding portion specific for a bacterial antigen and a constant region that does not bind a bacterial Fc-binding protein. In addition, the invention includes a composition containing a polyclonal antibody that is made up primarily of a mixture of two or more monoclonal antibodies, each of which has both an antigen-binding portion specific for a bacterial antigen and a constant region that does not bind a bacterial Fc-binding protein.
In one aspect of the invention, the antibodies featured in the above compositions are derived from an animal possessing immunoglobulins, such as a mammal (e.g., a rat, mouse, rabbit, guinea pig, hamster, cow, pig, sheep, goat, horse, dog, or cat). In another aspect of the invention, the antibodies are derived from a human.
Also within the invention are compositions including an antibody that has both an antigen-binding portion directed against gram-positive bacteria and a constant region that does not bind a bacterial Fc-binding protein. In one embodiment, the compositions of the invention include an antibody having both an antigen-binding portion specific for Staphylococcus strains expressing Protein A (e.g.,
S. aureus
) and a constant region that does not bind a bacterial Fc-binding protein. In another embodiment, the compositions include an antibody having both an antigen-binding portion specific for Streptococcus strains expressing Protein G (e.g., group C streptococci) and a constant region that does not bind a bacterial Fc-binding protein.
In one facet of the invention, the anti-bacterial antibodies featured in the above compositions have constant regions that do not bind to a particular Fc-binding protein. In one example, the featured antibody has a constant region that does.not bind Protein A. In another example, the featured antibody has a constant region that does not bind Protein G.
In various embodiments, the antibodies within the invention are unmodified (i.e., not conjugated to an exogenous molecule). In other embodiments, the antibodies within the invention are conjugated to an antibiotic.
The invention additionally features pharmaceutical compositions that include one of the foregoing antibody compositions and a pharmaceutically acceptable carrier. Thus, for example, the invention includes a composition having a purified polyclonal antibody enriched for immunoglobulins having both an antigen-binding portion specific for a bacterial antigen and a constant region that does not bind a bacterial Fc-binding protein, and a pharmaceutically acceptable carrier. Likewise, the invention features a composition including a purified monoclonal antibody having both an antigen-binding portion specific for a bacterial antigen and a constant region that does not bind a bacterial Fc-binding protein, and a pharmaceutically acceptable carrier.
Also within the invention are processes of preparing pharmaceutical compositions. One such process includes the steps of: obtaining isolated immunoglobulins from an animal; contacting the isolated immunoglobulins with a bacterial Fc-binding protein; collecting the immunoglobulins not bound to the bacterial Fc-binding protein; and adding a pharmaceutically acceptable carrier to the immunoglobulins not bound to the bacterial Fc-binding protein. Another process within the invention includes the steps of: immunizing an animal with at least one bacterial antigen; isolating immunoglobulins from the animal; contacting the isolated immunoglobulins with a bacterial Fc-binding protein; collecting the immunoglobulins not bound to the bacterial Fc-binding protein; and adding a pharmaceutically acceptable carrier to the immunoglobulins not bound to the bacterial Fc-binding protein. In one embodiment of the latter process, the bacterial antigen used to immunize the animal is derived from
Staphylococcus aureus.
In another embodiment of the latter process,

Affiliated with

Also associated with

Rating

Anti-bacterial antibodies and methods of use does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Anti-bacterial antibodies and methods of use, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Anti-bacterial antibodies and methods of use will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2986217