Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
1999-09-14
2002-03-12
Geist, Gary (Department: 1641)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S075000, C424S130100, C424S165100, C424S169100
Reexamination Certificate
active
06355625
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to compositions comprising &bgr;-glucans and specific immunoglobulins, and to methods of therapy using the compositions.
&bgr;-glucans are major structural components of yeast, fungi, and algae. Glucans are polymers of glucose that exist in both branched and unbranched forms. The polymers can exist as single strands with helical conformation, or as a complex of multiple strands that form a multi-stranded helix stabilized by hydrogen bonding.
&bgr;-glucans have been shown to have an effect upon various aspects of the immune response, such as humoral and cell-mediated immunity. When &bgr;-glucans are administered to experimental animals, the animals exhibit a wide range of immunomodulating and immunostimulating biological activities. These include nonspecific resistance against a variety of pathogenic challenges, promotion of wound healing, adjuvant effects when coadministered with any of bacterial, fungal, protozoal, or viral antigens, prolonged survival time in tumor-bearing animals, enhancement of bone marrow recovery and survival of lethally-irradiated mice, and reduction of serum cholesterol levels.
Administration of &bgr;-glucans, particularly (1→3)&bgr;-D-glucans, enhances host resistance to a variety of experimentally-induced bacterial (
S. aureus, E. coli, K. pneunomiae, S. pyogenes, M. tuberculosis, M. pyogenes
), viral (Murin viral hepatitis, Venezuelan equine encephalomyelitis virus, HIV), fungal (
C. albicans, C. neoformans
) and parasitic infections. &bgr;-glucans exert a significant beneficial effect on infectious episodes in animals with chemotherapy-induced immunosuppression.
All glucans, especially the soluble (1→3)&bgr;-glucans, and more particularly the branched (1→3)&bgr;-glucans, appear to be capable of inducing activation of macrophages and neutrophils, and are used as biological response mediators. Recent evidence suggests that the anti-infective efficacy of (1→3)&bgr;-glucans is attributable, at least in part, to macrophage activation induced by binding of the glucan to two specific receptors.
Studies of soluble &bgr;-glucans in animals and humans have shown them to be non-antigenic and non-virulent. While &bgr;-glucans induce toxicity, within certain ranges they can retain their activity in vivo without an unacceptable toxicity profile. &bgr;-glucans which do not induce high levels of cytokines in vivo generally exhibit lower toxicity at higher amounts, but also generally exhibit lower potency. However, the potential for particulate glucans in immunotherapy is tempered by findings that their intravenous injection is associated with undesirable side effects, including hepatosplenomegaly, granuloma formation and microembolism.
Conventional treatment of bacterial infection entails the administration of antibiotics and/or standard IGIV. Standard IGIV is a composition comprising non-specific immunoglobulin. It contains antibodies typically found in a donor population which has not been stimulated by immunization with specific antigens. Combinations of &bgr;-glucans with both antibiotics and standard IGIV have been reported. Reports of combinations of &bgr;-glucans with standard IGIV and zinc describe improved response to &bgr;-glucans as a result of a poorly-defined nonspecific stimulation of immune mechanisms by the standard IGIV and zinc, and combinations of the &bgr;-1,3-linked triple-helical glucans extracted from
S. cerevisiae
with conventional antibiotic therapies have demonstrated increased efficacy as compared to the &bgr;-glucan alone. No combination of &bgr;-glucan with antibodies specific to a single species of pathogenic microorganisms has been described. Indeed, where standard immunoglobulins and glucans have been combined, non-specific stimulation of immune mechanisms by the standard immunoglobulin, rather than any specific effect, has been credited with any observed differences in overall effect vis-a-vis the use of glucan alone. Soltys et al.,
Veterinary Immunology and Immunopathology
42:379-388 (1994).
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a composition, for use in a method of preventing or treating infection by a pathogenic microorganism, comprising a combination of &bgr;-glucans and antibodies specific to a single species of pathogenic microorganism.
It is a further object of the present invention to provide a composition, for use in a method of preventing or treating infection by a pathogenic microorganism, comprising a combination of &bgr;-glucans and antibodies specific to
S. aureus.
It is a particular object of the present invention to provide a composition, for use in a method of preventing or treating infection by a pathogenic microorganism, comprising a combination of &bgr;-glucans and antibodies specific to
S. aureus
Type 5 and/or Type 8 antigens and/or antibodies specific to a
S. aureus
antigen that comprises &bgr;-linked hexosamine, that contains no O-acetyl groups detectable by nuclear magnetic resonance spectroscopy and that reacts with antibodies to ATCC 55804. This latter antigen is denoted the 336 antigen and is disclosed in U.S. Pat. No. 5,770,208 issued Jun. 23, 1998.
It is yet another object of the present invention to provide a composition, for use in a method of preventing or treating infection by a pathogenic microorganism, comprising a combination of &bgr;-glucans and antibodies specific to
E. faecalis
and/or
E. faecium
antigens, particularly those antigens disclosed in U.S. application Ser. No. 08/949,757 filed Oct. 14, 1997.
It is a further object of the present invention to provide a composition, for use in a method of preventing or treating infection by a pathogenic microorganism, comprising a combination of &bgr;-glucans and antibodies specific to
S. epidermidis
antigens, particularly
S. epidermidis
antigens as disclosed in U.S. application Ser. No. 08/361,821.
These and other objects according to the invention are provided by a composition comprising a &bgr;-glucan and specific antibodies. The specific antibodies preferably are specific to antigens from one or more of Staphylococcus and Enterococcus. When the specific antibodies are specific to Staphylococcus, they preferably are specific to one or more of Type 5 antigen or Type 8 antigen of
S. aureus
, a
S. aureus
antigen that comprises &bgr;-linked hexosamine, that contains no O-acetyl groups detectable by nuclear magnetic resonance spectroscopy and that reacts with antibodies to ATCC 55804, and an antigen from
S. epidermidis
. When the specific antibodies are specific to Enterococcus, they preferably are specific to
E. faecium
or
E. faecalis
. Preferably, the &bgr;-glucan is a soluble &bgr;-glucan, and more preferably a chemically-derivatized &bgr;-glucan, particularly one that is selected from the group consisting of carboxymethyl glucan, sulfoethyl glucan, glucuronoglucan, glucan sulfate, phosphorylated glucan, and glucan amine. Preferred &bgr;-glucans are (1→3)&bgr;-glucans, particularly those that are branched.
The present invention also provides a kit that comprises a soluble &bgr;-glucan, specific antibodies, and instructions for sequential administration of the &bgr;-glucan and specific antibodies. The composition and kit are useful in a method of preventing or treating infection by a pathogenic microorganism, which comprises administering a soluble &bgr;-glucan to a subject, and introducing specific antibodies to a pathogenic microorganism into said subject. The specific antibodies may be introduced in the subject by vaccinating the subject with a vaccine, or they may be introduced by administering specific antibodies to the subject. In the latter case, the specific antibodies preferably comprise hyperimmune immunoglobulin.
Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by
Fattom Ali Ibrahim
Naso Robert B.
Pavliak Viliam
Foley & Lardner
Geist Gary
Khare Devesh
Nabi
LandOfFree
Compositions of &bgr;-glucans and specific IGIV does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compositions of &bgr;-glucans and specific IGIV, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions of &bgr;-glucans and specific IGIV will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2882529