Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2000-06-01
2001-05-22
Geist, Gary (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C424S001210, C424S078050, C424S078320, C536S017400, C536S017600, C536S018700
Reexamination Certificate
active
06235720
ABSTRACT:
BACKGROUND OF THE INVENTION
The infection of a host cell by a microbe, such as a virus, a bacterium or a protozoan, proceeds via initial attachment of the microbe to the host cell surface. This process is mediated by relatively weak attractive interactions between adhesion molecules on the surfaces of the microbe and the host cell. In general, microbe-host cell attachment is the product of a multiplicity of such interactions, via what has been referred to as the polyvalent effect. One well-studied example of such a process is the attachment of the influenza A virus to mammalian epithelial cells, which results from interaction of terminal N-acetylneuraminic acid groups of glycolipids and glycoproteins on the host cell surface with the attachment glycoprotein hemagglutinin on the viral surface.
The growing problem of bacterial resistance to conventional antibiotics and the paucity of effective antiviral agents both point to the need for new approaches to the treatment of microbial infections. The attachment step is an attractive target for such a treatment, and much activity has focused on the development of N-acetylneuraminic acid-containing compounds capable of binding to viral hemagglutinin, thus inhibiting viral attachment to host cells. Studies have demonstrated that polyvalent compounds, such as polymers bearing pendant N-acetylneuraminic acid groups, bind influenza virus with association constants which are several orders of magnitude higher than those of monomeric N-acetylneuraminic acid derivatives. To date, no polyvalent N-acetylneuraminic acid containing compounds are in clinical use for treatment or prevention of influenza.
A disadvantage of N-acetylneuraminic acid-functionalized compounds as therapeutic agents for the treatment of infection by influenza A virus and, possibly, other microbes, is the great expense of this sugar. In addition, the influenza virus has at its surface the enzyme neuramidinase, which cleaves N-acetylneuraminic acid moieties from such molecules, eventually destroying their ability to bind the virus. There is, thus, a need for inhibitors of microbial attachment to mammalian cells which have an improved effective lifetime, are readily prepared from inexpensive starting materials and have a broad spectrum of activity.
SUMMARY OF THE INVENTION
The present invention relates to polymers comprising one or more acid-functionalized glycoside moieties which can inhibit or prevent a microbial infection in a mammal, monomers which can serve as starting materials in the synthesis of such polymers, and methods of use of such polymers in the treatment of a microbial infection in a mammal.
The monomers of the present invention include polymerizable monomers comprising an acid-functionalized glycoside moiety. The acid functional group can be, for example, an O-sulfo group or an O-carboxymethyl group. In one embodiment, the monomer has a polymerizable functional group, such as an olefinic bond, to which the acid-functionalized glycoside moiety is attached by a spacer group. The spacer group is, for example, an alkylene group, or an alkylene group wherein one or more carbon atoms are substituted by heteroatoms, such as oxygen, nitrogen or sulfur atoms.
The polymers of the present invention comprise acid-functionalized glycoside moieties, such as pendant acid-functionalized glycoside moieties. Such a polymer can be a homopolymer or a copolymer, and can have, for example, a polyacrylamide, polyacrylate or polystyrene backbone. In one embodiment, the polymer is a copolymer comprising a acid-functionalized glycoside-bearing monomer and acrylamide.
In another embodiment, the present invention includes a method for treating a microbial infection in a mammal, for example, a human, by administering to the mammal a therapeutically effective amount of a polymer comprising one or more acid-functionalized glycoside moieties, such as pendant acid-functionalized glycoside moieties. The acid-functionalized glycoside moieties can be, for example, 3-O-sulfogalactoside moieties or 3-O-carboxymethylgalactoside moieties. The polymer can be a homopolymer or a co-polymer. In one embodiment, the polymer is a copolymer comprising an acid-functionalized glycoside-bearing monomer and acrylamide.
The present invention offers several advantages. It provides agents and a method for the treatment and prevention of microbial infection. In addition the acid-functionalized glycoside-bearing polymers can incorporate a relatively simple and inexpensive sugar.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to the incorporation of acid functionalized glycoside moieties into the side chains of synthetic polymers. This provides polyvalent polymers able to bind to a variety of microbes, thereby inhibiting attachment of these microbes to the surfaces of mammalian cells. Such polymers can thus prevent or inhibit a microbial infection in a mammal, such as a human.
The term “acid-functionalized glycoside moiety” as used herein, refers to a glycoside or sugar moiety which is substituted at one hydroxyl oxygen atom with an acidic functional group. Suitable acidic functional groups include the sulfo (—SO
3
H) group and the carboxymethyl (—CH
2
COOH) group. The acidic functional group can be protonated or it can be deprotonated to form the conjugate base, an anion which is associated with a counter cation, such as an alkali metal cation, for example a sodium, potassium or cesium ion, or an ammonium or substituted ammonium ion.
One aspect of the present invention includes a polymer comprising one or more acid-functionalized glycoside moieties, wherein the acid functionality is an O-sulfo group or an O-carboxymethyl group. Preferably, the acid-functionalized glycoside moieties are pendant acid-functionalized glycoside moieties.
The term “pendant”, as used herein, refers to a structural component of one or more polymer side chains which is not a part of the polymer backbone. Therefore, polymers of the present invention comprise side chains to which are attached acid-functionalized glycoside moieties.
The term “monomer”, as used herein, refers to both a molecule comprising one or more polymerizable functional groups prior to polymerization, and a repeating unit of a polymer. A copolymer is said to comprise two or more different monomers. An “acid-functionalized glycoside-bearing monomer” is a monomer, either polymerized or unpolymerized, which comprises an acid-functionalized glycoside moiety. Upon incorporation into a polymer, an acid-functionalized glycoside-bearing monomer comprises a pendant acid-functionalized glycoside moiety.
The present invention includes monomers which are starting materials for the synthesis of polymers which comprise one or more acid-functionalized glycoside moieties, wherein the acid functional group is an O-sulfo group or an O-carboxymethyl group. Such a monomer is linked at the anomeric carbon to a spacer group via an atom, which can be, for example, a carbon atom, or a heteroatom, such as an oxygen, nitrogen or sulfur atom.
In a preferred embodiment, the monomer is of Formula I,
wherein one of R
2
, R
3
, and R
4
is —SO
3
H or —CH
2
COOH, the remaining two are each a hydrogen atom, and R
6
is a hydrogen atom or a hydroxyl group; or each of R
2
, R
3
, and R
4
is a hydrogen atom and R
6
is —OSO
3
H or —OCH
2
COOH. X is a spacer group and can be a straight chain or branched, substituted or unsubstituted alkylene group wherein, optionally, one or more carbon atoms can be substituted by a heteroatom, such as an oxygen, nitrogen or sulfur atom. Examples include a —(CH
2
)
n
— group, wherein n is an integer from about 2 to about 12, a substituted alkylene group, an oxaalkylene group, such as —(CH
2
)
2
O[(CH
2
)
2
O]
n
(CH
2
)
2
—, wherein n is an integer from 0 to about 3, or a thiaalkylene group, such as —(CH
2
)
n
S(CH
2
)
m
—, where n and m are each an integer from 0 to about 10.
The acid-functionalized glycoside moiety can be an &agr;- or &bgr;-L-glycoside or an &agr;- or &bgr;-D-glycoside moiety. In Formula I, this is indicated by the wavy lin
Garigapati Venkata R.
Mandeville, III W. Harry
Crane L. E.
Geist Gary
GelTex Pharmaceuticals Inc.
Hamilton Brook Smith & Reynolds P.C.
LandOfFree
Acid-functionalized saccharide polymers does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Acid-functionalized saccharide polymers, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Acid-functionalized saccharide polymers will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2477062