Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Reexamination Certificate
2000-09-19
2003-12-09
Stucker, Jeffrey (Department: 1648)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
C530S324000, C530S325000, C530S326000, C530S331000, C530S382000, C530S807000, C435S007100
Reexamination Certificate
active
06660842
ABSTRACT:
FIELD OF THE INVENTION
The present invention generally relates to compositions and methods for preventing and treating human diseases including, but not limited to, pathogens such as bacteria, yeast, parasites, fungus, viruses, and cancer. More specifically, embodiments described herein concern the manufacture and use of ligand/receptor specificity exchangers, which redirect existing antibodies in a subject to receptors present on pathogens.
BACKGROUND OF THE INVENTION
Infection by pathogens, such as bacteria, yeast, parasites, fungus, and viruses, and the onset and spread of cancer present serious health concerns for all animals, including humans, farm livestock, and household pets. These health threats are exacerbated by the rise of strains that are resistant to vaccination and/or treatment. In the past, practitioners of pharmacology have relied on traditional methods of drug discovery to generate safe and efficacious compounds for the treatment of these diseases. Traditional drug discovery methods typically involve blindly testing potential drug candidate-molecules, often selected at random, in the hope that one might prove to be an effective treatment for some disease. With the advent of molecular biology, however, the focus of drug discovery has shifted to the identification of molecular targets associated with the etiological agent and the design of compounds that interact with these molecular targets.
One promising class of molecular targets are the receptors found on the surface of bacteria, yeast, parasites, fungus, viruses, and cancer cells, especially receptors that allow for attachment to a host cell or host protein (e.g., an extracellular matrix protein). Research in this area primarily focuses on the identification of the receptor and its ligand and the discovery of molecules that interrupt the interaction of the ligand with the receptor and, thereby, block adhesion to the host cell or protein. Although several receptor antagnosists have promising therapeutic potential, there still remains a need for new compositions and methods to treat and prevent infection by pathogens and other diseases.
BRIEF SUMMARY OF THE INVENTION
The invention described herein concerns the manufacture, characterization, and use of novel agents that bind receptors on pathogens and redirect antibodies present in a subject to the pathogen. Embodiments include a ligand/receptor specificity exchanger having at least one specificity domain comprising a ligand for a receptor and at least one antigenic domain joined to said specificity domain, wherein said antigenic domain comprises an epitope of a pathogen or toxin.
Some embodiments of the ligand/receptor specificity exchanger have a specificity domain that comprises at least three consecutive amino acids of a peptide selected from the group consisting of an extracellular matrix protein, a ligand for a receptor on a virus, and a ligand for a receptor on a cancer cell. In some aspects of this embodiment, for example, the peptide is an extracellular matrix protein selected from the group consisting of fibrinogen, collagen, vitronectin, laminin, plasminogen, thrombospondin, and fibronectin. Preferably, the extracellular matrix protein comprises at least 3 amino acids of the alpha-chain of fibrinogen and in the most preferred embodiments the ligand comprises the sequence Arginine-Glycine-Aspartate (RGD).
In other embodiments, the peptide described above is a ligand for a receptor on a virus selected from the group consisting of T4 glycoprotein and hepatitis B viral envelope protein. In still other aspects of this embodiment, the peptide is a ligand for a receptor on a cancer cell selected from the group consist of a ligand for HER-2
eu and a ligand for an integrin receptor. Preferred embodiments have a specificity domain that comprises a sequence provided by one of SEQ. ID. Nos. 1-42.
The ligand/receptor specificity exchangers described herein interact with a receptor found on a pathogen. In some embodiments, the receptor is a bacterial adhesion receptor, for example, a bacterial adhesion receptor selected from the group consisting of extracellular fibrinogen binding protein (Efb), collagen binding protein, vitronectin binding protein, laminin binding protein, plasminogen binding protein, thrombospondin binding protein, clumping factor A (ClfA), clumping factor B (ClfB), fibronectin binding protein, coagulase, and extracellular adherence protein.
The ligand/receptor specificity exchangers described herein also interact with a an antibody present in a subject. In some embodiments, for example, the antigenic domain comprises at least three amino acids of a peptide selected from the group consisting of a herpes simplex virus protein, a hepatitis B virus protein, a TT virus protein, and a poliovirus protein. In desirable embodiments, the ligand/receptor specificity exchanger has an antigenic domain that is a herpes simplex virus protein comprising a sequence selected from the group consisting of SEQ. ID. No. 53 and SEQ. ID. No. 54. In other desired embodiments, the antigenic domain is a hepatitis B virus protein comprising a sequence provided by one of SEQ. ID. No. 49, SEQ. ID. No. 50, SEQ. ID. No. 52, and SEQ. ID. No. 59.
Some ligand/receptor specificity exchangers also have an antigenic domain that is a TT virus protein comprising a sequence provided by one of SEQ. ID. Nos. 43-47 and SEQ. ID. Nos. 55-58. The ligand/receptor specificity exchangers can also have an antigenic domain that is a polio virus protein comprising a sequence selected from the group consisting of SEQ. ID. No. 48 and SEQ. ID. No. 51. Preferably, the ligand/receptor specificity exchanger has an antigenic domain that interacts with a high-titer antibody. In some embodiments, for example, the antigenic domain specifically binds to an antibody present in animal serum that has been diluted to between approximately 1:100 to 1:1000 or greater. The specificity exchangers of SEQ. ID. Nos. 60-105 are embodiments of the invention.
Aspects of the invention also concern method of treating or preventing a infection or proliferation of a pathogen. One approach for example, involves a method for treating and preventing bacterial infection. This method is practiced by providing a therapeutically effective amount of a ligand/receptor specificity exchanger to a subject, wherein said ligand/receptor specificity exchanger comprises a specificity domain that has a ligand that interacts with a receptor on a bacteria, and an antigenic domain that comprises an epitope for a pathogen or toxin. A method of treating or preventing viral infection is also an embodiment. Accordingly, a method of treating or preventing a viral infection is practiced by providing a therapeutically effective amount of a ligand/receptor specificity exchanger to a subject, wherein said ligand/receptor specificity exchanger comprises a specificity domain that has a ligand that interacts with a receptor on a virus, and an antigenic domain that comprises an epitope for a pathogen or toxin. Similarly, a method of treating or preventing cancer is an embodiment and this method can be practiced by providing a therapeutically effective amount of a ligand/receptor specificity exchanger to a subject, wherein said ligand/receptor specificity exchanger comprises a specificity domain that has a ligand that interacts with a receptor on a cancer cell, and an antigenic domain that comprises an epitope for a pathogen or toxin.
DETAILED DESCRIPTION OF THE INVENTION
The following describes the manufacture, characterization, and use of novel agents that bind receptors on pathogens and redirect antibodies present in a subject to the pathogen. The embodiments are collectively referred to as “ligand/receptor specificity exchangers”. The term “ligand/receptor specificity exchangers” refers a specificity exchanger that comprises a “specificity domain” that has at least one ligand for a receptor (a “ligand” is not an antibody or portion thereof) joined to an “antigenic domain” that has at least one epitope of a pathogen or toxin (e.g., pertussis toxin or
Knobbe Martens Olson & Bear LLP
Stucker Jeffrey
Tripep AB
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