Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Reexamination Certificate
1997-01-16
2002-10-22
Travers, Russell (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
Reexamination Certificate
active
06468991
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates generally to a method of treating viral infections, and more specifically to a method of treating rhinoviral infections.
BACKGROUND OF THE INVENTION
Acute afebrile upper respiratory disease, often grouped clinically as “the common cold,” is one of the most frequent afflictions of humans. Although the disease is typically not life-threatening, it causes much discomfort as well as the loss of over 200 million man-days of work and school each year in the United States alone. B. D. Davis et al.,
Microbiology
at 1114 (Third Edition, 1980). Since 1956, when viruses from patients suffering with the common cold were first isolated, over 113 immunologically distinct, yet biologically related viruses have been isolated. Id. at 1115. The chemical and physical characteristics of these viruses led to their classification as members of the picornavirus family, and more specifically into the genus known as the Rhinoviridiae, or the rhinoviruses. Rhinoviruses have been characterized as small (17-30 nm in diameter), non-enveloped, RNA-containing virions that are cubic in structure and resistant to ether treatment. It is now thought that rhinoviral infection is the cause of approximately 40 percent of all respiratory illnesses in children and adults. V. Knight, Common Viral Respiratory Illnesses, in
Harrison's Principles of Internal Medicine, Eighth Edition
at 988-990 (G. W. Thorn et al. eds., 1977).
Although several methods have been proposed as treatments for rhinoviral infection, including vaccination, air sterilization, and the administration of various pharmaceuticals, none of these methods has proved to be entirely effective. Problems that hinder the development of useful rhinovirus vaccines include the short duration of natural immunity to specific infecting types, the large number of different antigenic types of rhinovirus, and the variation of types present in a community from one year to the next. J. L. Melnick et al.,
McGraw
-
Hill Encyclopedia of Science and Technology, Seventh Edition
15, 454 (1992). Current methods of treatment are limited to the amelioration of symptoms, and often take the form of antihistamines and other drugs. There is therefore a desire to develop a method of treating rhinoviral infections that is effective, safe and practical.
SUMMARY OF THE INVENTION
In view of the foregoing, it is a first object of the present invention to provide a method for effectively and practically treating a rhinoviral infection.
A second object of the invention is to provide pharmaceutical formulations useful in the treatment of rhinoviral infections.
It has now been discovered that 2′-5′ oligoadenylates (2′,5′-A) and their analogs are surprisingly effective in the treatment of rhinoviral infections. Accordingly, a first aspect of the present invention is a method of treating a rhinoviral infection in a subject in need of such treatment. The method comprises administering to the subject a compound of Formula I:
wherein n is 0, 1, 2, or 3;
each R
1
and R
2
is independently selected from the group consisting of hydrogen, halogen, and N
3
;
each R
5
is independently hydrogen or —OH;
each R
6
is independently hydrogen or —OH;
R
7
is O
−
or —OH;
R
9
is hydrogen or —OH, with the proviso that
when R
9
is —OH, R
5
is hydrogen;
Y is
wherein m is 1, 2, or 3;
X is —CHOHCH
2
OH, or is selected from the group consisting of
wherein R
3
and R
4
are each independently selected from the group consisting of hydrogen, —OH, and —PO
4
−2
, or R
3
and R
4
together represent a cyclophosphate; and A is selected from the group consisting of
wherein each R
1
and R
2
are as provided above; and R
8
is selected from the group consisting of hydrogen, cyanogen, and amido;
each Z is independently O or S; and
each Z′ is independently O or S;
or a pharmaceutically acceptable salt thereof, (hereinafter referred to as the “active compound”), in amount effective to treat the rhinoviral infection.
In one preferred embodiment of the invention, Y is —OH. In another preferred embodiment of the invention, X is
R
1
and R
2
are hydrogen;
R
3
is —OH and R
4
is —PO
4
−2
, or
R
3
is PO
4
−2
and R
4
is —OH, or
R
3
and R
4
are both —OH, or
R
3
and R
4
together represent a cyclophosphate;
R
5
is —OH;
R
9
is hydrogen; and
Z and Z′ are both O.
A second aspect of the present invention is a pharmaceutical formulation for combatting rhinoviral infection comprising, in combination with a pharmaceutically acceptable carrier, an active compound as described above.
A third aspect of the present invention is the use of an active compound as disclosed herein for the manufacture of a medicament useful in carrying out a therapeutic method of treatment as given above.
DETAILED DESCRIPTION OF THE INVENTION
As noted above, the methods of the present invention are useful for treating infections caused by rhinoviruses. In general, rhinovirus infections (the “condition”) are characterized by nasal obstruction and discharge, sneezing, moderate sore throat and mild constitutional reaction, usually without fever. In young children, these symptoms may be further aggravated by cough, croup, and pneumonia. The methods of the present invention are useful for treating these conditions in that they inhibit the onset, growth, or spread of the condition, cause regression of the condition, cure the condition, or otherwise improve the general well-being of a subject afflicted with, or at risk of contracting the condition.
Subjects to be treated by the methods of the present invention are typically human subjects, although the methods of the present invention may be useful with any suitable subject known to those skilled in the art including mammals (e.g., horses, dogs, cats) for veterinary purposes. For example, the methods may be particularly useful in treating rhinoviral infections in performing or racing animals (e.g., greyhounds, racing horses or horses used in equestrian competitions, and circus animals).
As used herein, the term “rhinovirus” refers to viruses which are members of the picornavirus family, and more specifically to the members of the viral genus Rhinoviridiae. The rhinovirus virion is characterized as containing single stranded RNA, having a non-enveloped capsid and having cubic capsid symmetry. See Knight, supra, at 988. Rhinoviruses are sharply distinguished from other picornaviruses in that they are inactivated at low pH, maintain their infectivity at 50° C., and have higher buoyant density in CsCl. See Davis et al., supra, at 1115.
As noted above, over 113 immunologically distinct rhinoviruses (RV) have been isolated, with each individual serotype or “type” being designated by a numeral. Accordingly, rhinovirus type 1 is denoted RV-1; rhinovirus type 1, sub-type B is denoted RV-1B, etc. The present invention is useful in combatting a rhinoviral infection caused by any rhinovirus type. In a preferred embodiment, the method of the present invention is useful in combatting a rhinoviral infection caused by a rhinovirus type selected from the group consisting of rhinovirus type 1 (RV-1, including subtypes A (RV-1A) and B (RV-1B)), rhinovirus type 2 (RV-2), rhinovirus type 14 (RV-14), and rhinovirus type 39 (RV-39).
Active compounds of the present invention are, in general, 2′-5′ oligoadenylates and their analogs which have anti-rhinoviral activity. In particular, active compounds of the present invention are of Formula I, as set forth above.
In one particularly preferred embodiment of the invention, the Y group of the above Formula I is —OH. In another particularly preferred embodiment of the invention, X is
R
1
and R
2
are hydrogen;
R
3
is —OH and R
4
is PO
4
−2
; or
R
3
is PO
4
−2
and R
4
is —OH; or
R
3
and R
4
are both —OH; or
R
3
and R
4
together represent a cyclophosphate;
R
5
is —OH;
R
9
is hydrogen; and
Z and Z′ are both O.
2′-5′ oligoadenylate compounds and their analogs are known. Exemplary compounds include 2′-5&pri
Ackerman Samuel K.
Budowsky Edward I.
Cyclis Pharmaceuticals, Inc.
Elrifi Ivor R.
Marenberg Barry J.
Mintz Levin Cohn Ferris Glovsky and Popeo P.C.
Travers Russell
LandOfFree
Method of treating rhinoviral infections does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of treating rhinoviral infections, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of treating rhinoviral infections will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2996639