Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2002-02-27
2004-05-18
Weber, Jon P. (Department: 1651)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S012200, C530S300000, C530S324000, C530S325000, C530S350000, C530S855000, C530S858000
Reexamination Certificate
active
06737399
ABSTRACT:
The present invention relates to the discovery that various proteins isolated from ticks are effective in the treatment of conjunctivitis. These proteins may most suitably be applied topically to an affected area and are effective to ameliorate the symptoms of this condition.
Conjunctivitis, or “pink eye”, is the name given to the inflammation of the conjunctiva of the eye when exposed to bacteria, viruses or other irritants. Conjunctivitis is the most common eye disease in the developed world and can vary in severity from a mild inflammation with tearing to a severe inflammation that causes tissue injury. The most common cause of conjunctivitis is viral infection, caused mainly by adenovirus. Other types of conjunctivitis include bacterial and fungal disease, caused mainly by
Haemophilus influenzae
and
Streptococcus pneumoniae.
Non-infective, or allergic, conjunctivitis is characterised by ocular redness and itching and may involve mucus production in the eye. Other clinical manifestations are tearing (clear tears), crusting of the eyelids and photophobia. This condition is normally seasonal and is very frequent in patients that suffer from allergic rhinitis.
Conventionally, allergic conjunctivitis is treated using an ophthalmic preparation that contains a topical decongestant, either with or without an antihistamine agent. This condition may also respond to treatment for underlying allergies and may disappear when the causative allergen is removed. The occurrence of allergic conjunctivitis in susceptible individuals can also be prevented by the topical application of sodium chromoglycate. Recent developments in this field also support the usefulness of mast cell stabilising drugs in the treatment of ocular allergy.
Seasonal allergic conjunctivitis involves type-1 hypersensitivity (IgE), whilst the other main forms of ocular allergies, such as perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis, have a more complex immunological basis and a chronic inflammatory component. In order to control the ocular inflammation caused by these types of conjunctivitis, thoughtful patient management is needed in order to avoid incurring steroid-induced side effects that result from many treatment regimes. The widespread incidence of allergic conjunctivitis means that there is a continuing need for the discovery of novel agents that are effective to ameliorate the symptoms of this condition.
Antigen activates the release of mediators of ocular allergy from the mast cells found in the eye. Histamine is one of these mediators, which is present in the secretory granules of mast cells and basophils and is formed by decarboxylation of histidine.
Histamine has been implicated in the redness and itching found in seasonal eye allergy. Anti-histamine compounds that bind to histamine receptors in the eye have been found to be useful in treating the signs and symptoms of eye allergy. Most of these drugs are compounds that are structurally related to histamine and bind to its receptor(s), thereby obstructing the interaction of histamine with its receptor(s). However, the drugs that are currently available often have undesirable side effects (for example drowsiness) and are not always effective.
Conventional H
1
receptor antagonists are widely used as antihistamine agents for treating allergic reactions including allergic rhinitis (hay fever), urticaria, insect bites and drug hypersensitivities. H
1
receptor antagonists target the redness and inflammation that is associated with these conditions. However, there are numerous undesirable effects of the H
1
receptor antagonists currently used. When used for purely antihistamine actions, all of the effects on the central nervous system (CNS) are unwanted. When used for their sedative or anti-emetic actions, some of the CNS effects such as dizziness, tinnitus and fatigue are unwanted. Excessive doses can cause excitation and may produce convulsions in children. The peripheral anti-muscarinic actions are always undesirable. The commonest of these is dryness of the mouth, but blurred vision, constipation and retention of urine can also occur. Unwanted effects not related to the drug's pharmaceutical action are also seen. Thus, gastrointestinal disturbances are fairly common while allergic dermatitis can follow topical application of these drugs.
H
2
receptor antagonists are also used as anti-histamine agents. These agents target the itching that is associated with the condition as a result of activation of certain aspects of the nervous system.
In addition to the problems mentioned above, some histamine antagonists are troublesome if taken with alcohol or with drugs. For example, the antihistamine Seldane used in combination with antibiotics and antifungals may cause the threatening side-effects
It can therefore be seen that drugs used to control the actions of histamine are not always effective. The reasons why they may have limited efficacy may relate to the specificity of these drugs for only a subclass of histamine receptors, particularly when a certain class of conditions requires interference with a larger class of receptors. Indeed, it is now known that there are a large number of different chemoattractants and vasoactive substances implicated in allergic conjunctivitis, liberated not only by mast cells but also by eosinophils and other cells, that produce ocular allergy in patients with ocular allergic disorders.
There is thus a great need for agents that are effective in ameliorating the symptoms of this condition, but that do not generate the side-effects that detract from their attractiveness as therapeutic compounds. Molecules that target both H
1
and H
2
receptor-mediated effects would be particularly useful in this respect.
Molecules that are capable of binding to histamine have previously been identified in blood-feeding ectoparasites, such as ticks. For example, a salivary nitric oxide-carrying haeme protein (nitrophorin) of the triatome bug
Rhodnius prolixus
has been found to bind histamine (Ribeiro and Walker, 1994). The isolation of a family of vasoactive amine binding proteins from ticks is described in co-pending International Patent Application No. PCT/GB97/01372, which is owned by the Applicant for the present invention, the contents of which are incorporated into the present application in their entirety. These proteins bind to histamine and are closely related to one another. Some of these molecules also bind to serotonin. These molecules differ markedly from any of the H
1
, H
2
or H
3
receptor families and appear to bind to histamine in a different manner.
It has now been found, surprisingly, that these vasoactive amine binding proteins isolated from ticks, and related proteins, are remarkably effective in the treatment of conjunctivitis.
SUMMARY OF THE INVENTION
According to the present invention there is provided the use of a histacalin protein in the manufacture of a medicament for the treatment or prevention of conjunctivitis.
The present invention also provides a method for the treatment or prevention of conjunctivitis which comprises administering to a subject an effective amount of a histacalin protein.
The term “histacalin protein” in the present application denotes:
(a) any vasoactive amine binding protein that binds specifically to a vasoactive amine with a dissociation constant of less than 10
−7
M and which belongs to the same protein family as the proteins MS-HBP1, FS-HBP1 and HS-BBP-2 disclosed in co-pending International Patent Application No. PCT/GB97/01372 wherein a protein is considered to belong to this protein family if the primary, mature monomer sequence of the protein has no more than 260 amino acids and at least 30 of the amino acids in the protein's complete sequence are conserved as identical residues in an alignment of that protein and the proteins MS-HBP1, FS-HBP1 and FS-HBP-2, the alignment preferably having been obtained using GCG's pileup command (Program Manual for the Wisconsin Package, 1994; gap creating penal
Nuttall Patricia Anne
Paesen Guido Christiaan
Evolutec Ltd.
Klauber & Jackson
Srivastava Kailash C.
Weber Jon P.
LandOfFree
Treatment of conjunctivitis does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Treatment of conjunctivitis, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Treatment of conjunctivitis will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3189677