MXPA06002585A - Methods and compositions for treating herpes infections - Google Patents
Methods and compositions for treating herpes infectionsInfo
- Publication number
- MXPA06002585A MXPA06002585A MXPA/A/2006/002585A MXPA06002585A MXPA06002585A MX PA06002585 A MXPA06002585 A MX PA06002585A MX PA06002585 A MXPA06002585 A MX PA06002585A MX PA06002585 A MXPA06002585 A MX PA06002585A
- Authority
- MX
- Mexico
- Prior art keywords
- herpes
- composition
- disease
- treatment
- iga
- Prior art date
Links
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Abstract
A method of treatment or prophylaxis of herpes infections and associated disease states by administration of compositions comprising immunoglobulins, prepared from pooled human plasma. Methods comprising intravenous and topical administration of immunoglobulins are provided.
Description
METHODS AND COMPOSITIONS FOR THE TREATMENT OF HERPES INFECTIONS
FIELD OF THE INVENTION
The invention relates to the administration of compositions comprising immunoglobulins for the treatment / prophylaxis of herpes infections and associated disease states. The invention provides aspects that relate to the intravenous and topical administration of the compositions of the invention.
BACKGROUND OF THE INVENTION
Herpes viruses have evolved over millions of years and have spread widely in nature. Family members have been identified in humans, non-human primates, and most other mammals and vertebrates. Herpes viruses are double-stranded DNA viruses, coated, that infect cells that carry negatively charged structures such as heparin sulfate and / or glycosaminoglycans, in addition to a mediator of herpes viral entry, on their surface. A characteristic feature of these viruses is their ability to remain dormant in their host throughout life after primary infection and reactivate more or less frequently from a group of latent infected cells during various internal and external stimuli. The herpes simplex virus (HSV) can cause several infections with life-long treatment in immunocompromised patients and in the neonate, while exhibiting a self-limiting disease in an immunocompetent host. HSV is the main cause of sporadic acute encephalitis in the West, with a mortality that exceeds 70% when it is not treated. Neonatal HSV infection has a poor prognosis despite antiviral therapy (for example, with acyclovir). 25% of children who get herpes during childbirth will develop a disseminated herpetic infection and will suffer a 40% mortality despite antiviral therapy. As a result, new ways to treat HSV disease with lifelong treatment are urgently needed. Even in immunocompetent humans, HSV can cause a corneal infection which would lead to permanent scarring, loss of vision, and blindness. Epithelial keratitis is the most common presentation of ocular HSV infection. Despite the availability of antivirals and steroids to suppress the inflammation associated with acute herpetic disease, chronic HSV continues to cause significant ocular morbidity. As a result, new ways to treat ocular HSV disease are urgently needed.
BRIEF DESCRIPTION OF THE INVENTION
Thus, in one aspect, the invention relates to a method for the treatment or prophylaxis of herpes simplex virus (HSV) infections in mammals by intravenously administering to the mammal an effective amount of a composition comprising immunoglobulin A ( IgA) prepared from pooled human plasma. The mammal can be a neonatal human. The mammal can be immunocompromised and / or suffer from a herpetic disease. The herpetic disease can be encephalitis, pneumonia, hepatitis, eye herpes, bird varicella, herpes zoster, zoster oticus, varicella zoster, keratitis, digital herpes, facial herpes, genital herpes, herpes gladiatorum, or herpes stomatitis. More than one of any of the above may characterize the herpetic disease that afflicts the mammal. In some embodiments, IgA comprises at least about 35% to about 55% of any of the immunoglobulins present in the composition (the minimum amount of IgA as a percentage of the total immunoglobulin present may be about 35% close to 55%). In other embodiments, IgA may comprise at least about 60% to about 80% of any of the immunoglobulins present in the composition. In another aspect, the invention relates to a method for the treatment or prophylaxis of herpes simplex virus (HSV) infections in mammals by intravenously administering to the mammal an effective amount of a composition comprising monomeric IgA., Dimeric IgA, and immunoglobulin G (IgA) prepared from pooled human plasma, wherein the monomeric and dimeric IgA comprises at least about 35% to about 55% of the total immunoglobulins present in the composition. In some embodiments, the monomeric and dimeric IgA comprises at least about 60% to about 80% of the total immunoglobulins present in the composition. In other embodiments, the monomeric and dimeric IgA comprises at least about 70% to about 95% of the total immunoglobulins present in the composition. In still other embodiments, the monomeric and dimeric IgA comprises at least about 60%, at least about 80%, or at least about 90% of the total immunoglobulins present in the composition. In another aspect, the invention relates to a method for the treatment or prophylaxis of a herpetic disease in mammals by topically administering to the mammal an effective amount of a composition comprising IgG prepared from pooled human plasma. The herpetic disease can be chicken pox, herpes zoster, zoster oticus, varicella zoster, keratitis, digital herpes, facial herpes, genital herpes, herpes gladiatorum, or herpes stomatitis. In another aspect, the invention relates to a method for the treatment or prophylaxis of an ocular herpetic disease in mammals by administering topically to a mammal an effective amount of a composition comprising IgG prepared from pooled human plasma. . Herpetic disease can be keratitis. In yet another aspect, the method of treating or prophylaxis of ocular herpetic disease in mammals is by administering a suspension comprising an effective amount of IgG prepared from human plasma pooled directly to an infected eye of a mammal.
BRIEF DESCRIPTION OF THE FIGURES
Figures 1A and 1B show graphical representations of immunoglobulin elution profiles of first and second size exclusion chromatographic columns (gel filtration), respectively. Figure 2 shows SDS-PAGE of purified lgA (after a second chromatographic purification step by size exclusion), and migration as a major band at 160 kDa with a minor band at 150 kDa. Figures 3A and 3B show an unreduced SDS-PAGE and a western blot, respectively, of an IgA preparation of the invention (after a second chromatographic purification by size exclusion). In Figure 3A, the "frames" that surround the particular bands, from right to left, represent intact IgA, intact IgG, and Ig-chain of IgM, intact IgA. "IgA Bayer" is IgA prepared according to the method of the present invention. Figures 4A and 4B show reduced SDS-PAGE and a western blot, respectively, corresponding to the analysis under non-reducing conditions as shown in Figures 3A and 3B. In Figure 4A, the boxes surrounding the particular bands, from right to left, represent the h-chain (60 kDa), h-chain? (60 kDa), h-chain μ (60 kDa), and h-chain a (60 kDa).
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a novel method for the treatment and prevention of HSV disease disseminated by intravenous administration of monomeric IgA (mlgA) and / or IgA dimeric (dlgA) fractions of human serum. Contrary to the results achieved by the present invention, it is previously suggested that HSV protection can not be achieved through serum depleted with IgG (see Raizman, MB and CS Foster, Curr. Eye, Res. 7 / 823-829 ( 1988)). Accordingly, the IgA compositions of the present invention have not previously been used for the treatment of HSV infections. The IgA fractions constitute an enormous commercial value because they are normally discarded as by-products of the purification of human serum IgG. In addition, the use of IgA over other immunoglobulins is convenient because IgA does not activate the classical trajectory of the complement system and only slowly activates the alternate complement path. Consequently, IgA does not promote inflammation. The present invention also provides a novel method for the treatment and prevention of HSV disease by using purified human IgG from pooled human plasma through topical treatment. This aspect of the invention has the additional advantage that the immunoglobuiin injection is not necessary. Patients can treat themselves with topical IgG in an ophthalmic formulation. The pooled human plasma IgG is suitable for this purpose without the need to select blood donors based on their level of HSV neutralizing antibodies. With respect to the treatment or prophylaxis of ocular herpetic disease, the compositions of the invention can be administered directly onto the cornea of the infected eye. However, topical administration according to the invention is not limited to ocular disease. The IgG compositions of the invention can be administered topically to other manifestations of the HSV-related disease. The compounds as provided herein can be used for the treatment and prophylaxis of diseases caused by herpes simplex viruses. The following indications are listed as illustrative examples and are not intended to limit the scope of the invention: 1) treatment and / or prophylaxis of herpes simplex virus infections in patients with symptoms of disease such as eye, lip, genital, keratitis, encephalitis. , pneumonia, hepatitis, etc., caused by herpes virus; 2) treatment and / or prophylaxis of herpes simplex virus infections in immunocompromised patients (for example, with AIDS, transplant recipients, cancer patients, patients with genetically based immunodeficiency); 3) treatment and / or prophylaxis of herpes simplex virus infections in newborns, infants, children and children; 4) treatment and / or prophylaxis of positive herpes simplex virus patients to maintain or suppress recurrent herpes disease therapy; and 5) treatment and / or prophylaxis of herpes simplex virus disease in the elderly. As used herein, the term "effective amount" refers to an amount sufficient to produce a therapeutic result. Generally, the therapeutic result is an objective or subjective improvement of a disease or condition, which is achieved by inducing or improving a physiological process, blocking or inhibiting a physiological process, or in general terms performing a biological function that helps or contributes to the elimination or abatement of a disease or condition. Unless otherwise specified, the term "purified" refers to a substance that has been removed from its original environment, such that the relative abundance of the substance has been increased in the context of other components of the invention. Alternatively or additionally, the term can be used only to indicate that at least one particular contaminant has been reduced or eliminated from the composition comprising the substance. The term "pharmaceutically acceptable carrier" refers to any non-toxic, compatible material suitable for mixing with the active compounds of the present invention. The phrase "repaired from pooled plasma" refers to the fact that the immunoglobulin preparations modified by this phrase are recovered from pooled plasma that originates from blood donors. The compositions of the invention do not require such donors to be selected to determine their levels of HSV neutralizing antibodies. The present invention relates to compositions and their use in medical therapy for the treatment and / or prophylaxis of herpes virus infections including herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2), varicella virus zoster (VZV), cytomegalovirus (CMV), and epstein-Barr virus (EBV). The present invention can be used for the treatment and / or prophylaxis of recurrent herpes simplex virus type 1 or 2, herpes zoster (bird varicella, herpes zoster), zoster otisis, varicella zoster, genital warts, or herpes keratitis, herpes digitalis, facial herpes, genital herpes, herpes gladiatorum, and herpes stomatitis. Such diseases and conditions are well known and easily diagnosed by experienced physicians. The intravenously administered compositions of the invention can be used for the treatment and / or prophylaxis of disseminated infections, thus preventing herpes-related disease, such as herpetic encephalitis. Such compositions can be used for the treatment and / or prophylaxis of neonatal infections, thereby treating or preventing disseminated infections that commonly generate a high mortality rate. Immunocompromised individuals, including neonates and the elderly, are particularly susceptible to such diseases and benefit from the administration of the compositions of the invention. Although intravenous administration of compositions comprising IgA may provide particular benefits to subjects suffering from disseminated herpes infections, for example, infections that give rise to encephalitis, it will be recognized that such treatment may also benefit those suffering from either the usual manifestations of herpes infection. Similarly, although topical administration of the immunoglobulin compositions of the invention may directly benefit subjects suffering from topical manifestations of herpes infection, for example, keratitis, the administration of such compositions may provide benefits for those suffering from the effects of disseminated herpes infection. The compositions of the invention can be prepared by employing conventional techniques for combining the compounds of the invention with pharmaceutically acceptable carriers., and optionally, with pharmaceutically acceptable excipients employing standard and conventional techniques. A material that increases the absorption or penetration of the compounds of formula II or III through the skin or other affected areas can also be included in the topical formulations. The amount of active component, e.g., an immunoglobulin preparation of the invention, in a pharmaceutical composition can vary widely or adjust depending on the requirements of the patient, the severity of the viral infections, the potency of the particular compound to be used, the particular formulation and the desired concentration. Generally, the amount of active component will vary from about 0.05% to about 25% by weight of the composition, from about 0.1% to about 10%, or from about 3% to about 16% of the composition. composition. For infections of external tissues, for example, the mouth, eyes and skin, the formulations can be applied as an ointment or topical cream containing the active ingredient in an amount of, for example, about 0.05 to about 25% in weight of the composition, or about 0.1 to about 10% w / w. When formulated in an ointment, the active ingredients may be employed with a paraffinic ointment base or a water-miscible ointment base. Alternatively, the active ingredients can be formulated in a cream with an oil-in-water cream base. Formulations suitable for topical administration to the eyes include eye drops wherein a composition of the invention is dissolved or suspended in a suitable carrier, especially an aqueous solvent. The active ingredient can be presented in such formulations in a concentration of about 0.05 to about 25%, conveniently from about 0.5 to about 10%. Formulations suitable for topical administration in the mouth include tablets comprising a composition of the invention in flavored bases, for example, sucrose and acacia or tragacanth.; pills comprising the active ingredient in an inert base, for example, gelatin and glycerin, or sucrose and acacia; and mouth rinses comprising the active ingredient in a suitable liquid carrier. Ophthalmic dosage forms include solutions and suspensions prepared for use as eye drops to provide immediate therapeutic levels of the compositions of the invention and ophthalmic ointments designed to provide slower release rates or for use at bedtime. The eye drop dosage form of the invention optionally will include one or more acceptable pharmaceutically acceptable inactive excipients, including, but not limited to: preservatives of a group including, but not limited to, benzalkonium chloride, methyl paraben, disodium edetate, timersol, and chlorobutanol; pH regulators of a group including, but not limited to sodium citrate, sodium acetate, citric acid and sodium lactate; vehicles of a group including, but not limited to, polyvinyl alcohol, hydroxymethyl cellulose, cetyl alcohol, carboxymethyl cellulose, and hydroxypropylmethyl cellulose; pH adjusters of a group including, but not limited to, sulfuric acid, hydrochloric acid, sodium hydroxide, monosodium or disodium phosphate; purified water USP; poloxamer 407 or 188, polysorbate 80; and polyoxyethylene polyoxypropylene compound; and USP mineral oil. The above inactive excipients may serve in a variety of functions such as carriers, carriers, diluents, binders, preservatives, pH regulators, pH adjusters, emulsifiers and other formulation aids. A dosage form of ophthalmic ointment for the prolonged supply of the formulation or for use at bedtime to sleep optionally will include one or more pharmaceutically acceptable inactive excipients, including, but not limited to: chlorobutanol, polyethylene mineral oil gel, white petrolatum USP, USP mineral oil, petrolatum and lanolin alcohol, USP purified water, polyvinyl alcohol gel and similar products. The above excipients serve as a variety of functions such as carriers, carriers, diluents, binders, preservatives, pH regulators, pH adjusters, emulsifiers, and other formulation aids. The compositions of the present invention may also include solutions comprising the dosage form and suspensions prepared for use for application to the buccal mucosa to provide immediate therapeutic levels of the formulation. The buccal mucosa dosage form of the invention will optionally include one or more suitable inactive and pharmaceutically acceptable excipients, including but not limited to preservatives, pH regulators, vehicles, and pH adjusters as mentioned with respect to the forms of dosage of "eye drops". As noted, the above inactive excipients serve in a variety of functions as carriers, carriers, diluents, binders, preservatives, pH regulators, pH adjusters, emulsifiers and other formulation aids. The compositions of the present invention also include dosage forms for use in the topical treatment of cutaneous manifestations of HSV infections prepared in a variety of forms including ointments, gels and creams. These preparations optionally include one or more of the following suitable and pharmaceutically acceptable excipients: isopropyl myristate NF, trolamine NF, SD alcohol 40 (20%), white petrolatum USP, lanolin alcohols NF, mineral oil USP, polyvinyl alcohol gel, keto stearyl alcohol NF, lactic acid USP, calcium stearate, dextran, polyoxyl 40 stearate, methylparaben, propylene glycol, sodium lauryl sulfate, polyethylene glycol (PEG) base, synthetic beeswax (B wax), calcium acetate, water USP purified and similar products. The above excipients serve in a variety of functions as carriers, vehicles, diluents, binders, preservatives, pH regulators, pH adjusters, emulsifiers and other formulation aids. The compositions of the present invention also include dosage forms for local use in the treatment of female genital manifestations of HSV infections, especially HSV-2, and are prepared in dosage forms for vaginal insertion including vaginal suppositories, gels, and tablets. . These preparations may optionally include one or more of the following suitable and pharmaceutically acceptable excipients, including but not limited to: isopropyl myristate NF, mineral oil-USP, stearyl alcohol NF, benzoic acid USP, pegoxyl stearate 7, methylparaben, propylparaben, propylene glycol, butylated hydroxyanisole, coconut oil or palm kernel triglycerides, polysorbate 60 or polysorbate 8, pegylicol 5, PEG-100 stearate and sorbitan monostearate, calcium lactate, hydroxypropylmethylcellulose, polysaccharide carrageenan maize starch, lactose , calcium lactate, silicon dioxide and purified water USP, among others. The above excipients serve a variety of functions such as carriers, carriers, diluents, binders, preservatives, pH regulators, pH adjusters, emulsifiers and other formulation aids. For intravenous administration, the dosage of the immunoglobulin compositions of the invention and the method of administration will vary with the severity and nature of the particular condition to be treated, the duration of treatment, the adjunctive therapy used, the age and physical condition of the subject of treatment. However, individual doses for intravenous administration will typically range from about 50 mg to about 10 g per kg of body weight, or from about 100 mg to about 5 g per kg of body weight (unless Otherwise, the unit designated "mg / kg" or "g / kg", as used herein, refers to milligrams or grams per kilogram of body weight).
EXAMPLES
EXAMPLE 1 Growth of HSV and preparation of virus samples
The herpes simplex virus (HSV-1 Walki) is routinely propagated in African green monkey kidney cells (Vero cells; ATCC CCL-81); however, many tissue culture lines can be used for the development and quantification of HSV (Herpes Simplex Virus Protocols, 1998, Ed. S.M. Brown &A.R. MacLean, Humana Press, Totowa, New Jersey). Vero cells are grown in M199 media supplemented with 5% fetal calf serum (FCS), 2 mM glutamine, 100 lU / ml penicillin, 100 μg / ml streptomycin in cell culture flasks (eg 175 cm2 / 25-50 ml) at 37 ° C in the presence of 5% CO2. Cells are divided 1: 4 twice per week (cell viability> 95%). For infection by virus, the medium is removed, the cells are washed with Hank's solution, trypsin with 0.05% trypsin, 0.02% EDTA (Seromed, L2143), seeded at a density of 4x105 cells per ml in flasks of cell culture, and incubated for 24 hours at 37 ° C in the presence of 5% CO2. The medium is removed and the virus suspension is added to a multiplicity of infection (m.o.i) of < 0.05 in a volume of 2 ml per 172 cm2 of surface area. The flask is allowed to stand for 1 hour at 37 ° C in the presence of 5% CO2 with occasional agitation to uniformly distribute the virus on the cells. The medium is then added to a final volume of 50 ml per 175 cm2 tissue culture flask. The cultures are incubated until all the cells show signs of infection (approximately 2 to 3 days). To collect the virus, the flasks are frozen at -80 ° C and primed at 37 ° C (in a water bath) twice. The cell debris is removed by centrifugation (300 g, 10 min, 4 ° C) and the supernatant is stored in aliquots at -80 ° C. The titration of the virus sample is determined in a plaque assay. Briefly, Vero cells are seeded at a density of 4x105 cells per well of a 24-well tissue culture plate. After an incubation period of 24 hours (37 ° C, 5% C02) the cells are infected with dilutions of the virus sample ranging from 10"2 to 10" 8. The volume of infection is 100 μl per well. After 1 hour of incubation at 37 ° C, 5% CO2 after infection, the cells are gently removed, covered with 1 ml of layer medium (0.5% methylcellulose, 0.225% sodium bicarbonate, glutamine 2 mM, 100 lU / ml penicillin, 100 μg / ml streptomycin, 5% FCS in MEME (MEM-Eagle with Earle's salt)), and allowed to stand for 3 days at 37 ° C in the presence of 5% CO2. The cells are fixed with 4% formalin for at least 30 minutes, washed with water, stained with Giemsa solution (Merck, Darmstadt) for 30 minutes and washed again. After drying the plates, they are counted and the titration of the virus sample is calculated. ,
EXAMPLE 2 Lethal challenge model
Female Balb / cABom mice (weighing 19 g, and 7 weeks old) are purchased from (M &B A / S, Denmark) and inoculated one week later. 50 μl of a diluted virus suspension (HSV-1 Walki) in ice-cold PBS (~ 5 x 104 pfu) is applied to the nasal passages of mice anesthetized with ether slightly, resulting in a mortality of 90-100% after 7-10 days. Infected animals are inspected daily for signs of disease (encephalitis, paralysis, respiratory symptoms) and dying animals are killed intentionally.
EXAMPLE 3 Model of ocular herpes
Female Balb / cABom mice (weighing 19 g, 7 weeks old) are purchased from (M &B A / S, Denmark) and inoculated one week later. Mice are anesthetized with ether and the right cornea is scraped 3 times vertically and three times horizontally with a sterile 30 gauge needle. 5 μl of virus suspension (5 x 106 pfu HSV-1 Walki) are applied to the scraped cornea. The mice are inspected daily for signs of herpes infection (blepharitis, keratitis, encephalitis). Dying animals are killed intentionally.
EXAMPLE 4 Immunoglobulin fractions
The human immunoglobulin, IgG, IgA (MigA) and dimeric IgA (dlgA) fractions are prepared as follows. IgG used in the examples is commercial grade IgG (5% GAMIMMUNE N, Bayer Corp., Pittsburgh, PA) purified from pooled human plasma using a ll + fraction of Cohn as starting material. Monomeric IgA and IgA from human plasma are purified through two consecutive size exclusion chromatography steps in SUPERDEX 200 using a BIOLOGIC chromatographic station (Bio Rad Richmond, CA). The upper salt discharge of the Q-SEPHAROSE chromatography step, a residual stream of the IGIV-C process (see US Patent No. 6,307,028, fully incorporated herein by reference), is used as the starting material and contains 13 mg / ml of IgA with a purity of 45%. Briefly, 20 ml of starting material is applied to a 2 liter column of 200 XK 50/1 00 SUPERDEX 200 (5 cm x 93 cm, Pharmacia, Upsala, Sweden) and run at 10 ml / minute in pH buffer Saline Tris-regulated (Sigma, St. Louis, MO). The fractions are analyzed by nephelometry, SDS-PAGE, and size exclusion FPLC. Positive fractions for monomeric IgA are pooled, concentrated to a final volume of 10 ml with an AMICON concentration chamber (membrane YM 10, RT), and applied again to the SUPERDEX 200 column using the same run conditions as in the first run. The final product is formulated in 0.2 M glycine, pH 4.25 and filtered sterile using a 0.2 μm membrane. The elution profile (280 nm) of the first chromatography has 5 protein peaks, which are identified by immunonephelometry as IgM, dlgA, mlgA, IgG and albumin (see Figure 1A). The re-chromatography of the mlgA and the peak of dlgA on SUPERDEX 200 result in a larger protein peak and two small projections, containing mlgA, dlgA, and IgG, respectively (see Figure 1B). The fractions containing mlgA or dlgA are grouped. The identity of IgA is also confirmed by SDS-PAGE and western blots (see Figures 2, 3A, 3B, 4A, and 4B). The aliquots are stored in freezing at -70 ° C.
EXAMPLE 5 Human IgG for the prevention / treatment of ocular HSV disease
For the ocular herpes model, the immunoglobulin suspensions are diluted in PBS before the treatment of infected animals to a final concentration of 25 mg / ml. Mice are treated topically by applying 5 μl of the diluted immunoglobulin suspension directly to the cornea of the infected eye 3 times per day. On the day of infection, treatment is provided 1 hour before infection, 1 hour after infection (p.i.) and 5 hours p.i. From day 1 p.i. at day 4 p.i., the animals are treated 3 times a day at 7 a.m., 9 p.m. and 7 p.m. Mice are infected with HSV in the cornea of one eye and treated on the day of infection and in the following 4 days 3 times per day with human IgG, mlgA and dlgA as described above, or with placebo (exit solution with Regulated phosphate pH, PBS = 150 mM NaCl, 20 mM phosphate, pH 7.0-7.4). On day 7 after infection, among a total of 10 infected mice receiving each treatment, the following number survives:
TABLE 1
Seven days after infection, all animals treated with placebo alone have developed ocular HSV disease in combination with a lethal HSV encephalitis, while 7 out of 10 animals treated with topical IgG 3 times per day have survived and have not showed signs of ocular HSV disease.
EXAMPLE 6 human day for the prevention / treatment of disseminated HSV disease
In the lethal challenge model, the animals are treated by injection of the immunoglobulin suspension in the tail vein. Treatment is provided 1 hour before infection and 24 hours p.i. During the day of infection, 2 mg of immunoglobulin are applied; on the day after infection another 2 mg are provided. Mice are infected with HSV intranasally and treated on the day of infection and on the day after infection through intravenous infection of IgG, mlgA, dlgA or placebo (saline with pH regulated phosphate, PBS ). On day 7 after infection, among a total of 10 infected mice, the next number survives:
TABLE 2
Seven days after infection, all animals treated with placebo have succumbed to a lethal disseminated HSV infection, while 7 out of 10 animals treated with intravenous dlgA, and 5 out of 10 animals treated with intravenous mlgA, survived.
The above examples of the invention are only illustrative, and are not intended to limit the invention in any way. Those skilled in the art will recognize that several modifications of the foregoing are within the proposed scope of the invention.
Claims (20)
1. - The use of a composition comprising immunoglobulin
A (IgA) prepared from pooled human plasma, for the preparation of an intravenous drug for the treatment or prophylaxis of herpes simplex virus (HSV) infections in mammals. 2. The use claimed in claim 1, wherein the mammal is a neonatal human.
3. The use claimed in claim 1, wherein the mammal is immunocompromised.
4. The use claimed in claim 1, wherein the mammal suffers from a herpetic disease.
5. The use claimed in claim 4, wherein the disease is selected from the group consisting of encephalitis, pneumonia, hepatitis, eye herpes, chicken pox, herpes zoster, zoster oticus, varicella zoster, keratitis, herpes digitalis, facial herpes, genital herpes, herpes gladiatorum, or herpes stomatitis.
6. The use claimed in claim 4, wherein the disease is selected from the group consisting of encephalitis, pneumonia, hepatitis, herpes zoster, zoster oticus and varicella zoster.
7. - The use claimed in claim 4, wherein the disease is encephalitis.
8. The use claimed in claim 1, wherein the IgA comprises at least about 35% to about 55% of any of the immunoglobulins present in the composition.
9. The use claimed in claim 1, wherein the IgA comprises at least about 60% to about 80% of any of the immunoglobulins present in the composition.
10. The use of a composition comprising monomeric IgA, dimeric IgA, and IgG prepared from pooled human plasma, for the preparation of an intravenous drug for the treatment or prophylaxis of herpes simplex virus (HSV) infections in mammals wherein monomeric and dimeric IgA comprises at least about 35% to about 55% of the total immunoglobulins present in the composition.
11. The use claimed in claim 10, wherein the Monomeric and dimeric IgA comprises at least about 60% to about 80% of the total immunoglobulins present in the composition.
12. The use claimed in claim 10, wherein the monomeric and dimeric IgA comprises at least about 70% to about 95% of the total immunoglobulins present in the composition.
13. The use claimed in claim 10, wherein the monomeric and dimeric IgA comprises at least about 60% of the total immunoglobulins present in the composition.
14. - The use claimed in claim 10, wherein the monomeric and dimeric IgA comprises at least about 80% of the total immunoglobulins present in the composition.
15. The use claimed in claim 10, wherein the monomeric and dimeric IgA comprises at least about 90% of the total immunoglobulins present in the composition.
16. The use of a composition comprising immunoglobulin G (IgG) prepared from pooled human plasma for the preparation of a topical medicament for the treatment or prophylaxis of herpetic disease in mammals.
17. The use claimed in claim 16, wherein the herpetic disease is selected from a group consisting of chicken pox, herpes zoster, zoster oticus, varicella zoster, keratitis, digital herpes, facial herpes, genital herpes. , herpes gladiatorum, or herpes stomatitis.
18. The use of a composition comprising immunoglobulin G (IgG) prepared from pooled human plasma, for the preparation of a medicament for the treatment or prophylaxis of ocular herpetic disease in mammals.
19. The use claimed in claim 18, wherein the herpetic disease is keratitis.
20. The use of immunoglobulin G (IgG) prepared from pooled human plasma, for the preparation of a suspension for the treatment or prophylaxis of ocular herpetic disease in mammals.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US10656781 | 2003-09-05 |
Publications (1)
Publication Number | Publication Date |
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MXPA06002585A true MXPA06002585A (en) | 2006-12-13 |
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