WO2006105216A1 - Famciclovir for the treatment of recurrent herpes labialis using a one-day treatment - Google Patents
Famciclovir for the treatment of recurrent herpes labialis using a one-day treatment Download PDFInfo
- Publication number
- WO2006105216A1 WO2006105216A1 PCT/US2006/011498 US2006011498W WO2006105216A1 WO 2006105216 A1 WO2006105216 A1 WO 2006105216A1 US 2006011498 W US2006011498 W US 2006011498W WO 2006105216 A1 WO2006105216 A1 WO 2006105216A1
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- WO
- WIPO (PCT)
- Prior art keywords
- treatment
- lesions
- day
- famciclovir
- healing
- Prior art date
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- LCHNYYWLCABSKF-UHFFFAOYSA-O CN(CN1CC(CO)CO)C2=C1N=C(N)NC1C2[OH+]C1 Chemical compound CN(CN1CC(CO)CO)C2=C1N=C(N)NC1C2[OH+]C1 LCHNYYWLCABSKF-UHFFFAOYSA-O 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- This invention relates to the treatment of recurrent herpes labialis using a one- day treatment regimen and to the use of compounds in the preparation of a medicament for use in a one-day treatment regimen of this condition.
- EP-A-141927 (Beecham Group p.l.c.) discloses penciclovir, the compound of formula (A):
- penciclovir and salts, phosphate esters and acyl derivatives thereof, as antiviral agents.
- the sodium salt hydrate of penciclovir is disclosed in EP-A-216459 (Beecham Group p.l.c). Penciclovir and its antiviral activity is also disclosed in Abstract P. V11-5, p.193 of Abstracts of 14 th Int. Congress of Microbiology, Manchester, England, Sep. 7-13, 1986 (Boyd et. al.).
- Orally active bioprecursors of the compound of formula (A) are of formula (B):
- X Ci. 6 alk ⁇ xy, NH 2 or hydrogen.
- the compounds of formula (B) wherein X is Ci -6 alkoxy or NH 2 are disclosed in EP-A-141927 and the compounds of formula (B), wherein X is hydrogen, disclosed in EP-A-182024 (Beecham Group p.l.c.) are preferred prodrugs.
- a particularly preferred example of a compound of formula (B) is that wherein X is hydrogen and wherein the two OH groups are in the form of the acetyl derivative, described in Example 2 of EP-A-182Q24, hereinafter referred to as famciclovir.
- HSV-1 herpes simplex type 1
- HSV-2 herpes simplex type 2
- varicella-zoster varicella-zoster
- Epstein- Barr viruses such as herpes simplex type 1 (HSV-1), herpes simplex type 2 (HSV-2), varicella-zoster and Epstein- Barr viruses.
- HSV-1 is the main cause of herpes labialis.
- herpes labialis is a common disease occurring in up to 40% of the adult population. It is caused mostly by HSV-1 , which is usually acquired during childhood with a seroprevalence as high as 90% in persons over the age of 50 years. Although benign in most cases, herpes labialis may be associated with transient but real consequences such as significant irritation, pain, and discomfort in a social milieu. In susceptible persons, like neonates and immunocompromised patients, HSV can lead to significant morbidity.
- Topical treatments containing either acyclovir or penciclovir reduce the duration of herpes labialis episodes with faster lesion healing and resolution of pain as compared to placebo. Typically they require multiple applications for several days and do not prevent the development of lesions (Jensen 2004).
- Oral acyclovir is not approved for the treatment of orolabial herpes infection.
- patients treated with acyclovir 200 mg or 400 mg five times a day for five days
- Valacyclovir was recently approved for the treatment of herpes labialis at a recommended dosage of 2,000 mg twice a day for one day. The efficacy of this treatment was evaluated in two randomized, double-blind, placebo-controlled studies in immunocompetent adult patients with more than three episodes during the previous year.
- the present invention is to the use of compounds of Formulae (A) and (B) as described herein, preferably famciclovir or penciclovir, for the treatment, of recurrent herpes labialis using a one-day treatment regimen.
- the present invention provides a method of treatment of recurrent herpes labialis in humans, which method comprises the administration for a treatment period of one day to the human in need of such treatment, an effective amount of a compound of formula (A):
- acyl derivative is used herein to include any derivative of the compounds of formula (A) in which one or more acyl groups are present. Such derivatives are included as bioprecursors of the compounds of formula (A) in addition to those derivatives which are per se biologically active.
- the compound of formula (A) may be in one of the forms disclosed in EP-A-216459 (Beecham Group p.l.c). -A-
- a particular compound of formula (B) of interest is 9-(4-acetoxy-3- acetoxymethylbut-1-yl)-2-aminopurine, known as famciclovir (FCV), the well-absorbed oral form of penciclovir (PCV).
- FCV famciclovir
- PCV penciclovir
- the compound in particular, famciclovir, may be administered by the oral route to humans and may be compounded in the form of syrup, tablets or capsule.
- any pharmaceutical carrier suitable for formulating such solid compositions may be used, e.g., magnesium stearate, starch, lactose, glucose, rice, flour and chalk.
- the compound may also be in the form of an ingestible capsule, e.g., of gelatin, to contain the compound, or in the form of a syrup, a solution or a suspension.
- Suitable liquid pharmaceutical carriers include ethyl alcohol, glycerine, saline and water to which flavouring or colouring agents may be added to form syrups.
- Sustained release formulations for example tablets containing an enteric coating, are also envisaged.
- fluid unit dose forms are prepared containing the compound and a sterile vehicle.
- the compound depending on the vehicle and the concentration, can be either suspended or dissolved.
- Parenteral solutions are normally prepared by dissolving the compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing.
- adjuvants such as a local anaesthetic, preservatives and buffering agents are also dissolved in the vehicle.
- the composition can be frozen after filling into the vial and the water removed under vacuum.
- Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by exposure to ethylene oxide before suspending in the sterile vehicle.
- a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound of the invention.
- Preferred parenteral formulations include aqueous formulations using sterile water or normal saline, at a pH of around 7.4 or greater, in particular, containing penciclovir sodium salt hydrate.
- compositions will usually be accompanied by written or printed directions for use in the medical treatment concerned.
- a suitable dosage unit might contain from 50-1 ,500 g of active ingredient, e.g., 250-1 ,000 mg. Such doses may be administered as a one-day treatment, such as 250 mg six times in one day, 500 mg three times in one day, 750 mg twice in one day or 1 ,500 mg once in one day or any suitable dosing scheme resulting in 1 ,500 mg dose in one day.
- the treatment period is 1 day.
- the short course treatment of the present invention is preferably carried out as soon as possible after the onset of the prodrome that precedes clinical signs of recurrent herpes labialis, usually within 24 hours, preferably within 12 hours, more preferably within one hour of the first prodromal symptom without any clinical signs of visible lesions.
- Prodrome refers to focal itching, burning, tingling and/or pain at the site where cold sores have occurred in the past and felt by the study patient to be premonitory, for him or her, of the onset of a cold sore.
- Erythema refers to any redness, but without evidence of a more advanced stage. The presence of any physical sign of an episode indicates the end of the prodrome even if itching, pain, etc., associated with the prodrome continues.
- Paper refers to any swelling or solid elevation of the skin without evidence of a more advanced stage.
- Vesicle refers to any presence of a blister-like skin elevation of the skin in which fluid is visible through the stratum corneum, without evidence of a more advanced stage. Development of any evidence of vesiculation, ulceration or crusting defines lesions as vesicular, also referred to as "classical”. When vesicles, ulcers and/or hard crusts are present together, then the stage of the vesicular (classical) lesion shall be described according to the predominant stage.
- Ulcer/soft crust refers to the blister has collapsed or ruptured forming an ulcer.
- the floor of the ulcer may be moist or contain some soft cake-like exudate.
- Hard crust refers to the drying of the ulcer has continued to form a noticeably hard, consolidated, unpliable mass, or a scab, an eschar.
- vesicles, ulcers and/or hard crusts are present together, then the stage of the (vesicular) classical lesion shall be described according to the predominant stage.
- Residual abnormalities refers to swelling, dry skin flakes and/or erythema that may be present after loss of the hard crust.
- Normal skin refers to complete disappearance of all signs of the disease.
- Healed, (vesicular) classical lesions refers to complete loss of crust. Residual abnormalities may still be present.
- Healed, aborted lesions refers to complete disappearance of all signs of the disease (normal skin).
- the present invention also provides the use of a compound of formula (A) or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing, in the preparation of a medicament for use in a one day treatment regimen of herpes labialis and in particular in reducing the time to healing of herpes labialis lesions. Such treatment may be carried out in the manner as described herein.
- the present invention further provides a pharmaceutical composition for use in a one day treatment regimen of recurrent herpes labialis, and in particular in reducing the time to healing of herpes labialis lesions, which comprises an effective amount of a . compound of formula (A) or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing, and a pharmaceutically acceptable carrier.
- Such compositions may be prepared in the manner as hereinafter described.
- This study design is a parallel-group, double-blind, double-dummy, randomized placebo- controlled trial of patient initiated therapy in adult immunocompetent patients with recurrent herpes labialis.
- Table 1 summarizes the study design for herpes labialis treatment.
- the criteria for evaluation include the primary efficacy variable and secondary efficacy variables.
- the primary efficacy variable is the investigator-assessed time to healing (re-epithelialization) of the non-aborted primary lesion complex, defined as the time from start of treatment until loss of crust (erythema may have been present).
- Secondary efficacy variables include time to healing of all non-aborted lesions (primary lesion complex and secondary lesions), time to healing of all lesions (non-aborted and aborted; latter assigned a time to healing of zero), and proportion of patients with aborted lesions.
- Lesion healing for vesicular lesions is defined as loss of crust, although erythema may still be present.
- the investigator makes assessments based on both the investigator examination of the current visit and patient diary entries since the previous visit. If healing is confirmed, the time of healing is defined as the earliest time it was reported and continuously maintained in the diary. This convention applies to the assessment of both the primary lesion complex and all vesicular lesions.
- Primary lesion complex refers to the first lesions that appear during the . recurrent episode, additional lesions appearing on the same day as the first lesions, or lesions appearing later but within 1 cm of the previous lesions
- Secondary lesions refer to lesions that appear more than 24 hours outside of the 1 cm vicinity of the primary lesion complex.
- Non-aborted lesions refers to all lesions requiring re-epithelialization (i.e., lesions undergoing vesicular, ulcer, soft crust and/or hard crust formation)
- Aborted lesions refers to lesions that did not evolve beyond the papule stage.
- the investigator identifies patients whose herpes labialis recurrence did not progress beyond the papule stage based on the examination and diary entries. If this determination cannot be made due to missed visits and diary entries, the patient is assumed to have had classical (vesicular) lesions in the unobserved period.
- the primary efficacy analysis of this study compares the time to healing of the primary lesion complex in a single episode of herpes labialis for each of the active treatment regimens with placebo. The comparisons are presented using estimated median times to healing and their confidence intervals, as well as inferential analyses on the time to healing.
- Inferential analyses of the primary outcome assesses the superiority of either of the famciclovir short-course regimens to placebo, as measured by the time to healing of the primary lesion complex.
- the overall type-one error rate is maintained at the 5% level for these tests.
- the Kaplan-Meier method is used to estimate the distribution of time to healing for each treatment group and the median time to healing. Estimated survival curves are plotted. The 95% confidence intervals for the median times to healing are constructed based on the first-order Taylor series approximation of their standard errors using the standard errors of the estimated survival functions. The 95% confidence intervals for between-treatment median differences are constructed using standard errors.
- Covariates and interactions are assessed by adding their respective terms separately into the primary efficacy analysis model: Covariates and interactions include: gender, age, treatment-by-gender interaction, treatment-by-center interaction, number of herpes labiaiis recurrences in the previous year (dichotomized), any other covariates may be added in the analysis plan.
- the safety and ITT populations include all randomized patients who are exposed to (take any) study medication. Using the above definitions, the safety and ITT populations comprise the same patients. For compatibility with the standard presentations, all safety summaries are referenced using the Safety population while appropriate efficacy summaries (for secondary parameters involving both vesicular and non-vesicular lesions) are referenced using the ITT population.
- the modified ITT population includes all patients who develop herpes labialis vesicular lesions during the treated recurrence.
- the evaluable population used in sample size and power estimation includes all modified ITT patients who remain in the study until the time of healing can be determined.
- This population includes all modified ITT patients without any major violations from study procedures. Deviations from the protocol that will be considered major violations include: taking the first dose of study medication more than one hour after the first prodromes; and taking antiviral medication other than the study medication between the day prior to the first dose of study medication to healing of primary lesion complex. For sensitivity and exploratory reasons, the primary efficacy analysis is repeated for the per-protocol population.
- the planned sample size of the study is 150 evaluable patients per treatment group. It is chosen to provide reliable estimates for treatment effects of two regimens of famciclovir (1 ,500 mg as a single dose or 750 mg b.i.d. for one day), as compared to that of placebo, based on the median time to healing of the primary vesicular lesion complex.
- the width of the confidence interval for the median time is anticipated.
- the minimum size of median difference that will be detected as significant is found. This test on median difference is converted by parameterization to an equivalent hypothesis test for the hazard ratio.
- Table 2 is used directly in assessing the power of testing the following two hypotheses based on the primary efficacy variable, time to healing of the primary lesion complex (for any active treatment T, ⁇ ⁇ stands for its log-hazard ratio compared to placebo):
- any particular active treatment group has a hazard ratio of 1.45, the power to detect its difference from placebo following the Bonferroni-Hochberg procedure is not less than 82%.
- Variable 1 the primary efficacy variable, is the investigator-assessed time to healing of the primary lesion complex, defined as the time from start of treatment until loss of crust (for vesicular (classical) lesions progressing through the vesicle/ulcer stage only, erythema is allowed).
- the primary efficacy variable is analyzed over the modified ITT population in two approaches: the primary estimation is based on the Kaplan-Meier method, and statistical testing is based on the proportional hazards model.
- Secondary efficacy variables include variables 2-7.
- Variable 2 is the time to healing (lost of crust) of the primary lesion complex (non-vesicular lesions will be assigned a time of zero).
- Variable 3 is the time to healing (loss of crust) of all vesicular lesions (nonvesicular lesions will be assigned a time of zero).
- Variable 4 is the time to return to normal skin for all lesions (no erythema).
- Variable 5 is the proportion of patients with aborted lesions (i.e., non-vesicular).
- Variable 6 is the percentage of patients with lesion tenderness and pain.
- Variable 7 is the duration of lesion tenderness and pain, defined from the onset to the time of disappearance.
- both famciclovir 750 mg b.i.d. for one day and famciclovir 1 ,500 mg as a single dose are superior to placebo in reducing investigator- assessed time to healing of the primary lesion complex (p ⁇ 0.001).
- the famciclovir 750 mg and famciclovir 1 ,500 mg-placebo hazard ratios for time to healing were 2.05 and 1.64, respectively.
- the estimated median times to healing of the primary lesion complex were 4.0, 4.4 and 6.2 days for famciclovir 750 mg, famciclovir 1500 mg and placebo, respectively. Similar results are obtained when the analysis is conducted for the PP population.
- one-day treatment with famciclovir either 750 mg b.i.d. or 1 ,500 mg q.d. significantly reduced the time to healing of lesions as compared to placebo.
- One day treatment with famciclovir for recurrent herpes labialis in immunocompetent patients is a, safe, well-tolerated and effective treatment which is superior to placebo in reducing time to healing of non-aborted primary lesions, non-aborted primary and secondary lesions, and all (non-aborted and aborted) lesions of recurrent herpes labialis.
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Abstract
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Priority Applications (16)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES06739956T ES2382664T3 (en) | 2005-03-30 | 2006-03-29 | Famciclovir for the treatment of recurrent cold sores using a one-day treatment |
JP2008504316A JP2008534603A (en) | 2005-03-30 | 2006-03-29 | Famciclovir for the treatment of recurrent cold sore using once-daily treatment |
DK06739956.8T DK1865961T3 (en) | 2005-03-30 | 2006-03-29 | Famciclovir for the treatment of recurrent herpes labialis in a one-day treatment |
PL06739956T PL1865961T3 (en) | 2005-03-30 | 2006-03-29 | Famciclovir for the treatment of recurrent herpes labialis using a one-day treatment |
AU2006230291A AU2006230291A1 (en) | 2005-03-30 | 2006-03-29 | Famciclovir for the treatment of recurrent herpes labialis using a one-day treatment |
EP06739956A EP1865961B1 (en) | 2005-03-30 | 2006-03-29 | Famciclovir for the treatment of recurrent herpes labialis using a one-day treatment |
BRPI0609793-6A BRPI0609793A2 (en) | 2005-03-30 | 2006-03-29 | famciclovir for the treatment of recurrent cold sores in one-day treatment |
KR1020077024918A KR101312820B1 (en) | 2005-03-30 | 2006-03-29 | Famciclovir for the treatment of recurrent herpes labialis using a one-day treatment |
CA002602641A CA2602641A1 (en) | 2005-03-30 | 2006-03-29 | Famciclovir for the treatment of recurrent herpes labialis using a one-day treatment |
AT06739956T ATE545419T1 (en) | 2005-03-30 | 2006-03-29 | FAMCICLOVIR FOR THE TREATMENT OF RECURRENT HERPES LABIALIS USING A ONCE-DAILY TREATMENT |
AU2010201836A AU2010201836C1 (en) | 2005-03-30 | 2010-05-06 | Famciclovir for the treatment of recurrent herpes labialis using a one-day treatment |
US12/803,649 US20100298353A1 (en) | 2005-03-30 | 2010-07-01 | Famciclovir for the treatment of recurrent herpes labialis using a one-day treatment |
US13/330,979 US20120088781A1 (en) | 2005-03-30 | 2011-12-20 | Famciclovir for the Treatment of Recurrent genital Herpes Labialis with a one day application |
US13/604,955 US20120329814A1 (en) | 2005-03-30 | 2012-09-06 | Famciclovir for the treatment of recurrent herpes labialis using a one-day treatment |
US13/606,219 US20120329815A1 (en) | 2005-03-30 | 2012-09-07 | Famciclovir for the Treatment of Recurrent Herpes Labialis using a One-Day Treatment |
US14/270,931 US20170252345A9 (en) | 2005-03-30 | 2014-05-06 | Famciclovir for the Treatment of Recurrent Herpes Labialis Using a One-Day Treatment |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US66653705P | 2005-03-30 | 2005-03-30 | |
US60/666,537 | 2005-03-30 |
Related Child Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11887303 A-371-Of-International | 2006-03-29 | ||
US11/887,303 Continuation US20110245277A1 (en) | 2005-03-30 | 2007-09-27 | Famciclovir for the Treatment of Recurrent Herpes Labialis Using a One-Day Treatment |
US63604909A Continuation | 2005-03-30 | 2009-12-11 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2006105216A1 true WO2006105216A1 (en) | 2006-10-05 |
Family
ID=36685678
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2006/011498 WO2006105216A1 (en) | 2005-03-30 | 2006-03-29 | Famciclovir for the treatment of recurrent herpes labialis using a one-day treatment |
Country Status (9)
Country | Link |
---|---|
US (1) | US20110257204A1 (en) |
EP (2) | EP1865960A2 (en) |
JP (1) | JP2008534602A (en) |
AU (1) | AU2010201836C1 (en) |
BR (1) | BRPI0609592A2 (en) |
CA (1) | CA2602691A1 (en) |
CL (1) | CL2006000697A1 (en) |
MX (1) | MX2007012104A (en) |
WO (1) | WO2006105216A1 (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5916893A (en) * | 1994-12-12 | 1999-06-29 | Smithkline Beecham P.L.C. | Treatment of a latent infection of herpes virus |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ZA96525B (en) * | 1995-02-06 | 1996-08-06 | Astra Ab | Novel pharmaceutical compositions |
DZ1966A1 (en) * | 1995-02-06 | 2002-10-15 | Astra Ab | New pharmaceutical combination. |
US6440980B1 (en) * | 1996-09-17 | 2002-08-27 | Avanir Pharmaceuticals | Synergistic inhibition of viral replication by long-chain hydrocarbons and nucleoside analogs |
-
2006
- 2006-03-29 CA CA002602691A patent/CA2602691A1/en not_active Abandoned
- 2006-03-29 EP EP06758222A patent/EP1865960A2/en not_active Withdrawn
- 2006-03-29 WO PCT/US2006/011498 patent/WO2006105216A1/en active Application Filing
- 2006-03-29 MX MX2007012104A patent/MX2007012104A/en not_active Application Discontinuation
- 2006-03-29 BR BRPI0609592-5A patent/BRPI0609592A2/en not_active IP Right Cessation
- 2006-03-29 EP EP10178109A patent/EP2394651A1/en not_active Withdrawn
- 2006-03-29 JP JP2008504311A patent/JP2008534602A/en active Pending
- 2006-03-29 CL CL200600697A patent/CL2006000697A1/en unknown
-
2010
- 2010-05-06 AU AU2010201836A patent/AU2010201836C1/en not_active Ceased
-
2011
- 2011-02-16 US US13/028,680 patent/US20110257204A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5916893A (en) * | 1994-12-12 | 1999-06-29 | Smithkline Beecham P.L.C. | Treatment of a latent infection of herpes virus |
Non-Patent Citations (1)
Title |
---|
SPRUANCE ET AL: "Treatment of herpes simplex labialis", HERPES, vol. 9, no. 3, 2002 - 2002, pages 64 - 69, XP009070057 * |
Also Published As
Publication number | Publication date |
---|---|
EP1865960A2 (en) | 2007-12-19 |
AU2010201836A1 (en) | 2010-05-27 |
AU2010201836B2 (en) | 2013-05-02 |
JP2008534602A (en) | 2008-08-28 |
US20110257204A1 (en) | 2011-10-20 |
CA2602691A1 (en) | 2006-10-05 |
BRPI0609592A2 (en) | 2010-04-20 |
CL2006000697A1 (en) | 2008-05-09 |
MX2007012104A (en) | 2008-03-11 |
EP2394651A1 (en) | 2011-12-14 |
AU2010201836C1 (en) | 2014-07-03 |
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