Epidemic-Curve Graph (Top) and Field Position Diagram (Bottom) of Cases of MRSA Infection among St....
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Transcript of Epidemic-Curve Graph (Top) and Field Position Diagram (Bottom) of Cases of MRSA Infection among St....
Epidemic-Curve Graph (Top) and Field Position Diagram (Bottom) of Cases of MRSA Infection among St. Louis Rams Football Players in 2003
Epidemic-Curve Graph (Top) and Field Position Diagram (Bottom) of Cases of MRSA Infection among St. Louis Rams Football Players in 2003
Kazakova, S. V. et al. N Engl J Med 2005;352:468-475
The New CampaignThe New Campaign
The New CampaignThe New Campaign
4. Marketing4. Marketing
3. Product Development3. Product Development
1. Meeting an unmet need1. Meeting an unmet need 2. “Cahiers Des Charges”2. “Cahiers Des Charges”
• Must place market needs as the focal point• “as articulated by the customer.”
Customer CentricCustomer Centric
• Attributes• Features• Performance• “I need a moisturizer that is
better than the leading brand”
Establishing the productEstablishing the productblueprintblueprint
Outcome DrivenOutcome Driven
Brand PlanBrand Plan
The Otx Sales ProcessThe Otx Sales Process
Meeting Product GuidelinesMeeting Product Guidelines
• Innovative formulation• Novel vehicles• Clinical assessment• Commercialization
None
Neutro.elastase
Ela2
19p13.3
AD
German, English, French,N. Am.
Cryopirin
CIAS1
1q44
AD
Dutch French
Mevalonatekinase
Mevalonatekinase
12q24
AR
Scottish,Irish
TNFR type 1
TNFRSF1A
12p13
AD
Jewish,Turkish, Arab,Armenian
PyrinMarenostrin
MEFV
16p13
AR
Ancest
Protein
Gene
Chrom
Inherit
CHMWS/FCUHIDSTRAPSFMF
Familial Periodic Fever SyndromesFamilial Periodic Fever Syndromes
ParentsRelativesCCCCCHIn-home Care
Data from Children’s Defense Fund. CDF Publications 1998
CCC = Child care centerCCH = Family CCC
Distribution of Child Care USDistribution of Child Care US
Rare Tlr 4 Mutations Are AssociatedWith Meningococcal Susceptibility
~7.5% meningococcal sepsis can be attributed to rare mutations at TLR4 locus
Smirnova I, et al. Proc Natl Acad Sci USA. 2003;100:6075-6080.
West Nile Virus (WNV)
http://www.dierentuin.net/pictures/huismuis.jpghttp://www.dierentuin.net/pictures/huismuis.jpg
anatomy.ucsf.edu/Pages/mouseclub/mousejournalclub.htmlanatomy.ucsf.edu/Pages/mouseclub/mousejournalclub.html
wildlife.usask.ca/WestNileAlertHTML/viron.jpgwildlife.usask.ca/WestNileAlertHTML/viron.jpg
A stop codon in exon 4 of the interferon response gene, 2’-5’-oligoadenylate synthetase/L1 isoform (Oas1) may be responsible for susceptibility to WNV and other flaviviruses
Perelygin AA, et al. Proc Natl Acad Sci USA. 2002;99:9322-9327.Mashimo T, et al. Proc Natl Acad Sci USA. 2002;99:11311-11316.
WNV
20% symptomatic 1/150 with meningitis or encephalitis
Relevance to Humans?Relevance to Humans?
20% symptomatic 1/150 with meningitis or encephalitis
• 600 potential vaccine candidates identified
• 350 proteins expressed in E. coli
• 344 proteins used to immunize mice
• 355 sera tested
• 91 novel surface-exposedproteins identified
• 29 novel proteins induce
bactericidal activity
5 vaccinecandidate
s
18 months
24 months
Scale-upGMP / IND
1 year
Men B Vaccine: A Genomic ApproachMen B Vaccine: A Genomic Approach
Clinical trialClinical trial
Alefacept in PsoriasisAlefacept in Psoriasis
Krueger GG, et al. J Amer Acad Dermatol. 2002;47:821-833; Lebwohl M, et al. Arch Dermatol. 2003;139:719-727.
Weeks
Placebo
Alefacept 7.5 mg
Weeks 1–12Dosing
Weeks 13–24Follow-up
2 4 6 8 10 12 14 16 18 20 22 24
Primary EfficacyEnd Point
IV = 14%IV = 14%IM = 21%IM = 21%First CourseFirst Course IV = 25%IV = 25%
IM = 28%IM = 28%
PASI 75 Responders
PosttreatmentResponse Rate
IV = 11%IV = 11%IM = 7%IM = 7%+
Phase 3 Efficacy Results
Wunderink, R. G. et al. Chest 2003;124:1789-1797
Clinical cure rates for linezolid and vancomycin therapy in patients with Gram-positive, nosocomial pneumonia
Linezolid for MRSA pneumonia?Linezolid for MRSA pneumonia?
Binding sites for both macrolides & telithromycin
Mechanism of Mechanism of ActionAction
Domain IIDomain II Domain VDomain V
Telithromycinbinds 10X more strongly than macrolidesbecause of its better domain II contact
Site ofmethylation
Douthwait et al Mol Micro 36:183, 2000Douthwait et al Mol Micro 36:183, 2000