Claims for Patent: 10,501,444

Summary for Patent: 10,501,444

Title:	Inhibitors of influenza virus replication, application methods and uses thereof
Abstract:	The invention provides a novel class of compounds as inhibitors of influenza virus replication, preparation methods thereof, pharmaceutical compositions containing these compounds, and uses of these compounds and pharmaceutical compositions thereof in the treatment of influenza.
Inventor(s):	Ren; Qingyun (Dongguan, CN), Tang; Changhua (Dongguan, CN), Yin; Junjun (Dongguan, CN), Yi; Kai (Dongguan, CN), Zhang; Yingjun (Dongguan, CN)
Assignee:	SUNSHINE LAKE PHARMA CO., LTD. (Dongguan, Guangdong, CN) NORTH & SOUTH BROTHER PHARMACY INVESTMENT COMPANY LIMITED (Wanchai, HK)
Application Number:	16/326,189
Patent Claims:	1. A compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, or a pharmaceutically acceptable salt thereof, ##STR00160## wherein, U is N or CR.sup.5; each of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 is independently H, D, F, Cl, Br, CN, NO.sub.2, --C(.dbd.O)R.sup.a, --C(.dbd.O)OR.sup.b, --C(.dbd.O)NR.sup.cR.sup.d, OR.sup.b, --NR.sup.cR.sup.d, R.sup.bO--C.sub.1-4 alkylene, R.sup.dR.sup.cN--C.sub.1-4 alkylene, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl, and wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl and C.sub.2-6 alkynyl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, OR.sup.b, --NR.sup.cR.sup.d, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, R.sup.bO--C.sub.1-4 alkylene or R.sup.dR.sup.cN--C.sub.1-4 alkylene; R.sup.6 is OR.sup.b, C.sub.2-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-12 carbocyclyl, C.sub.3-12 carbocyclyl-C.sub.1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 16-membered heteroaryl or (5- to 16-membered heteroaryl)-C.sub.1-4 alkylene, and wherein each of the C.sub.2-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-12 carbocyclyl, C.sub.3-12 carbocyclyl-C.sub.1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 16-membered heteroaryl and (5- to 16-membered heteroaryl)-C.sub.1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R'; R.sup.7 is H, D, F, Cl, Br, CN, NO.sub.2, --C(.dbd.O)R.sup.a, --C(.dbd.O)OR.sup.b, --C(.dbd.O)NR.sup.cR.sup.d, OR.sup.b, --NR.sup.cR.sup.d, R.sup.bO--C.sub.1-4 alkylene, R.sup.dR.sup.cN--C.sub.1-4 alkylene, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-12 cycloalkyl, C.sub.3-12 cycloalkyl-C.sub.1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 10-membered heteroaryl or (5- to 10-membered heteroaryl)-C.sub.1-4 alkylene, and wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-12 cycloalkyl, C.sub.3-12 cycloalkyl-C.sub.1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 10-membered heteroaryl and (5- to 10-membered heteroaryl)-C.sub.1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R'; or, R.sup.6 and R.sup.7, together with the carbon atoms to which they are attached, form a C.sub.3-12 carbocyclic ring, 3- to 12-membered heterocyclic ring, C.sub.6-10 aromatic ring or 5- to 10-membered heteroaromatic ring, and wherein each of the C.sub.3-12 carbocyclic ring, 3- to 12-membered heterocyclic ring, C.sub.6-10 aromatic ring and 5- to 10-membered heteroaromatic ring is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R'; each R' is independently D, F, Cl, Br, CN, NO.sub.2, OR.sup.b, --NR.sup.cR.sup.d, R.sup.bO--C.sub.1-4 alkylene, R.sup.dR.sup.cN--C.sub.1-4 alkylene, --C(.dbd.O)R.sup.a, --C(.dbd.O)OR.sup.b, --C(.dbd.O)NR.sup.cR.sup.d, C.sub.1-12 alkyl, C.sub.1-6 haloalkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-4 alkylene, 3- to 8-membered heterocyclyl, (3- to 8-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 8-membered heteroaryl or (5- to 8-membered heteroaryl)-C.sub.1-4 alkylene, and wherein each of the C.sub.1-12 alkyl, C.sub.1-6 haloalkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-4 alkylene, 3- to 8-membered heterocyclyl, (3- to 8-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 8-membered heteroaryl and (5- to 8-membered heteroaryl)-C.sub.1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, NO.sub.2, OR.sup.b, --NR.sup.cR.sup.d, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, R.sup.bO--C.sub.1-4 alkylene or R.sup.dR.sup.cN--C.sub.1-4 alkylene; R.sup.8 is H, D or C.sub.1-6 alkyl, and wherein C.sub.1-6 alkyl is optionally substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, NO.sub.2 or OR.sup.b; W is one of the following sub-formulae: ##STR00161## wherein n is 0, 1, 2, 3, or 4; each R.sup.w is independently D, F, Cl, Br, CN, NO.sub.2, oxo (.dbd.O), --C(.dbd.O)R.sup.a, --C(.dbd.O)OR.sup.b, --NR.sup.eC(.dbd.O)R.sup.a, --NR.sup.eC(.dbd.O)NR.sup.cR.sup.d, --S(.dbd.O).sub.2R.sup.f, --S(.dbd.O).sub.2NR.sup.eC(.dbd.O)R.sup.a, --S(.dbd.O).sub.2NR.sup.cR.sup.d, (R.sup.bO).sub.2P(.dbd.O)--C.sub.0-2 alkylene, OR.sup.b, R.sup.bO--C.sub.1-2 alkylene, C.sub.1-6 alkyl or 5- to 6-membered heteroaryl, and wherein each of the C.sub.1-6 alkyl and 5- to 6-membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, N.sub.3, oxo (.dbd.O), NO.sub.2, OR.sup.b, C.sub.1-6 alkyl or C.sub.1-6 haloalkyl; each R.sup.a, R.sup.b, R.sup.c, R.sup.d, R.sup.e and R.sup.f is independently H, D, C.sub.1-6 haloalkyl, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 carbocyclyl, C.sub.3-6 carbocyclyl-C.sub.1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 10-membered heteroaryl, (5- to 10-membered heteroaryl)-C.sub.1-4 alkylene; or, R.sup.c and R.sup.d, together with the nitrogen atom to which they are attached, form 3- to 8-membered heterocyclyl or 5- to 8-membered heteroaryl, and wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 carbocyclyl, C.sub.3-6 carbocyclyl-C.sub.1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 10-membered heteroaryl, (5- to 10-membered heteroaryl)-C.sub.1-4 alkylene, 3- to 8-membered heterocyclyl and 5- to 8-membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, CN, OH, NH.sub.2, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 alkoxy or C.sub.1-6 alkylamino. 2. The compound of claim 1 having Formula (II), ##STR00162## 3. The compound of claim 1 having Formula (III), ##STR00163## wherein, A is a C.sub.3-12 carbocyclic ring, 3- to 12-membered heterocyclic ring, C.sub.6-10 aromatic ring or 5- to 10-membered heteroaromatic ring; and q is 0, 1, 2, 3, 4 or 5. 4. The compound of claim 1, wherein each of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 is independently H, D, F, Cl, Br, CN, NO.sub.2, --C(.dbd.O)R.sup.a, --C(.dbd.O)OR.sup.b, --C(.dbd.O)NR.sup.cR.sup.d, OR.sup.b, --NR.sup.cR.sup.d, methyl, ethyl, n-propyl or i-propyl, and wherein each of methyl, ethyl, n-propyl and i-propyl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, OR.sup.b, --NR.sup.cR.sup.d or C.sub.1-3 haloalkyl. 5. The compound of claim 1, wherein R.sup.6 is OR.sup.b, C.sub.2-3 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, C.sub.3-6 carbocyclyl, C.sub.3-6 carbocyclyl-C.sub.1-4 alkylene, 5- to 6-membered heterocyclyl, (5- to 6-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 14-membered heteroaryl or (5- to 14-membered heteroaryl)-C.sub.1-4 alkylene, and wherein each of the C.sub.2-3 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, C.sub.3-6 carbocyclyl, C.sub.3-6 carbocyclyl-C.sub.1-4 alkylene, 5- to 6-membered heterocyclyl, (5- to 6-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 14-membered heteroaryl and (5- to 14-membered heteroaryl)-C.sub.1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R'; R.sup.7 is H, D, F, Cl, Br, CN, NO.sub.2, --C(.dbd.O)R.sup.a, --C(.dbd.O)OR.sup.b, --C(.dbd.O)NR.sup.cR.sup.d, OR.sup.b, --NR.sup.cR.sup.d, C.sub.1-3 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-4 alkylene, 5- to 6-membered heterocyclyl, (5- to 6-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 6-membered heteroaryl or (5- to 6-membered heteroaryl)-C.sub.1-4 alkylene, and wherein each of the C.sub.1-3 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-4 alkylene, 5- to 6-membered heterocyclyl, (5- to 6-membered heterocyclyl)-C.sub.1-4 alkylene, C.sub.6-10 aryl, C.sub.6-10 aryl-C.sub.1-4 alkylene, 5- to 6-membered heteroaryl and (5- to 6-membered heteroaryl)-C.sub.1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R'; or, R.sup.6 and R.sup.7, together with the carbon atoms to which they are attached, form a C.sub.3-6 carbocyclic ring, 3- to 6-membered heterocyclic ring, C.sub.6-10 aromatic ring or 5- to 10-membered heteroaromatic ring, and wherein each of the C.sub.3-6 carbocyclic ring, 3- to 6-membered heterocyclic ring, C.sub.6-10 aromatic ring and 5- to 10-membered heteroaromatic ring is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R'. 6. The compound of claim 1, wherein each R' is independently D, F, Cl, Br, CN, NO.sub.2, OR.sup.b, --NR.sup.cR.sup.d, --C(.dbd.O)R.sup.a, --C(.dbd.O)NR.sup.cR.sup.d, C.sub.1-9 alkyl, C.sub.1-3 haloalkyl, C.sub.3-6 cycloalkyl, 5- to 6-membered heterocyclyl, phenyl, phenyl-C.sub.1-2 alkylene or 5- to 6-membered heteroaryl, and wherein each of the C.sub.1-9 alkyl, C.sub.1-3 haloalkyl, C.sub.3-6 cycloalkyl, 5- to 6-membered heterocyclyl, phenyl, phenyl-C.sub.1-2 alkylene and 5- to 6-membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, NO.sub.2, OR.sup.b, --NR.sup.cR.sup.d, methyl, ethyl, n-propyl or i-propyl. 7. The compound of claim 1, wherein R.sup.8 is H, D, CF.sub.3, methyl, ethyl, n-propyl or i-propyl. 8. The compound of claim 1, wherein each R.sup.w is independently D, F, Cl, Br, CN, NO.sub.2, oxo (.dbd.O), --C(.dbd.O)OCH.sub.3, --C(.dbd.O)OCH.sub.2CH.sub.3, --C(.dbd.O)OH, --NHC(.dbd.O)R.sup.a, --NHC(.dbd.O)NR.sup.cR.sup.d, --S(.dbd.O).sub.2R.sup.f, --S(.dbd.O).sub.2NHC(.dbd.O)R.sup.a, --S(.dbd.O).sub.2NR.sup.eR.sup.d, (R.sup.bO).sub.2P(.dbd.O)--C.sub.0-2 alkylene, OR.sup.b, methyl, ethyl, n-propyl, i-propyl, furyl, pyrrolyl, pyridyl, pyrazolyl, imdazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, 1,3,5-triazinyl, thiazolyl, thienyl, pyrazinyl, pyridazinyl or primidinyl, and wherein each of methyl, ethyl, n-propyl, i-propyl, furyl, pyrrolyl, pyridyl, pyrazolyl, imdazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, 1,3,5-triazinyl, thiazolyl, thienyl, pyrazinyl, pyridazinyl and primidinyl independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, N.sub.3, oxo (.dbd.O), NO.sub.2, --OCH.sub.3, C.sub.1-3 alkyl or C.sub.1-3 haloalkyl. 9. The compound of claim 1, wherein each R.sup.a, R.sup.b, R.sup.c, R.sup.d, R.sup.e and R.sup.f is independently H, D, trifluoromethyl, methyl, ethyl, i-propyl, n-propyl, n-butyl, t-butyl, C.sub.3-6 carbocyclyl, 5- to 6-membered heterocyclyl, phenyl, 5- to 6-membered heteroaryl, (5- to 6-membered heteroaryl)-C.sub.1-4 alkylene; or, R.sup.c and R.sup.d, together with the nitrogen atom to which they are attached, form a 5- to 6-membered heterocyclyl or 5- to 6-membered heteroaryl, and wherein each of methyl, ethyl, i-propyl, n-propyl, n-butyl, t-butyl, C.sub.3-6 carbocyclyl, 5- to 6-membered heterocyclyl, phenyl, 5- to 6-membered heteroaryl and (5- to 6-membered heteroaryl)-C.sub.1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, CN, OH, NH.sub.2, C.sub.1-3 alkyl, C.sub.1-3 haloalkyl or methoxy. 10. The compound of claim 3, wherein, A is a C.sub.3-6 carbocyclic ring, 3- to 6-membered heterocyclic ring, C.sub.6-10 aromatic ring or 5- to 10-membered heteroaryl. 11. The compound of claim 1, wherein R.sup.6 is OR.sup.b, C.sub.2-4 alkynyl, C.sub.3-6 carbocyclyl, 5- to 6-membered heterocyclyl, phenyl, naphthyl, furyl, benzofuryl, pyrrolyl, pyridyl, pyrazolyl, imdazolyl, benzimdazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, 1,3,5-triazinyl, thiazolyl, thienyl, benzothienyl, pyrazinyl, pyridazinyl, pyrimidinyl, indolyl, purinyl, quinolyl, isoquinolyl, phenoxathiinyl, ##STR00164## and wherein each of C.sub.2-4 alkynyl, C.sub.3-6 carbocyclyl, 5- to 6-membered heterocyclyl, phenyl, naphthyl, furyl, benzofuryl, pyrrolyl, pyridyl, pyrazolyl, imdazolyl, benzimdazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, 1,3,5-triazinyl, thiazolyl, thienyl, benzothienyl, pyrazinyl, pyridazinyl, pyrimidinyl, indolyl, purinyl, quinolyl, isoquinolyl, phenoxathiinyl, ##STR00165## is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R'. 12. The compound of claim 3, wherein A is a C.sub.3-6 carbocyclic ring, 3- to 6-membered heterocyclic ring, benzene, naphthalene, furan, benzofuran, pyrrole, pyridine, pyrazole, imidazole, benzoimidazole, triazole, tetrazole, oxazole, oxadiazole, 1,3,5-triazine, thiazole, thiophene, benzothiphene, pyrazine, pyridazine, pyrimidine, indole, purine, quinoline or isoquinoline. 13. The compound of claim 1 having Formula (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV) or (XV), ##STR00166## ##STR00167## ##STR00168## wherein, A is a C.sub.3-12 carbocyclic ring, 3- to 12-membered heterocyclic ring, C.sub.6-10 aromatic ring or 5- to 10-membered heteroaromatic ring; and q is 0, 1,2,3, 4 or 5. 14. A compound having one of the following structures, ##STR00169## ##STR00170## ##STR00171## ##STR00172## ##STR00173## ##STR00174## ##STR00175## ##STR00176## ##STR00177## ##STR00178## ##STR00179## ##STR00180## ##STR00181## ##STR00182## ##STR00183## ##STR00184## ##STR00185## ##STR00186## ##STR00187## ##STR00188## ##STR00189## ##STR00190## ##STR00191## ##STR00192## ##STR00193## ##STR00194## ##STR00195## ##STR00196## ##STR00197## ##STR00198## ##STR00199## ##STR00200## ##STR00201## ##STR00202## ##STR00203## ##STR00204## ##STR00205## ##STR00206## ##STR00207## ##STR00208## ##STR00209## ##STR00210## ##STR00211## ##STR00212## ##STR00213## ##STR00214## ##STR00215## ##STR00216## ##STR00217## ##STR00218## ##STR00219## ##STR00220## ##STR00221## ##STR00222## ##STR00223## ##STR00224## or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, or a pharmaceutically acceptable salt thereof. 15. A pharmaceutical composition comprising the compound of claim 1, optionally, the pharmaceutical composition further comprising a pharmaceutically acceptable carrier, adjuvant, vehicle or a combination thereof. 16. The pharmaceutical composition of claim 15 further comprising one or more other therapeutic agents, and wherein the other therapeutic agent is an anti-influenza virus agent or anti-influenza virus vaccine. 17. The pharmaceutical composition of claim 16, wherein the other therapeutic agent is amantadine, rimantadine, oseltamivir, zanamivir, peramivir, laninamivir, laninamivir octanoate hydrate, favipiravir, arbidol, ribavirin, stachyflin, ingavirin, fludase, CAS no. 1422050-75-6, JNJ-872, an influenza vaccine or a combination thereof. 18. A method of managing, treating or lessening a disorder or disease caused by a virus infection in a patient, comprising administering to the patient in need thereof a therapeutically effective amount of the compound of claim 1, wherein the virus infection is an influenza virus infection. 19. A method of inhibiting an influenza virus RNA polymerase in a patient, comprising administering to the patient in need thereof a therapeutically effective amount of the compound of claim 1. 20. A method of managing, treating or lessening a disorder or disease caused by a virus infection in a patient, comprising administering to the patient in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 15, wherein the virus infection is an influenza virus infection. 21. A method of inhibiting an influenza virus RNA polymerase in a patient, comprising administering to the patient in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 15.

Details for Patent 10,501,444

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Seqirus Vaccines Limited	FLUVIRIN	influenza virus vaccine	Injection	103837	November 03, 1998	10,501,444	2037-08-15
Sanofi Pasteur Inc.	FLUZONE, FLUZONE HD QUADRIVALENT, FLUZONE HIGH DOSE, FLUZONE INTRADERMAL, FLUZONE QUADRIVALENT	influenza virus vaccine	Injection	103914	December 09, 1999	10,501,444	2037-08-15
Sanofi Pasteur Inc.	FLUZONE, FLUZONE HD QUADRIVALENT, FLUZONE HIGH DOSE, FLUZONE INTRADERMAL, FLUZONE QUADRIVALENT	influenza virus vaccine	Injection	103914	December 23, 2009	10,501,444	2037-08-15
Sanofi Pasteur Inc.	FLUZONE, FLUZONE HD QUADRIVALENT, FLUZONE HIGH DOSE, FLUZONE INTRADERMAL, FLUZONE QUADRIVALENT	influenza virus vaccine	Injection	103914	May 09, 2011	10,501,444	2037-08-15
Sanofi Pasteur Inc.	FLUZONE, FLUZONE HD QUADRIVALENT, FLUZONE HIGH DOSE, FLUZONE INTRADERMAL, FLUZONE QUADRIVALENT	influenza virus vaccine	Injection	103914	June 07, 2013	10,501,444	2037-08-15