U.S. Patent No. 8,927,606
`Claims
`
`1. A method for treating an
`inflammatory disease of an
`eye, the method comprising
`administering to said eye a
`stable aqueous liquid
`preparation that comprises:
`(a) a first component; and
`(b) a second component;
`wherein the first component is
`2-amino-3-(4-bromobenzoyl)
`phenylacetic acid or a
`pharmacologically acceptable
`salt thereof or a hydrate
`thereof,wherein the hydrate is
`at least one selected from a ½
`hydrate, 1 hydrate, and 3/2
`hydrate;
`the first component is the sole
`pharmaceutical active
`ingredient contained in the
`preparation;
`the second component is
`tyloxapol and is present in
`said liquid preparation in an
`amount sufficient to stabilize
`said first component;
`wherein said stable liquid
`preparation is formulated for
`ophthalmic administration;
`and
`wherein said liquid
`preparation is administered to
`said eye at a dose and a
`frequency effective to treat
`said inflammatory disease.
`
`INDEPENDENT CLAIMS
`
`11. A method for treating an
`inflammatory disease of an
`eye, the method comprising
`administering to said eye a
`stable aqueous liquid
`preparation that comprises:
`(a) a first component; and
`(b) a second component;
`wherein the first component is
`2-amino-3-(4-bromobenzoyl)
`phenylacetic acid or a
`pharmacologically acceptable
`salt thereof or a hydrate
`thereof, wherein the hydrate is
`at least one selected from a 1/2
`hydrate, 1 hydrate, and 3/2
`hydrate;
`the first component is the sole
`pharmaceutical active
`ingredient contained in the
`preparation;
`the second component is
`tyloxapol;
`wherein said stable liquid
`preparation is formulated for
`ophthalmic administration;
`wherein the stable aqueous
`liquid preparation is
`characterized in that greater
`than about 90% of the original
`amount of the first component
`remains in the preparation
`after storage at about 60°C. for
`4 weeks; and
`wherein said liquid
`preparation is administered to
`said eye at a dose and a
`frequency effective to treat
`said inflammatory disease.
`
`1
`
`19. A method for treating an
`inflammatory disease of an
`eye, the method comprising
`administering to said eye a
`stable aqueous liquid
`preparation that comprises:
`(a) a first component; and
`(b) a second component;
`wherein the first component is
`2-amino-3-(4-bromobenzoyl)
`phenylacetic acid or a
`pharmacologically acceptable
`salt thereof or a hydrate
`thereof, wherein the hydrate is
`at least one selected from a 1/2
`hydrate, 1 hydrate, and 3/2
`hydrate;
`the first component is the sole
`pharmaceutical active
`ingredient contained in the
`preparation;
`the second component is
`tyloxapol;
`wherein said stable liquid
`preparation is formulated for
`ophthalmic administration;
`provided that the liquid
`preparation does not include
`mannitol; and
`wherein said liquid
`preparation is administered to
`said eye at a dose and a
`frequency effective to treat
`said inflammatory disease.
`
`LUPIN EX 1026
`
`

`

`U.S. Patent No. 8,927,606
`Claims
`
`DISEASE INDICATIONS
`
`2. The method according to claim 1, wherein said inflammatory disease is a disease of an
`anterior or posterior segment of said eye.
`
`3. The method according to claim 2, wherein said disease is postoperative inflammation.
`
`13. The method according to claim 11, wherein said inflammatory disease is a disease of an
`anterior or posterior segment of said eye.
`
`14. The method according to claim 13, wherein said disease is postoperative inflammation.
`
`20. The method according to claim 19, wherein said inflammatory disease is a disease of an
`anterior or posterior segment of said eye.
`
`21. The method according to claim 20, wherein said disease is postoperative inflammation.
`
`10. The method according to claim 1, wherein said dose comprises one or two drops.
`
`DOSAGE INFORMATION
`
`STABILITY
`
`12. The method according to claim 11, wherein the stable aqueous liquid preparation is
`characterized in that greater than about 92% of the original amount of the first component
`remains in the preparation after storage at about 60°C. for 4 weeks.
`
`26. The method according to claim 20, wherein the stable aqueous liquid preparation is
`characterized in that greater than about 90% of the original amount of the first component
`remains in the preparation after storage at about 60°C. for 4 weeks.
`
`PHARMACOLOGICALLY ACCEPTABLE SALTS
`
`4. The method according to claim 1, wherein the first component is a 2-amino-3-(4-
`bromobenzoyl)phenylacetic acid sodium salt.
`
`7. The method according to claim 5, wherein the aqueous liquid preparation further comprises a
`quaternary ammonium salt.
`
`17. The method according to claim 11, further comprising a quaternary ammonium salt.
`
`22. The method according to claim 19, wherein the first component is a 2-amino-3-(4-
`bromobenzoyl)phenylacetic acid sodium salt.
`
`CONCENTRATION OF COMPONENTS
`
`5. The method according to claim 1, wherein the concentration of tyloxapol is from about 0.01
`
`2
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`

`

`U.S. Patent No. 8,927,606
`Claims
`
`w/v % to about 0.05 w/v %; and
`wherein the first component is a 2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt,
`wherein the concentration of the 2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt is
`from about 0.01 to about 0.2 w/v %.
`
`6. The method according to claim 5, wherein the concentration of the 2-amino-3-(4-
`bromobenzoyl) phenylacetic acid sodium salt is from about 0.02 w/v % to about 0.1 w/v %.
`
`8. The method according to claim 5, wherein the concentration of the 2-amino-3-(4-
`bromobenzoyl) phenylacetic acid sodium salt is about 0.1 w/v %.
`
`9. The method according to claim 1, wherein the stable aqueous liquid preparation consists
`essentially of:
`(a) 2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt,
`(d) sodium tetraborate,
`(e) EDTA sodium salt,
`(f) benzalkonium chloride,
`(g) polyvinylpyrrolidone, and
`(h) sodium sulfite,
`wherein said liquid preparation is formulated for ophthalmic administration, and
`wherein the concentration of the 2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt is
`from about 0.02 w/v % to about 0.1 w/v %.
`
`15. The method according to claim 11, wherein the concentration of tyloxapol is from about 0.01
`w/v % to about 0.05 w/v %; and
`wherein the first component is a 2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt,
`wherein the concentration of the 2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt is
`from about 0.01 to about 0.2 w/v %.
`
`16. The method according to claim 15, wherein the concentration of the 2-amino-3-(4-
`bromobenzoyl) phenylacetic acid sodium salt is from about 0.02 w/v % to about 0.1 w/v %.
`
`18. The method according to claim 11, wherein the stable aqueous liquid preparation consists
`essentially of:
`(a) 2-amino-3-(4-bromobenzoyl)phenylacetic acid or a pharmacologically acceptable salt thereof
`or a hydrate thereof, wherein the hydrate is at least one selected from a 1/2 hydrate, 1 hydrate,
`and 3/2 hydrate;
`(b) tyloxapol;
`(c) boric acid;
`(d) sodium tetraborate;
`(e) EDTA sodium salt;
`(f) benzalkonium chloride;
`(g) polyvinylpyrrolidone; and
`
`3
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`

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`U.S. Patent No. 8,927,606
`Claims
`
`(h) sodium sulfite; and
`wherein the concentration of the 2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt is
`from about 0.02 w/v % to about 0.1 w/v %.
`
`23. The method according to claim 22, wherein the concentration of tyloxapol is from about 0.01
`w/v % to about 0.05 w/v % and
`the concentration of the 2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt is from about
`0.05 to about 0.2 w/v %.
`
`24. The method according to claim 22, wherein the concentration of the 2-amino-3-(4-
`bromobenzoyl) phenylacetic acid sodium salt is from about 0.02 w/v % to about 0.1 w/v %.
`
`25. The method according to claim 20; wherein the stable aqueous liquid preparation consists
`essentially of:
`(a) 2-amino-3-(4-bromobenzoyl)phenylacetic acid or a pharmacologically acceptable salt thereof
`or a hydrate thereof, wherein the hydrate is at least one selected from a 1/2 hydrate, 1 hydrate,
`and 3/2 hydrate;
`(b) tyloxapol;
`(c) boric acid;
`(d) sodium tetraborate;
`(e) EDTA sodium salt;
`(f) benzalkonium chloride;
`(g) polyvinylpyrrolidone; and
`(h) sodium sulfite;
`wherein the concentration of the 2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt is
`from about 0.02 w/v % to about 0.1 w/v %.
`
`27. The method according to claim 20,
`wherein the concentration of tyloxapol is from about 0.01 w/v % to about 0.05 w/v %; and
`wherein the first component is a 2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt,
`wherein the concentration of the 2-amino-3-(4-bromobenzoyl)phenylacetic acid sodium salt is
`from about 0.02 to about 0.1 w/v %.
`
`EP-criteria B
`
`28. The method according to claim 1, wherein the aqueous liquid preparation further satisfies the
`preservative efficacy standard of EP-criteria B of the European Pharmacopoeia as follows:
`viable cell counts of bacteria (S. aureus, P. aeruginosa) 24 hours and 7 days after inoculation
`decrease to not more than 1/10 and not more than 1/1000, respectively, and thereafter, the cell
`count levels off or decreases; and viable cell count of fungi (C. albicans, A. niger) 14 days after
`inoculation decreases to not more than 1/10, and thereafter, the cell count keeps the same level as
`that of 14 days after inoculation.
`
`4
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`

`U.S. Patent No. 8,927,606
`Claims
`
`29. The method according to claim 11, wherein the aqueous liquid preparation further satisfies
`the preservative efficacy standard of EP-criteria B of the European Pharmacopoeia as follows:
`viable cell counts of bacteria (S. aureus, P. aeruginosa) 24 hours and 7 days after inoculation
`decrease to not more than 1/10 and not more than 1/1000, respectively, and thereafter, the cell
`count levels off or decreases; and viable cell count of fungi (C. albicans, A. niger) 14 days after
`inoculation decreases to not more than 1/10, and thereafter, the cell count keeps the same level as
`that of 14 days after inoculation.
`
`30. The method according to claim 19, wherein the aqueous liquid preparation further satisfies
`the preservative efficacy standard of EP-criteria B of the European Pharmacopoeia as follows:
`viable cell counts of bacteria (S. aureus, P. aeruginosa) 24 hours and 7 days after inoculation
`decrease to not more than 1/10 and not more than 1/1000, respectively, and thereafter, the cell
`count levels off or decreases; and viable cell count of fungi (C. albicans, A. niger) 14 days after
`inoculation decreases to not more than 1/10, and thereafter, the cell count keeps the same level as
`that of 14 days after inoculation.
`
`5
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