IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`In re application of
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`Shirou SAW A et al.
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`Serial No. 10/525,006
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`Filed March 28, 2005
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`AQUEOUS LIQUID PREPARATION
`CONTAINING 2-AMIN0-3-(4-
`BROMOBENZOYL )PHENYLACETIC ACID
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`Attorney Docket No. 2005 _ 0232A
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`Confirmation No. 1756
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`Group Art Unit 1627
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`Examiner Layla Soroush
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`Mail Stop: Amendment
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`AMENDMENT
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`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
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`Sir:
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`Responsive to the Official Action dated May 6, 20 11, the time for responding thereto
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`being extended for one month in accordance with a petition for extension submitted concurrently
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`herewith, please amend the above-identified application as follows:
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`The Commissioner is authorized to charge any deficiency or to credit any overpayment associated with this communication to
`Deposit Account No. 23-0975, with the EXCEPTION of deficiencies in fees for multiple dependent claims in new applications.
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`LUPIN EX1029, Page 1
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`REMARKS
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`Favorable reconsideration is respectfully solicited in view of the foregoing amendments
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`and following remarks.
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`Applicants wish to thank the Examiner Soroush and SPE Padmanabhan for their courtesy
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`and assistance provided to the Applicants' representative during the personal interview held on
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`September 1, 2011.
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`The claims have been amended as proposed by the Applicants and as suggested by the
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`Examiners. Specifically, the second component has been limited to tyloxapol to expedite
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`allowance. Such limitation is made without prejudice to the filing of a divisional application.
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`Claim 41 has been amended to remove the "limited to" phrase, and method claims 61-62 are
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`cancelled without prejudice.
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`Turning to the rejections, claims 41-48, 50-51, 53-55 and 58-59 are rejected under 35
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`USC 103 as unpatentable over Yanni in view of Guy. Such rejection is respectfully traversed as
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`applied to the amended claims.
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`As discussed during the interview, the rejection appears to take the position that Yanni
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`discloses in Preparation XV a composition ofbromfenac with polysorbate 80. However
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`Preparation XV does not disclose bromfenac, the acid, but an amide derivative thereof.
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`Moreover, Yanni teaches that bromfenac acids have problems such as difficulty in
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`formulating stable solutions, and provoking ocular irritation. See column 1, line 60 to column 2,
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`line 3. The object ofYanni is to make amide and ester derivatives ofbromfenac which the
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`inventors found to have better stability while having similar anti-inflammatory activity. See for
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`example column 2, lines 23-43.
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`Bromfenac is mentioned in Yanni in Table 1, merely as a reference compound for
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`comparison purposes with the novel amide and ester derivatives of Yanni. It can be seen from
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`the description of the anti-inflammatory tests described in columns 13 and 14 that bromfenac
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`was tested merely in a 0.1% solution of the compound, and not in a pharmaceutical composition.
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`The pharmaceutical compositions disclosed in the Tables of columns 16 and 17 of Yanni
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`are directed to compositions of an "Active Agent" with polysorbate 80 and other components.
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`The "Active Agent" is defined on lines 50-51 of column 16 to mean "one or more compounds of
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`Formula I". The compounds of Formula I are described from the bottom of column 2 to 3. From
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`LUPIN EX1029, Page 2
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`the definition of "Y" in the compounds, it is apparent that these compounds are limited to the
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`amide or ester of bromfenac and do not encompass the bromfenac acid itself.
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`In summary, neither Preparation XV nor the remainder of Yanni disclose a composition
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`ofbromfenac as claimed, or its salt or hydrate, together with polysorbate 80 as contended in the
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`rejection.
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`Moreover, Yanni teach away from using bromfenac as claimed, due to problems with
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`obtaining stable solutions and provoking ocular irritation. See column 1 line 60 to column 2 line
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`3.
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`80.
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`Therefore Yanni do not teach or suggest a composition ofbromfenac with polysorbate
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`Guy is cited for teaching the equivalency of polysorbate 80 and tyloxapol.
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`However Guy is directed to solving the problem of agglomeration of water insoluble
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`steroid compounds such as loteprednol etabonate. See for example column 2, lines 45-65. On the
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`other hand, bromfenac is a nonsteroidal compound.
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`Therefore one skilled in the art would not have been motivated to combine the teachings
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`of Yanni directed to nonsteroidal compositions with Guy directed to steroidal compositions.
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`According to the USTPO guidelines, "[i]t is improper to combine references where the
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`references teach away from their combination." See MPEP § 2145, citing In re Grasselli, 713
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`F.2d 731, 743 (Fed. Cir. 1983); see also McGinley v. Franklin Sports, Inc., 262 F.3d 1339, 1354
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`(Fed.Cir. 2001) ("It is well-established that references which "teach away cannot serve to create
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`a prima facie case of obviousness.") (citations omitted).
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`Moreover, the present inventors have found that tyloxapol is not equivalent to
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`polysorbate 80 when combined with bromfenac.
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`The present inventors have discovered that tyloxapol has an unexpected property in
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`stabilizing an aqueous solution ofbromfenac in comparison with polysorbate 80. Please see the
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`description of Experimental Example 1 and Table 1 on pages 14-16 of the specification.
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`In the Experimental Example, the stability of an aqueous solution ofbromfenac was
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`measured by storing the bromfenac solution with polysorbate 80 (see Comparison Example 1)
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`and, separately, with tyloxapol (see A-02), under conditions of pH 7.0 at 60°C for 4 weeks. The
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`remaining rate % of bromfenac was measured after the test.
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`LUPIN EX1029, Page 3
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`As shown in Table 1, only 51.3% ofbromfenac remained in the aqueous solution when
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`stored with polysorbate 80. In contrast, 73.8% ofbromfenac remained in the aqueous solution
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`when stored with tyloxapol.
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`Thus the present inventors have found that tyloxapol has an unexpected stabilizing effect
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`on an aqueous solution ofbromfenac in comparison to polysorbate 80. Therefore the present
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`inventors have found that tyloxapol and polysorbate 80 are not equivalent compounds. Such
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`unequivalency, and such remarkable effects, could not have been obvious to one skilled in the art
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`from the cited references.
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`For the foregoing reasons, it is respectfully submitted that the teachings of the cited
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`references do not suggest the claimed bromfenac preparation as amended, nor the unexpected
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`properties of the preparation.
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`Claims 49, 56, 60 and 64-68 are rejected under 103 as unpatentable over Yanni, Guy and
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`Gamache.
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`The rejection of these claims is believed to be overcome in view of the foregoing
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`amendments and remarks.
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`Lastly, claims 41-51,53-56,58-60 and 64-68 are provisionally rejected on the ground of
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`non-statutory obviousness-type double patenting as being unpatentable over claims 1-43 of
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`copending application Serial No. 11/755,662.
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`It is believed that all other grounds of rejection have been overcome in view of the instant
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`response. Accordingly, it is respectfully submitted that this provisional ground of rejection
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`should be withdrawn and the application passed on to allowance.
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`LUPIN EX1029, Page 4
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`In summary, it is believed that each ground of rejection set forth in the Official Action
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`has been overcome, and that the application is now in condition for allowance. Accordingly
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`such allowance is solicited.
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`Respectfully submitted,
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`Shirou SAW A et al.
`/Warren M.
`By Cheek/
`Warren M. Cheek
`Registration No. 33,367
`Attorney for Applicants
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`Digitally signed by /Warren M. Cheek/
`DN: cn=/Warren M. Cheek!, o, ou,
`email=wcheek@wenderoth.com, c=US
`Date: 2011.09.06 13:39:04 -04'00'
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`WMC/dlk
`Washington, D.C. 20005-1503
`Telephone (202) 721-8200
`Facsimile (202) 721-8250
`September 6, 2011
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`LUPIN EX1029, Page 5