UNITED STA 1ES p A 1ENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`www.uspto.gov
`
`APPLICATION NO.
`
`FILING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONFIRMATION NO.
`
`13/687,242
`
`11128/2012
`
`ShirouSAWA
`
`2012_5420
`
`1577
`
`02/11/2014
`7590
`513
`WENDEROTH, LIND & PONACK, L.L.P.
`1030 15th Street, N.W.,
`Suite 400 East
`Washington, DC 20005-1503
`
`EXAMINER
`
`SOROUSH, LAYLA
`
`ART UNIT
`
`PAPER NUMBER
`
`1627
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`02/1112014
`
`ELECTRONIC
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
`following e-mail address(es):
`ddalecki @wenderoth.com
`eoa@wenderoth.com
`
`PTOL-90A (Rev. 04/07)
`
`Page 1 of 130
`
`SENJU EXHIBIT 2006
`METRICS v. SENJU
`IPR2014-01041
`
`

`

`Notice of Allowability
`
`Application No.
`
`13/687,242
`Examiner
`
`Applicant(s)
`
`SAWA ET AL.
`Art Unit
`
`LAYLA SOROUSH
`
`1627
`
`-- The MAILING DATE of this communication appears on the cover sheet with the correspondence address-(cid:173)
`All claims being allowable, PROSECUTION ON THE MERITS IS (OR REMAINS) CLOSED in this application. If not included
`herewith (or previously mailed), a Notice of Allowance (PTOL-85) or other appropriate communication will be mailed in due course. THIS
`NOTICE OF ALLOW ABILITY IS NOT A GRANT OF PATENT RIGHTS. This application is subject to withdrawal from issue at the initiative
`of the Office or upon petition by the applicant. See 37 CFR 1.313 and MPEP 1308.
`1. 1:8] This communication is responsive to the amendments made on 10122113.
`2. D An election was made by the applicant in response to a restriction requirement set forth during the interview on __ ; the restriction
`requirement and election have been incorporated into this action.
`3. 1:8] The allowed claim(s) is/are 19-48.
`4. 1:8] Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`b) D Some*
`c) D None
`a) 1:8] All
`of the:
`1. D Certified copies of the priority documents have been received.
`2. 1:8] Certified copies of the priority documents have been received in Application No. 101525.006.
`3. D Copies of the certified copies of the priority documents have been received in this national stage application from the
`International Bureau (PCT Rule 17.2(a)).
`* Certified copies not received: __ .
`
`Applicant has THREE MONTHS FROM THE "MAILING DATE" of this communication to file a reply complying with the requirements
`noted below. Failure to timely comply will result in ABANDONMENT of this application.
`THIS THREE-MONTH PERIOD IS NOT EXTENDABLE.
`5. 0 A SUBSTITUTE OATH OR DECLARATION must be submitted. Note the attached EXAMINER'S AMENDMENT or NOTICE OF
`INFORMAL PATENT APPLICATION (PT0-152) which gives reason(s) why the oath or declaration is deficient.
`6. D CORRECTED DRAWINGS (as "replacement sheets") must be submitted.
`(a) D including changes required by the Notice of Draftsperson's Patent Drawing Review ( PT0-948) attached
`1) D hereto or 2) D to Paper No./Mail Date __ .
`(b) D including changes required by the attached Examiner's Amendment I Comment or in the Office action of
`Paper No./Mail Date __ .
`Identifying indicia such as the application number {see 37 CFR 1.84{c)) should be written on the drawings in the front {not the back) of
`each sheet. Replacement sheet{s) should be labeled as such in the header according to 37 CFR 1.121{d).
`7. 0 DEPOSIT OF and/or INFORMATION about the deposit of BIOLOGICAL MATERIAL must be submitted. Note the
`attached Examiner's comment regarding REQUIREMENT FOR THE DEPOSIT OF BIOLOGICAL MATERIAL.
`
`Attachment(s)
`1. D Notice of References Cited (PT0-892)
`2. D Notice of Draftperson's Patent Drawing Review (PT0-948)
`
`3. [8llnformation Disclosure Statements (PTO/SB/08),
`Paper No./Mail Date 1/15/14 1/17114
`4. D Examiner's Comment Regarding Requirement for Deposit
`of Biological Material
`
`5. D Notice of Informal Patent Application
`6. D Interview Summary (PT0-413),
`Paper No./Mail Date __ .
`7. 1:8] Examiner's Amendment/Comment
`
`8. 1:8] Examiner's Statement of Reasons for Allowance
`9. D Other __ .
`
`U.S. Patent and Trademark Off1ce
`PTOL-37 (Rev. 03·11)
`
`Notice of Allowability
`
`Part of Paper No./Mail Date 20140206
`
`Page 2 of 130
`
`

`

`Application/Control Number: 13/687,242
`Art Unit: 1627
`
`Page 2
`
`The present application is being examined under the pre-AlA first to invent
`
`provisions.
`
`Acknowledgement of Receipt
`
`Applicant's response filed on 10/22/2013 to the Office Action mailed on
`
`08/01/2013 is acknowledged.
`
`Claim Status
`
`Claims 19-48 are pending.
`
`Claims 19-48 are allowed.
`
`Withdrawn Rejections
`
`The rejection of claims 44-48 under 35 U.S. C. 112(b) or 35 U.S. C. 112 (pre-AlA),
`
`second paragraph is withdrawn in view of the amendments made to the claims.
`
`The rejection of claims 19, 21-24, 26, 28-30, 32, 34-36, 38, 40-42, and 44-48
`
`under 35 U.S.C. 1 03(a) as being unpatentable over Gamache, et al. (WO 01/15677 A2;
`
`03/2001) is withdrawn in view of the amendments made to the claims.
`
`The rejection of claims 20, 27, 33, and 39 under 35 U.S.C. 1 03(a) as being
`
`unpatentable over Gamache, et al. (WO 01/15677 A2; 03/2001 ), as applied to claims
`
`19, 21-24, 26, 28-30, 32, 34-36, 38, 40-42, and 44-48 and further in view of Desai, et al.
`
`(5558876) is withdrawn in view of the amendments made to the claims.
`
`The rejection of claims 25, 31, 37, and 43 under 35 U.S.C. 1 03(a) as being
`
`unpatentable over Gamache, et al. (WO 01/15677 A2; 03/2001 ), as applied to claims
`
`19, 21-24, 26, 28-30, 32, 34-36, 38, 40-42, and 44-48 and further in view of Ogawa, et
`
`Page 3 of 130
`
`

`

`Application/Control Number: 13/687,242
`Art Unit: 1627
`
`Page 3
`
`al. (US 4910225 A) and De Bruiju et al. (US 6162393 A) is withdrawn in view of the
`
`amendments made to the claims.
`
`The Double Patenting rejections over U.S. Patent No. 7829544, U.S. Patent No.
`
`8129431, copending Application No. 13353653 is withdrawn in view of the TO's filed on
`
`11/2/13.
`
`The Double Patenting rejections over copending Application No. 11755662 is
`
`withdrawn in view of the abandonment of the case.
`
`EXAMINER'S AMENDMENT
`
`An examiner's amendment to the record appears below. Should the changes
`
`and/or additions be unacceptable to applicant, an amendment may be filed as provided
`
`by 37 CFR 1.312. To ensure consideration of such an amendment, it MUST be
`
`submitted no later than the payment of the issue fee.
`
`Authorization for this examiner's amendment was given in a telephone interview
`
`with Warren M. Cheek on 1/8/14.
`
`The application has been amended as follows:
`
`In claim 26 line 5 after hydrate; insert "the first component is the sole
`
`pharmaceutical active ingredient contained in the preparation;"
`
`In claim 27 lines 2-3 after salt delete-, and wherein the first component is the
`
`sole pharmaceutical active ingredient contained in the preparation -- .
`
`Page 4 of 130
`
`

`

`Application/Control Number: 13/687,242
`Art Unit: 1627
`
`Page 4
`
`Reasons for Allowance
`
`The following is an examiner's statement of reasons for allowance:
`
`The composition as claimed are found to be patentable over the prior art
`
`because the prior art does not teach or fairly suggest a stable aqueous liquid
`
`preparation comprising: (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 and is present in said liquid preparation in an amount sufficient
`
`to stabilize said first component; and wherein said stable liquid preparation is formulated
`
`for ophthalmic administration.
`
`The closest prior arts of record, namely Chen et al. (US 6383471 ), teach a
`
`pharmaceutical composition including a hydrophobic therapeutic agent having at least
`
`one ionizable functional group, and a carrier. The carrier includes an ionizing agent
`
`capable of ionizing the functional group, a surfactant, and optionally solubilizers,
`
`triglycerides, and neutralizing agents (abstract). The reference teaches a hydrophobic
`
`therapeutic agent to include bromfenac (2-amino-3-(4-bromobenzoyl)phenalyacetic
`
`acid)(see claim 4). The hydrophobic therapeutic agent is used in less than about 1% by
`
`weight, and typically less than about 0.1% or 0.01% by weight (see col 4 lines 58-60)
`
`(renders obvious the limitation of claims 8 and 24). The reference further teaches
`
`surfactants inclusive of polyethylene glycol fatty acid esters and additionally teaches
`
`Page 5 of 130
`
`

`

`Application/Control Number: 13/687,242
`Art Unit: 1627
`
`Page 5
`
`polyethylene glycol fatty acid monoesters such as peg-15 stearate, etc (see claims 21-
`
`22 24 and 27). The surfactants are selected from the group consisting of alcohols;
`
`polyoxyethylene alkylethers; fatty acids; glycerol fatty acid esters; acetylated glycerol
`
`fatty acid esters; lower alcohol fatty acids esters; polyethylene glycol fatty acids esters;
`
`polyethylene glycol glycerol fatty acid esters; polypropylene glycol fatty acid esters;
`
`polyoxyethylene glycerides; lactic acid derivatives of mono/diglycerides; propylene
`
`glycol diglycerides; sorbitan fatty acid esters; polyoxyethylene sorbitan fatty acid esters;
`
`polyoxyethylene-polyoxypropylene block copolymers; transesterified vegetable oils;
`
`sterols; sterol derivatives; sugar esters; sugar ethers; sucroglycerides; polyoxyethylene
`
`vegetable oils; and polyoxyethylene hydrogenated vegetable oils. The pharmaceutical
`
`compositions of the present invention can be provided in the form of a solution
`
`preconcentrate; i.e., a composition as described above, and intended to be dispersed
`
`with water, either prior to administration, in the form of a drink, or dispersed in vivo (col
`
`34 lines 63-68) (reads on an aqueous liquid preparation). The reference also teaches
`
`preservatives (see claim 64). Although formulations specifically suited to oral
`
`administration are presently preferred, the compositions of the present invention can
`
`also be formulated for topical, transdermal, ocular, pulmonary, vaginal, rectal,
`
`transmucosal or parenteral administration (col 35 lines 9-20). Chen et al. further
`
`teaches components that can be incorporated into the composition include inorganic
`
`acids inclusive of boric acid (col 46, line 6), solubilizer such as polyvinylpyrrolidone
`
`(claim 49), exemplifications of carriers comprising Edetate Disodium (col 4 table 20
`
`formulations 65 and 66), and ionizing agents that deprotonate the acidic functional
`
`Page 6 of 130
`
`

`

`Application/Control Number: 13/687,242
`Art Unit: 1627
`
`Page 6
`
`groups of the therapeutic agent are pharmaceutically acceptable organic or inorganic
`
`bases, inclusive of sodium hydroxide (col 11 lines 12-13) (reads on the limitations of
`
`claim 22).
`
`However, Applicant presents excellent effects are clearly demonstrated by
`
`Experiments 1 to 3 of the present specification. Experiment 1 --Stability of sodium 2-
`
`amino-3-(4-bromobenzoyl)phenyl acetate was evaluated. Namely, two eye drops of
`
`sodium 2-amino-3-(4-bromobenzoyl) phenylacetate comprising the components as
`
`shown in Table 1 were prepared, filled respectively into a polypropylene container and
`
`subjected to a stability test at 60°C for 4 weeks. As is apparent from Table 1, the
`
`stability test was carried out under the conditions of pH 7.0 at 60°C for 4 weeks. Table 1
`
`clearly shows that sodium 2-amino-3- (4-bromobenzoyl)phenylacetate in polyoxyl 40
`
`stearate-containing preparation was more stable than that in polysorbate 80- containing
`
`preparation. As is apparent from Table 2, the remaining rate of sodium 2-amino-3-(4-
`
`bromobenzoyl)phenylacetate in the compositions A-07 and A-08 containing 0.02 w/v %
`and 0.05 w/v % of polyoxyl 40 stearate is not less than 90 % after storage at 60 oc for 4
`
`weeks. Table 2 clearly shows that the compositions containing 0.02 w/v% and 0.05 w/v
`
`%of polyoxyl 40 stearate have sufficient stability for eye drops. The arguments are
`
`persuasive.
`
`The composition as claimed are found to be patentable over the prior art
`
`because the prior art does not teach or fairly suggest a stable aqueous liquid
`
`preparation comprising: (a) a first component; and (b) a second component; wherein the
`
`first component is 2-amino-3-(4- bromobenzoyl)phenylacetic acid or a
`
`Page 7 of 130
`
`

`

`Application/Control Number: 13/687,242
`Art Unit: 1627
`
`Page 7
`
`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 and is present in said liquid preparation in an amount sufficient
`
`to stabilize said first component; and wherein said stable liquid preparation is formulated
`
`for ophthalmic administration.
`
`Any comments considered necessary by applicant must be submitted no later
`
`than the payment of the issue fee and, to avoid processing delays, should preferably
`
`accompany the issue fee. Such submissions should be clearly labeled "Comments on
`
`Statement of Reasons for Allowance."
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to LAYLA SOROUSH whose telephone number is
`
`(571 )272-5008. The examiner can normally be reached on 8:30a.m.-5:00p.m ..
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
`
`supervisor, Sreenivasan Padmanabhan can be reached on (571 )272-0629. The fax
`
`phone number for the organization where this application or proceeding is assigned is
`
`571-273-8300.
`
`Information regarding the status of an application may be obtained from the
`
`Patent Application Information Retrieval (PAIR) system. Status information for
`
`published applications may be obtained from either Private PAIR or Public PAIR.
`
`Status information for unpublished applications is available through Private PAIR only.
`
`For more information about the PAIR system, see http://pair-direct.uspto.gov. Should
`
`Page 8 of 130
`
`

`

`Application/Control Number: 13/687,242
`Art Unit: 1627
`
`Page 8
`
`you have questions on access to the Private PAIR system, contact the Electronic
`
`Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a
`
`USPTO Customer Service Representative or access to the automated information
`
`system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
`
`/Layla Soroush/
`
`Examiner, Art Unit 1627
`
`Page 9 of 130
`
`

`

`Sheet 1 of 1
`
`INFORMATION DISCLOSURE STATEMENT
`
`FORM PTO/SB/08 A&B (modified)
`
`U.S. DEPARTMENT OF COMMERCE
`PATENT AND TRADEMARK OFFICE
`
`LIST OF REFERENCES CITED BY APPLICANT(S)
`(Use several sheets if necessary)
`
`Date Submitted to PTO: January 15, 2014
`
`ATTY DOCKET NO.
`2012-5420
`
`FIRST NAMED INVENTOR
`Shirou SAWA
`
`FILING DATE
`November 28, 2012
`
`U.S. PATENT DOCUMENTS
`
`SERIAL NO.
`13/687,242
`
`GROUP
`1627
`
`*EXAMINER
`INITIAL
`
`DOCUMENT
`NUMBER
`
`DATE
`
`NAME
`
`CLASS
`
`SUBCLASS
`
`FILING DATE
`IF APPROPRIATE
`
`/L.S./
`/L.S./
`
`/L.S./
`
`AA
`
`4,910,225
`
`3/1990
`
`Ogawa et al.
`
`6,274,609
`
`8/2001
`
`Y asueda et al.
`
`DOCUMENT
`NUMBER
`
`DATE
`
`COUNTRY
`
`CLASS
`
`SUBCLASS
`
`TRANSLATION
`
`YES
`
`NO
`
`FOREIGN PATENT DOCUMENTS
`
`0 306 984
`
`3/1989
`
`EP
`
`OTHER DOCUMENT(S) (Including Author, Title, Date, Pertinent Pages, Etc.)
`
`H. Scott et al., "Comparing the Surface Chemical Properties and the Effect of Salts on the Cloud Point of a Conventional
`Nonionic Surfactant, Octoxynol 9 (Triton X-1 00), and of its Oligomer, Tyloxapol (Triton WR-1339)", Journal of Colloid and
`Interface Science, Vol. 205, pp. 496-502, 1998.
`
`AB
`
`AC
`
`AD
`
`AE
`
`AF
`
`AG
`
`AH
`
`AI
`
`BA
`
`BB
`
`BC
`
`BD
`
`BE
`
`CA
`
`CB
`
`cc
`
`CD
`
`EXAMINER
`
`/Layla Soroushi
`
`I DATE CONSIDERED
`
`*Examiner: initial if reference considered, whether or not citation is in conformance with MPEP 609; draw line through
`citation if not in conformance and not considered. Include copy of this form with next communication to applicant.
`
`Page 10 of 130
`
`

`

`Sheet 1 of 1
`
`INFORMATION DISCLOSURE STATEMENT
`
`FORM PTO/SB/08 A&B (modified)
`
`U.S. DEPARTMENT OF COMMERCE
`PATENT AND TRADEMARK OFFICE
`
`LIST OF REFERENCES CITED BY APPLICANT(S)
`(Use several sheets if necessary)
`
`Date Submitted to PTO: January 17, 2014
`
`ATTY DOCKET NO.
`2012-5420
`
`FIRST NAMED INVENTOR
`Shirou SAWA
`
`FILING DATE
`November 28, 2012
`
`U.S. PATENT DOCUMENTS
`
`SERIAL NO.
`13/687,242
`
`GROUP
`1627
`
`*EXAMINER
`INITIAL
`/L.S./
`
`il.S.i
`
`/L.S./
`
`DOCUMENT
`NUMBER
`
`DATE
`
`NAME
`
`CLASS
`
`SUBCLASS
`
`FILING DATE
`IF APPROPRIATE
`
`AA
`
`4,910,225
`
`3/1990
`
`Ogawaet al.
`
`6,274,609
`
`8/2001
`
`Y asueda et al.
`
`DOCUMENT
`NUMBER
`
`DATE
`
`COUNTRY
`
`CLASS
`
`SUBCLASS
`
`TRANSLATION
`
`YES
`
`NO
`
`FOREIGN PATENT DOCUMENTS
`
`0 306 984
`
`3/1989
`
`EP
`
`OTHER DOCUMENT(S) (Including Author, Title, Date, Pertinent Pages, Etc.)
`
`H. Scott et al., "Comparing the Surface Chemical Properties and the Effect of Salts on the Cloud Point of a Conventional
`Nonionic Surfactant, Octoxynol 9 (Triton X-1 00), and of its Oligomer, Tyloxapol (Triton WR-1339)", Journal of Colloid and
`Interface Science, Vol. 205, pp. 496-502, 1998.
`
`AB
`
`AC
`
`AD
`
`AE
`
`AF
`
`AG
`
`AH
`
`AI
`
`BA
`
`BB
`
`BC
`
`BD
`
`BE
`
`CA
`
`CB
`
`cc
`
`CD
`
`EXAMINER
`
`/Layla Soroushi
`
`I DATE CONSIDERED
`
`*Examiner: initial if reference considered, whether or not citation is in conformance with MPEP 609; draw line through
`citation if not in conformance and not considered. Include copy of this form with next communication to applicant.
`
`Page 11 of 130
`
`

`

`Sheet 1 of 1
`
`INFORMATION DISCLOSURE STATEMENT
`
`FORM PTO/SB/08 A&B (modified)
`
`U.S. DEPARTMENT OF COMMERCE
`PATENT AND TRADEMARK OFFICE
`
`LIST OF REFERENCES CITED BY APPLICANT(S)
`(Use several sheets if necessary)
`
`Date Submitted to PTO: January 17, 2014
`
`ATTY DOCKET NO.
`2012-5420
`
`FIRST NAMED INVENTOR
`Shirou SAWA
`
`FILING DATE
`November 28, 2012
`
`U.S. PATENT DOCUMENTS
`
`SERIAL NO.
`13/687,242
`
`GROUP
`1627
`
`*EXAMINER
`INITIAL
`
`DOCUMENT
`NUMBER
`
`DATE
`
`NAME
`
`CLASS
`
`SUBCLASS
`
`FILING DATE
`IF APPROPRIATE
`
`AA
`
`4,910,225
`
`3/1990
`
`Ogawaet al.
`
`6,274,609
`
`8/2001
`
`Y asueda et al.
`
`DOCUMENT
`NUMBER
`
`DATE
`
`COUNTRY
`
`CLASS
`
`SUBCLASS
`
`TRANSLATION
`
`YES
`
`NO
`
`FOREIGN PATENT DOCUMENTS
`
`0 306 984
`
`3/1989
`
`EP
`
`OTHER DOCUMENT(S) (Including Author, Title, Date, Pertinent Pages, Etc.)
`
`H. Scott et al., "Comparing the Surface Chemical Properties and the Effect of Salts on the Cloud Point of a Conventional
`Nonionic Surfactant, Octoxynol 9 (Triton X-1 00), and of its Oligomer, Tyloxapol (Triton WR-1339)", Journal of Colloid and
`Interface Science, Vol. 205, pp. 496-502, 1998.
`
`AB
`
`AC
`
`AD
`
`AE
`
`AF
`
`AG
`
`AH
`
`AI
`
`BA
`
`BB
`
`BC
`
`BD
`
`BE
`
`CA
`
`CB
`
`cc
`
`CD
`
`EXAMINER
`
`I DATE CONSIDERED
`
`*Examiner: initial if reference considered, whether or not citation is in conformance with MPEP 609; draw line through
`citation if not in conformance and not considered. Include copy of this form with next communication to applicant.
`
`Page 12 of 130
`
`

`

`Examiner-Initiated Interview Summary
`
`Application No.
`
`13/687,242
`
`Examiner
`
`LA YLA SOROUSH
`
`Applicant(s)
`
`SAWA ET AL.
`
`Art Unit
`
`1627
`
`All participants (applicant, applicant's representative, PTO personnel):
`
`(1) LA YLA SOROUSH.
`
`(2) Warren Cheek.
`
`(3) __ .
`
`(4) __ .
`
`Date of Interview: 118114.
`Type: ~ Telephonic 0 Video Conference
`0 Personal [copy given to: 0 applicant
`Exhibit shown or demonstration conducted: 0 Yes
`If Yes, brief description: __ .
`
`0 applicant's representative]
`
`0No.
`
`Issues Discussed 0101 0112 0102 0103 OOthers
`(For each of the checked box( es) above, please describe below the issue and detailed description of the discussion)
`
`Claim(s) discussed: __ .
`
`Identification of prior art discussed: __ .
`
`Substance of Interview
`(For each issue discussed, provide a detailed description and indicate if agreement was reached. Some topics may include: identification or clarification of a
`reference or a portion thereof, claim interpretation, proposed amendments, arguments of any applied references etc ... )
`
`In the interest of compact prosecution, a proposal was made to the Applicant to overcome the remaining issues and proceed to
`allowance. In the interest of compact prosecution, a proposal was made to the Applicant to overcome the remaining issues and
`proceed to allowance. Applicant agreed and gave the Examiner authorization to make the appropriate claim amendments in an
`Examiner's Amendment .
`
`Applicant recordation instructions: It is not necessary for applicant to provide a separate record of the substance of interview.
`
`Examiner recordation instructions: Examiners must summarize the substance of any interview of record. A complete and proper recordation of
`the substance of an interview should include the items listed in MPEP 713.04 for complete and proper recordation including the identification of the
`general thrust of each argument or issue discussed, a general indication of any other pertinent matters discussed regarding patentability and the
`general results or outcome of the interview, to include an indication as to whether or not agreement was reached on the issues raised.
`0 Attachment
`/Layla Soroush/
`Examiner, Art Unit 1627
`
`U.S. Patent and Trademark Off1ce
`PTOL·413B (Rev. 8/11/2010)
`
`Interview Summary
`
`Paper No. 20140107
`
`Page 13 of 130
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`

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`Sheet 1 of 1
`
`INFORMATION DISCLOSURE STATEMENT
`
`FORM PTO/SB/08 A&B (modified)
`
`U.S. DEPARTMENT OF COMMERCE
`PATENT AND TRADEMARK OFFICE
`
`LIST OF REFERENCES CITED BY APPLICANT(S)
`(Use several sheets if necessary)
`
`Date Submitted to PTO: January 15, 2014
`
`ATTY DOCKET NO.
`2012-5420
`
`FIRST NAMED INVENTOR
`Shirou SAWA
`
`FILING DATE
`November 28, 2012
`
`U.S. PATENT DOCUMENTS
`
`SERIAL NO.
`13/687,242
`
`GROUP
`1627
`
`*EXAMINER
`INITIAL
`
`DOCUMENT
`NUMBER
`
`DATE
`
`NAME
`
`CLASS
`
`SUBCLASS
`
`FILING DATE
`IF APPROPRIATE
`
`AA
`
`4,910,225
`
`3/1990
`
`Ogawa et al.
`
`6,274,609
`
`8/2001
`
`Y asueda et al.
`
`DOCUMENT
`NUMBER
`
`DATE
`
`COUNTRY
`
`CLASS
`
`SUBCLASS
`
`TRANSLATION
`
`YES
`
`NO
`
`FOREIGN PATENT DOCUMENTS
`
`0 306 984
`
`3/1989
`
`EP
`
`OTHER DOCUMENT(S) (Including Author, Title, Date, Pertinent Pages, Etc.)
`
`H. Scott et al., "Comparing the Surface Chemical Properties and the Effect of Salts on the Cloud Point of a Conventional
`Nonionic Surfactant, Octoxynol 9 (Triton X-1 00), and of its Oligomer, Tyloxapol (Triton WR-1339)", Journal of Colloid and
`Interface Science, Vol. 205, pp. 496-502, 1998.
`
`AB
`
`AC
`
`AD
`
`AE
`
`AF
`
`AG
`
`AH
`
`AI
`
`BA
`
`BB
`
`BC
`
`BD
`
`BE
`
`CA
`
`CB
`
`cc
`
`CD
`
`EXAMINER
`
`I DATE CONSIDERED
`
`*Examiner: initial if reference considered, whether or not citation is in conformance with MPEP 609; draw line through
`citation if not in conformance and not considered. Include copy of this form with next communication to applicant.
`
`Page 14 of 130
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`

`

`Europaisches Patentamt
`
`European Patent Office
`
`Office europeen des brevets
`
`® Publication number:
`
`0 306 984
`A1
`
`@
`
`EUROPEAN PATENT APPLICATION
`
`@ Application number: 88114804.3
`
`@) Int. Cl.4: A61 K 9/06 , A61 K 47/00
`
`@ Date of filing: 09.09.88
`
`@) Priority: 11.09.87 US 96173
`
`@ Date of publication of application:
`15.03.89 Bulletin 89/11
`
`@) Designated Contracting States:
`AT BE CH DE FR GB IT Ll LU NL SE
`
`@ Applicant: SYNTEX (U.S.A.) INC.
`3401 Hillview Avenue
`PaiQ Alto, California 94304(US)
`
`@ Inventor: Roger Fu, Cherng-Chyi
`14050 Shadow Oaks Way
`Saratoga California 95070(US)
`Inventor: Udgate, Deborah M.
`325 Arboleda Drive
`Los Altos California 94022(US)
`® Representative: Barz, Peter, Dr. et al
`Patentanwalte Dr. V. Schmied-Kowarzik
`Dipl.-lng. G. Dannenberg Dr. P. Weinhold Dr.
`D. Gudel Dipl.-lng. S. Schubert Dr. P. Barz
`Siegfriedstrasse 8
`D-8000 MUnchen 40(DE)
`
`@ Preservative system forophthalmic formulations.
`
`@ Stable, clear, antimicrobially effective, ophthalmic formulations include an ophthalmologically effective
`amount of a drug, especially a -COOH group-containing drug or a NSAID, and a preservative system formed of a
`quaternary ammonium preservative and a nonionic surfactant, all in an aqueous vehicle. These formulations are
`useful for treating diseases that are either caused by, associated with or accompanied by inflammatory
`processes, including, among others, glaucoma, cystoid macular edema, uveitis, diabetic retinopathy, and
`conjunctivitis, or any trauma caused by eye surgery or eye injury.
`
`( ..
`
`Xerox Copy Centre
`
`Page 15 of 130
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`

`

`EP 0 306 984 A1
`
`PRESERVATIVE SYSTEM FOR OPHTHALMIC FORMULATIONS
`
`5
`
`10
`
`25
`
`The present invention relates to improved ophthalmic formulations, particularly to ophthalmic formula(cid:173)
`tions for anti-inflammatory drugs, and specifically to an improved preservative system for ophthalmic
`formulations of carboxyl ( .. ·COOH .. ) group-containing drugs, especially non-steroidal anti-inflammatory
`drugs ( .. NSAIDs").
`The invention also relates to methods of using these formulations for treating diseases that are either
`caused by, associated with or accompanied by inflammatory processes, including, among others. glau(cid:173)
`coma, cystoid macular edema, uveitis, diabetic retinopathy, and conjunctivitis, or any trauma caused by eye
`surgery or eye injury.
`The topical use of NSAIDs, particularly pyrrolo pyrroles, in the treatment of ophthalmic diseases was
`first taught in U.S. Patent No. 4.454,151, where NSAID compounds (such as those described in U.S. Patents
`4,089,969; 4,232,038; 4,087,539 and 4,097,579) were exemplified in formulation with NaH2P04•H20,
`Na2HP04•H20, NaCI, benzalkonium chloride ("BAG .. ) and sterilized water. While the formulations described
`in the '151 patent were efficacious, an insoluble complex was found to form between the NSAID and the
`15 BAG. The formulations became cloudy or turbid and did not, therefore, have the stability desired for shelf
`life in commercial applications. A reasonable minimum shelf life (that is, the time during which a solution
`remains clear and retains its pharmaceutical activity) is at least about one year. representing sufficient time
`to package, ship, and store a formulation without having to replace expired stock too frequently. The
`solutions of the present invention have shown a shelf life of at least one year. Thus, the present invention
`20 entails an improvement over the formulations described in the '151 patent.
`In general, an opthalmic formulation contains an active compound and various ophthalmologically
`acceptable excipients, in the form of a solution, an ointment, a suspension, etc. An excipient is ophthal(cid:173)
`mologically acceptable if it is non-irritating to the eye and if its active ingredient penetrates the blood(cid:173)
`aqueous barrier and/or diffuses through the various ocular substructures to the site where it is pharmaco-
`logically active. The excipients can include a tonicifier, a preservative, a surfactant, a buffering system. a
`chelating agent, a viscosity agent as well as other stabilizing agents. Ophthalmic formulations must be
`sterile, and if intended for multiple dosing regimens, must be preserved with an effective anti-microbial
`agent.
`Organo-mercurials (e.g., thimerosal, phenylmercuric acetate and phenylmercuric nitrate) have been
`30 used extensively as the preservative in ophthalmic solutions. These compounds, however, pose difficulties
`due to potential mercury toxicity as well as poor chemical stability. Benzalkonium chloride, a quaternary
`ammonium compound, has been widely used in ophthalmic solutions, and is considered to be the
`preservative of choice. However, BAG has typically been considered to be incompatible with anionic drugs
`(e.g., salicylates or nitrates, etc.). forming insoluble complexes which cause the solution to become cloudy
`35 or turbid. Such a complex between the anionic drug and benzalkonium chloride can cause a decrease in
`the pharmaceutical activity of the anionic drug.
`Many NSAIDs (such as ketorolac, indomethacin, flurbiprofen and diclofenac) are being developed for
`ocular use because of their activity as anti-inflammatory agents including their ability to prevent cystoid
`macular edema.
`In the past, as in the case with other ophthalmic drugs that contain a -GOOH group, antiinflammatory
`solutions of NSAIDs for occular use have proven to be incompatible with quaternary ammonium compounds
`such as BAG. This incompatibility is due to the fact that the -GOOH group can form a complex with the
`quaternary ammonium compounds, rendering the preservative less available to serve its function. and
`reducing the activity of the active ingredient. Indomethacin ophthalmic formulations have been prepared,
`45 however, these are suspensions, not solutions. Ocufen Ophthalmic solution, an NSAID (flurbiprofen)
`approved by the FDA for ophthalmic use, incorporates thimerosal (with EDT A) as its preservative system. In
`U.S. patent 4.454,151 there is a disclosure of an ophthalmic formulation using ketorolac, benzalkonium
`chloride (as the preservative) and polysorbate 80, however the solution became cloudy or turbid after a
`short period of time.
`It has remained desired to provide a stable, clear. antimicrobially effective ophthalmic formulation with a
`prolonged shelf life for -GOOH group containing ophthalmic drugs, especially NSAIDs. using BAG as the
`preservative.
`It has now been discovered that stable, clear and antimicrobially effective. NSAID-containing ophthalmic
`formulations can be prepared which include a quaternary ammonium preservative. These solutions have an
`improved shelf life, exhibiting no cloudiness or turbidity over extended periods.
`
`40
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`so
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`2
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`Page 16 of 130
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`EP 0 306 984 A1
`
`10
`
`In one aspect of the invention, these compositions include an ophthalmologically effective amount of a
`NSAID, a quaternary ammonium preservative and a stabilizing amount of an ethoxylated octylphenol as a
`nonionic surfactant, all in an aqueous vehicle.
`Another aspect is an ophthalmic composition including an ophthalmologically effective amount of a
`5 NSAID, a quaternary ammonium preservative and a stabilizing amount of an ethoxylated octylphenol as a
`nonionic surfactant.
`Another aspect is an ophthalmic composition including an ophthalmologically effective amount of a
`NSAID, benzalkonium chloride as a preservative and a stabilizing amount of an ethoxylated octylphenol as a
`nonionic surfactant.
`Another aspect is an ophthalmic composition including an ophthalmologically effective amount of a
`NSAID, benzalkonium chloride as a preservative and a stabilizing amount of Octoxynol 40 as a nonionic
`surfactant.
`Another aspect is an ophthalmic composition including an ophthalmologically effective amount of
`ketorolac or an isomer, an ester, or a pharmaceutically acceptable salt thereof, benzalkonium chloride as a
`15 preservative and a stabilizing amount of Octoxynol 40 as a nonionic surfactant.
`In another aspect of the invention, methods for treating ophthalmic diseases in mammals using the
`ophthalmic pharmaceutical formulations of the invention are also disclosed. These diseases are those that
`are either caused by, associated with or accompanied by inflammatory processes, including, among others,
`glaucoma, cystoid macular edema, uveitis, diabetic retinopathy and conjunctivitis, or any trauma caused by
`20 eye surgery or eye injury.
`
`Definitions
`
`As used herein, the term "NSAID" means an ophthalmologically acceptable non-steroidal anti-inflam-
`matory drug. The NSAID's include, for example, flurbiprofen, ketorolac, diclofenac, indomethacin, and the
`isomers, esters, and pharmaceutically acceptable salts thereof.
`As used herein, the term "q.s." means adding a quantity sufficient to achieve a state function, e.g., to
`bring a solution to the desired volume (i.e., 1 00% ).
`As used 'herein, the term "treatment" or "treating" means any treatment of a disease in a mammal,
`including:
`(i) preventing the disease, that is, causing the clinical symptoms of the disease not to develop;
`(ii) inhibiting the disease, that is, arresting the development of clinical symptoms; and/or
`(iii) relieving the disease.-