Applicentist I Application No.
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`103502.685
`GOVIND ET AL.
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`Examiner
`Office Action Summary
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`Alton N. Pryor
`- The MAIUNG DA TE of this communication appears on the cover sheet with the correspondence address -
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`Period for Reply
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE §_MONTH(S) OR THIRTY (30) DAYS,
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`WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.
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`- Extensions of time may be available under the provisions of 3? CFR 1.136(3).
`In no event however. may a reply be timely tiled
`3116!‘ 5|?‘ (5) MONTHS from the mailing date ol this communication.
`it hit) period for reply is specified above. the rnaxirnum statutory period will apply and will expire SIX (6) MONTHS from the mailing date at this communication.
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`- Failure to reply within the set or extended period tor reply will, by statute. cause the application to become ABANDONED (35 us. C. § 133).
`Any reply received by the Dffice later than three months after the mailing date of this communication. even it timely tiled, may reduce any
`earned patent tenn adjustment. See 3? CFR 1.?0-tilt).
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`1)E_ Responsive to communication(s) filed on 21' August 2007.
`2a)El This action is FINAL.
`2b) This action is non-final.
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`3)I:I Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
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`closed in accordance with the practice under Ex parte Quayle, 1935 CD. 11, 453 (3.6. 213.
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`Status
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`Disposition of Claims
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`40% Claims) 1'-3 5-9.12-24 islare pending in the application.
`4a) Of the above c|aim(s) __ isiare withdrawn from consideration.
`5)|:I _Claim(s) __ isiare allowed.
`6)E Claim{s) 1-3 5-9.12-24 isiare rejected.
`?)I:l Claim(s) __ islare objected to.
`8)D Clairn(s) __ are subject to restriction andtor election requirement.
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`Application Papers
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`9}|:l The specification is objected to by the Examiner.
`10)Ij The drawing(s) filed on __ isiarez a)l:l acceptedpr b)I:| objected to by the Examiner.
`Applicant may not request that any objection to the dravving(s) be held in abeyance. See 3?‘ CFR 1.85(a).
`Replacement drawing sheetts) including the correction is required if the drawing(s) is objected to. See 3'.’ CFR 1.121(d).
`11)Ij The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO-152.
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`Priority under 35 U.S.C. § 119
`12)I:| Acknowledgment is made of a claim for ‘foreign priority under 35 U.S.C. § 119(a}-(d) or (f).
`a)Cl All
`b)I:| Some ' c)|:l None of:
`1.|___l Certified copies of the priority documents have been received.
`2.E| Certified copies of the priority documents have been received in Application No.
`3.l:I 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)).
`* See the attached detailed Office action for a list of the certified copies not received.
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`
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`Attachrnenttsj
`4) El Interview Summary (PTO-413)
`1) E] Notice of References Cited (PTO-B92}
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`Paper Notsllltlail Dale.
`2) D Notice of Draflspersonb Patent Drawing Review (PTO-943)
`5) El Notice of Informal Patent Application
`3) El information Disclosure Statement(s) (l='rorseros)
`at El Other:
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`Paper No(s)iMai| Date
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`u.s. Patent and Trademark Office
`PTOL-326 (Rev. 03-06]
`I
`Office Actlonsfiufnrnary
`Part of Paper Noflvlail Date 20071111
`Complex Ex. 1002, part 2 of 2
`Complex Ex. 1002, part 2 of 2
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`301
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`Applicationlcontrol Number: 10l502,635
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`Page.2
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`Art Unit: 1616
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`DETAILED ACTION
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`Claim Rejections - 35 USC § 112
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`The following is a quotation of the second paragraph of 35 U.S.C. 112:
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`-
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`The Specification shall conclude with one or more claims particularly pointing out and distinctly
`claiming the subject matter which the applicant regards as his invention.
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`Claims 1-3.5-9.12-24 are rejected under 35 U.S.C. 112, second paragraph, as
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`being indefinite for failing to particularly point out and distinctly claim the subject matter
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`which applicant regards as the invention.
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`_
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`Claims 1-3,5-9.12-24 are rejected because of abbreviations (PVP. HFA 22?,
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`PEG, etc.). Replace abbreviations with terms.
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`The following is a quotation of the first paragraph of 35 U.S.C. 112:
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`The specification shall contain a written description of the invention, and of the manner and process of
`making and using it. in such full, clear, concise. and exact terms as to enable any person skilled in the
`art to which it pertains. or with which it is most neany connected. to make and use the same and shall
`set forth the best mode contemplated by the inventor of carrying out his invention.
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`Claims 1—3,5-9,12-16 are rejected under 35 U.S.C. 112, first paragraph, as failing
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`to comply with the written description requirement. The c|aim(s) contains subject matter
`which was not described in the specification in such'a way as to reasonably convey to
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`one skilled in the relevant art that the inventor(s), at the time the application was filed,
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`had possession of the claimed invention. Claims reciting 2 mg/ml and 4 mg/ml
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`budesonide set forth new matter issues.
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`_ Declarations
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`Declarations provide unexpected stability results for compositions 0.001% wlw to
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`0.01% wlw budesonide.
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`302
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`302
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`

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`Applicationlcontrol Number: 10l502.685
`Art Unit: 1616
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`-
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`Page 3
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`Telephonic Inquiry
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`Any inquiry concerning this communication or earlier communications from the
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`examiner should be directed to Alton N. Pryor whose telephone number is 571-272-
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`0621. The examiner can normally be reached on 8:00 a.m. - 4:30 p.m..
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`'
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`If attempts to reach the examiner by telephone are unsuccessful. the examiner's
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`supervisor, Johann Richter can be reached on 571-272-0646. The fax phone number
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`for_the organization where this application or proceeding is assigned is 571-273-8300.
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`Information regarding the status of an application may be obtained from the
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`Patent Application Information Retrieval (PAIR) system. Status information for
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`published applications may be obtained from either Private PAIR or Public PAIR.
`Status infonnation for unpublished applications is available through Private PAIR only.
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`For more infonnation about the PAIR system, see httpzllpair-direct.uspto.gov. Should
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`you have questions on access to the Private PAIR system. contact the Electronic
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`Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a
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`USPTO Customer Service Representative or access to the automated information
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`system, call 800-736-9199 (IN USA OR CANADA) or 571-272-1000.
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`I4-
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`Alton Pryor
`Primary Examiner
`AU 1616
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`303
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`303
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`Index of Claims
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`Applicationlcontrol No.
`
`10!502.685
`Examiner
`
`AppIicant{s)!Patent under
`Reexamination
`GOVIND ET AL.
`Art Unit
`
`Alton N. Pr or
`
`1 616
`
`‘*"'°c*;%.';2.:'::.°'“'*
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`Non-Elected
`
`
`gmnu-mnnum-nnuuuulllllmIIIIIIIIIIIIIIIIIIIIIIII
`IIIIIIIIIIIIIIIIIIIDDMMMIIIIIIIIIIIIIIIIIIIIIIIIII
`IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII
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`IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII
`IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII
`IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII
`IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII
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`IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII
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`9
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`0
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`U.S. Patent and Trademark Office
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`Part of Paper No. 20071 1 1 1
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`304
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`304
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` AppIicant{s}lPatent under
`Apr.-Iicationfcontrol No.
`Reexamination
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`1or502.6é5
`Examiner
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`GOVIND ET AL.
`Art Unit
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`Alton N. P or
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`1616
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`SEARCH NOTES
`(INCLUDING SEARCH STRATEGY)
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`ANP
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` INTERFERENCE SEARCHED
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`' us. Patent and Trademark Office
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`Part of Paper No. ZOOT1 1 1 1
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`305
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`R
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` Search Notes
`Wllfilliil
`llllll
`mum»
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`SEARCHED
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`45 .43. 1“B2007
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`305
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`

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`G FISH s: RICHARDSON p.c.
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`Substitute Forrn PTOiSE!l3o (5-03)
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`Request
`For
`continued Examination (ROE)
`Transmittal
`
`Address to:
`Mail Stop ROE
`Commissioner for Patents
`PD. Box 1450
`Alexandria. VA 22313-1450
`
`Appiication Number
`Fiiing Date
`First Named inventor
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`Group An‘ Unit
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`Cor.-f No.
`.
`Examiner Name
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`101502.685
`July 27, 2oo4
`Na na Govlnd et al
`3’
`1616
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`'
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`7568
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`Alton Pryor
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`Attorne Docket Number
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`06275-410US1
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`1995. or to any design application. See Instruction Sheet for RCEs {not to be submitted to the USPTO) on page 2.
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`This Is a Request for Continued Examination {ROE} under 37 C.F.R. §1.114 of the above-Identified application.
`Request for Continued Examination (ROE) practice under 37 CFR 1.11-1 does not apply to any utility or plant application filed prior to June 8.
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` i. I] Consider the arguments in the Appeal Brief or Reply Brief previously filed on
`ii. CI Other
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`If
`amendments enclosed with the RCE will be entered in the order in which they were filed unless applicant instructs otherwise.
`applicant does not wish to have any previously filed unentered amendmentis} entered. applicant must request non-entry of such
`arnendrnent(s)
`a. CI
`Previously submitted. If a final Office action is outstanding. any amendment filed after the final Ofiice action may be
`considered as a submission even if this box is not checked.
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`1.
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`Submission required under 37 C.F.R. §1.114
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`Note: If the RCE is proper. any previously filed unentered amendments and
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`ii.
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`Affidavit(s}IDeclaraticn(s)
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`iv.
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`E
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`Other Exhibits A-C and firmgl Dfimflgs
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` b.‘ ‘E Enclosed
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`2. Miscellaneous
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`a. CI Suspension of action on the above-identified application is requested under 37 C.F.R. §1.103(c) for a
`period of
`months. (Period of suspension shall not exceed 3 months; Fee under 37 C.F.R. §1.17(i} required)
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`b. [I Other
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`The-ROE-fee-under 37 C.'F.R. §1.-17(e) is required by 37 C.F.R. §1.114 when the RCE is filed.
`The Director is hereby authorized to charge the following fees, or credit any overpayments. to
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`a.
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`>11
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` 3. --
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`b. I] Check in the amount of $_ enclosed
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`c. I] Payment by credit card (Form PTO-2038 enclosed)
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`IE _.RC_E.iee_reqUired Under. 3?. CFR 1-1719)
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`ii.
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`III Extension ottime fee (37 CFR 1.136 and 1.17)
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`iii. 8 Other Excess claims fees and any deficiencies
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`Name {Print/Type)
`sense
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`SIGNATURE OF APPLICANT, ATTORNEY OR AGENT REQUIRED
`. Fraser. Ph.
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`Registration No. (Attorney/Agent}
`swaz
`._ .21 2.00
`I
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`34,819
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`
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`CERTIFICATE OF MAILING OR TRANSMISSION
`I hereby certify that this correspondence is being deposited with the United States Postal Service as first class mail In an envelope addressed to Mail Stop ROE,
`Comrnissionerfor Paents. P.0. Box 1450. Alexandria. VA 22313-1450 or facsimile transmitted to the U.3. Patent and Trademark Olfice on the date shown below.
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`306
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`306
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`Attorney's Docket No.: 06275—410US1 $100629-1P US
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`: 1616
`Art Unit
`Applicants: Nayna Govind et at‘.
`Examiner : Alton Pryor
`Serial No.
`: 103501685
`Conf. No.
`: 7568
`Filed
`: July 27, 2004
`Title
`: COMPOSITION FOR INHALATION
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`MAIL STOP RCE
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`Commissioner for Patents
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`PO. Box 1450
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`Alexandria, _VA 22313-1450
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`SUBMISSION UNDER 3? CFR 1.114 0
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`Please amend the above-identified application as follows:
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`.......................................................................................................................................................................................................................................................................................................
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`307
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`Applicant
`Serial No.
`Filed
`Page
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`: Nayna Govind et at’.
`:
`l0r'502,685
`2 July 27, 2004
`: 2 of 12
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`Amendments to the Claims:
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`Attorney's Docket No.: 06275-4l0USl I 100629-ll’ US
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`This listing of claims replaces all prior versions and listings of claims in the application:
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`L§t_in of Claims:
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`l._ (Currently amended) A pharmaceutical composition comprising formoterol or a salt
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` —4
`or solvate thereof or a solvate of a salt'[[,]] budesonide[[,]]; HFA 227[[,]]; PVP and PEG,
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`wherein ’§h_ePVP is present at a concentration f 0.001% w/w to 0.01% W/W and
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`the budesonide is present at a concentration of 4 mg(
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`1.
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`2. (Currently amended) A ph armaceutical composition according to claim 1 wherein the
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`
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`PEG tistrtesettmmat%t°°s9¢aF#sti°n fem sbwt 0-05 *0 a'?9PFt9:3.5% WW-
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`3. (Previously presented) A pharmaceutical composition according to claim 1 in which
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`the PVP is PVP K25.
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`4. (Canceled)
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`tttttttttttttttttttttttttttttt t 3?: t<P¥¢Vi°#%i1:rPrts$°!1F+?<1)ttattaharmacsutitsaltt¢9mP9$iti°nta9°°rdin8 *0 claim 1 in which
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`_
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`the PEG is PEG 1000.
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`6. (Currently amended) A pharmaceutical composition according to claim 1 in which
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`the PEG is present at a concentration in—an-amount of 0.3% wlw.
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`7. (Previously presented) A pharmaceutical composition according to claim 1 in which
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`formoterol is in the form of its fumarate dihydrate salt.
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`8. (Currently amended) A pharmaceutical composition according to claim 1 in which
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`the formoterol or salt or solvate thereof or solvate of a salt is in the form of the single R, R-
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`enantiomer.
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`9. (Currently amended) A pharmaceutical composition according to claim 1 in which
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`the
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`budesonide is in the form of the 22R~¢imfl .
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`10-11. (Canceled)
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`12. (Currently amended) A method of treating or—pi=e¥enti&g the symptoms of a
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`respiratory disorder, comprising administering to a patient a pharmaceutical composition
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`according to claim 1, wherein the respiratory disorder is asthma, rhinitis, or chronic obstructive
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`13. (Previously presented) The method of claim 12, wherein the respiratory disorder is
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`asthma.
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`rhinitis.
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`COPD.
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`14. (Previously presented) The method of claim 12, wherein the respiratory disorder is
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`15. (Previously presented) The method "of claim 12,'wherein the respiratory disorder is
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`"
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`"
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`16. (New) A pharmaceutical composition comprising formoterol, or a salt or solvate
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`thereof, or a solvate of a salt; budesonide; HFA 227; PVP; and PEG, wherein the PVP is present
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`at a concentration of 0.0 01% wiw and the budesonide is present at a concentration of 2 mg/ml.
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`17. (New) A pharmaceutical composition comprising forrnoterol, or a salt or solvate
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`thereof, or a solvate of a salt; budesonide; HFA 227; PVP; and PEG, wherein the PVP is present
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`Serial No.
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`: Ju1y2'?, 2004
`: 4 of 12
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`at a concentration of 0.001 % wfw to 0.01% W/w and the budesonide is present at a concentration
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`of 8 mg/ml.
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`18. (New) A pharmaceutical composition comprising formoterol, or a salt or solvate
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`thereof, or a solvate of a salt; budesonide; HFA 227; PVP; and PEG, wherein the PVP is present
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`at a concentration of 0.0001 % to 0. 001% wfw and the budesonide is present at a concentration of
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`19. (New) The pharmaceutical composition of claim 1, wherein the concentration of
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`PVP is 0.001% or 0.01% w/W.
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`20. (New) The pharmaceutical composition of claim 1, wherein the concentration of
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`.. ..PVP.is.0.001%.w/w.
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`..... ..
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`21. (New) The pharmaceutical composition of claim 17, wherein the concentration of
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`PVP is 0.001% or 0.01% w/W.
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`22. (New) The pharmaceutical composition of claim 17, wherein the concentration of
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`PVP is 0.001% w/w.
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`.............................................
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`The Phal-n-laceuticaloofnpositionDfclain-1 8’ wherein the concentration
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`PVP is 0.0001%, 0.0005 %, or 0.001% W/W.
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`24. (New) The pharmaceutical composition of claim 18, wherein the concentration of
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`PVP is 0.001% W/W.
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`310
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`Serial No.
`Filed
`Page
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`: 10f502,635
`: July 27, 2004
`: 5 of 12
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`Amendments to the Drawings:
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`The attached replacement sheets of drawings (including FIGS. 1-16) include changes to FIGS 2
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`and 3. In FIGS. 2 and 3, the legends were deleted, and the concentration of PVP for each data set
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`is indicated within the graphs themselves.
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`The attached FIGS. 1-15 are formal drawings .....;;;.;n,n,1;.;;a;.;gaggggitngaggggtt;;;.;i;.a;t.;;e“
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`F
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`FIGS. 1-16.
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`311
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`311
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`Applicant
`Serial No.
`Filed
`Page
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`: Nayna Govind er al.
`:
`lO!502,685
`: July 27, 2004
`: 6 of 12
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`Attorney’s Docket No.: 06275-410USl #100629-1P US
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`REMARKS
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`This submission includes an amendment and remarks responsive to the Final Office
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`Action dated January 29, 2007.
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`Upon entry of the amendment, claims 1-3, 5-9 and 12-24 will be pending in the
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`application. Claims .1, 2, 6, 8, 9, and 12 are amended and new claims 16-24 added. Claims 4,
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`10, and 11 were canceled by a previous amendment. Support for the amended and new claims
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`'""Eaii"15e't‘oiiiid'ifi"tliespecification"'and"clai'ni§'as"6iigina11'3F'ii1edI"'l5oi"'eiEaiiip1e,"siipport'f6'fW""""""""'""
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`amended claim 1 and new claims 19 and 20 can be found at least in FIG. 4 and at
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`paragraphs [0005]-[0009] and [003 6] of the published application (US2005!0089478). Support
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`for new claim 16 can be found at least in FIG. 5 and in paragraphs [0005]—[0009] and [003 6].
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`Support for new claims 17, 21, and 22 can be found at least in paragraphs [0005]-[0009] and
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`[0036] and the table at [0056]. Support for new claims 18, 23, and 24 can be found at least in
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`-- FIG. 6 and in paragraphs [0005]-[0009] and [003 6]. (The support for independent claimsl and '
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`____________________________i_.§§_n3 fl+§ad .
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`. ..
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`Applicants also submit herewith formal drawings and a Declaration of inventor Nayna
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`Govind under 37 CFR § 1.132, containing Exhibits A, B, and C, which illustrate suspension
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`stability data of certain formulations with varying concentrations of PVP. Exhibit A is a graph
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`of OSCAR (Optical Suspension Characterization)‘ data for a formulation containing 1 mg/ml
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`budesonide (i.e., 40 pg per dose)? Exhibits B and C are graphs of OSCAR and Turbiscan3 data,
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`----------------- --respectively,--for a formulation containing 8 mg/ml budesonide.
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`-
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`' See paragraphs [0019]-[(1023].
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`2 The graphs in this declaration and the graphs and tables in the specification characterize various formulations as
`delivering a specified amount of budesonide per dose (or per actuation), rather than stating the concentration of
`budesouide per se in each formulation. However, one can readily correlate the per—dose amounts, which range from
`40 pg to 320 ug, to the corresponding concentration of budesonide in the formulation, based on a description of the
`fonnulations in the specification at paragraph [0036]. According to this description, the formulations that were
`tested in the experiments contained a constant level of formoterol lirmarate dihydrate and a concentration of
`budesonide that varied from 1 mg/ml to 8 mg/ml. Each formulation was loaded into a canister with a valve that
`delivered a set volume that did not vary. The formulation that contained 1 mg/ml budesonide delivered 40 pg
`budesonide per actuation (or “dose"). Thus, any data presented as corresponding to a 40 pg dose of budesonide was
`obtained with a formulation containing 1 mggml budesonide. Likewise, the formulation that contained 2 mgfml
`budesonide delivered 30 pg hudegonide, the formulation that contained 4 mgjml budeggnide delivered 169 pg
`budesonide, and the formulation that contained 8 mg/ml budesonide delivered 320 pg budesonide.
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`3 See paragraphs [0024] to [c033].
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`_
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`312
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`Serial No.
`Filed
`Page
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`: 10/502,685
`: July 27, 2004
`1 7 of 12
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`Applicants respectfully request that the Examiner consider the references on the
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`Information Disclosure Statement submitted November 3, 2006, and indicate that he has done so
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`by returning an initialed copy of the form PTO-1449.
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`All of the pending claims were rejected on one or more grounds, as discussed below.
`
`NW"i‘Jlai'iii's"1'2l'l'5 'aré'iéj'eeied'iiiidér'3'S'UI'Sli."1I"§"I'l'2',"fii‘st'pai‘agiap1i,"for""failing"to"satisfy"'the"'""""'"W"
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`35 U.S.C. § 112, first paragraph
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`enablement requirement, because the claims “recite preventing language.” Ofiice Action at
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`page 2, paragraph I. Applicants do not concede that the claims lack enablement for this or any
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`other reason. However, solely in the interest of furthering prosecution, Applicants have amended
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`claim 12 to delete the term “preventing,” while reserving the right to pursue such scope in a
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`continuation application. In view of the amendment, Applicants respectfully request that the
`
`'---rejection-under 35-USC §-112, 1-“ paragraph, for -lack -of enablement be withdrawn.---
`
`-
`
`--
`
`35 U.S.C.
`
`103
`
`Claims 1-3, 5-9 and 12-15 are rejected under 35 U.S.C. § 103 (a) as being unpatentably
`
`obvious over Meade er at’. (US 20030018019). Office Action at page 2. The Ofiice Action does
`
`not say that Meade er al. is cited in combination with any other reference, which would suggest
`
`that it is cited alone. However, since a second reference, Weers er al. (US 6,3 09,623), was
`
`- ----combined-with-Meade -er at--in the -previous Office Act-ion mailed May 4, 2006, and Weers et al. -
`
`"""""""""""""" "is mentioned a'few*times'in'the “Examiner argues”'section ofpage'3 ofthe present 0ffice""
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`Action, Applicants surmise that the Examiner may have intended it to still be part of the
`
`rejection. Clarification is requested.
`
`In sections (a) through ((1) below, Applicants respond to each ofthe E:-:a1niner’s
`
`arguments labeled (a) through (d), respectively, at page 3 of the Office Action.
`
`(a) The Examiner states that “[s]ince the prior art does not disclose any particular range
`
`of PVP, it is imperative that Applicant show the criticality of the invention comprising
`
`0.001% wiw PVP by testing the invention comprising slightly more and less than 0.001% w/w
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`PVP.”
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`313
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`313
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`

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`Serial No.
`Filed
`Page
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`l0l502,685
`:
`: July 27, 2004
`: 8 of 12
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`Applicants disagree that they must show experimental evidence to overcome the
`
`obviousness rejection, as the Examiner has not met his burden of establishing that it was prima
`
`facie obvious to use 0.001% wfw PVP (or any other particular concentration of PVP) in the
`
`claimed formulations. Nevertheless, Applicants note that such evidence is present in the
`
`application as filed, and is further supported by supplemental data presented in the attached
`
`Declaration and exhibits.
`
`'é1s'ééi'fi'¢ati6fi"dés;t$fiEé§"5lfiiifiifiéfar'oSC1o;R"afia'Tfi&b'il§éah"fiiéa§iii*éiiiéiifél'6f""'”"""""“"""""""
`
`'
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`suspension stability carried out on formulations containing budesonide at concentrations of
`
`1 mgfn1L, 2 mg/mL, 4 mg/mL, and 8 mg/mL (equivalent to 40 ,ug, 80 pg, 160 pig, and 320 ,ug
`
`budesonide per actuation) and various concentrations of PVP ranging from 0.000l% to
`
`0.05% w/w. See the description of these test formulations in the specification at paragraph
`
`[003 6]. The results of these experiments are shown in FIGS. 2-6 in the application and in
`
`-- Exhibits -A,--B," and-C -attached to-the enclosed -Declaration of Nanya Govind. - For the -Examiner’-s
`
`-
`
`Budesonide
`
`Budesonide er
`
`OSCAR
`
`Turbiscan
`
`Preferred PVP
`
`40 pg
`
`Exhibit A
`
`FIG. as
`
`0.o001%-0.001%
`
`
`
`........Eflfibit.C............._0...O01.%;0.;01.%................................ ..
`
`In addition to the OSCAR and Turbiscan measurements, the specification at paragraphs [0040] to
`
`[0055] describes digital photographic analyses of the same formulations, with the data from
`
`those analyses set forth in the table at paragraph [0056] of the specification.
`
`Because the data, taken as a whole, indicate that the preferred amount of PVP varies
`
`somewhat with the concentration of budesonide in the formulation, Applicants present four
`
`independent claims, each limited to a different concentration of budesonide and a corresponding
`
`level or range of PVP. For example, claim 1 is now limited to one particular concentration of
`
`314
`
`314
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`

`
`Applicant
`Serial No.
`Filed
`Page
`
`: Nayna Govind et al.
`: 10I'502,685
`: July 27, 2004
`: 9 of 12
`
`Attorney's Docket No.: 06275-4 l0USl I 100629-1P US
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`budesonide, 4 mg/ml (corresponding to 160 pg budesonide per actuation in the experiments
`
`reported in the application, as explained in footnote 2 above), while new independent claims 16-
`
`18 are respectively limited to 2, 8 and 1 mg/ml budesonide. The concentration of PVP specified
`
`in each of the four independent claims is derived from data in the specification indicating the
`
`best concentration or range of concentrationsof PVP to use with each particular concentration of
`
`budesonide, as explained below. Though not necessary for support, additional data in
`"""E)'iliil:ii'ts'K',' 'B','"a'iid"C' of'thFD'éclar"atioii"ar'é"proiiided"for conipleter'iess'.'"""""""""""""""""""""""""""""""""""""""""""""""""
`
`Amended claim 1 now specifies that the concentration of budesonide is 4 mg/ml and the
`
`concentration of PVP is 0.001% w/w to 0.01% W/w. These concentrations of PVP are derived
`
`from the data in FIG. 4 (obtained using the Turbiscan method) and in the table at [0056]
`
`(obtained using a digital photograph analysis such as illustrated in FIGS. 9-11), all regarding a
`
`formulation that in the experiments described in the specification contains 4 mg/ml and delivers
`
`-
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`160 pg budesonide per actuation. As can be seen-both in this table and in FIG. 4, for-a --
`
`-
`
`0.001 % wiw to 0.01% w/w would be expected to give the best suspension stability over time,
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`better than higher (0.03 and 0.05%) or lower (0.0001%) concentrations of PVP produced with
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`this amount of budesonide.4 Nothing in the prior art would have led one to expect that this
`
`amount of PVP would produce superior results with 4 mg/ml budesonide (or any other
`
`concentration of budesonide, for that matter).
`
`New claim 16 is limited to a budesonide concentration of 2-mg/ml (corresponding to a
`
`""""""""""""" "dose-of-80-pg per actuation-in-the experiments described in the specification)-and aPVP
`
`--
`
`--
`
`concentration of 0.001% w/w. The criticality of 0.001% W/w PVP in a formulation containing
`
`2 mg/ml budesonide is -illustrated in FIGs. 3 and 5; this concentration of PVP also produced the
`
`best results when measured by digital photography as indicated in the table at [0056]. These data
`
`show that formulations with higher or lower concentrations of PVP were less able to maintain a
`
`good suspension of a 2 mg/ml budesonide formulation over time. Nothing in the prior art would
`
`4 The data in FIG. 2 (also obtained with 4 mg/ml budesonide, but using the OSCAR method) also support the
`superiority of 0.001% PVP in particular, and to a lesser extent that of 0.01%; however, it is clear that the range from
`0.01% to 0.001% would be better than higher or lower concentrations ofPVP.
`
`315
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`315
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`

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`Serial No.
`Filed
`Page
`
`: 10f502,68S
`: July 27, 2004
`: 10 of 12
`
`have led one to expect that 0.001% wfw PVP would provide this benefit in a formulation
`
`containing 2 mg/ml budesonide (or any other concentration of budesonide, for that matter).
`
`New claim 17 is limited to a budesonide concentration of 8 mg/ml (corresponding to a
`
`dose of 320 pg per actuation in the experiments described in the specification) and a PVP
`
`concentration of 0.001%.-.w!w. to .0.01_% w/.w._ This PV-P concentration range is derived from the
`
`digital photographic data summarized in the table at [0056].
`
`It can be seen from the table that,
`
`"""refs"faaai11aa6a'saa'taifiiag"3'ai;g7fii1"s'aassssias;"o;'0 l'%'w?\FPVP produced optii'1'i'5I'§'t'z'|}3i1ity "
`
`'
`
`'
`
`"
`
`results when analyzed by the digital photographic method, with 0.001% also producing good
`
`results. Further data regarding formulations containing this concentration ofbudesonide are
`
`shown in Exhibits B and C attached to the enclosed Declaration. Exhibit B shows that, when
`
`measured by OSCAR over a 2 minute time period, 0.01% PVP produces the most stable
`
`formulations with 8 mg/ml budesonide. When the stability of the 8 mg/ml fonnulations was
`
`measured by the Turbiscan method over a 15 min time period, 0.01% and 0.001% PVP both --
`
`- -
`
`proved far more mHe4 mmm£P¥P{sw Ex-hibiteG).a------------------------------------
`
`-
`
`New claim 18 is limited to a budesonide concentration of I mg/ml (corresponding to a
`
`dose of 40 pg per actuation in the experiments described in the specification) and a PVP
`
`concentration of 0.0001 % wlw to 0.001% wfw. This range of PVP concentrations is derived
`
`fi'om the FIG. 6 Turbiscan data and the digital photographic data shown in the table at [0056] for
`
`1 mg/ml budesonide formulations. As shown in both FIG. 6 and the table, concentrations of
`
`- PVP at or below 0.001% produced relatively stable formulations of 1 mg/ml budesonide. This
`
`.......................... .. cOnc1uSiOn_iS_bumeSSed_by the OSCA_R_data provided in_Exhibit_A_ attached tomeenclosed..................
`
`Declaration.
`
`There is no suggestion in Meade that varying concentrations of PVP would have any
`
`effect on suspension stability whatsoever, and there is further no indication which concentrations
`
`of PVP are best suited for any composition containing budesonide, much 13 the particular
`
`budesonide concentrations specified in the present claims. It is clear from the data in the
`
`specification that the stability of any given budesonide formulation depends on the concentration
`
`of PVP utilized. One can derive a few generalizations from these data: (1) higher budesonide
`
`concentrations tended to require more PVP to maintain a stable suspension; (2) all of the
`
`budesonide concentrations tested (from 1 mg/ml to 8 mg/ml) were more stable if the PVP
`
`316
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`316
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`

`
`Serial No.
`Filed
`Page
`
`: 10f502,685
`: July 27, 2004
`:
`ll of 12
`
`concentration was kept below 0.05% w/W; and (3) the best results overall were obtained using
`
`0.001% PVP wfw. None of those results could have been predicted based on the prior art cited
`
`by the Examiner, which in fact gave no reason to expect any improvement in stability by adding
`
`PVP, much less by keeping the concentration of PVP below 0.05% wfw.
`
`(b) The Examiner states that “[i]t is improper to conclude that amount of
`
`phosphatidylcholineused in Weers wc'uld‘eq'uate to the amount of‘PVP that shouldbe used since
`
`structures differ in both chemical and physical properties. In addition it is important to note that
`
`Weers is not relied upon for the use of PVP since Meade uses PVP.” As explained in the
`
`November 3'6 reply at page 10, neither Meade nor Weers discloses fly particular concentration
`
`of PVP, and neither provides any motivation to select the particular concentration or range of
`
`concentrations of PVP required by Applicants’ claims. As amended, the claims specify the
`
`......................... ..preferred.concentration.of P.VP..to be usedwith.specified.concent:rations ofbudesonide. There is
`
`.
`
`-----------------------------ncuteaching or.suggcstionJr1_Ld.ca.de_o:_V'{ee:s_thaL\uou1dJ.eadom:_to s11ch_a p1:efe1::ed_._.._.
`
`..
`
`..
`
`.
`
`concentration.
`
`(c) and (d) The Examiner states that Applicants failed “to provide examples, which show
`
`the criticality of 0.001% w/w PVP versus the invention where the PVP concentration is slightly
`
`greater or less than 0.001% w/w PVP.” Applicants do not understand why the Examiner
`
`believes the examples need to concern concentrations that are “slightly greater or less than
`
`........................... .. 0_001% W/W _pVp_~_»’_es any diff-erenees in effeet _fe1._differem _eeneenu.atiens ef pm: would appear...
`
`to be surprising in view of prior art that taught nothing about specific concentrations of PVP and
`
`nothing about improved stability ofbudesonide suspensions or other benefits attributable to PVP.
`
`Applicants submit that the examples provided in the specification and discussed above are more
`
`than ample to support the ncncbviousness of the present claims.
`
`In view of the foregoing, Applicants respectfully request that the rejection under 35 USC
`
`§ 103(a) be withdrawn.
`
`317
`
`317
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`

`
`Applicant
`Serial No.
`Filed
`Page
`
`: Nayna Govind at al.
`: 10,502,685
`: July 27, 2004
`: 12 of 12
`
`Attorney's Docket No.: 06275-410USI I 100629-1P US
`
`Please apply the excess claims fee of $400 and any other necessary charges or credits to
`
`Deposit Account No. 06-1050, referencing Attorney Docket No. 06275-410USl.
`
`Respect - lly submitted,
`
`
`
`
`5.
`
`iK. Fraser, Ph.
`J
`Reg. No. 34,819
`
`Fish & Richardson P.C.
`
`225 Franklin Street
`
`Boston, MA 02110
`Telephone: (617) 542-5070
`Facsimile: (617) 542-8906
`
`DocNo 21559455
`
`318
`
`318
`
`

`
`Attorney's Docket Nth: ‘$16275-4l0U3| I M0629-I P US
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Applicant
`Serial No.
`Filed
`Title
`
`Art Unit
`: Nayne Govind eral.
`Examiner
`:
`ll}!502,68S
`Com".No.
`: July 27, 2004
`: COMPOSITION FOR INHALATION
`
`16 I6
`:
`: Allan Pryor
`: 7568
`
`Mail Stop Amendment
`Cornmissionar for
`P.O. Box I450
`
`Alexandria, VA 22313-I450
`
`--
`
`--
`
`-- -
`
`DE‘.CLARA'l‘ION FNAYNA
`
`V
`
`l, Nayna Govind. a citizen of the UK residing in Nottingham U.K.. hereby declare as
`
`follows:
`
`"T..'cTuflil:'«'::'i-'t':L‘igh‘."l reeeI'\'iE'
`
`E l’l1'tirr'Il'(l'lon§)'(iegree'iri PI1-a'n‘1ia'i:ji' fi'om Bradford University.
`
`I
`
`have over 12 years experience in the field of pressurized metered dose inhalers.
`
`I have published
`
`over 6 scientific articles. A copy of‘ my CV is attached as E