Status
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`Applicant(s) Application No,
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`GOVIND ET AL.
`10/802 ,685
` Office Action Summary
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`Art Unit
`Examiner
`1616
`Alton N. Pryor
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`~. The MAILING DATEof this communication appears on the cover sheetwith the correspondence address --
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`Period for Reply
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 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 37 CFR 1.138(a).
`In no event, however, may a feply be limety filed
`after SIX (6) MONTHS from the mailing date of this communication,
`+
`INO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS fram the Mailing date of this communication.
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`- Failure to reply within the set or extended peried for reply wit, by statute, cause the application to become ABANDONED (35 U.3.C_ § 133).
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`Any reply received by the Dffice later than three months afierthe mailing date of this communication, even if timely filed, may reduce any
`eared patent term adjustment. See 37 CFR 1.704(b}.
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`1)]_ Responsive to communication(s)filed on 27 August 2007,
`2a)L) This action is FINAL.
`2b) This actionis non-final.
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`3)C] Sincethis application is in condition for allowance exceptfor formal matters, prosecution as to the merits is
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`closed in accordance with the practice under Ex parte Quayle, 1935 C.D. 141, 453 0.G. 213.
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`Disposition of Claims
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`4)&] Claim(s) 1-3,5-9.12-24 is/are pending in the application.
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`4a) Of the above claim(s)
`is/are withdrawn from consideration.
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`5)C] Ctaim(s)
`isfare allowed.
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`6) Claim(s) 1-3,5-9.12-24 is/are rejected.
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`7)L. Claim(s)__ is/are objectedto.
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`8)L) Claim(s)
`are subject to restriction and/or election requirement.
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`Application Papers
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`9) The specification is objected to by the Examiner.
`|
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`10)C] The drawing(s) filed on
`is/are: a)[_] acceptedor b)L] objected te by the Examiner.
`Applicant may not request that any objection to the drawing(s} be held in abeyance. See 37 CFR 1.85(a).
`
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`Replacement drawing sheet(s) including the correction is requiredif the drawing(s) is objectedto. See 37 CFR 1.121(d).
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`11)C] 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 36 U.S.C. § 119
`42)0] Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a}-(d) or(A.
`a)L] All
`b)L] Some * c)C] None of.
`1.0) Certified copies of the priority documents have been received.
`2.[] Certified copies of the priority documents have been received in Application No.
`3.7] Copiesofthe certified copies of the priority documents have been receivedin this National Stage
`application from the International Bureau (PCT Rule 17.2{a)).
`* See the attached detaited Office action fora list of the certified copies not received.
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`Attachment(s}
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`1} CT Notice of References Cited (PTO-892)
`4) CT Interview Summary (PTO-413)
`.
`2) [[] Notice of Drafisperson’s Patent Drawing Review (PTO-948)
`Paper No(s)/Mail Date.
`3) [1] information Disclosure Statement(s) (PTO/SB/08)
`5) L_] Notice of Informal Patent Application
`Paper No(s)/Mail Date
`.
`6} (L] other:
`.
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`
`
`US. Petent and Trademark Office
`PTOL-326 (Rev. 08-06)
`Office Action,Fummary
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`Part of Paper No./Mail 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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`Application/Control Number: 10/502,685
`Art Unit: 1616
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`Page 2
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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.
`Claims 1-3,5-9.12-24 are rejected under 35 U.S.C. 112, second paragraph, as
`being indefinite forfailing to particularly point out and distinctly claim the subject matter
`which applicant regards as the invention.
`Claims 1-3,5-9.12-24 are rejected because of abbreviations (PVP, HFA 227,
`PEG,etc.}. Replace abbreviations with terms.
`The following is a quotationofthe first paragraph of 35 U.S.C. 112:
`The specification shall contain a written description of the invention, and of the manner and process of
`making and usingit, in suchfull, clear, concise, and exact terms as to enable any person skilled in the
`art to whichit pertains, or with whichit is most nearly connected, to make and use the sameand shall
`set forth the best mode contemplated by the inventor of carrying out his invention.
`Claims 1-3,5-9,12-16 are rejected under 35 U.S.C. 112, first paragraph,asfailing
`to comply with the written description requirement. The claim(s} contains subject matter
`which was not described in the specification in such’a way as to reasonably convey to
`one skilled in the relevant art that the inventor(s), at the time the application wasfiled,
`had possessionof 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 unexpectedstability results for compositions 0.001% wiw to
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`0.01% wiw budesonide.
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`302
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`302
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`

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`Application/Control Number: 10/502,685
`Art Unit: 1616
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`Page 3
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`Telephonic inquiry
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`Any inquiry concerning this communication orearlier communications from the
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`examiner should be directed to Alton N. Pryor whose telephone numberis 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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`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
`"
`supervisor, Johann Richter can be reached on 571-272-0646. The fax phone number
`for the organization where this application or proceedingis assigned is 571-273-8300.
`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
`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
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`you have questions on accessto the Private PAIR system, contact the Electronic
`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 accessto the automated information
`system, call 800-786-9199 (IN USA OR CANADA)or 571-272-1000.
`
`Alton Pryor
`Primary Examiner
`AU 1616
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`303
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`index of Ciaims
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`Mt
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`mn
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`wonadNowo~Qo=
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`=.o&oa..£=zcFosxwe<f
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`—oO
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`Applicant(sPatent under
`Reexamination
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`GOVIND ETAL.
`Art Unit
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`1616
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`(Through numeral)
`Cancelled
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`Restricted
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`t
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`=6z
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`32o2uu
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`1 Interference
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`Rejected
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`A Allowed
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`ToorSBSSREISSEEERFE
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`[n
`jo
`Objected
`
` Application/Control No.
`-rtUs|eEP|oo1o> H:
`TUTETOE
`Pees
`wasuo|-|folelole[-lololel=(ellalalel=lelelelsisfelalelelnaleleisie/sisisisia/alela
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`oloroo/o/oIrr|-wpll™™AONESPROtdoromle+—tTi
`roeqeoclcieelcleeplerll--ele[ol[cilrl--|
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`U.S. Patent and Trademark Office
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`Part of Paper No. 20071111
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`304
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`304
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`Application/Control No. Search Notes~A
` Applicant(s)/Patent under
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`Reexamination
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`GOVINDET AL.
`10/502,685
`Examiner
`Art Unit
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`Alton N. Pryor
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`1616
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`SEARCHED
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`Class
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`45,48,
`m@
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`11/6/2007
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`ANP
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`INTERFERENCE SEARCHED
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`(INCLUDING SEARCH STRATEGY)
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` SEARCH NOTES
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`"U.S. Patent and Trademark Office
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`Part of Paper No. 20071111
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`305
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`305
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`® Fisu & RICHARDSON P.c.
`
`Substitute Form PTO/SEV30 (5-03)
`
`Request
`For
`Continued Examination (RCE)
`Transmittal
`
`Addressto:
`Mail Stop RCE
`Caer or at
`P.O,
`Box
`Box
`1450
`Alexandria, VA 22313-1450
`
`Application Number
`Filing Date
`First Named inventor
`Group Art Unit
`
`10/502,635
`July 27, 2004
`Nayna Govind etal.
`1616
`
`7588
`
`Alton Pryor
`
`Attorney Docket Nurnber
`
`06275-410US1
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`
`
`2.
`
`
`
`|
`a. 0 Suspensionof action on the above-identified application is requested under 37 C.F.R. $1.103(c} for a
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`period of
`months. (Period of suspension shall not exceed 3 months; Fee under 37 C.F.R. §1.17(i required)
`b. () Other
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`iv.
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`&
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`Other Exhibits A-C and formal Drawings
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`The RCEfee under 37 C.F.R. §1:17(e) is required by 37 C.F.R. §1.114 when the RCEis filed.
`3.
`a. BJ=The Director is hereby authorized to charge the following fees, or credit any overpayments, to
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`This Is a Request for Continued Examination (RCE} under 37 C.F.R. §1.114 of the above-Identified application.
`
`Request for Continued Examination (RCE) practice under 37 CFR 1.114 does not apply to any utility or plant application filed prior to June 3,
`1995, or ta any design application. See Instruction Sheet for RCEs (not to ba submitted to the USPTO) on page 2.
`
`1.|Submission required under 37 C.F.R. §1.114|Note: Ifthe RCEis proper, any previously filed unentered amendments and
`amendments enclosed with the RCE will be entered in the order in which they were filed unless applicant instructs otherwise.
`If
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`applicant does not wish to have any previously filed unentered amendment(s} entered, applicant must request non-entry of such
`amendment(s}
`a. [1
`Previously submitted. If a final Office action is outstanding, any amendmentfiled after the final Office action may be
`considered as a submission evenif this box is not checked.
`
` i.
`(0 Considerthe arguments in the Appeal Brief or Reply Brief previously filed on
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`i. Other
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`b. & Enclosed
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`
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`ii.
`Affidavit(s}/Declaration(s)
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`_
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`it, RX RCE fee required under 37CFR 1.17(e)
`ii. 0 Extension of time fee (37 CFR 1.136 and 1.17)
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`iii. &) Other Excess claims fees and anydeficiencies
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`
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`b. [J Chackin the amount of $
`enclosed
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`c. © Payment by credit card (Form PTO-2038 enclosed)
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`SIGNATURE OF APPLICANT, ATTORNEY OR AGENT REQUIRED
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`Name (Print/Type) Registration No, (Aftomey/Agent)|34,819. Fraser, Ph.D,,1.D:
`
`Signature tastame,_—i|Pate|4,na. -2{, 200
`
`
`[Signatureete
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`CERTIFICATE OF MAILING OR TRANSMISSION
`Thereby certify that this correspondence is being deposited with the United States Postal Service asfirst class mail in an envelope addressed to Mail Stop RCE,
`Commissionerfor Patents, P.O. Box 1450, Alexandra, VA 22313-1450 of facsimile transmitied to the U.S. Patent and Trademark Office on the date shown below.
`
`[Name(PrinType)
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`306
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`306
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`Attorney's Docket No.: 06275410081 7 100629-1P US
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`: 1616
`Art Unit
`Applicants: Nayna Govind e¢ al,
`Examiner : Alton Pryor
`Serial No.
`: 10/502,685
`Conf. No.
`: 7568
`Filed
`: July 27, 2004
`Title
`: COMPOSITION FOR INHALATION
`
`MAIL STOP RCE
`Commissioner for Patents
`P.O. Box 1450
`Alexandria,VA 22313-1450
`
`SUBMISSION UNDER 37 CER§1.114(c
`
`Please amend the above-identified application as follows:
`
`wee eee ne ce eee ee enn ne nee re eee ee nee ee ee nn ee ee eee eae ee cee ee nee nee cee eee eaten seen Gan ene een aee cee cree eee se eee nee ns cone cee area ceereeataben cae cee nap areeeenseeceeeneeceben coticneeh coceeee aeececceeereeeeereeecetees ef ne neeeeee
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`307
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`Applicant
`Seria! No.
`Filed
`Page
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`: Nayna Govind et al.
`: 10/502,685
`: July 27, 2004
`: 2of 12
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`Amendments to the Claims:
`
`Attomey’s Docket No.: 06275-410US1 / 100629-1P US
`
`This listing of claims replacesall prior versions and listings of claimsin the application:
`
`Listing of Claims:
`
`1. (Currently amended) A pharmaceutical composition comprising formoterol or a salt
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`or solvate thereof, or a solvate of a salt:[[,}] budesonide[[,]],; HFA 227[[,]]; PVP and PEG,
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`wherein thePYP is present ata concentration in-an-ameuntof 0.001% w/w _to 0.01% w/w and
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`the budesonideis present at a concentration of 4 mg/ml.
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`2. (Currently amended) A pharmaceutical composition according to claim 1 wherein the
`PEGispresentat aconcentrationfrom about 0.05 to about 0.35% w/w.
`
`3. (Previously presented) A pharmaceutical composition according to claim | in which
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`the PVP is PVP K25,
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`4. (Canceled)
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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 is-an-ameunt of 0.3% w/w.
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`7. (Previously presented) A pharmaceutical composition according to claim 1 in which
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`formoterolis in the form of its fumarate dihydrate salt.
`
`308
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`308
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`

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`"Applicant; NaynaGovinderal =--——=~C*~C*S*«Attorney"s DoctNo: 06275-410US1/100629-IPUS
`Serial No.
`: 10/502,685
`Filed
`: Jaly 27, 2004
`Page
`: 30f 12
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`8. (Currently amended) A pharmaceutical composition according fo 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 second-activeinpredientis budesonide is in the form of the 22R-epimer-efbudesonide.
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`10-11. (Canceled)
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`12. (Currently amended) A methodoftreating er-preventing 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 disorderis asthma, rhinitis, or chronic obstructive
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`ee ne cee eee eee eee eee pulmonary disease (COPD)... wee
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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 ofclaim 12, wherein the respiratory disorder is
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`15. (Previously presented) The method of claim 12, wherein the respiratory disorderis ~ ©
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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 0.001% w/w and the budesonide is present at a concentration of 2 mg/ml.
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`17. (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
`
`309
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`309
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`

`

`Applicant
`Serial No.
`Filed
`Page
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`: Nayna Govind ef al.
`: 10/502,685
`: July 27, 2004
`: 4of1i2
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`Attomey’s Docket No.: 06275-410031 / 100629-1P US
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`at a concentration of 0.001% w/w 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% w/w 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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`PVPis 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% wiv...
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`cee cette ee
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`21. (New) The pharmaceutical composition of claim 17, wherein the concentration of
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`PVPis 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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`coos cs sniseutettuvitis setteuetteneesee23.-(New) The pharmaceutical composition of claim 18, wherein the concentration of2-00
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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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`310
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`Applicant
`Serial No.
`Filed
`Page
`
`: Nayna Govind et al.
`: 10/502,685
`: July 27, 2004
`: Sof 12
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`Attormey’s Docket No,: 06275-410US1 / 100629-1P US
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`Amendments to the Drawings:
`
`The attached replacementsheets 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. 1-16 are formal drawings that replace the original sheets including
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`FIGs. 1-16.
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`311
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`311
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`

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`Applicant
`Serial No.
`Filed
`Page
`
`: Nayna Govind efal,
`: 10/502,685
`» July 27, 2004
`: 60f 12
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`Attorney’s Docket No.: 06275-410US1 7 100629-1P US
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`This submission includes an amendment and remarks responsive to the Final Office
`
`REMARKS
`
`Action dated January 29, 2007.
`
`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. Claims4,
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`10, and 11 were canceled by a previous amendment. Support for the amended and new claims
`~ canbe foundinthe specificationandclaimsasoriginallyfiled. Forexample, supportfor
`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 [0036] of the published application (U$2005/0089478). Support
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`for new claim 16 can be foundat least in FIG, 5 and in paragraphs [0005]-[0009] and [0036].
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`Support for new claims 17, 21, and 22 can be foundat 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 foundatleast in
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`~ FIG. 6 and in paragraphs [0005]-[0009] and [0036]. (The support for independent claims 1 and -
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`servtercemeneecainrta“4-184sfurtherdetailedbelow.Nonewmatteris-addedbytheamendment—---
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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
`of OSCAR (Optical Suspension Characterization)’ data for a formulation containing 1 mg/ml
`budesonide {i.e., 40 pg per dose).? Exhibits B and C are graphs of OSCAR and Turbiscan’ data,
`
`orerespectively, for a formulation containing 8 mg/ml budesonide.
`
`-
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`' See paragraphs (0019]-[0023].
`
`2 The graphs in this declaration and the graphs andtables in the specification characterize various formulations as
`delivering a specified amount ofbudesonide per dose (or per actuation), rather than stating the concentration of
`budesonide per se in each formulation. However, one can readily correlate the per-dose amounts, which range from
`40 pg to 320 pg, to the corresponding concentration of budesonide in the formulation, based on a description of the
`formulations in the specification at paragraph [0036]. According to this description, the formulations that were
`tested in the experiments contained a constant level of formoterol fumarate 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 volumethat did not vary. The formulation that contained 1 mg/m] budesonide delivered 40 pg
`budesonide per actuation (or “dose”). Thus, any data presented as corresponding to a 40 ue dose of budesonide was
`obtained with a formulation containing 1 mg/ml budesonide. Likewise, the formulation that contained 2 mg/ml
`budesonide delivered 80 up budesonide, the formulation that contamed 4 mg/ml budesonide delivered 160 pe
`budesonide, and the formulation that contained 8 mg/ml budesonide delivered 320 ue budesonide.
`
`3 See paragraphs [0024] to [0033].
`
`.
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`312
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`

`Applicant
`Serial No.
`Filed
`Page
`
`: Nayna Govind er al.
`; 10/502,685
`: July 27, 2004
`: Fofl2
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`Attorney’s Docket No.: 06275-410US1 / 100629-LP US
`
`Applicants respectfully request that the Examiner consider the references on the
`Information Disclosure Statement submitted November 3, 2006, and indicate that he has done so
`
`by returning an initialed copy of the form PTO-1449.
`All of the pending claims were rejected on one or more grounds, as discussed below.
`
`35 U.S.C. § 112, first paragraph
`
`~~ Claims12-15 arerejected under35 U.S.C.§ 112,firstparagraph,forfailingto satisfy the=
`enablement requirement, because the claims “recite preventing language.” Office Action at
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`page 2, paragraph I. Applicants do not concede that the claims lack enablementfor this or any
`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 respecttully request that the
`--yejection under 35USC § 112, 1° paragraph,for lack of enablement be withdrawn: = ~~
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`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
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`obvious over Meadeef a/, (US 20030018019). Office Action at page 2. The Office Action does
`
`not say that Meadeefal. is cited in combination with any other reference, which would suggest
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`that it is cited alone. However, since a second reference, Weers et al. (US 6,309,623), was
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`---combined-with Meade et al.in the previous Office Action mailed May 4, 2006, and Weerset ai. .
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`oe” is mentioned a few-times inthe “Examiner argues” section ofpage 3 of the presentOffice
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`Action, Applicants surmise that the Examiner may have intended it to still be part of the
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`rejection. Clarification is requested.
`
`In sections (a) through (d) below, Applicants respond to each ofthe Examiner’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
`ofPVP,it is imperative that Applicant show the criticality of the invention comprising
`0.001% w/w PVP bytesting the invention comprising slightly more and less than 0.001% w/w
`
`PVP.”
`
`313
`
`313
`
`

`

`Applicant
`Serial No,
`Filed
`Page
`
`: Nayna Govind ef al.
`: 10/502,685
`: July 27, 2004
`: Sof 12
`
`Attorney’s Docket No.: 06275-410US! / 100629-1P US
`
`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% w/w 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.
`
`~ ‘ThespecificationdescribesanumberofOSCARandTurbiscan measurementsOf=
`suspension stability carried out on formulations containing budesonide at concentrations of
`
`1 mg/mL, 2 mg/mL, 4 mg/mL,and 8 mg/mL (equivalent to 40 pg, 80 zg, 160 zg, and 320 pg
`
`budesonide per actuation) and various concentrations of PVP ranging from 0.0001% to
`
`0.05% w/w. See the description of these test formulations in the specification at paragraph
`
`[0036]. 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
`
`Budesonideper
`
`OSCAR
`
`Turbiscan
`
`FIG. 6
`
`0.0001%-0.001%
`
`“EhTT Eahibi© -0.001%-0.01%
`PreferredPVPel1Trg|40 pg
`ExhibitA
`
`
`
`
`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.
`
`Becausethe 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
`
`

`

`Applicant
`Serial No,
`Filed
`Page
`
`: Nayna Govind e#ai,
`: 10/502,685
`: July 27, 2004
`: Sof 12
`
`Attorney’s Docket No.: 06275-410U$1 / 100629-1P US
`
`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 ofthe 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
`“ExhibitsA,B,andCoftheDeclarationareprovidedfor completeness,eee
`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) andin 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/mi and delivers
`
`160 pg budesonide per actuation. As can be seen both in this table and in FIG. 4, fora.
`
`-
`
`0.001% wiw to 0.01% w/w would be expected to give the best suspensionstability over time,
`
`better than ‘higher (0.03 and 0.05%) or lower (0.0001 %) concentrations of PVP produced with
`this amountofbudesonide.* Nothingin 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 2mg/ml (corresponding to a
`
`er dose of80-yg per actuation inthe experiments described in the specification)andaPVP- = = = >>
`
`concentration of 0.001% w/w. Thecriticality of 0.001% w/w PVP in a formulation containing
`
`2 mg/ml budesonide isillustrated 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
`
`* 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
`
`315
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`

`

`Applicant
`Serial No.
`Filed
`Page
`
`: Nayna Govind e7 al.
`| 10/502,685
`: July 27, 2004
`: 10 of 12
`
`Attorney’s Docket No.: 06275-410US1 / 100629-1P US
`
`have led one to expect that 0.001% w/w 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 (correspondingto a
`
`dose of 320 yg per actuation in the experiments described in the specification) and a PVP
`
`concentration of 0.001%.w/wto 0.01% w/w. This PVPconcentration range is derived from the
`
`digital photographic data summarized in the table at [0056].
`
`It can be seen from thetable that,
`
`~ “foraformulationcontaining8mg/m!budesonide,0:01%w/wPVP produced optimalstability: ~~
`
`results when analyzed by the digital photographic method, with 0.001% also producing good
`
`results. Further data regarding formulations containing this concentration ofbudesonide are
`
`shownin Exhibits B and C attached to the enclosed Declaration. Exhibit B showsthat, when
`
`measured by OSCARover a 2 minute time period, 0.01% PVP produces the most stable
`
`formulations with 8 mg/m] budesonide. When thestability of the 8 mg/ml formulations was
`
`measured by the Turbiscan method over a 15 min time period, 0.01% and 0.001% PVP both .- --
`
`proved far more stable-thanhigher-or-lower-concentrations-ofPVP(see ExhibitC)—----------=
`
`New claim 18 is limited to a budesonide concentration of I mg/ml (correspondingto a
`
`dose of 40 gg per actuation in the experiments described in the specification) and a PVP
`
`concentration of 0.0001% w/w to 0.001% w/w, This range of PVP concentrations is derived
`
`from the FIG. 6 Turbiscan data and the digital photographic data shown in the table at [0056] for
`
`1 mg/m] 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
`
`ce vtntnee conclusion-is-buttressedby the OSCAR data provided in Exhibit Aattached tothe enclosed“8
`
`Declaration.
`
`There is no suggestion in Meadethat 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, muchless 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 concentrationstested (from 1 mg/ml to 8 mg/ml) were morestable if the PVP
`
`316
`
`316
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`

`

`Applicant
`Serial No.
`Filed
`Page
`
`: Nayna Govindefal,
`: 10/502,685
`: July 27, 2004
`: Llof 12
`
`Attorney’s Docket No.: 06275-410US1 / 100629-1P US
`
`concentration was kept below 0.05% w/w; and (3) the best results overall were obtained using
`0.001% PVP w/w. None ofthose results could have been predicted based on the priorart cited
`by the Examiner, which in fact gave no reason to expect any improvementin stability by adding
`
`PVP, muchless by keeping the concentration of PVP below 0.05% w/w.
`
`(b) The Examiner states that “[i]t is improper to conclude that amount of
`phosphatidylcholine used in Weers wouldequate to the amount ofPVP that should'be used since
`
`structures differ in both chemical and physical properties. In addition it is important to note that
`
`Weersis notrelied upon for the use of PVP since Meade uses PVP.” As explained in the
`November 3™ reply at page 10, neither Meade nor Weers discloses any particular concentration
`
`of PYP, 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
`
`voce ce eeeenseese preferred concentration of PVP. to be used with specified concentrations ofbudesonide. ‘Thereis....
`
`wececesses setaeno_teaching or-suggestioninMeade_orWeersthatwouldleadonetosucha preferred...
`
`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 concentrationis 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
`
`csr eeneennen ne 0.001% w/w PVP”, as any differences in effect for-different concentrations of PVP would appear
`
`to be surprising in view ofpriorart 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 nonobviousness 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 ef al,
`: 1002,685
`: July 27, 2004
`:
`IZ of 12
`
`Attorney’s Docket No.: 06275-410US1 / 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. 06275-4100S1.
`
`Respectfully submitted,
`
`
`
`OX oa
`
`
`JanisK. Fraser, Ph.D., J.D.
`Reg, No. 34,819
`
`Fish & Richardson P.C.
`225 Franklin Street
`Boston, MA 02110
`Telephone: (617) 542-5070
`Facsimile: (617) 542-8906
`
`DocNo 21659466
`
`318
`
`318
`
`

`

`Altomey's Docket No: 06273-4(OUS8I / 100629-1P US
`
`TN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Applicant
`Serial No.
`Filed
`Title
`
`Art Unit
`: Nayna Govind ef al.
`Rxaminer
`: 10/502,685
`Conf. No.
`+ July 27, 2004
`: COMPOSITION FOR INHALATION
`
`; 1616
`: Alton Pryor
`: 7568
`
`Mail Stop Amendment
`Commissionerfor Patents9-0 ee ee cece eee neta nncsnnn sna itaesnaeinians sae cunneunniig ae set Gonntsaneinneinnninnneinniinnns sae ttn anne
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`DECLARATION OF NAYNA
`
`GOV
`
`1, Nayna Govind, a citizen of the UK residing in Nottingham U.K. hereby declare as
`
`follows:
`
`1 Lama‘TeamManageratAstraZeneca AB, employedat AstraZeneca Charnwood,
`* Louthborough. 7) received my &. Pharm (Hons) degree in Pharmacyfrom Bradford University, |"|
`have over 12 years experience in the field of pressurized metered dose inhalers.
`| have published
`
`overs 6 scientific articles. A copy af my CV is attached as Exhibit D.
`
`[ have reviewed the above-referenced patent application and the U.S. Patent and
`2.
`Trademark Office Action mailed January 29, 2007. The data presented below andin the
`attached Exhibits A-C supplement the data prov