IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Application No. 11/894,676
`Attorney Docket No. 0287000.130.US3
`
`Applicants:
`
`Hannon et al.
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`Confirmation No.:
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`8161
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`Application No:
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`11/894,676
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`Art Unit:
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`1635
`
`Filed:
`
`Title:
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`August 20, 2007
`
`Examiner:
`
`K. CHONG
`
`METHODS AND COMPOSITIONS FOR RNA INTERFERENCE
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`INTERVIEW SUMMARY AND SUPPLEMENTAL AMENDMENT
`AND RESPONSE TO OFFICE ACTION
`
`This paper is further to the response filed on November 4, 2009 to the May 4, 2009
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`Office Action. The Director is authorized to charge any fees occasioned by this paper to Deposit
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`Account No. 08-0219.
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`Amendments to the Claims begin on page 2.
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`Remarks begin on page 4.
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`Benitec - Exhibit 1002 - page 550
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`

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`Application No. 11/894,676
`Attorney Docket No. 0287000.130.US3
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`AMENDMENT
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`In the Claims
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`Please amend the claims as follows, without prejudice. This listing of the claims will
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`replace all prior versions and listings of claims in the application:
`
`1-49.
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`(Cancelled)
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`50.
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`(Previously presented) A method for attenuating expression of a target gene in a
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`mammalian cell, the method comprising
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`introducing into a mammalian cell a library of RNA expression constructs, each
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`expression construct comprising:
`
`(i)
`
`(ii)
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`an RNA polymerase promoter, and
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`a sequence encoding a short hairpin RNA molecule comprising a double-stranded
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`region wherein the double-stranded region consists of at least 20 nucleotides but not more than
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`29 nucleotides, such that the short hairpin RNA does not trigger a protein kinase RNA-activated
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`(PKR) response in the mammalian cells,
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`wherein the double-stranded region of the short hairpin RNA molecule comprises a
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`sequence that is complementary to a portion of the target gene, and
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`wherein the short hairpin RNA molecule is stably expressed in the mammalian cell in an
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`amount sufficient to attenuate expression of the target gene in a sequence specific manner,
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`whereby expression of the target gene is inhibited.
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`51.
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`52.
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`(Cancelled)
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`(Previously presented) The method of claim 50, wherein the expression construct
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`further comprises L TR sequences located 5' and 3' of the sequence encoding the short hairpin
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`RNA molecule.
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`53.
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`54.
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`(Cancelled)
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`(Previously presented) The method of claim 50, wherein the short hairpin RNA
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`molecule comprises a double-stranded region consisting of at least 21 nucleotides.
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`55.
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`(Previously presented) The method of claim 50, wherein the short hairpin RNA
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`molecule comprises a double-stranded region consisting of at least 22 nucleotides.
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`Benitec - Exhibit 1002 - page 551
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`Application No. 11/894,676
`Attorney Docket No. 0287000.130.US3
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`56.
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`(Previously presented) The method of claim 50, wherein the short hairpin RNA
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`molecule comprises a double-stranded region consisting of at least 25 nucleotides.
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`57.
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`(Previously presented) The method of claim 50, wherein the short hairpin RNA
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`molecule comprises a double-stranded region consisting of 29 nucleotides.
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`58.
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`(Previously presented) The method of claim 50, wherein the short hairpin RNA
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`molecule has a total length of about 70 nucleotides.
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`59.
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`(Previously presented) The method of claim 50, wherein the RNA polymerase
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`promoter comprises a pol II promoter or a pol III promoter.
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`60.
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`(Previously presented) The method of claim 59, wherein the pol III promoter
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`comprises a U6, an HI, or an SRP promoter.
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`61.
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`(Withdrawn) The method of claim 59, wherein the pol II promoter comprises a
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`Ul or a CMV promoter.
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`62.
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`(Previously presented) The method of claim 50, wherein the short hairpin RNA
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`molecule attenuates expression of the target gene in the mammalian cell by at least about 60%.
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`63.
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`(Previously presented) The method of claim 50, wherein the short hairpin RNA
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`molecule attenuates expression of the target gene in the mammalian cell by about 60% to about
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`90%.
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`64.
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`(New) A method for attenuating expression of a target gene in a mammalian cell,
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`the method comprising introducing into a mammalian cell a library of RNA expression
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`constructs, each expression construct comprising:
`
`(i)
`
`(ii)
`
`an RNA polymerase promoter, and
`
`a sequence encoding a short hairpin RNA molecule comprising a double-stranded
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`region wherein the double-stranded region consists of between 25 and 30 nucleotides, such that
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`the short hairpin RNA does not trigger a protein kinase RNA-activated (PKR) response in the
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`mammalian cells,
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`wherein the double-stranded region of the short hairpin RNA molecule comprises a
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`sequence that is complementary to a portion of the target gene, and
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`wherein the short hairpin RNA molecule is stably expressed in the mammalian cell in an
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`amount sufficient to attenuate expression of the target gene in a sequence specific manner,
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`whereby expression of the target gene is inhibited.
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`Benitec - Exhibit 1002 - page 552
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`

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`Application No. 11/894,676
`Attorney Docket No. 0287000.130.US3
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`REMARKS
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`I.
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`INTERVIEW SUMMARY
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`A telephonic interview regarding the present application took place on December 17,
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`2009 among Examiner Chong, Acting SPE Vivlemore; Dr. Vladimir Drozdoff and Mr. John
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`Maroney, both of Cold Spring Harbor Laboratory; and Dr. Anne-Marie Yvon and Dr. Jane Love,
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`both ofWilmerHale. Applicants explained that the intention of the interview was to advance
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`what has been a very lengthy prosecution by providing any information that might assist the
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`Examiners in view of the last response filed, and to reduce and clarify the issues in the case.
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`A.
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`Claim Amendments filed on November 4, 2009
`
`Applicants pointed out the amendments made to the claims and specifically explained the
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`basis in the specification for support of those amendments in the pending application and in the
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`parent '797 application. Applicants also discussed In re Werthiem as relevant case law in
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`supporting the amendment reciting the length of the double-stranded region as "at least 20
`
`nucleotides but not more than 29 nucleotides." Examiners Chong and Vivlemore stated that they
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`did not see any written description issue with the claim amendment and agreed that the
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`amendment is supported by adequate written description in the specification.
`
`B.
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`Length of Double-stranded Region As Claimed Not Disclosed in Fire et al.
`(U.S. Patent No. 6,506,599)
`
`Applicants explained that Fire et al. does not anticipate the pending claims because Fire
`
`does not disclose all of the limitations of the claimed invention, as arranged in the claimed
`
`invention.
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`First, Applicants explained that Fire is silent with respect to the length of the double(cid:173)
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`stranded region. The Examiner pointed to the language in Fire at column 8, lines 5-6 which
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`recites "The length of the identical nucleotide sequences may be at least 25, 50, ... "and claim
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`15. Applicants pointed out that this disclosure in Fire reciting "identical nucleotides" refers back
`
`to the first sentence of that paragraph, at column 7, line 53, which recites "RNA containing a
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`nucleotide sequences (sic) identical to a portion of the target gene are preferred .... " Therefore,
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`applicants made the point that the disclosure in Fire only refers to the length of the region that is
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`complementary to the target gene, and does not refer to the length of the double-stranded region.
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`Benitec - Exhibit 1002 - page 553
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`Application No. 11/894,676
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`Applicants pointed out that the length of the double-stranded region in the context of the
`
`Fire disclosure could be much, much longer. Examiner Chong did not agree and maintained that
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`Fire did disclose an embodiment having a 25-nucleotide double-stranded region.
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`Overlap in Ranges Is Not Sufficient for Anticipation
`C.
`Applicants made the further point that even if, arguendo, Fire teaches a double-stranded
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`region of 25 nucleotides (which Applicants dispute), the range recited in the pending claims, i.e.,
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`"wherein the double-stranded region consists of at least 20 nucleotides but not more than 29
`
`nucleotides ... ," only very slightly overlaps with Fire's recited range, i.e., from "at least 25"
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`nucleotides to an unspecified upper limit. Applicants stressed that according to the case law
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`precedent in Atofina, a slight overlap in ranges is not anticipation.
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`Examiner Chong stated it was her position that the disclosure of "at least 25" not only
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`discloses a range, but also discloses the 25 base length as a single species. The Examiner
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`pointed to the recitation in the Fire document of "at least 25, 50, 100, 200, 300 or 400 bases as
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`disclosing individual embodiments.
`
`Applicants argued that the "at least 25, 50, ... "recitation in Fire is a disclosure only of
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`ranges, that the numbers refer only to the lower limit of those ranges, and that those ranges have
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`no upper limit. In support, Applicants referred to the use of "at least. .. " language to describe
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`ranges in In re Werthiem, 541 F.2d 257 (C.C.P.A. 1976). Additionally, Applicants referred to
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`the Atofina case, which expressly notes that "[T]he disclosure of a range is no more a disclosure
`
`of the end points of the range than it is each of the intermediate points." Atofina v. Great Lakes
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`Chem. Corp., 441 F.3d 991, 1000, 78 U.S.P.Q. 2d 1417, 1424 (Fed. Cir. 2006), as cited by
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`M.P.E.P. § 2131.03 (II).
`
`Stable Expression Claim Recitation Is Not Disclosed in Fire
`D.
`Applicants argued that the claim requirement of "stable expression" of the vector is not
`
`disclosed in Fire. Applicants pointed to language in Paragraph [0019] of the '797 publication
`
`regarding stable expression.
`
`Examiner Chong inquired as to whether stable expression is a function of the construct.
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`Applicants indicated that it is a function of its design in that it is designed for and can be used for
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`stable expression. However, to avoid any misunderstanding, Applicants now clarify that as the
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`Benitec - Exhibit 1002 - page 554
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`Application No. 11/894,676
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`construct can also be used for transient expression, stable expression is not an inherent, that is,
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`necessary function of the design.
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`Examiner Chong indicated that she would need to look further at the Fire disclosure and
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`commented that if she could not find disclosure of "stable expression" in Fire, then this would be
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`a good argument against anticipation.
`
`E.
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`Kreutzer (US 2004/0102408) Not a Proper Reference Under 35 U.S.C. §
`102(e)
`
`Applicants pointed out that the Kreutzer reference cited by the Examiner in the related
`
`'086 application is not a proper reference under 35 U.S.C. § 102( e ). Since the 102( e) rejection
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`was made in the '086 application, Applicants have not previously submitted that argument in
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`writing on the record in this case.
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`F.
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`Declaration of Dr. Hernandez Evidence of Non-obviousness
`
`Applicants explained that a 132 Declaration was filed to provide further factual evidence
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`that one skilled in the art at the time of the invention would have understood the state of the art to
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`teach away from the pending claims because longer dsRNA molecules elicit a PKR response and
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`shorter dsRNA molecules were not thought to be effective.
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`G.
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`Next steps
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`Applicants discussed the filing of this Interview Summary and Supplemental Response.
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`Examiner Chong indicated that the '676 application next appears on her docket at about the
`
`middle of January 2010.
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`II.
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`STATUS OF THE CLAIMS: ADDITION OF NEW CLAIM
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`Claims 50, 52, and 54-64 are pending in this application. Claim 64 is added. Claim 64
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`recites that "the double-stranded region consists of between 25 and 30 nucleotides." "Between"
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`is the interval defined by two endpoints. Therefore, in claim 64, the interval between 25 and
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`30 defines a double-stranded region of 26, 27, 28, or 29 nucleotides. No new matter is added.
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`For the same reasons discussed during the interview, new claim 64 is fully supported by
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`the specification and the parent application, U.S.S.N. 10,055,797 ("the '797 application") under
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`35 U.S.C. § 112. The facts of the present case are analogous to those in In re Wertheim, 541
`
`F.2d 257 (C.C.P.A. 1976).
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`Benitec - Exhibit 1002 - page 555
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`Application No. 11/894,676
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`In Wertheim, the Applicant disclosed a range of 25-60% soluble solids in a freeze-dried
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`coffee extract, and exemplified soluble solids of 36% and 50%. The court found that Wertheim
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`had written description for 35-60% because "as a factual matter, persons skilled in the art would
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`consider processes employing a 35-60% solids content range to be part of appellants' invention
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`and would be led by the Swiss [priority] disclosure so to conclude." Id. at 265. In the present
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`application, as in Wertheim, Applicants disclosed the setting of an upper limit based on an
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`exemplified embodiment of the claimed invention. The upper limit is taught in the specification
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`to be significant and necessary limit on the length of the double-stranded region, in order to
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`avoid a PKR response in cells. As in Wertheim, one of skill in the art would therefore consider
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`use of a short hairpin RNA having between 25 and 30 base pairs to all be part of the same
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`invention the specification discloses for attenuating gene expression in mammalian cells without
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`triggering a PKR response.
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`III.
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`PENDING CLAIMS ARE NOT ANTICIPATED BY OR OBVIOUS OVER FIRE
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`A.
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`Examiners Are Required to Provide Reasoned Rebuttal to Applicant's
`Arguments
`
`According to M.P.E.P. § 707.07(f):
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`1.
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`"Where the applicant traverses any rejection, the examiner should, if he or
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`she repeats the rejection, take note of the applicant's argument and answer
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`the substance of it."
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`2.
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`"If it is the examiner's considered opinion that the asserted advantages are
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`not sufficient to overcome the rejection(s) ofrecord, he or she should state
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`the reasons for his or her position in the record, preferably in the action
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`following the assertion or argument relative to such advantages. By so
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`doing the applicant will know that the asserted advantages have actually
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`been considered by the examiner and, if appeal is taken, the Board of
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`Patent Appeals and Interferences will also be advised."
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`If the amendments and arguments provided in the response and this supplemental
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`response do not put the application in condition for allowance, Applicants request that the
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`Benitec - Exhibit 1002 - page 556
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`Application No. 11/894,676
`Attorney Docket No. 0287000.130.US3
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`Examiner, in her response, point out the specific reasons for continued rejection of the claims
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`and the basis in the art and the precedential case law for those rejections.
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`B.
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`Issue Clarified by Examiner Interview - Whether Fire Describes and,
`Therefore, Anticipates the Claimed Invention
`1.
`Legal Standard of Anticipation
`
`Anticipation requires that the prior art reference disclose each and every element recited
`
`in the pending claim. However, it is not enough that the reference disclose distinct teachings of
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`each element of the claim within its four comers. The law requires that the elements in an
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`anticipatory reference "be arranged as recited in the claim." Net MoneyIN, Inc. v. Verisign, Inc.,
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`545 F.3d 1362, 1371 (Fed. Cir. 2008).
`
`The Federal Circuit in Net Money IN clarifies the law of anticipation:
`
`As we have stated numerous times (language on which VeriSign
`relies), in order to demonstrate anticipation, the proponent must
`show "that the four comers of a single, prior art document describe
`every element of the claimed invention." This statement embodies
`the requirement in section 102 that the anticipating invention be
`"described
`in a printed publication," and
`is, of course,
`unimpeachable. But it does not tell the whole story. Because the
`hallmark of anticipation is prior invention, the prior art reference(cid:173)
`in order to anticipate under 35 U.S.C. § 102-must not only
`disclose all elements of the claim within the four comers of the
`document, but must also disclose those elements "arranged as in
`the claim.".
`
`Id. at 1369 (citations omitted).
`
`Ecolochem, Inc. v. Southern California Edison Co., 227 F.3d 1361 (Fed. Cir. 2000), is
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`another case in which the Federal Circuit found that there was no anticipation due to the cited
`
`reference lacking disclosure that linked or arranged the elements as claimed. The court in Net
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`MoneyIN commented on the Ecolochem case:
`
`After determining that the relevant figure and accompanying text
`described only the use of hydrogen to deoxygenate water, we
`concluded that the reference could not anticipate the claimed
`invention because there was no link between that figure and the
`general discussion of hydrazine as a deoxygenating agent. In other
`words, we concluded that although the reference taught all
`elements of the claim, it did not contain a discussion suggesting or
`linking hydrazine with the mixed bed in the figure, and thus did
`not show the invention arranged as in the claim.
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`Benitec - Exhibit 1002 - page 557
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`Net MoneyIN, Inc., 545 F.3d at 1370 (citation omitted).
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`In Applicants' case, the prior art reference is Fire and the Examiner has identified
`
`locations in Fire that allegedly support anticipation of the claimed invention. In contrast, it is
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`Applicants' position that for the sake of argument, even assuming that Fire does disclose every
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`element of the claimed invention, by analogy to Ecolochem, there is no discussion in Fire
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`suggesting or linking stable expression with use of a hairpin RNA having a double-stranded
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`region of at least 20 nucleotides but no more than 29 nucleotides, and therefore Fire does not
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`show the invention arranged as in the claim.
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`2.
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`Fire does not anticipate the presently claimed range.
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`Fire does not disclose a short hairpin RNA molecule, where "the double-stranded region
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`consists of at least 20 nucleotides but not more than 29 nucleotides."
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`M.P.E.P. § 2131.03, entitled "Anticipation of Ranges" makes it clear that disclosure of a
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`large range does not anticipate a smaller, overlapping range. Relying upon the Atofina case, the
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`M.P .E.P. also instructs that disclosure of a range is not disclosure of the endpoints of the range.
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`Section 2131.03 states that in order to anticipate the claims, the claimed subject matter
`
`must be disclosed in the reference with "sufficient specificity to constitute an anticipation under
`
`the statute." It goes on to state:
`
`What constitutes a "sufficient specificity" is fact dependent. If the
`claims are directed to a narrow range, and the reference teaches a
`broad range, depending on the other facts of the case, it may be
`reasonable to conclude that the narrow range is not disclosed with
`"sufficient specificity" to constitute an anticipation of the claims.
`See, e.g., Atofina v. Great Lakes Chem. Corp, 441 F.3d 991, 999,
`78 U.S.P.Q. 2d 1417, 1423 (Fed. Cir. 2006) wherein the court held
`that a reference temperature range of 100-500 degrees C did not
`describe the claimed range of 330-450 degrees C with sufficient
`specificity to be anticipatory. Further, while there was a slight
`overlap between the reference's preferred range (150-350 degrees
`C) and the claimed range, that overlap was not sufficient for
`anticipation. "[T]he disclosure of a range is no more a disclosure
`of the end points of the range than it is each of the intermediate
`points." Id. at 1000, 78 U.S.P.Q. 2d at 1424.
`
`M.P.E.P. § 2131.03 (II).
`
`The pending claims of the present application are directed to a narrow range (at least 20
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`nucleotides but not more than 29 nucleotides; between 25 and 30). The Fire reference discloses
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`Benitec - Exhibit 1002 - page 558
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`a very broad range (at least 25 nucleotides, with no upper limit). Although there is a slight
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`overlap in our case, just as in Atofina, this overlap is not sufficient for anticipation.
`
`Here, Applicants understand the Examiner's position to be that Fire's disclosure, "[t]he
`
`length of the identical nucleotide sequences may be at least 25, 50, 100, 200, 300 or 400 bases,"
`
`not only discloses a range, but serves as a species disclosure, that is, a length of 25 nucleotides.
`
`The Examiner's position conflicts with binding precedent, as acknowledged by the M.P.E.P.,
`
`which holds that simply because ranges must necessarily describe end points, describing an end
`
`point does not disclose that end point as a species: "[T]he disclosure of a range is no more a
`
`disclosure of the end points of the range than it is each of the intermediate points." Atofina, 441
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`F.3d at 1000; see also, M.P.E.P. § 2131.03 (II)( citing Atofina); M.P.E.P. § 2163.05 (III) ("at
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`least ... " describing a range).
`
`The court in Atofina ruled that even though the broad range fully encompassed the
`
`narrower range, there was a "considerable difference between the claimed range and the range in
`
`the prior art" such that "no reasonable fact finder could conclude that the prior art describes the
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`claimed range with sufficient specificity to anticipate this limitation of the claim." Atofina, 441
`
`F.3d at 999.
`
`The court's finding with respect to the preferred prior art range is also instructive. The
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`court said that the slightly overlapping prior art range of 150-350° C did not anticipate the
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`claimed range of 330-450° C. The court stated that the disclosure of a range "does not constitute
`
`a specific disclosure of the endpoints of that range." Id. at 1000. The court went on to say:
`
`"The disclosure is only that of a range, not a specific temperature in that range, and the
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`disclosure of a range is no more a disclosure of the end points of the range than it is of each of
`
`the intermediate points." Id.
`
`The supposed range disclosed by Fire is of a complementary region of at least 25
`
`nucleotides, with no disclosed endpoint. The present claims recite a double-stranded region of at
`
`least 20 but not more than 29 nucleotides. The alleged overlap with Fire's range is even more
`
`slight here than in Atofina.
`
`Furthermore, new claim 64 is not anticipated by Fire because, if, arguendo, one takes the
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`Examiner's position as true (which Applicants do not) that Fire anticipates the species of a
`
`double-stranded region having a length of 25 nucleotides, then a claim requiring a length of
`
`double-stranded region of "between 25 and 30" is not anticipated by Fire. The alleged species
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`Benitec - Exhibit 1002 - page 559
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`Application No. 11/894,676
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`that the Examiner contends is disclosed by Fire of 25 nucleotides in length is excluded from the
`
`range recited in new claim 64. Accordingly, the alleged species disclosed by Fire falls outside
`
`the scope of the claim, and therefore does not anticipate new claim 64.
`
`Fire's disclosure of length ranges refers to "a nucleotide sequence
`3.
`identical to a portion of a target gene" or the complementary region, and not to
`the claimed element of a "double-stranded region."
`The Examiner relies upon col. 7-8 and claim 15 of Fire to support alleged anticipation. In
`
`particular, the Examiner relies on Fire's statement: "The length of the identical nucleotide
`
`sequences may be at least 25, 50, 100, 200, 300 or 400 bases." This statement in Fire uses the
`
`term "identical nucleotide sequences" which the Examiner believes to be the same as the
`
`"double-stranded region" in the pending claims. Applicants disagree.
`
`The antecedent for "the identical nucleotide sequences" in Fire can be found at the
`
`beginning of that same paragraph, at col. 7, lines 53-55. Here, Fire states "RNA containing a
`
`nucleotide sequences [sic] identical to a portion of the target gene are referred for inhibition."
`
`Fire is merely describing the length of the complementary region of the RNA molecule, not the
`
`length of the double-stranded region. These two regions can be of very different lengths.
`
`The Examiner's interpretation of the statement in Fire is inconsistent with the context of
`
`the surrounding disclosure. The only lengths mentioned by Fire are with respect to the region
`
`that is complementary to the target gene sequence. A complementary region of "at least 25"
`
`nucleotides could imply a much longer double-stranded region. In fact, Fire exemplifies
`
`dsRNAs several hundred base pairs in length. (See Table 1.) There is no explicit or inherent
`
`disclosure in Fire regarding the length of the double-stranded region of a hairpin RNA.
`
`Claim 15 of Fire is expressly limited to a two-stranded RNA molecule. Therefore, the
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`reference to "said double-stranded ribonucleic structure is at least 25 bases in length" refers only
`
`to the range of double-stranded region lengths in a two-stranded RNA molecule. This fails to
`
`disclose anything about a short hairpin RNA molecule. Under Net Money IN and Ecolochem, it
`
`would be improper to extrapolate the recitation in Fire claim 15, which refers to a two-stranded
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`RNA molecule, to a different structure, e.g., a single hairpin RNA, as Applicants are presently
`
`claiming.
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`Benitec - Exhibit 1002 - page 560
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`Application No. 11/894,676
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`Fire does not link the elements of the claimed invention together as they
`4.
`appear in the presently pending claims.
`We understand that the Examiner's position is that she can take the disclosure of Fire into
`
`consideration as a whole. Nowhere, however, in Fire is there any description or discussion of
`
`using an expression construct as presently claimed for stable expression of a short hairpin RNA
`
`molecule. Moreover, Fire does not link or connect, in his disclosure, the use of a short hairpin
`
`RNA molecule with stable expression of that molecule in a mammalian cell. In addition, Fire
`
`does not link or connect the element of a hairpin RNA molecule with the element of the hairpin
`
`comprising a double-stranded region consisting of at least 20 nucleotides but not more than 29
`
`nucleotides. Fire therefore does not show or describe the invention arranged as in the claims.,
`
`These deficiencies in the Fire disclosure, under Net Money IN and Ecolochem, therefore
`
`demonstrate that Fire does not anticipate the claimed invention.
`
`C.
`
`Kreutzer Is Not a Proper Section 102(e) Reference, And the Claims Are Not
`Anticipated by Kreutzer
`
`Kreutzer et al. as cited in the parent application, U.S.S.N. § 10/997,086, is not proper
`
`prior art under 35 U.S.C. §102(e). Kreutzer et al. is based on an international application filed
`
`prior to November 29, 2000 and is therefore subject to the pre-"American Inventors Protection
`
`Act (AIPA) of 1999" version of 35 U.S.C. § 102(e). See M.P.E.P. 706.02(a) (II.B). The former
`
`version of Section 102( e) states:
`
`A person shall be entitled to a patent unless-
`
`( e) the invention was described in a patent granted on an
`application for patent by another filed in the United States before
`the invention thereof by the applicant for patent, or on an
`international application by another who has
`fulfilled
`the
`requirements of paragraphs (1), (2), and (4) of section 371(c) of
`this title before the invention thereof by the applicant for patent.
`
`The parent of the Kreutzer et al. publication cited in the Office Action was U.S.
`
`application Serial No. 09/889,802 ("the '802 application), which is now abandoned. The '802
`
`application has no 102( e) date because it never issued as a patent. The 102( e) date of the cited
`
`Kreutzer et al. publication is its filing date, March 6, 2003, which is later than the January 22,
`
`2002 priority date of the present application. See Example 6 ofM.P.E.P. § 706.02(±)(1) and note
`
`USlDOCS 7414074vl
`
`12
`
`Benitec - Exhibit 1002 - page 561
`
`

`
`Application No. 11/894,676
`Attorney Docket No. 0287000.130.US3
`
`the section on Additional Benefit Claims. Therefore, Kreutzer et al. is not a proper reference
`
`under Section 102( e ).
`
`Regardless, Kreutzer does not teach target gene attenuation by expression of a short
`
`hairpin RNA in a mammalian cell. The only place in Kreutzer that expressly mentions a hairpin
`
`is Paragraph [0019], which discusses chemical modification of the nucleotides in the loop region
`
`to protect against degradation. This discussion does not describe a hairpin expressed in a
`
`mammalian cell, which cannot have such chemical modification. Instead, this paragraph is
`
`directed to a hairpin that is synthesized before being introduced into a mammalian cell, "in
`
`particular, when using a vector according to the invention," that is "by means of T7 and SP6 in(cid:173)
`
`vitro transcription" (Kreutzer, Use Example 2 Paragraph [0068]).
`
`Paragraph [0019] is in the midst of several paragraphs teaching how to chemically link
`
`the dsRNA to prevent dissociation of the strands. Taken in context, the hairpin mentioned in
`
`Paragraph [0019] of Kreutzer is not one that is or could ever be expressed from a vector in the
`
`cell containing the target gene.
`
`Consequently, Kreutzer did not use "hairpin" in any part of the disclosure that may
`
`describe expression of a double-stranded RNA from a vector in a cell.
`
`D.
`
`Non-Obviousness Over The Prior Art
`
`The submitted 132 Declaration by Dr. Nouria Hernandez demonstrates that one of
`
`ordinary skill in the art would have had no expectation of successfully carrying out the claimed
`
`methods. The scientific literature taught away from the expression of short hairpins to attenuate
`
`target gene expression.
`
`USlDOCS 7414074vl
`
`13
`
`Benitec - Exhibit 1002 - page 562
`
`

`
`Application No. 11/894,676
`Attorney Docket No. 0287000.130.US3
`
`Consideration of this paper and allowance of this application are requested. If it would
`
`advance prosecution, the Examiner is invited to contact the undersigned to discuss the contents
`
`CONCLUSION
`
`of this paper.
`
`Dated: January 12, 2010
`
`Wilmer Cutler Pickering Hale and Dorr LLP
`399 Park Avenue
`New York, New York 10022
`(212) 230-8800 (telephone)
`(212) 230-8888 (facsimile)
`
`Respectfully submitted,
`
`/Anne-Marie C. Yvon/
`
`Jane M. Love, Ph.D.
`Registration No. 42,812
`
`Anne-Marie C. Yvon, Ph.D.
`Registration No. 52,390
`
`Attorneys for Applicant(s)
`
`USlDOCS 7414074vl
`
`14
`
`Benitec - Exhibit 1002 - page 563
`
`

`
`Electronic Acknowledgement Receipt
`
`EFSID:
`
`Application Number:
`
`6794878
`
`11894676
`
`International Application Number:
`
`Confirmation Number:
`
`8161
`
`Title of Invention:
`
`Methods and compositions for RNA interference
`
`First Named Inventor/Applicant Name:
`
`Gregory J. Hannon
`
`Customer Number:
`
`84834
`
`Filer:
`
`Anne-Marie Yvon/Patricia lerardi
`
`Filer Authorized By:
`
`Anne-Marie Yvon
`
`Attorney Docket Number:
`
`287000.130US3
`
`Receipt Date:
`
`Filing Date:
`
`Time Stamp:
`
`12-JAN-2010
`
`20-AUG-2007
`
`16:04:59
`
`Application Type:
`
`Utility under 35 USC 111 (a)
`
`Payment information:
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`Submitted with Payment
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`I no
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`File Listing:
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`Document
`Number
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`1
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`Document Description
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`File Name
`
`File Size( Bytes)/
`Message Digest
`
`Multi
`Part /.zip
`
`Pages
`(if appl.)
`
`287000_ 130US3_SuppAmend_
`011210.pdf
`
`177414
`
`82e93 d 0999 580b891 382 6a 7fe03 286e3 5 60
`0492a
`
`yes
`
`14
`
`Benitec - Exhibit 1002 - page 564
`
`

`
`Multipart Description/PDF files in .zip description
`
`Document Description
`
`Start
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`End
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`Supplemental Response or Supplemental Amendment
`
`Claims
`
`Applicant Arguments/Remarks Made in an Amendment
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`1
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`2
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`4
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`1
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`3
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`14
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`Warnings:
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`Information:
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`Total Files Size (in bytes)
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`177414
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`This Acknowledgement Receipt evidences receipt on the noted date by the USPTO of the indicated documents,
`characterized by the applicant, and including page counts, where applicable. It serves as evidence of receipt similar to a
`Post Card, as described in MPEP 503.
`
`New A~~lications Under 35 U.S.C. 111
`If a new application is being filed and the application includes the necessary components for a filing date (see 37 CFR
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