6
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`m
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`Docket No. UF.572XC1
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`Serial No. 12/664,172
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`Claims 1-18 are pending in the subject application. By this Amendment, Applicants
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`have amended claims 1, 4, and 5. Support for the amendments can be found throughout the
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`subject specification and in the claims as originally filed. Entry and consideration of the
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`amendments presented herein is respectfully requested. Accordingly, claims 1—12 are currently
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`before the Examiner. Favorable consideration of the pending claims is respectfully requested.
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`The application was filed with Figures 1—21. The Office Action Summary page did not
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`indicate that the drawings were accepted or objected to by the Examiner. Applicants respectfully
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`request
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`that
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`the Examiner consider
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`the figures and indicate their
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`status
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`in the next
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`communication.
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`Applicants appreciate permission of an Examiner Interview after final rejection to discuss
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`the basis of the Applieants’ position concerning the teachings of art cited in the Office Action.
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`Applicants respectfully submit that this amendment will require no further search or
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`examination on the part of the Examiner and does not constitute new matter.
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`Claims l—12 are rejected under 35 U.S.C.
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`§ 112, second paragraph, as indefinite.
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`Applicants respectfully assert that the claims as filed are definite.
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`Claim 1 is amended to clearly define that the carbon is specifically the carbon substituted
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`with the biologically active molecule of a repeating diene monomer unit of the polymer
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`backbone and to clarify the separation between adjacent carbons of this type. Accordingly,
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`reconsideration and withdrawal of the rejection under 35 U.S.C. § 112, second paragraph, is
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`respectfully requested.
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`Claims 1, 2, 4, 5 and 10-12 stand rejected under 35 U.S.C. § 103(a) as obvious over
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`Valenti et a].
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`(Macromolecules, 1998) and Elvira et a].
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`(Molecule, 2005). Applicants
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`respectfully assert
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`that
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`the claimed invention as amended is not obvious over the cited
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`references.
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`As is appreciated by the Patent Office:
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`7
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`Docket No. UF.572XC1
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`Serial No. 12/664,172
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`In re Hughes holds that “Words in a reference are to be construed in
`light of the relevant surrounding circumstances in each case, In re Folkenroth,
`275 F.2d 732, 47 CCPA 812, and a reference in any event is good only for that
`which it clearly and definitely discloses. (emphasis added)
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`The Office Action correctly indicates that Valenti et al. teaches the synthesis of well-
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`defined polyalcohol homopolymers and suggests their use as "binding substrates in the
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`preparation of a series of drug release macromolecules" (page 2773, col. 1, paragraph 1).
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`Respectfully, the Examiner infers that the polyalcohols are not for directly binding drugs, but
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`that they are taught for synthesis of a covalently bound drug. Applicants, which include a
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`coauthor of Valenti et al., hold that this statement did not suggest that binding is the use of the
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`homopolymers therein as synthetic intermediates to prepare other homopolymers. There is no
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`disclosure to transformation of the disclosed homopolymers with hydroxy groups
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`to
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`homopolymers with drug attachment to repeating units. Rather, Valenti et al., uses drug binding
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`of the traditional definition, that being “Interacting selectively and non-covalently with a drug”
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`(European Bioinformatics
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`Institute - Databases, http://www.ebi.ac.uk/QuickGO/GTerm?id
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`=GO:0008144) (emphasis added)
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`Furthermore, Valenti et al. clearly states that “We intend to use these well-defined
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`polyalcohol polymers as binding substrates in the preparation of drug release macromolecules.”
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`One skilled in the art would not look to a polyalcohol homopolymer for conversion of every
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`hydroxyl group to a homopolymer having “a plurality of repeating diene monomer units, each of
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`the repeating diene monomer units having coupled thereto at
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`least one biologically active
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`molecule”, as in the instant claimed invention.
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`It is well appreciated by those skilled in the art
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`that very few organic homopolymers can be transformed by reaction of the side groups into a
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`different homopolymer.
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`The general View of those skilled in the art
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`is that chemical
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`transformation of side groups to form a second homopolymer from a first homopolymer is the
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`exception and not the “obvious” rule. Arguably, the most used synthetic polymer textbook of all
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`time is George Odian, Principles of Polymerization, wherein, as recited in the Third Edition,
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`Chapter 9, pages 691 and 692, homopolymer preparation from another homopolymer is
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`discouraged:
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`“It is usually assumed that the reactivity of a functional group in a polymer
`and a small organic molecule are the same... However, in many instances, the
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`8
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`Docket No. UF.572XC1
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`Serial No. 12/664,172
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`reaction rates and maximum conversion observed in the reactions of polymer
`functional groups differ significantly from those for the corresponding low~
`molecular weight homologues. Polymer reaction rates and conversions are
`usually lower,. . .” p. 69] (emphasis added)
`“Yield or conversion in reactions of polymers means something quite
`different than in small molecule reactions when the conversion is less than
`100%. For example, 80% yield in the hydrolysis of methyl propanoate has no
`effect on the purity of the propraonic acid that can be obtained...The 80% yield
`simply limits the maximum amount of pure propanoic acid that can be obtained to
`80% of theoretical yield. However, 80% yield in the corresponding hydrolysis of
`poly(methyl acrylate) does not result in 80% yield of polyy(acrylic acid) with
`20% unreacted poly(methyl acrylate).
`The product contains copolymer
`molecules, each of which, on the average, contain 80% acrylic acid repeating
`units and 20% methyl acrylate units randomly placed alone the polymer chain.
`Unlike the corresponding small molecule reaction, the unreacted ester groups
`cannot be separatedfrom the product since both are part of the same molecule.”
`p. 692 (emphasis added)
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`This teaching of Odian, though perhaps more clearly stated, is consistent with that taught
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`in other common polymer textbooks. For example, Harry R. Allcock and Fredric W. Lampe,
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`Contemporary Polymer Chemistry, Second Edition, pages 149-50 recites:
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`the vast arsenal of conventional organic and inorganic reaction
`In theory,
`chemistry could be used to modify the side groups in a polymer.
`In practice, limitations
`exist. Reactions that proceed rapidly and efficiently at the small-molecule level may
`not take place effectively with a high polymer” p. 149—50 (emphasis added)
`in which
`“There
`exists one
`polymer
`system -the
`polyphosphazines-
`macromolecular substitution reactions are so efficient that such reactions are the main
`method of polymer
`synthesis
`and structural diversity. . . Unfortunately,
`such
`intermediates are all too rare among organic polymer systems. p. 150 (emphasis added)
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`Clearly, even if the Valenti et al. statement of "binding substrates in the preparation of a
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`series of drug release macromolecules" (page 2773, col. 1, paragraph 1) would encourage their
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`chemical modification to form a macromolecule with bonded drugs, one of ordinary skill in the
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`art would appreciate that a copolymer is suggested and not a homopolymer “consisting of a
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`plurality of repeating diene monomer units, each of the repeating diene monomer units having
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`coupled thereto at least one biologically active molecule,” of amended claim 1. Clearly, in more
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`than 17 years since the submission of the preliminary manuscript that led to Valenti et al. on
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`October 8, 1997, no disclosure of a homopolymer with bioactive agents on every repeating unit
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`9
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`Docket No. UF.572XC1
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`Serial No. 12/664,172
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`from the well-defined polyalcohol polymers of Valenti et a]. has resulted from that research
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`group or any other.
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`Elvira et al. teaches drug delivery systems containing a polymeric backbone conjugated
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`at pendant groups to a bioactive molecule. Elvira et al. teaches a variety of hydrolyzable or
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`biodegradable linkers: esters; carbonates; anhydrides; urethanes; orthoesters; and amides that
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`have been used to make polymer-drug conjugates. Elvira et a]. does not teach a single polymeric
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`system where the pendant drugs are at a regular interval along the backbone of a homopolymer
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`chain or a polymeric chain prepared by step—growth polymerization. Elvira et a]. only teaches
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`the preparation of copolymers, where bioactive agents are on one or more repeating units of a
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`polymer prepared by a chain-growth polymerization, and does not suggest the preparation of a
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`homopolymer. Elvira et a].
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`teaches pendent group systems, where it clearly states in the
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`introduction, page 119, where these pendent group systems are directed exclusively to
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`copolymers. All pendent systems disclosed therein are copolymers.
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`Therefore, those of ordinary skill in the art, as evident the teaching of Odian in Principles
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`of Polymerization, would not be motivated to carry out a polymer modification of the
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`polyalcohol polymer of Valenti et (11., to yield a homopolymer with biologically active molecules
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`attached to every repeating unit. Elvira er al. reinforces Applicants’ View that the polymer
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`modification indicated in the Office Action would not be considered a viable synthesis of a
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`homopolymer such as that of the instant
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`invention, as Elvira et al. exclusively teaches
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`copolymers, including copolymers prepared by polymer modification that does not proceed to a
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`homopolymer. Hence, the homopolymers of the amended claimed invention cannot be obvious
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`in View of the copolymers taught in Elvira et a]. and the binding substrate suggested in Valenti et
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`al.
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`Claims 3 and 6-9 stand rejected under 35 U.S.C.
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`§ 103(a) as obvious over the
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`combination of Valenti et al. (Macromolecules, 1998) and Elvira et a1. (Molecule, 2005), as
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`applied to claims 1-2, 4-5, 10-12, above and further in view of Zhu (Acc. Chem Res, 2002).
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`Applicants respectfully assert that the claimed invention is not obvious over the cited reference.
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`10
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`Docket No. UF.572XC1
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`Serial No. 12/664,172
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`The Office Action indicates that the combination of Valenti et‘ al. and Elvira et a]. fail to
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`teach a linker that comprises an ether group and a carbamate group. The combination of Valenti
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`et al. and Elvira et al. also fail to teach an ethylene glycol or multiple ethylene glycol spacers.
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`As indicated above Valenti et a].
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`in view of Elvira et al. does not obviate the instant
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`claimed invention, as a homopolymer is neither taught nor suggested by the combination. Zhu
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`does not cure the deficiency of Valenti et al. in view of Elvira et al. There is not a single
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`polymer taught in Valenti et al., Elvira et 61]., or Zhu that is a regular step—growth polymer with
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`pendant biologically active groups. All polymers with pendant biologically active groups are
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`copolymers. The present
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`application discloses new compositions of matter
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`that
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`are
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`homopolymers and these homopolymers are neither taught nor suggested by Valenti et al.
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`in
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`view of Elvira et al. further in view of Zhu. Accordingly, reconsideration and withdrawal of the
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`rejections under 35 U.S.C. § 103(a) is respectfully requested.
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`It should be understood that the amendments presented herein have been made my to
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`expedite prosecution of the subject application to completion and should not be construed as an
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`indication of Applicants” agreement with or acquiescence in the Examiner’s position. Applicants
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`expressly reserve the right to pursue the invention(s) disclosed in the subject application,
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`including any subject matter canceled or not pursued during prosecution of the subject
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`application, in a related application.
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`In view of the foregoing remarks and amendments to the claims, Applicants believe that
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`the currently pending claims are in condition for allowance, and such action is respectfully
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`requested.
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`The Commissioner is hereby authorized to charge any fees under 37 CPR. §§1.16 or
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`1.17 as required by this paper to Deposit Account No. 19-0065.
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`1 1
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`Docket No. UF.572XC1
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`Serial No. 12/664,172
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`Applicants invite the Examiner to call the undersigned if clarification is needed on any of
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`this response, or if the Examiner believes a telephonic interview would expedite the prosecution
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`of the subject application to completion.
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`Respectfully submitted,
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`472253;”
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`Mark A. Buese, PhD.
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`Patent Agent
`Registration No. 52,669
`Phone No.:
`352-375-8100
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`Fax No.:
`Address:
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`352—372—5800
`PO. Box 142950
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`Gainesville, FL 32614-2950
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`MAB/ps
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