Ex Parte GmeinerDownload PDFBoard of Patent Appeals and InterferencesNov 18, 201011704090 (B.P.A.I. Nov. 18, 2010) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 11/704,090 02/08/2007 William H. Gmeiner 9151-63 6307 20792 7590 11/18/2010 MYERS BIGEL SIBLEY & SAJOVEC PO BOX 37428 RALEIGH, NC 27627 EXAMINER STEELE, AMBER D ART UNIT PAPER NUMBER 1639 MAIL DATE DELIVERY MODE 11/18/2010 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte WILLIAM H. GMEINER __________ Appeal 2010-004807 Application 11/704,090 Technology Center 1600 __________ Before BRADLEY R. GARRIS, LINDA M. GAUDETTE, and MELANIE L. McCOLLUM, Administrative Patent Judges. McCOLLUM, Administrative Patent Judge. DECISION ON APPEAL1 This is an appeal under 35 U.S.C. § 134 involving claims to a nucleic acid generation method. The Examiner has rejected the claims on appeal as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 The two-month time period for filing an appeal or commencing a civil action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing, as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE” (paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery mode) shown on the PTOL-90A cover letter attached to this decision. Appeal 2010-004807 Application 11/704,090 2 STATEMENT OF THE CASE Claims 1, 2, 5, 6, 9-18, 21, 24-32, and 34 are on appeal. Claims 3, 4, 7, 8, 19, 20, 22, and 23 are also pending but have been withdrawn from consideration by the Examiner. (App. Br. 3.) We will focus on claims 1, 11, and 17, which read as follows: 1. A method of generating a nucleic acid of interest, which nucleic acid specifically binds to an extracellular surface protein expressed by a cell of interest, and which nucleic acid is capable of being internalized by said cell of interest, said method comprising the steps of: combining a first pool comprising different nucleic acids with said extracellular surface protein; selecting a first subpopulation of nucleic acids from said first pool, said first subpopulation comprising at least one nucleic acid that specifically binds to said extracellular surface protein; amplifying said at least one nucleic acid of said first subpopulation; and selecting a second subpopulation comprising at least one nucleic acid species from said first subpopulation which is internalized by said cell of interest, wherein said selecting step is performed by fluorescence microscopy or flow cytometry. 11. The method of claim [1, wherein said nucleic acid comprises cytotoxic nucleotides, said cytotoxic nucleotides comprise poly-FdUMP, and] said poly-FdUMP comprises FdUMP[9] or FdUMP[10]. 17. A method of generating a nucleic acid of interest, which nucleic acid specifically binds to an extracellular surface protein expressed by a cell of interest, which nucleic acid is capable of being internalized by said cell of interest, and which nucleic acid comprises one or more types of compounds of interest to be delivered to said cell of interest, said method comprising the steps of: combining a first pool comprising different nucleic acids with said extracellular surface protein; selecting a first subpopulation of nucleic acids from said first pool, said first subpopulation comprising at least one nucleic acid that specifically binds to said extracellular surface protein; Appeal 2010-004807 Application 11/704,090 3 amplifying said at least one nucleic acid of said first subpopulation; selecting a second subpopulation comprising at least one nucleic acid species from said first subpopulation which is internalized by said cell of interest; determining a first chemical structure of a nucleic acid from said second population; determining a second chemical structure of a nucleic acid which is an analog of said nucleic acid from said second population, said analog comprising one or more types of said compounds of interest; analyzing the folding properties of said first chemical structure; analyzing the folding properties of said second chemical structure; comparing the folding properties of said first chemical structure with that of said second chemical structure; and generating a nucleic acid of interest based upon said comparing. Claims 1, 2, 5, 6, and 9-16 stand rejected under 35 U.S.C. § 103(a) as obvious over Stanton et al. (US 2004/0249130 A1, Dec. 9, 2004) and Gmeiner (US 6,342,485 B1, Jan. 29, 2002) (Ans. 4). Claims 1, 2, 5, 6, 9-18, 21, 24-32, and 34 stand rejected under 35 U.S.C. § 103(a) as obvious over Stanton, Gmeiner, and Shi et al. (US 2005/0282190 A1, Dec. 22, 2005) (Ans. 6-7). PRINCIPLES OF LAW “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). Obviousness “analysis need not seek out precise teachings directed to the specific subject matter of the challenged claim.” Id. at 418. Instead, it proper to “take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. “A person of ordinary skill is also a person of ordinary creativity, not an automaton.” Id. at 421. Appeal 2010-004807 Application 11/704,090 4 I In rejecting claim 1, for example, the Examiner relies on Stanton for teaching methods of generating nucleic acids of interest comprising preparing a pool of nucleic acids (i.e. aptamers), combining the aptamers with an extracellular surface protein of interest, selecting aptamers that bind to the extracellular surface protein of interest, amplifying the aptamers, utilizing a cell expressing the extracellular surface protein of interest to select an aptamer that is internalized by the cell. (Ans. 4-5.) In addition, the Examiner finds that “the aptamer can be conjugated to toxins including fluorouracil” (id. at 5). The Examiner relies on Gmeiner for teaching “FdUMP[9] or FdUMP[10] as toxins that can be utilized to treat cancer alone or in combination with fluorouracil and analysis via flow cytometry” (id.). The Examiner concludes that it would have been obvious “to modify the toxins utilized in the method taught by Stanton et al. with the FdUMP[9] or FdUMP[10] taught by Gmeiner” (id.). The Examiner additionally concludes that “the claims would have been obvious because . . . flow cytometry to detect fluorescence[] was recognized as part of the ordinary capabilities of one skilled in the art” (id. at 6). Appellant argues: the combination of Stanton et al. and Gmeiner neither teaches nor directs one of ordinary skill in the art to select a second subpopulation comprising at least one nucleic acid species from said first subpopulation which is internalized by said cell of interest, wherein said selecting step is performed by fluorescence microscopy or flow cytometry. Appeal 2010-004807 Application 11/704,090 5 (App. Br. 7.) In particular, Appellant argues that “a particular known technique being ‘part of the ordinary capabilities’ of one of ordinary skill in the art does not show motivation for one of ordinary skill in the art to perform this technique in order to arrive at Appellant’s claimed invention” (id.). Appellant also argues that, with regard to the elected species, “FdUMP[9], one of ordinary skill in the art is . . . not directed down the path to modify Stanton et al. with the particular toxins found in the Gmeiner reference” (id.). In particular, Appellant argues that “Fluorouracil (5-4 fluorouracil, in particular) is found among a general listing of known chemotherapeutic agents in paragraph [0232] of Stanton et al., and one of ordinary skill in the art is not directed to fluorouracil, or to specific variations thereof, in particular” (id. at 8). Issues Does the evidence support the Examiner’s conclusion that it would have been obvious to use flow cytometry to select nucleic acids in Stanton’s method? Does the evidence support the Examiner’s conclusion that it would have been obvious to link FdUMP[9] to Stanton’s aptamer? Analysis Stanton discloses that “[a]ptamer selection is accomplished by passing a solution of oligonucleotides through a column containing the target molecule” (Stanton, ¶ [0117]). Stanton also discloses that “[p]harmacokinetics and biodistribution of aptamer conjugates in biological samples are quantified radiometrically and by a hybridization-based dual Appeal 2010-004807 Application 11/704,090 6 probe capture assay with enzyme-linked fluorescent readout” (id. at ¶ [0186]). However, we agree with the Examiner that it would have been obvious to select aptamers by flow cytometry, as disclosed in Gmeiner. We are not persuaded by Appellant’s argument to the contrary because the Examiner provides reasons to combine the references in the Examiner’s Answer at pages 12-13 and Appellant has not adequately explained why these reasons are inadequate. In addition, Stanton discloses “linking a nucleic acid aptamer to cytotoxic agents and delivering the aptamer-toxin conjugate to a target” (Stanton, ¶ [0002]). Stanton also discloses that “[e]xamples of suitable toxins include, e.g., chemotherapeutic agents,” such as 5-4 fluorouracil (id. at ¶ [0232]). Gmeiner discloses the use of homo-oligomeric FdUMP as cytotoxic agents in the treatment of cancer (Gmeiner, col. 1, ll. 12-21, & col. 2, ll. 4-6). In particular, Gmeiner discloses a “homooligomer of FdUMP [that] ranges from about 9-11 monomers” (id. at col. 2, ll. 63-65). We agree with the Examiner that it would have been obvious to link homooligomers of FdUMP ranging from 9-11 monomers, including FdUMP[9] and FdUMP[10], recited in claim 11, to Stanton’s aptamers as the cytotoxic agent. We are not persuaded by Appellant’s argument to the contrary because we conclude that the selection of a known toxin, as disclosed in Gmeiner, is prima facie obvious over the teaching in Stanton of a broad range of toxins. Conclusion The evidence supports the Examiner’s conclusion that it would have been obvious to use flow cytometry to select nucleic acids in Stanton’s Appeal 2010-004807 Application 11/704,090 7 method. The evidence also supports the Examiner’s conclusion that it would have been obvious to link FdUMP[9] to Stanton’s aptamer. We therefore affirm the obviousness rejection of claim 1 over Stanton and Gmeiner. Claims 2, 5, 6, and 9-16 have not been argued separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii). II In rejecting claim 17, for example, the Examiner additionally relies on Shi for teaching “methods of analyzing the folding properties of nucleic acids including aptamers with the Mfold program by Zuker” (Ans. 8). The Examiner concludes that it would have been obvious “to modify . . . the method taught by Stanton et al. with . . . the folding analysis taught by Shi” (id.). Appellant argues: [I]t is unreasonable to conclude that one of ordinary skill in art would be motivated to analyze the folding properties of an aptamer made according to the teachings of Stanton et al. No mention is made in Stanton et al. of a problem with the folding properties of the aptamers such that one of ordinary skill in the art would have been motivated to analyze the nucleic acid structure/folding. Indeed, the toxin in Stanton et al. is conjugated to an aptamer by way of a linker (see, e.g., Example 5), which serves to physically separate the aptamer from the toxin and preserve the toxin’s pharmacological activity (see paragraph [0309]). This physical separation negates a need or motivation to analyze the folding structure in Stanton et al. (App. Br. 10). Appellant also argues: [N]o mention is made of “an analog” of the nucleic acid “comprising one or more types of said compounds of interest” in any of these references, which is recited in Appellant’s Appeal 2010-004807 Application 11/704,090 8 claim 17. As is known in the art, an analog is a compound which is structurally similar. The Advisory Action of February 26, 2009, on Page 6 states that analogs are found in Stanton et al. However, a motivation for one of ordinary skill in the art to use an analog in the same way as the claimed methods is not articulated. (Id.) Issue Does the evidence support the Examiner’s conclusion that it would have been obvious to compare the folding properties of a nucleic acid selected by Stanton’s method to the folding properties of an analog of the selected nucleic acid that comprises a compound of interest? Analysis Shi discloses “a method of using a multivalent nucleic acid aptamer to bring a first and second target molecule into proximity of one another” (Shi, ¶ [0014]). Shi also discloses: This method involves providing a multivalent aptamer comprising first, second, and third aptamer sequences, wherein the first and second aptamer sequences are operably linked by a three-way junction, and the third aptamer sequence is operably linked to the first and second aptamer sequences, and wherein each of the first and second aptamer sequences is capable of binding the first target molecule, and the third aptamer sequence is capable of binding the second target molecule, which is different from the first target molecule. (Id.) In addition, Shi discloses “FIG. 3B shows a construct (SEQ ID NO: 17) designed by fusing together through stems one reduced RA1-HSF with two reduced S1’s. . . . The secondary structure depicted here has been checked by Mfold . . . to ensure the correct folded form of each aptamer components in this composite structure.” (Id. at ¶ [0022].) Appeal 2010-004807 Application 11/704,090 9 Stanton discloses linking a compound of interest, that is, a cytotoxic agent, to a nucleic acid aptamer to form an aptamer-toxin conjugate (Stanton, ¶ [0002]). We agree with the Examiner that it would have been obvious to compare the secondary structure of the aptamer to the secondary structure of the conjugate, which is an analog of the aptamer comprising a compound of interest, to ensure that the aptamer of the conjugate has the correct folded form. We are not persuaded by Appellant’s argument to the contrary because we agree with the Examiner that Stanton discloses an analog, i.e., the conjugate, and Shi teaches that it is desirable to check the secondary structure of an aptamer “to ensure the correct folded form of each aptamer components in this composite structure” (Shi, ¶ [0022]). In order to confirm that the aptamer of the conjugate has the correct folded form, it would be obvious to compare it to the aptamer that has not been linked to the toxin to form a conjugate. Even if physical separation between the aptamer and the toxin diminishes the need to analyze the folding structure in Stanton, we agree with the Examiner that one of ordinary skill in the art would still consider it helpful to confirm that the secondary structure is correct. Conclusion The evidence supports the Examiner’s conclusion that it would have been obvious to compare the folding properties of a nucleic acid selected by Stanton’s method to the folding properties of an analog of the selected nucleic acid that comprises a compound of interest. We therefore affirm the obviousness rejection of claim 17 over Stanton, Gmeiner, and Shi. Appeal 2010-004807 Application 11/704,090 10 Claims 1, 2, 5, 6, 9-16, 18, 21, 24-32, and 34 have not been argued separately and therefore fall with claim 17. 37 C.F.R. § 41.37(c)(1)(vii). TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED cdc MYERS BIGEL SIBLEY & SAJOVEC PO BOX 37428 RALEIGH, NC 27627 Copy with citationCopy as parenthetical citation