Ex Parte Nair et alDownload PDFBoard of Patent Appeals and InterferencesJun 25, 201011264452 (B.P.A.I. Jun. 25, 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. 11/264,452 11/01/2005 Sankar Nair 60140.0004US01 4618 23552 7590 06/25/2010 MERCHANT & GOULD PC P.O. BOX 2903 MINNEAPOLIS, MN 55402-0903 EXAMINER SKOWRONEK, KARLHEINZ R ART UNIT PAPER NUMBER 1631 MAIL DATE DELIVERY MODE 06/25/2010 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 SANKAR NAIR, SOUMENDU BHATTACHARYA, VISHWANATH NATARAJAN, and ABHIJIT CHATTERJEE __________ Appeal 2009-014830 Application 11/264,452 Technology Center 1600 __________ Decided: June 25, 2010 __________ Before ERIC GRIMES, DONALD E. ADAMS, and DEMETRA J. MILLS, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a system for determining the length of DNA molecules. The Examiner has rejected some of the claims as directed to nonstatutory subject matter or including new matter, and has rejected all of the claims for obviousness. We have Appeal 2009-014830 Application 11/264,452 2 jurisdiction under 35 U.S.C. § 6(b). We affirm the rejection for nonstatutory subject matter but reverse the other rejections. STATEMENT OF THE CASE The Specification discloses determining the length of DNA molecules based on the time it takes for an individual DNA molecule to pass through a nanopore under the influence of an electric field (id. at 9, ¶ 30). The Specification discloses that “[a]n initial DC stimulus produces a coarse size distribution assay of the sample that can then be refined by an optimized AC stimuli [sic] specific to each region of the size distribution produced by the DC stimulus” (id. at 9, ¶ 29). That is, because of random forces acting on the DNA molecules, two molecules of similar size might not be distinguishable based on the DC stimulus alone (id. at 17, ¶ 50). However, “if a sinusoidal [AC] signal with carefully adjusted frequency, amplitude, and phase is added to the DC signal, the sensitivity for certain pairs of bases can be enhanced significantly” (id. at 18, ¶ 51). Claims 8-10, 12-16, 18-20, and 26-32 are on appeal. Claim 8 is representative and reads as follows: 8. A system for evaluating the length of biopolymers in a sample, the system comprising: a memory storage for maintaining a database; and a processing unit coupled to the memory storage, wherein the processing unit is operative to: use a direct current stimulus to determine a direct current base length region corresponding to at least a portion of the sample, the direct current base length region appearing to correspond to biopolymers of only one length after the direct current stimulus is used; determine an initial value for at least one alternating current stimulus characteristic; use a combination stimulus comprising a combination of the direct current stimulus and an alternating current stimulus to determine that the Appeal 2009-014830 Application 11/264,452 3 direct current base length region corresponds to a first set of biopolymers and a second set of biopolymers, the first set of biopolymers having a first base length and the second set of biopolymers having a second base length, wherein the processing unit being operative to use the combination stimulus comprises the processing unit operative to iteratively optimize the at least one alternating current stimulus characteristic, starting with the determined initial value, to increase the sensitivity of the determined direct current base length region wherein the processing unit being operative to iteratively optimize comprises the processing unit being operative to iteratively adjust the alternating current stimulus characteristic from the determined initial value to increase a difference between a mean translocation time corresponding to the first set of biopolymers and a mean translocation time corresponding to the second set of biopolymers; use the at least one optimized alternating current stimulus characteristic value to determine a length of a biopolymer in the sample; and output the determined length of the biopolymer. The claims stand rejected as follows: • Claims 14-16 and 18-20 under 35 U.S.C. § 101 as directed to nonstatutory subject matter (Ans. 4); • Claims 27 and 28 under 35 U.S.C. § 112, first paragraph, as including new matter (Ans. 5); • Claims 8-10, 12-16, and 18-20 under 35 U.S.C. § 103(a) as obvious in view of Cao,1 Flory,2 and Demana3 (Ans. 6); • Claims 8, 14, 26, and 30 under 35 U.S.C. § 103(a) as obvious in view of Cao, Flory, Demana, and Sauer4 (Ans. 10); 1 Cao et al., US 2004-0033515 A1, published Feb. 19, 2004. 2 Flory, US 2004-0149580 A1, published Aug. 5, 2004. 3 Tshenge Demana et al., Improved Separation of Nucleic Acids with Analyte Velocity Modulation Capillary Electrophoresis, 83 ANAL. CHEM. 2795-2797 (1991). 4 Sauer et al., US Patent 6,413,792 B1, issued July 2, 2002. Appeal 2009-014830 Application 11/264,452 4 • Claims 8, 27, and 28 under 35 U.S.C. § 103(a) as obvious in view of Cao, Flory, Demana, and Chen5 (Ans. 11-12); and • Claims 31 and 32 under 35 U.S.C. § 103(a) as obvious in view of Schwartz,6 Chen, Sauer, Demana, and Walters7 (Ans. 13). I. The Examiner has rejected claims 14-16 and 18-20 under 35 U.S.C. § 101 as being directed to nonstatutory subject matter. The claims have not been argued separately and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii). The rejected claims are directed to a “computer-readable storage medium” that stores instructions for carrying out steps like those performed by the processing unit of claim 8. The Examiner finds that the Specification defines “computer-readable medium” to include “a carrier wave from the Internet,” and therefore the claims encompass non-statutory subject matter under In re Nuijten, 500 F.3d 1346 (Fed. Cir. 2008) (Ans. 4). We agree with the Examiner’s finding and conclusion. Appellants point out that the claims were “amended to recite ‘A computer-readable storage medium’” and argue that “the reference in the specification to a carrier wave validly implies accessing, via a network, computer-readable instructions for executing the claimed method” (Reply Br. 3). 5 C.-M. Chen et al., Nanopore sequencing of polynucleotides assisted by a rotating electric field, 82 APPLIED PHYSICS LETTERS 1308-1310 (Feb. 24, 2003) 6 Schwartz et al., US Patent 6,221,592 B1, issued Apr. 24, 2001. 7 Walters et al., EP Patent Application 1 329 502 A2, published July 23, 2003. Appeal 2009-014830 Application 11/264,452 5 Appellants’ argument does not persuade us that the rejection is in error. The Specification states that “although embodiments of the present invention have been described as being associated with data stored in memory and other storage mediums, aspects can also be stored on or read from other types of computer-readable media, such as . . . a carrier wave from the Internet” (Spec. 24, ¶ 66, emphases added). Contrary to Appellants’ argument, the Specification does not state or imply that a carrier wave is not a storage medium. The Specification’s description is reasonably interpreted to mean that aspects of the invention can be either stored on or read from any of the listed media, including a carrier wave. Carrier waves are not patentable subject matter. Nuijten, 500 F.3d at 1357 (“A transitory, propagating signal . . . is not a ‘process, machine, manufacture, or composition of matter’ . . . ; thus, such a signal cannot be patentable subject matter.”). We affirm the rejection of claims 14- 16 and 18-20 under 35 U.S.C. § 101. II. The Examiner has rejected claims 27 and 28 under 35 U.S.C. § 112, first paragraph, as including new matter (Ans. 5). Claims 27 and 28 depend from claim 8 and add the limitation that the combination of the direct current stimulus and alternating current stimulus is derived using a “realistic physics-based model.” The Examiner finds that the realistic physics-based model described in the Specification “only takes into account the DC driving voltage and DC sensitivity. . . . The specification does not disclose a physics-based[ ] model that combines the effects of a combination AC and DC current.” (Ans. 6.) Appeal 2009-014830 Application 11/264,452 6 Appellants contend that the Specification describes the disputed limitation because it “discloses that a physics model based on Newtonian motion may be used to derive a characteristic for an alternating current component of a combination stimulus” (Appeal Br. 8). Appellants point to the physics-based model described on pages 16-17 of the Specification and the description on page 21 of using the model to derive an initial alternating current characteristic (Appeal Br. 7). We agree with Appellants that the Examiner has not adequately shown that a skilled worker would not recognize in the Specification a description of the disputed limitation. The Examiner acknowledges that the Specification describes a realistic physics-based model (Ans. 5). The Specification describes simulating the behavior of DNA molecules based on DC and AC stimuli: For example, a solution with base lengths 1390, 1760, 2680, and 2760 may be used. Sensing unit 105 output from this solution may be simulated with a DC stimulus of 100 mV. . . . Next each region shown in FIG. 11 was simulated with an AC stimulus. The initial AC frequency choice for stimulus was calculated from the inverse of the mean translocation time of the region. (Spec. 21, ¶¶ 58-59.) The Examiner has not explained why a skilled worker would not recognize in the passages cited by Appellants a description of deriving a combination AC/DC stimulus using a realistic physics-based model. We therefore reverse the new matter rejection. Appeal 2009-014830 Application 11/264,452 7 III. Issue The Examiner has rejected claims 8-10, 12-16, and 18-20 as obvious in view of Cao, Flory, and Demana (Ans. 6); claims 8, 14, 26, and 30 as obvious in view of Cao, Flory, Demana, and Sauer (Ans. 10); and claims 8, 27, and 28 as obvious in view of Cao, Flory, Demana, and Chen (Ans. 11-12). The same issue is dispositive for each of these rejections, so we will consider them together. The Examiner finds that Cao teaches “a system with memory storage and a processing unit” that determines the length of macromolecules such as DNA using “direct current, alternating current, and combinations thereof” (Ans. 7). The Examiner finds that Flory teaches altering AC current parameters to eliminate non-uniform translocation of biopolymers through nanopores (id. at 7-8) and that Demana teaches iteratively optimizing AC current parameters in a combination AC/DC field to increase the sensitivity of separation of different-sized DNA fragments (id. at 8-9). The Examiner concludes that it would have been obvious to modify the system taught by Cao “with the apparatus and method of controlling the translocation of biopolymers of Flory” (id. at 9) and “to modify the system of nanopore electrophoresis of Cao et al. in view of Flory with the alteration in separation resolution using a combination AC-DC field of Demana et al. because Demana et al. shows that a combination AC-DC field will shorten nucleic acid transit times and improve resolution” (id. at 10). Appellants contend that “Cao, Flory and Demana, either individually or in combination, at least do not disclose a ‘processing unit operative to iteratively optimize the at least one alternating current stimulus Appeal 2009-014830 Application 11/264,452 8 characteristic, starting with the determined initial value, to increase the sensitivity of the determined direct current base length region,’ as recited by independent Claim 8” (Appeal Br. 11-12). The issue with respect to this rejection is: Do the cited references support the Examiner’s conclusion that it would have been obvious to modify Cao’s system to include an iteratively optimized combination AC/DC field? Findings of Fact 1. Cao teaches that “[n]anofabrication of extremely small fluidic structures, such as channels, can be used in bionanotechnology for the direct manipulation and analysis of biomolecules, such as DNA, and proteins at single molecule resolution” (Cao 1, ¶ 5). 2. Cao discloses that DNA “tends to form a disordered tangle of compact random coils in free solution” (id. at 1, ¶ 6) and “[i]t is challenging to efficiently move long DNA arranged as a blob into the small channels, since it is energetically unfavorable for long biopolymers to spontaneously elongate and enter nanochannels” (id. at 1, ¶ 7). Thus, “problems such as DNA clogging at the junction of nano-and macro-environment have arisen” (id.). 3. Cao addresses this problem by providing a “gradient interface area . . . formed of lateral spatial gradient structures for narrowing the cross section . . . from the micron to the nanometer length scale. . . . The gradient structures can be used to squeeze and funnel biomolecules into a small nanofluidic area.” (Id. at 1, ¶ 12.) Appeal 2009-014830 Application 11/264,452 9 4. Cao’s Figure 2 is reproduced below: Figure 2 shows how “[g]radient interface area 12 is used to effectively stretch and align biopolymers 22 before they approach nanofluidic area 16. Biopolymers 22 can be preliminarily stretched between adjacent pairs of microposts 18 before entering nanochannels 21.” (Id. at 3, ¶ 42.) 5. Cao discloses that “the distance D2 between gradient structures 23 is reduced in a range of about a radius of gyration of biopolymer 22 to substantially a diameter of biopolymer 22” (id. at 3, ¶ 43). 6. Cao discloses that its apparatus can be used to analyze macromolecules, “includ[ing] the sizing of one DNA macromolecule” (id. at 5, ¶ 71). 7. Cao discloses that “[t]he length of a single DNA can be detected/reported and intensity profile can be plotted. In various embodiments . . . , the method of analyzing a macromolecule includes correlating the detected signal to at least one of the following properties: length, conformation, and chemical composition.” (Id. at 5-6, ¶ 72.) Appeal 2009-014830 Application 11/264,452 10 8. The Examiner concludes that Demana would have made it obvious to modify Cao’s system in a way that meets the requirement of claim 8 to “iteratively optimize” an alternating current characteristic (Ans. 10). 9. Demana describes separation using polyacrylamide gel electrophoresis of a mixture of DNA fragments ranging in size from 72 bp to 1353 bp (Demana 2795, right col. and 2796, Figure 1). 10. Demana discloses that “the three fragments larger than about 700 bp (872, 1078, and 1353 bp) are poorly resolved in our gel with a dc field only” (id. at 2796, left col.). 11. Demana describes superimposing on the DC field an AC field at frequencies of 52, 78, 98, and 107 Hz (id. at 2796, legend to Fig. 1). 12. Demana discloses that the larger “fragments are easily resolved by the imposition of an ac field. The best resolution is observed at 78 Hz. Above that frequency the peaks again move closer together” (id. at 2796, left col.). 13. Demana concludes that “[s]uperimposition of an ac field causes a decrease in migration time and an improvement in resolution” (id. at 2795, right col.). Analysis Cao discloses a device that moves a mixture of DNA molecules through a “gradient interface area” that stretches the individual DNA molecules from their tangled, random-coil conformation to a stretched, elongated conformation that can more easily enter a nanochannel. Cao discloses that the distance between the structures in the gradient interface area is reduced to substantially the diameter of the biopolymer (DNA) and Appeal 2009-014830 Application 11/264,452 11 that the device can be used to analyze single DNA molecules, confirming that each nanochannel in its device analyzes an individual DNA molecule. Demana discloses that when a mixture of DNA fragments was moved through a polyacrylamide gel using a DC field only, the fragments having the three largest sizes all moved at about the same rate, resulting in detection of a single peak. Demana discloses that superimposing an AC field on the DC field allowed resolution of the three largest fragments, with the best resolution resulting from a 78-Hz AC field. The Examiner has not adequately explained why a person of ordinary skill in the art would have found it obvious to combine Demana’s combination AC/DC field with Cao’s device. Demana’s technique addresses the problem of multiple DNA fragments moving through a substrate at similar rates, so that they are not distinguished as different DNA molecules. But Cao’s device separates each individual DNA molecule in a sample, from all the other DNA molecules in the sample, before the DNA molecule enters a nanochannel for analysis. Thus, in Cao’s system, there is no possibility that multiple DNA molecules would be detected as a single molecule. Since Demana’s technique is directed to a problem that would not exist in Cao’s system, the Examiner has not adequately explained why a person of ordinary skill in the art would have combined the two. Conclusion of Law The cited references do not support the Examiner’s conclusion that it would have been obvious to modify Cao’s system to include an iteratively optimized combination AC/DC field. Appeal 2009-014830 Application 11/264,452 12 IV. Issue The Examiner has rejected claims 31 and 32 as obvious in view of Schwartz, Chen, Sauer, Demana, and Walters (Ans. 13). The Examiner finds that “Schwartz et al. shows using direct current to determine DNA lengths” (Ans. 14) and concludes that it would have been obvious to modify Schwartz’s system by, among other things, including “the alteration in separation resolution using a combination AC-DC field of Demana et al. because Demana et al. shows that a combination AC-DC field will shorten nucleic acid transit times and improve resolution” (id. at 17). Appellants contend that the Examiner has acknowledged that “Schwartz, even in combination with Chen and Sauer, does not disclose either applying a combination of AC and DC currents or analyzing molecules that correspond to different lengths under DC and combination stimuli” (Appeal Br. 15) and the other cited references do not make up for this deficiency (id. at 15-16). The issue with respect to this rejection is: Do the cited references support the Examiner’s conclusion that it would have been obvious to modify Schwartz’s system to include an iteratively optimized combination AC/DC field? Additional Findings of Fact 14. Schwartz discloses “methods and systems for determining the nucleotide sequence of individual double stranded nucleic acid molecules elongated and fixed to a solid-surface by nicking the nucleic acid molecule, enzymatically adding labeled nucleotides and imaging the labeled nucleotides” (Schwartz, abstract). Appeal 2009-014830 Application 11/264,452 13 15. The only part of Schwartz cited by the Examiner in the rejection is Figure 11 (Ans. 14). 16. Schwartz’s Figure 11 shows a standard computer system, with keyboard, display, CPU, RAM, and software (Schwartz, Fig. 11 and col. 58, ll. 1-23). Analysis The Examiner finds that “Schwartz et al. shows using direct current to determine DNA lengths” (Ans. 1 4) but does not cite any specific passage in Schwartz to support this finding. We do not find any disclosure in Schwartz of using direct current to determine DNA length. On the contrary, Schwartz describes a method of sequencing DNA in which the DNA molecules are fixed to a surface. By contrast, Demana separates DNA fragments by moving them through a substrate using a combination of AC and DC fields. The Examiner has not adequately explained why a person of ordinary skill in the art would have found it obvious to combine Demana’s combination AC/DC field with Schwartz’s system, when the purpose of Demana’s AC/DC field is to move DNA molecules through a substrate and Schwartz’s DNA molecules are fixed to a substrate and unable to move regardless of whether an electric field is imposed. Conclusion of Law The cited references do not support the Examiner’s conclusion that it would have been obvious to modify Schwartz’s system to include an iteratively optimized combination AC/DC field. Appeal 2009-014830 Application 11/264,452 14 SUMMARY We affirm the rejection of claims 14-16 and 18-20 under 35 U.S.C. § 101. We reverse the new matter and obviousness rejections. 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-IN-PART lp MERCHANT & GOULD PC P.O. BOX 2903 MINNEAPOLIS MN 55402-0903 Copy with citationCopy as parenthetical citation