Ex Parte Gordon et al

Patent Trial and Appeal BoardJan 10, 2019

13898064 (P.T.A.B. Jan. 10, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 13/898,064 05/20/2013 115138 7590 01/14/2019 Medlen & Carroll, LLP 1440 Broadway SUITE 1010 Oakland, CA 94612 FIRST NAMED INVENTOR Steven Gordon 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 ATTORNEY DOCKET NO. CONFIRMATION NO. INTELLI-17532 3857 EXAMINER CHUNDURU, SURYAPRABHA ART UNIT PAPER NUMBER 1637 NOTIFICATION DATE DELIVERY MODE 01/14/2019 ELECTRONIC 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. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): rldalton@medlencarroll.com cjcollins@medlencarroll.com docketing@medlencarroll.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte STEVEN GORDON and PHILLIP A. VEATCH Appeal2017-007859 Application 13/898,064 Technology Center 1600 Before ULRIKE W. JENKS, RYAN H. FLAX, and DAVID COTTA, Administrative Patent Judges. JENKS, Administrative Patent Judge. DECISION ON APPEAL Appellant1 submits this appeal under 35 U.S.C. Â§ 134(a) involving claims directed to a method of enriching a template using PCR. Examiner rejected the claims as anticipated. We have jurisdiction under 35 U.S.C. Â§ 6(b). We REVERSE. STATEMENT OF THE CASE Claims 7, 8, 11-17, and 20-23 are on appeal, and can be found in the Claims Appendix of the Appeal Brief. Claim 7 is representative of the claims on appeal, and reads as follows: 1 Appellant, is the Applicant, Intelligent Bio-Systems, Inc., of Waltham, MA, which according to the Brief, is the real party in interest. Br. 3 Appeal2017-007859 Application 13/898,064 7. A method of enriching, comprising: a) providing i) an aqueous mix comprising PCR reagents, ii) template, iii) first and second PCR primers, said first PCR primers immobilized on emulsion beads for emulsion PCR, said second PCR primers comprising biotin, iv) an oil/detergent mix, and v) enrichment beads, wherein said enrichment beads comprise streptavidin; b) adding said template, said first and second primers, said aqueous mix and said oil/detergent mix together so as to create one or more microemulsions, said one or more microemulsions comprising an aqueous compartment, each compartment comprising on average less than one template molecule; c) temperature cycling said one or more microemulsions so as to amplify at least some of said template on at least some of said emulsion beads so as to create amplified product comprising biotin; and d) enriching for beads with amplified template among said emulsion beads by contacting with said enrichment beads, wherein said emulsion beads with amplified template bind to said enrichment beads. Appellant requests review of Examiner's rejection of claims 7, 8, 11- 17, and 20-23 under 35 U.S.C. Â§ I02(a)(l) as being anticipated by Shimkets. 2 The issue is: Does the preponderance of evidence of record support Examiner's finding that Shimkets teaches the creation of amplified product comprising biotin within the microemulsion environment as claimed? Findings of Fact FF 1. Shimkets teaches sequence amplification using microreactors. One method uses beads coated with oligonucleotides to capture and 2 Shimkets et al., US 2005/0221341 Al, published Oct. 6, 2005 ("Shimkets"). 2 Appeal2017-007859 Application 13/898,064 amplify nucleic acids in a microemulsion. The method has the following steps: First, magnetic beads are covalently coated with streptavidin and then bound to biotinylated oligonucleotides designed to capture two or more genes of interest from a single cell .... Second, an aqueous mixture comprising hundreds of thousands to millions of microreactors are generated by mixing together the components for PCR, primer-bound beads, the cell population of interest, and an oil/ detergent mixture to create a microemulsion. The aqueous compartments ... include an average of less than one cell and less than one bead. Third, the microemulsion is temperature-cycled, e.g., in a conventional PCR machine, such that the bead bound oligonucleotides can act as primers for amplification for cells having the target genes .... Fourth, the emulsion is broken and the beads comprising the amplified genes of interest are isolated, e.g., by magnet. Fifth, after denaturation, the bead are incubated with oligonucleotides that serve as primers for the genes of interest, while at least one primer is added in a de-activated form. Sixth, sequencing is performed on the beads to determine the first sequence of interest. Seventh, the next primer is activated and sequencing is performed on the next gene, e.g., a member of a gene pair. ... Primers can be added sequentially to sequence additional genes captured by this method (i.e., three or more genes). Shimkets ,r 97; see Ans. 2. FF2. Shimkets teaches that "[a]n amplicon is defined as any nucleic acid molecule[] produced by an in vitro nucleic amplification technique." Id. ,I 168. FF3. Shimkets teaches bead emulsion PCR amplification that creates an amplicon bound bead. See id. ,r,r 134--140. "'[B]ead emulsion amplification' is performed by attaching a template nucleic acid ( e.g., DNA) to be amplified to a solid support, preferably in the form of a generally spherical bead." Id. ,r 136. In this amplification, primer Bis 3 Appeal2017-007859 Application 13/898,064 linked to the bead. Id. ,r 137. The beads linked with primer Bare then annealed to template DNA, and these beads are then mixed with a solution based PCR primer pair (primer A and primer B) to form an aqueous reaction mixture. Id. This mixture is then encapsulated into a water-and-oil emulsion and thermocycled in an asymmetric PCR reaction. Id. "Thermostable polymerases then utilize the A strand as a template to synthesize an immobilized, bead bound B strand of the amplicon." Id. ,r 139. After completion of the PCR reaction the emulsion is broken and the immobilized product is rendered single- stranded by denaturing (by heat, pH etc.) which removes the complementary A strand and leaves the single strand B attached to the bead. Id. ,r 140. FF4. Shimkets teaches an enrichment process that starts with an amplicon bound bead. Shimkets ,r 172; see Ans. 5. The process starts with (1) an amplicon bound bead mixed with a biotinylated primer complementary to the amplicon (Shimkets ,r 172); (2) this is followed by adding DNA polymerase and the four natural deoxynucleotides triphosphates ( dNTPs) to create a mixture (id.); (3) introducing streptavidin coated beads susceptible to attraction by a magnetic field ("magnetic streptavidin beads") to the mixtures created in step 2 in order to arrive at a biotin-streptavidin bead mixture (id.); (4) placing a magnet in proximity to the biotin-streptavidin bead mixture (id., see also id. at Fig. 17); (5) applying a magnetic field (id. ,r 173); and (6) separating the extended biotinylated primer strand from the amplicon strand by "melting" (id. ,r 173). 4 Appeal2017-007859 Application 13/898,064 Principle of Law To anticipate, every element and limitation of the claimed invention must be found in a single prior art reference, arranged as in the claim. Karsten Mfg. Corp. v. Cleveland Golf Co., 242 F.3d 1376, 1383 (Fed. Cir. 2001). Analysis Appellant contends that the claims require two types of beads ( emulsion beads and enrichment beads) and these beads are not found in the amplification disclosed in paragraph 97 of Shimkets. Br. 7. Appellant also contends that the claims require that the amplicon containing biotin be created in the microemulsion (see claim 7 step ( c ), see claim 16 step ( c)) and this is not taught in paragraphs 172-17 6 of Shimkets. Br. 6. Examiner's position is that "[t]he cited paragraphs 0097, 0172-0176 clearly teach separate emulsion beads ( capture beads) and enrichment beads (streptavidin coated magnetic beads) as required by the claims." Ans. 5. In the Answer, Examiner finds that Shimkets "also teach[ es] said capture bead bound primers in other parts of the document." Id. On this record, we find that Appellant has the better position. Here, Examiner is relying on multiple parts of the disclosure other than that of cited paragraphs 0097 and 0172---0176 to teach either a second type of bead, or a particular capture bead structure. See Ans. 5. Relying on multiple different disclosures to cobble together the various elements as recited in the claim in order to arrive at the finding that these multiple disclosures anticipate the claim is not permissible. As stated inArkley, an anticipatory reference under 35 U.S.C. Â§ 102 must clearly and unequivocally disclose the claimed compound 5 Appeal2017-007859 Application 13/898,064 or direct those skilled in the art to the compound without any need for picking, choosing, and combining various disclosures not directly related to each other by the teachings of the cited reference. Such picking and choosing may be entirely proper in the making of a 103, obviousness rejection, where the applicant must be afforded an opportunity to rebut with objective evidence any inference of obviousness which may arise from the similarity of the subject matter which he claims to the prior art, but it has no place in the making of a 102, anticipation rejection. In re Arkley, 455 F.2d 586, 587-588 (CCP A 1972). Because the method of claim 7 requires both emulsion beads and enrichment beads, we agree with Appellant that the method taught in paragraph 97 of Shimkets disclosing only a single type of bead does not anticipate. See FF 1. Specifically, Shimkets' s method takes magnetic beads coated with streptavidin and binds biotinylated oligonucleotides to these beads to create the primer-bound beads. Id. It is these beads that are then used in a PCR microemulsion mixture. Id. Based on these disclosures in Shimkets, we agree with Appellant that this particular method, relied on by Examiner, does not anticipate the presently claimed enrichment method because it only uses one type of bead. Examiner relies on a different portion of Shimkets to establish that the reference teaches two types of beads. See Ans. 5. We do not disagree with Examiner's assessment that Shimkets teaches two types of beads. See FF 1- FF 4. Specifically, Shimkets teaches amplicons attached to a bead that are enriched with another bead containing streptavidin. See FF4. The problem is, as pointed out by Appellant, that the disclosure Examiner relies on in Shimkets does not "amplify ... said emulsion beads so as to create amplified product comprising biotin" as recited in claim 7 ( c) because the 6 Appeal2017-007859 Application 13/898,064 beads in Shimkets are not incubated in the presence of a biotinylated primer within the microemulsion. Br. 5---6. The production of the amplicon-bound bead in Shimkets does utilize a microemulsion. But this process, as pointed out by Appellant, does not use a primer that contains biotin. See Br. 6; FF3. Shimkets teaches that after PCR amplification is complete the amplicon-bound bead product is denatured in order to create a single-stranded product attached to the bead. FF3. It is this single-stranded-amplicon-bead product that is used in the bead purification method of Shimkets. Here, the purification as set out in paragraphs 172-17 6 of Shimkets, found by Examiner to be anticipating, does not create another microemulsion that introduces the biotinylated primer with the amplicon bead product "to create amplified product comprising biotin" as required by the claim. FF4; see also Shimkets Fig. 17. Because the addition of the biotinylated primer and primer extension does not occur within a microemulsion, we agree with Appellant's contention that these disclosures do not anticipate the claim. Examiner's position that Shimkets teaches various types of capture beads and bound primers within the reference does not persuade us that the reference anticipates. It is not enough to find every limitation recited in the claim within a single prior art reference but these limitations must also be taught to be arranged as they are in the claim. See Karsten Mfg. Corp., 242 F.3d at 1383. For the reasons discussed above, we agree with Appellant that the prior art features are not arranged as are the limitations presented in the claim. 7 Appeal2017-007859 Application 13/898,064 On the record before us, we reverse Examiner's decision rejecting all claims as anticipated by Shimkets under 35 U.S.C. Â§ 102. Whether the recited reference renders the claims obvious is not a question before us. SUMMARY We reverse the anticipation rejection of all claims. REVERSED 8