Ex Parte Sampas et alDownload PDFPatent Trials and Appeals BoardMay 22, 201914684028 - (D) (P.T.A.B. May. 22, 2019) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 14/684,028 04/10/2015 22878 7590 Agilent Technologies, Inc. Global IP Operations 5301 Stevens Creek Blvd Santa Clara, CA 95051 05/24/2019 FIRST NAMED INVENTOR Nicholas M. Sampas 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. 20140064-02 1028 EXAMINER KAUP, SAHANA S ART UNIT PAPER NUMBER 1639 NOTIFICATION DATE DELIVERY MODE 05/24/2019 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): IPOPS.LEGAL@agilent.com Agilentdocketing@cpaglobal.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte NICHOLAS M. SAMP AS and RICHARD P. TELLA (APPLICANT: Agilent Technologies, Inc.) Appeal 2018-007410 Application 14/684,028 1 Technology Center 1600 Before DONALD E. ADAMS, ERIC B. GRIMES, and JOHN E. SCHNEIDER, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL This Appeal under 35 U.S.C. § 134(a) involves claims 7-12 and 14-20 (App. Br. 2). Examiner entered rejections under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM-IN-PART. 1 Appellants identify "Agilent Technologies, Inc." as the real party in interest (Appellants' December 20, 2017 Appeal Brief (App. Br.) 1). Appeal 2018-007410 Application 14/684,028 STATEMENT OF THE CASE Appellants' disclosure relates to a method of making an emulsion (see generally Spec. 1 ). Appellants' claims 7, 16, 19, and 20 are representative and reproduced below: 7. A method of making an emulsion, comprising: (a) obtaining an array of polymeric compounds on the surface of a substrate, wherein the polymeric compounds are bound to the substrate via a cleavable linker and wherein the areas that contain said polymeric compounds on the surface of the substrate are hydrophilic relative to the remainder of the surface of the substrate; (b) selectively hydrating the areas that contain said polymeric compounds by flooding the substrate with an aqueous reagent and then removing the aqueous reagent from the substrate to leave discrete droplets of the aqueous reagent on the areas that contain said polymeric compounds, wherein each droplet contains a single polymeric compound or a pre- defined combination of polymeric compounds that are adjacent to one another on the substrate; and ( c) releasing the polymeric compounds from the surface of the substrate by cleaving the cleavable linker, either before, during or after the hydrating step (b ). (App. Br. 9 (emphasis added).) 16. The method of claim 7, wherein the releasing step ( c) is done during or after the selectively hydrating step (b ). (Id. at 10.) 19. The method of claim 16, wherein the releasing step ( c) is done by immersing the array in an immiscible agent that contains a cleavage agent, thereby cleaving a cleavage agent- sensitive linkage that attaches the polymeric compounds to the substrate. (Id. at 11.) 2 Appeal 2018-007410 Application 14/684,028 20. The method of claim 7 further comprising: ( d) collecting the droplets in an immiscible liquid, thereby producing an emulsion containing discrete droplets; each of which containing in the solution phase, a single polymeric compound or a combination of polymeric compounds that are adjacent to one another on the substrate. (Id ( emphasis added).) Grounds of rejection before this Panel for review: I. Claims 7-12, 14-18, and 20 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Jacobson2 and Kim. 3 II. Claim 19 stands rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Jacobson, Kim, and Hindson.4 ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? FACTUAL FINDINGS (FF) We adopt Examiner's findings concerning the scope and content of the prior art (Final Act. 5 3-12 and Ans. 6 3-10), and provide the following findings for emphasis. FF 1. Jacobson discloses "[ m Jethods and devices provided herein generally relat[ing] to the preparation of high content gene libraries and libraries of polypeptides expressed therefrom. More particularly, the methods and 2 Jacobson et al., WO 2012/064975 Al, published May 18, 2012. 3 Kim et al., US 2012/0035063 Al, published Feb. 9, 2012. 4 Hindson et al., WO 2014/028537 Al, published Feb. 20, 2014. 5 Examiner's May 26, 2017 Final Office Action. 6 Examiner's May 10, 2018 Answer. 3 Appeal 2018-007410 Application 14/684,028 devices involve microvolume reactions, gene assembly, on-surface expression, high throughput analysis, and/or pathway development on a solid support" (Jacobson ,i 2; see generally Ans. 3 and 8). FF 2. Jacobson discloses oligonucleotides ... synthesized on an array format. For example, single-stranded oligonucleotides ... synthesized in situ on a common support wherein each oligonucleotide is synthesized on a separate or discrete feature ( or spot) on the substrate. In preferred embodiments, single stranded oligonucleotides are bound to the surface of the support or feature. As used [in Jacobson] the term "array" refers to an arrangement of discrete features for storing, routing, amplifying and releasing oligonucleotides or complementary oligonucleotides for further reactions. In a preferred embodiment, [Jacobson's] support or array is addressable: the support includes two or more discrete addressable features at a particular predetermined location (i.e., an "address") on the support. Therefore, each oligonucleotide molecule of the array is localized to a known and defined location on the support. The sequence of each oligonucleotide can be determined from its position on the support .... [F]eatures [ on Jacobson's array] are typically, but need not be, separated by interfeature spaces to ensure that droplets between two adjacent features do not merge. Interfeatures will typically not carry any oligonucleotide on their surface and will correspond to inert space. In some embodiments, features and interfeatures may differ in their hydrophilicity or hydrophobicity properties. (Jacobson ,i 36; see also id. ,i,i 50-51 (Jacobson discloses "methods and devices[, such as inkjet devices,] for amplification and/or assembly of polynucleotide sequences in small volume [ miscible or non-miscible solution] droplets on separate and addressable features of a support"); id. ,i 51 (Jacobson discloses that "the arrays are stored dry for subsequent reactions" and the "support immobilized oligonucleotides can be hydrated independently with an aqueous solution," wherein the "[ a Jqueous solution 4 Appeal 2018-007410 Application 14/684,028 includes, but is not limited to water, buffer, primers, master mix, release chemicals, enzymes, or any combination thereof'); see Ans. 3-5 and 7-9.) FF 3. Jacobson discloses "oligonucleotide[] synthesis [] performed using a device that generates emulsion droplets comprising aqueous droplets within immiscible oil. The droplets may comprise an aqueous phase, an immiscible oil phase, and a surfactant and/or other stabilizing molecules to maintain the integrity of the droplet," wherein "compounds can be deposited into the oil phase in the form of droplets generated using inkjet printing technology or piezoelectric drop-on-demand (DOD) inkjet printing technology" (Jacobson ,i 48; cf Spec. 10: 11-13 (Appellants define an "emulsion" as "a mixture of two or more liquids that are normally immiscible, in which one liquid forms droplets that are dispersed within another liquid"); Jacobson ,i 63 ( discussing controlling the hydrophilicity/hydrophobicity of a substrate's surface properties); see Ans. 3-4). FF 4. Jacobson discloses that "oligonucleotides are attached or synthesized via a [ cleavable] linker molecule and subsequently detached and release" (Jacobson ,i 82; see Ans. 3-7 and 9). FF 5. Jacobson discloses that"[ o ]ligonucleotides may be amplified before or after being detached from the support and/or eluted in a droplet" (Jacobson ,i 69; see also id. ,i 70; see Ans. 4-6). FF 6. Examiner finds that Jacobson fails to disclose "flooding the substrate with an aqueous reagent and then removing the aqueous reagent from the substrate" (Ans. 7). FF 7. Kim "relates to systems and methods for handling small volumes of liquids and, more particularly, ... to systems and methods for facilitating assays in small volumes" (Kim ,i 2; see Ans. 7). 5 Appeal 2018-007410 Application 14/684,028 FF 8. Kim discloses "a method for controlling a residual volume of an aqueous solution bathing an array comprising a plurality of hydrophilic elements on a hydrophobic background," wherein "[t]he method comprises adding an aqueous liquid so as to contact the hydrophilic elements, tilting the array to a selected angle from a horizontal reference plane ... , and allowing the aqueous liquid to drain while leaving a residual volume adhered to the elements" (Kim ,i 17; see also id. ,i 18 ("In a related embodiment, the method comprises selecting a desired residual volume and selecting a corresponding angle so as to leave behind the desired residual volume"); see Ans. 7). FF 9. Examiner finds that the combination of Jacobson and Kim does "not expressly teach the embodiment of a cleavage reagent added to the non- miscible fluid overlay on an oligonucleotide array" (Ans. 9). FF 10. Hindson "provides compositions and methods for a microcapsule array device" (Hindson ,i 4). FF 11. Hindson's Figure IA is reproduced below: Fi~, 1A J1JO·. Hindson's "Figure IA is a schematic of an exemplary microcapsule comprising an internal compartment 120 enveloped by a second layer 130, which is encapsulated by a solid or semi-permeable shell or membrane 11 O" (Hindson ,i 30 (emphasis omitted); see generally id. ,i 18 (Hindson's "Fig. 6 Appeal 2018-007410 Application 14/684,028 IA is a schematic representation of a microcapsule or inner regent droplet"); Ans. 9). FF 12. Hindson discloses that shell 110 separates the internal compartment( s) from their immediate environment ( e.g., interior of a microwell). The internal compartments, e.g., 120, 130, may comprise materials such as reagents. As depicted in Figure IA, the reagents 100 may be present in the internal compartment 120. However, in some cases, the reagents are located in the enveloping layer 130 or in both compartments. Generally, the microcapsule may release the inner materials, or a portion thereof, following the introduction of a particular trigger. The trigger may cause disruption of the shell layer 110 and/ or the internal enveloping layer 130, thereby permitting contact of the internal compartment 100, 120 with the outside environment, such as the cavity of a microwell. (Hindson ,i 30; see also Ans. 9 (Examiner finds that Hindson discloses that "the enveloping layer 130 may be a non-aqueous fluid such as an oil as in [Hindson's] para 0031 ... ," such as an "immiscible fluid [that] is loaded with additional materials or reagents as in [Hindson's] para 0036 ... ," wherein "[ a ]ny fluid or buffer that is physiologically compatible with the analytes (e.g., cells, molecules) or reagents used in the device may be used").) FF 13. Hindson discloses that "[t]he microcapsule may comprise several fluidic phases and may comprise an emulsion ( e.g. water-in-oil emulsion, oil-in-water emulsion)" (Hindson ,i 31; Ans. 9). FF 14. Hindson discloses restriction enzymes and nucleases as exemplary reagents for use in Hindson' s microcapsule (see Hindson ,i 62; see also id. ,i 36 (further defining microcapsule compartments and reagents); Ans. 9). 7 Appeal 2018-007410 Application 14/684,028 FF 15. Examiner finds that Hindson discloses "[e]xemplary [non-aqueous] fluids includ[ing] but ... not limited to: oils, non-polar solvent, hydrocarbon oil, decane (e.g., tetradecane or hexadecane), fluorocarbon oil, fluorinated oil, silicone oil, mineral oil, or other oil as in [Hindson's] para 0084" (Ans. 9). ANALYSIS Rejection I: Jacobson discloses, inter alia, attaching oligonucleotides to a hydrophilic portion of an array through the use of a cleavable linker (see FF 2 and 4). Jacobson discloses that an array comprising oligonucleotides attached to the array through a cleavable linker may be dried and subsequently rehydrated (see FF 2). Kim discloses a method of rehydrating an array, wherein, as Appellants recognize, "Kim discloses flooding a solid support with an aqueous liquid, and allowing the aqueous liquid to drain from the support," to leave "a residual volume adhered to [hydrophilic] elements" of the solid support (App. Br. 5; see FF 8). Thus, a person of ordinary skill in this art would have found it prima facie obvious to use Kim's methodology to rehydrate Jacobson's dry array (see Ans. 8). Jacobson discloses that oligonucleotides attached to the array through the use of a cleavable linker may be released from the array (see FF 4-5). Thus, based on the combination of Jacobson and Kim, a person of ordinary skill in this art would have found it prima facie obvious to attach oligonucleotides to an array through the use of a cleavable linker, dry the array, rehydrate the array using Kim's methodology, and subsequently release the oligonucleotide from the array (see FF 2, 4, 5, and 8; see also Ans. 8; see generally FF 1-8). As Examiner explains, the modification of Jacobson 8 Appeal 2018-007410 Application 14/684,028 with Kim is nothing more than the "substitution of one [known] technique of hydrating an array, such as spotting [an] aqueous solution on discrete regions as taught by Jacobson et al. for another [known] technique, such as flooding the array as taught by Kim" to yield a predictable result, specifically hydrating an array (Ans. 8). See KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). Claim 7: For the foregoing reasons, we are not persuaded by Appellants' contention that flooding Jacobson's "support with an aqueous liquid as taught by Kim ... would destroy Jacobson's droplets," because "[f]looding Jacobson's substrate would wash away its precisely-deposited droplets" (App. Br. 5 ( emphasis omitted); see also id. at 6 ("the precisely-deposited amount of solution would be washed away by flooding") ( emphasis omitted); see Reply Br. 3). For the same reasons, we are not persuaded by Appellants' contention that "the predictable outcome of flooding Jacobson's substrate would be to wash away the precisely-deposited droplets" (App. Br. 6; see Reply Br. 4-5). Appellants do not identify, and we do not find, a requirement in Jacobson that requires precise droplets be used to rehydrated Jacobson's dry array (see id.; cf FF 2). Appellants also provide no persuasive evidence or argument to support a conclusion that Kim's method of flooding an array, such as Jacobson's dry array, with an aqueous liquid "and allowing the aqueous liquid to drain while leaving a residual volume adhered to the [hydrophilic] elements," which comprise Jacobson's oligonucleotides, would be ineffective in rehydrating Jacobson's array (see FF 8; see also FF 9 Appeal 2018-007410 Application 14/684,028 2). Therefore, we are not persuaded by Appellants' contention that Kim "does not disclose or suggest that flooding provides discrete droplets containing a single polymeric compound or a pre-defined combination of polymeric compounds that are adjacent to one another on a substrate" (App. Br. 6; see Reply Br. 5). Claim 20: Appellants' claim 20 depends from and further limits Appellants' claim 7 to further comprise "collecting the droplets in an immiscible liquid, thereby producing an emulsion containing discrete droplets, each of which contain[ s ], in the solution phase, a single polymeric compound or a combination of polymeric compounds that are adjacent to one another on the substrate" (App. Br. 11; see also id. at 7 (separately arguing claim 20)). As discussed above, the combination of Jacobson and Kim, suggests a method comprising, inter alia, rehydrating oligonucleotides releasably attached to an array by flooding the array with an aqueous liquid and releasing the oligonucleotides from the array (see FF 2, 4, 5, and 8). Thus, a person of ordinary skill in this art would understand the combination of Jacobson and Kim to suggest the release of oligonucleotides into an aqueous liquid. Although Examiner asserts that Jacobson discloses the use of non- aqueous, immiscible, and water-immiscible liquids (see Ans. 7 and 13; see also FF 2-3), Examiner failed to explain how Jacobson's array would comprise an immiscible liquid after it is dried and subsequently flooded with Kim's aqueous liquid (see generally App. Br. 7; Reply Br. 6-7). We therefore reverse the rejection of claim 20. 10 Appeal 2018-007410 Application 14/684,028 Rejection II: As discussed above, Jacobson discloses, inter alia, attaching oligonucleotides to a hydrophilic portion of an array, drying the array with attached oligonucleotides, and subsequently rehydrating the oligonucleotides on the array (see FF 2). As Appellants explain, Examiner "alleges that Kim discloses flooding a solid support with an aqueous liquid, and allowing the aqueous liquid to drain from the support," to leave "a residual volume adhered to [hydrophilic] elements" of the solid support (App. Br. 5; see FF 8). Examiner finds, however, that the combination of Jacobson and Kim does "not expressly teach the embodiment of a cleavage reagent added to [a] non-miscible fluid overlay on an oligonucleotide array" (FF 9) and relies on Hindson to make up for this deficiency in the combination of Jacobson and Kim (see FF 9-15). As Examiner explains, "Hindson is relied on to show that application of cleavage agents through a water-immiscible fluid are known in the art" (Ans. 14; see also FF 10-15). Therefore, based on the combination of Jacobson, Kim, and Hindson, Examiner concludes that, at the time Appellants' invention was made, it would have been prima facie obvious to modify the method suggested by the combination of Jacobson and Kim by applying Hindson's "physiologically compatible, water-immiscible fluid containing a cleaving reagent (i.e. restriction enzyme)" to the aqueous liquid on the rehydrated array, because such a modification "would yield the predictable result of ... applying a reagent solution to the oligonucleotides bound to an array and cleaving oligonucleotides from the substrate" (Ans. 10 and 14; see FF 1-15). See KSR Int'! Co. v. Teleflex Inc., 550 U.S. at 416. We are not persuaded. 11 Appeal 2018-007410 Application 14/684,028 As discussed above, the combination of Jacobson and Kim suggests a method comprising, inter alia, rehydrating oligonucleotides releasably attached to Jacobson's array by flooding the array with an aqueous liquid and subsequently releasing the oligonucleotides from the array (see FF 2, 4, 5, and 8). Thus, a person of ordinary skill in this art would understand that although Jacobson discloses overlaying aqueous liquids with, for example, an immiscible oil (FF 3), the composition resulting from the method suggested by the combination of Jacobson and Kim is an aqueous liquid droplet, or plurality of droplets, that comprise(s) oligonucleotides that were cleaved from the substrate. Therefore, we are not persuaded that Examiner established an evidentiary basis to support Examiner's assertion that a person of ordinary skill in this art would have modif1ied] the method ... taught by [the combination of] Jacobson and Kim to include adding a physiologically compatible, water-immiscible fluid containing a cleaving reagent (i.e. restriction enzyme) as taught by Hindson ... as a skilled artisan would have recognized that substituting the water-immiscible fluid of Jacobson with the physiologically compatible, water-immiscible fluid containing a cleaving reagent of Hindson would yield the predictable result of a method of applying a reagent solution to the oligonucleotides bound to an array and cleaving oligonucleotides from the substrate. (Ans. 14.) For the reasons set forth above, any such modification would be prior to Kim's step of flooding the array with an aqueous liquid. Thus, Examiner fails to explain how any oligonucleotides cleaved from the substrate prior to the flooding step would have been retained on the array for collection. Examiner further fails to explain how such a modification would be applied after Kim's step of flooding the array with an aqueous liquid. 12 Appeal 2018-007410 Application 14/684,028 In sum, we are not persuaded that Examiner established an evidentiary basis to support a conclusion that the combination of Jacobson, Kim, and Hindson makes obvious a releasing step that is done by immersing the array in an immiscible agent that contains a cleavage agent as is required by Appellants' claim 19 (see App. Br. 7). In this regard, we note that it is Examiner's "initial burden, on review of the prior art ... , [to] present[] a primafacie case ofunpatentability." In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). CONCLUSION The preponderance of evidence relied upon by Examiner supports a conclusion of obviousness with respect to Appellants' claims 7-12 and 14- 18. The rejection of claim 7 under 35 U.S.C. § 103(a) as unpatentable over the combination of Jacobson and Kim is affirmed. Claims 8-12 and 14-18 are not separately argued and fall with claim 7. The preponderance of evidence relied upon by Examiner fails to support a conclusion of obviousness with respect to Appellants' claims 19 and 20. The rejection of claim 19 under 35 U.S.C. § 103(a) as unpatentable over the combination of Jacobson, Kim, and Hindson is reversed. The rejection of claim 20 under 35 U.S.C. § 103(a) as unpatentable over the combination of Jacobson and Kim is reversed. 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. § l .136(a)(l )(iv). AFFIRMED-IN-PART 13 Copy with citationCopy as parenthetical citation