Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-10 are pending and the subject of this NON-FINAL Office Action.
Claim Rejection - 35 USC § 112 – Written Description
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claim 1-10 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the full scope of the claimed invention.
The specification fails to demonstrate possession of the full scope of any and all “second substrate comprising a plurality of cell traps formed on the second substrate, the plurality of cell traps extending into the droplet operations gap and wherein each cell trap of the plurality of cell traps is located above each microwell of the plurality of microwells.” Claim 1 generically states that the “system” includes both a “droplet actuator” with “droplet operations gap, the droplet actuator including droplet operations electrodes arranged proximate to the droplet operations gap”; and “microwell device” including a “first substrate comprising a plurality of microwells formed in the first substrate, the plurality of microwells opening onto a droplet operations surface of the microwell device, the microwell device coupled to the droplet actuator and positioned such that the microwells face the droplet operations gap.” In other words, the “droplet actuator” “gap” need only “face” the microwells of the “first substrate.” This means not only can the “first substrate” be any material, moreover it can be located anywhere with any “facing” with the “gap.” In addition, the “droplet actuator” is any generic droplet component with any generic electrodes merely “proximate” (near, which is any subjective distance) to the gap. To summarize the droplet actuator and first substrate configuration, it is very broad, encompassing any “gap” for any purpose located at any position of a generic “droplet actuator,” along with any generic substrate with microwells merely “facing” the gap.
The “second substrate” is then generically claimed as generic “cell traps” which “extend[] into the droplet operations gap and wherein each cell trap of the plurality of cell traps is located above each microwell of the plurality of microwells.” Again, this encompasses any “cell trap” structure located anywhere above a microwell, and any microwell structure.
In contrast to this breadth, the specification discloses, at best, a single example. It is shown in Figure 18:
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At minimum, this single example requires the following: cell trap structure in/on lid 1710 over single-cell-dimensioned wells; and electrowetting structure 215 using electrodes 220 to move droplets. None of this is required in the claims. Moreover, from this very specific example, the full scope of the very broadly-claimed invention is not possessed. This single example requires a specific electrowetting configured tied to a specific cell trap configuration on/in the lid over the single-cell microwells. Yet, as shown in the anticipation rejections below, the broad claims encompass vastly different configurations nowhere contemplated in the specification.
Even more, the specification completely fails to explain how, and by what structures, the single cells are trapped on/in the lid. The specification is simply silent about any such “cell traps” formed on the only “second substrate” disclosed, which is the lid in Figure 18. Instead, Figure 18 only shows rectangles labeled “cell trapping structure.” The specification fails to contain any detail whatsoever about these “traps,” much less how they integrate with the “gap” and “droplet operations electrodes” of the “droplet actuator,” or even how this yields the claimed functions (e.g. “each cell trap of the plurality of cell traps is located above each microwell of the plurality of microwells such that each cell trap of the plurality of cell traps are configured such that cells of interest are trapped by the plurality of cell traps and are deposited into the plurality of microwells”).
Thus, the specification fails to provide a “written description of the invention . . . in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same.”
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention;
(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 1-10 are rejected under 35 U.S.C. § 102(a)(2) as being anticipated by BREINLINGER (US20160199837).
As to claim 1, BREINLINGER teaches digital fluidics system, comprising:
(a) a droplet actuator including a droplet operations gap, the droplet actuator including droplet operations electrodes arranged proximate to the droplet operations gap (lid/cover with single-cell traps, and electrowetting movement into and out of traps; Figs. 5-6 & 11; paras. 0101, 0111, 0113, 0115, 0127, 0130-34);
(b) a microwell device including:
(1) a first substrate comprising a plurality of microwells formed in the first substrate, the plurality of microwells opening onto a droplet operations surface of the microwell device, the microwell device coupled to the droplet actuator and positioned such that the microwells face the droplet operations gap (id.); and
(2) a second substrate comprising a plurality of cell traps formed on the second substrate, the plurality of cell traps extending into the droplet operations gap and wherein each cell trap of the plurality of cell traps is located above each microwell of the plurality of microwells such that each cell trap of the plurality of cell traps are configured such that cells of interest are trapped by the plurality of cell traps and are deposited into the plurality of microwells (wells 258, that include dimensioned for single cell; Figs. 5-6 & 11);
(c) a controller (e.g. para. 0163) configured to execute program instructions to:
(1) direct the droplet actuator to transport a sample droplet to a microwell device, the sample droplet including cells of interest (paras. 0073, 0082, 0200-01 and Figs. 5-6 & 11);
(2) introduce capture beads to the microwells, wherein capture elements are immobilized on the capture beads (id.); and
(3) direct the droplet actuator to transport a cell lysis reagent droplet to the microwell device, wherein portions of the lysis reagent droplet enter the microwells and, during an incubation period, cause the cells of interest to release analyte(s) that is/are captured by the capture elements on the capture beads (id.).
As to claim 2, BREINLINGER teaches the second substrate includes a hydrophobic layer disposed on the surface facing the droplet operations gap, and wherein the hydrophobic layer is not disposed on the first substrate comprising the plurality of microwells (para. 0091).
As to claim 3, BREINLINGER teaches the droplet operations gap is configured to retain a filler fluid including the sample droplet containing the cells of interest (Figs. 5-6 & 11 and paras. 0101, 0111, 0113, 0115, 0127, 0130-34).
As to claim 4, BREINLINGER teaches the microwells 258 have a size and pitch dimensioned to receive only a single cell and to receive only a single capture bead (Figs. 6E-G, for example).
As to claim 5, BREINLINGER teaches the microwells have a depth of between 30 μm and 50 μm (para. 0182).
As to claim 6, BREINLINGER teaches the microwells have a diameter of between 3 μm and 60 μm (id.)
As to claim 7, BREINLINGER teaches the plurality of microwells are spaced from one another by a pitch no greater than 80 μm (id.)
As to claim 8, BREINLINGER teaches the controller is further configured to execute program instructions to (4) direct the droplet actuator to transport a fluid immiscible with the cell lysis reagent droplet to the microwell device, wherein the immiscible fluid does not enter the microwells and cell traps (para. 0132).
As to claim 9, BREINLINGER teaches the droplet actuator comprises a compartment that is shaped and dimensioned to receive the microwell device (Figs. 5-6 & 11).
As to claim 10, BREINLINGER teaches each cell trap of the plurality of cell traps are sized such that only one of the cells of interest fits in each cell trap of the plurality of cell traps (paras. 0108-09).
Claim 1-10 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by COLLINS (US20130244906).
As to claim 1, COLLINS teaches digital fluidics system, comprising:
(a) a droplet actuator including a droplet operations gap, the droplet actuator including droplet operations electrodes arranged proximate to the droplet operations gap (Figs. 5 & 7 and paras. 0014, 0019, 0030 & 0070);
(b) a microwell device including:
(1) a first substrate comprising a plurality of microwells formed in the first substrate, the plurality of microwells opening onto a droplet operations surface of the microwell device, the microwell device coupled to the droplet actuator and positioned such that the microwells face the droplet operations gap (wells in bottom substrate in Fig. 7 and paras. 0056ff); and
(2) a second substrate comprising a plurality of cell traps 185 formed on the second substrate, the plurality of cell traps extending into the droplet operations gap and wherein each cell trap of the plurality of cell traps is located above each microwell of the plurality of microwells such that each cell trap of the plurality of cell traps are configured such that cells of interest are trapped by the plurality of cell traps and are deposited into the plurality of microwells (traps in top substrate in Fig. 7);
(c) a controller configured to execute program instructions to:
(1) direct the droplet actuator to transport a sample droplet to a microwell device, the sample droplet including cells of interest (id.);
(2) introduce capture beads to the microwells, wherein capture elements are immobilized on the capture beads (id.); and
(3) direct the droplet actuator to transport a cell lysis reagent droplet to the microwell device, wherein portions of the lysis reagent droplet enter the microwells and, during an incubation period, cause the cells of interest to release analyte(s) that is/are captured by the capture elements on the capture beads (id.).
As to claim 2, COLLINS teaches the second substrate includes a hydrophobic layer disposed on the surface facing the droplet operations gap, and wherein the hydrophobic layer is not disposed on the first substrate comprising the plurality of microwells (id.)
As to claim 3, COLLINS teaches the droplet operations gap is configured to retain a filler fluid including the sample droplet containing the cells of interest (id.)
As to claim 4, COLLINS teaches the microwells have a size and pitch dimensioned to receive only a single cell and to receive only a single capture bead (id.)
As to claim 5, COLLINS teaches the microwells have a depth of between 30 μm and 50 μm (paras. 0060).
As to claim 6, COLLINS teaches the microwells have a diameter of between 3 μm and 60 μm (id.)
As to claim 7, COLLINS teaches the plurality of microwells are spaced from one another by a pitch no greater than 80 μm (id.)
As to claim 8, COLLINS teaches the controller is further configured to execute program instructions to (4) direct the droplet actuator to transport a fluid immiscible with the cell lysis reagent droplet to the microwell device, wherein the immiscible fluid does not enter the microwells and cell traps (paras. 0008, 0010, 0057, 0062).
As to claim 9, COLLINS teaches the droplet actuator comprises a compartment that is shaped and dimensioned to receive the microwell device (Figs. 1-8).
As to claim 10, COLLINS teaches each cell trap of the plurality of cell traps are sized such that only one of the cells of interest fits in each cell trap of the plurality of cell traps (Fig. 5).
Double Patenting- Obvious Type
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Instant claims 1-10 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-9 of U.S. 12011719.
First, although the Application here is filed as a DIV of 17/555013 (which matured to US 12011719), yet consonance was not maintained between the unelected system of Invention II (claims 10-12) and the elected method of Invention I in 17/555013. Specifically, the original elected claims 1-9 did not contain top/second substrate comprising cell traps “that extend into the droplet operations surface of the microwell device and are located above each of the plurality of microwells, wherein the plurality of microwells and the plurality of molded cell traps are configured such that the cells of interest are trapped by the plurality of molded cell traps and are thereby deposited into the plurality of microwells.” This was added to the claims after the election of Invention I. Yet, Invention II (claim 10) originally included “a second substrate, the microwell device including cell traps formed on the second substrate, the cell traps opening onto the droplet operations surface of the microwell device.” In contrast, original Invention I (claim 1) recited “a plurality of cell traps that open onto the droplet operations surface of the microwell device.” In other words, the line of demarcation was the “second substrate, the microwell device including cell traps formed on the second substrate, the cell traps opening onto the droplet operations surface of the microwell device,” which was crossed by the amendment to Invention I (claim 1) of “a second top substrate comprising a plurality of molded cell traps that extend into the droplet operations surface of the microwell device and are located above each of the plurality of microwells, wherein the plurality of microwells and the plurality of molded cell traps are configured such that the cells of interest are trapped by the plurality of molded cell traps and are thereby deposited into the plurality of microwells.” Thus, Section 121 safe harbor does not apply to the issued claims in US 12011719.
The instant claims are obvious over the conflicting claims because the conflicting claims teach the same fluidics system here with the same microwell-trap configuration, along with method to control droplet actuator to transport sample, introduce capture beads and transport cell lysis. Specifically, the conflicting claims teach:
1. A method comprising:
(a) utilizing a droplet actuator to transport a sample droplet to a microwell device, the sample droplet including cells of interest, the microwell device including
a bottom substrate having a plurality of microwells that open onto a droplet operations surface of the microwell device, and
a top substrate comprising a plurality of molded cell traps that extend into the droplet operations surface of the microwell device and are located above each of the plurality of microwells, wherein the plurality of microwells and the plurality of molded cell traps are configured such that the cells of interest are trapped by the plurality of molded cell traps and are thereby deposited into the plurality of microwells;
(b) introducing capture beads to the microwells, wherein capture elements are immobilized on the capture beads; and
(c) utilizing the droplet actuator to transport a cell lysis reagent droplet to the microwell device, wherein portions of the cell lysis reagent droplet enter the microwells and, during an incubation period, cause the cells of interest to lyse and release analyte that is captured by the capture elements on the capture beads.
2. The method of claim 1, wherein the capture beads are sized such that only one of the capture beads fits in one of the microwells.
3. The method of claim 1, wherein the molded cell traps are sized such that only one of the cells of interest fits in one of the molded cell traps.
4. The method of claim 1, further comprising:
(d) during and/or prior to the incubation period, utilizing the droplet actuator to transport a fluid immiscible with the cell lysis reagent droplet to the microwell device, wherein the immiscible fluid does not enter the microwells and molded cell traps, thereby encapsulating single beads with single cells with cell lysis reagent.
5. The method of claim 1, further comprising removing the capture beads with the analyte captured thereon from the microwells.
6. The method of claim 5, wherein the removing operation includes positioning a magnet proximate to the microwells to form a magnetic field that pulls the capture beads from the microwells.
7. The method of claim 1, further comprising utilizing a magnetic field to move the capture beads to and away from the microwells.
8. The method of claim 1, wherein each of the capture beads includes a plurality of the capture elements.
9. The method of claim 8, wherein the plurality of capture elements include a capture sequence and a unique barcode sequence, wherein the capture sequence is optionally one of i) a poly-T sequence for capture of total mRNA, or ii) a plurality of transcript-specific capture sequences that target a panel of genes of interest.
Thus, the conflicting claims render the instant claims anticipated because they disclose a system used in the conflicting claim method that includes the same components as here.
Prior Art
The following prior art is also pertinent to electrowetting-based trapping and cell manipulation: US 20160158748; US 20150166326.
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/YUNG-SHENG M TSUI/ Primary Examiner, Art Unit 1684
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