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 Application
Claims 1-11, 14-16, 18 and 21-24 are pending and under examination.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Umapathi and Fallah-Araghi et al.
Claim(s) 1-5,7, 9-11, 14,16, 21 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Umapathi (US20190262829) in view of Fallah-Araghi et al. ("A completely in vitro ultrahigh-throughput droplet-based microfluidic screening system for protein engineering and directed evolution." Lab on a Chip 12.5 (2012): 882-891; cited in IDS filed 12 August 2022).
Umapathi teaches droplet-based methods for biochemical analysis comprising using EWOD with an electrowetting device comprising an array of tracks of electrode pads, i.e. segmented electrodes, to control the movement of droplets. Umapathi teaches methods wherein liquid droplets are applied to the surface of the device on the electrode pad tracks which induce different droplet manipulations, including droplet movement, merging , mixing and splitting. Umapathi teaches these droplet operations are used to perform different biochemical reactions, including cell free protein expression (e.g. Entire Umapathi reference and especially Abstract; para 003,pg. 1; para 0007-0008, pg. 1-2; para 0061-0062; para 0067-0070, pg. 3; EWOD as in 0071-0072,pg. 3; para 0176-0191,pg. 9; cell free protein expression as in para 0191; Fig. 1-5; Fig. 10 A-I).
Furthermore, Umapathi teaches electrowetting devices comprising liquid -liquid-gas interface wherein in a water droplet transits on an oil layer and is surrounded by air or gas(e.g. para 0067-0068, pg. 3).Furthermore, Umapathi teaches the oil carrier fluid includes silicone oil, DuPont Krytox oil, Fluorinert FC-70 or other oil (e.g. Entire Umapathi reference and especially para 0139-0149, pg. 7-8; silicone oil, DuPont Krytox oil, Fluorinert FC-70 or other oil as in para 0149, pg. 7-8).
Furthermore, Umapathi teaches components of their devices that control oxygen concentration (e.g. para 0185, pg. 9).
Furthermore, Umapathi teaches droplets containing samples of nucleic acids, proteins, cells, enzymes and reagents (e.g. para 0191,pg. 9; para 0201-0205, pg. 10; An electrowetting device 100 placed above (FIG.ll(i)) the source plate captures the droplets 1168 ejected from the well plate and holds the droplets through electrowetting force. In this manner, samples containing nucleic acids, proteins, cells, salts, buffers, enzymes and any other biological and chemical reagent may be dispensed onto an electrowetting chip… as in para 0213,pg. 10-11).
Furthermore, Umapathi teaches embodiments of their devices in a two plate configuration wherein droplets are sandwiched between the plates and fluids or air fill the space between the plates (e.g. para 0220-0221, pg. 11).
Furthermore, Umapathi teaches their devices may comprise an incubation station which allows mixing of reaction droplets, wherein the mixing occurs by moving fused droplets in patterns through a 3X3 grid, i.e. two dimensional array of planar electrodes ( e.g. mixed by running the merged droplet around the outer eight electrodes of the 3x3 grid, or running through other patterns designed to mix the two original droplets… as in para 0195, pg. 9; an electrowetting chip may include one or more incubation stations 1128. Each individual incubator 1128 may integrate one or more functions to be applied to liquid samples such as mixing, heating (for example, to temperatures up to 150° Celsius), cooling (for example, to -20° Celsius), compensating for fluid loss due to evaporation as well as homogenizing temperature of a sample… as in para 0198,pg. 10).
Furthermore, Umapathi teaches reaction products are detected buy an optical system (e.g. para 0206-0212, pg. 10; Fig. 11A-J).
Regarding the step of mixing one or more droplets containing nucleic acid template with droplets containing a cell-free system having components for protein expression in an oil-filled or humidified gaseous environment as recited in the instant claims:
As noted above, Umapathi teaches methods are known comprising droplet operations of droplet movement, merging , mixing and splitting. Furthermore, Umapathi teaches droplets containing samples of nucleic acids, proteins, cells, enzymes and reagents. Furthermore, Umapathi teaches their devices may comprise an incubation station which allows mixing of reaction droplets, wherein the mixing occurs by moving fused droplets in patterns through a 3X3 grid, i.e. two dimensional array of planar electrodes. Furthermore, Umapathi teaches these droplet operations are used to perform different biochemical reactions, including cell free protein expression.
Umapathi does not expressly teach method steps for droplet-based cell protein expression.
Furthermore, Umapathi does not expressly teach the limitations: the method comprising: a) taking a first plurality of droplets each having a different nucleic acid template,
b) taking a second plurality of droplets each containing a cell-free system having the components for protein expression, c) combining the first plurality of droplets of (a) and the second plurality of droplets of (b) using electrowetting-on-dielectric (EWoD) to produce a third plurality of droplets capable of expressing proteins of different sequences, d) mixing the third plurality of droplets to enable cell-free protein expression, and, e) detecting protein expression within individual droplets as recited in claim 1.
However, prior to the effective filing date of the claimed invention, Fallah-Araghi et al. teach droplet- based synthesis of proteins comprising providing a first population of droplets comprising template DNA and a second population of droplets comprising in vitro transcription – translation (IVTT) reagents; subjecting the two droplet populations to electrode-mediated forces that cause droplet merging and incubating the fused droplets for two hours at 37°C to allow completion of protein synthesis, wherein the resulting protein is detected by fluorescence (e.g. Entire Fallah-Araghi reference and especially Results section, pg. 883-885; Fig. 2, pg. 884).
Therefore, as both Umapathi and Fallah-Araghi et al. teach droplet based methods for cell free protein expression and detection, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Umapathi using an electrowetting device to include having a two plate configuration to control movement of droplets in an oil or air - filled environment as taught in one embodiment of Umapathi and to include droplets containing samples of nucleic acids, proteins, cells, enzymes and reagents as taught in other embodiments of Umapathi and to include droplet transit and droplet merging as taught in other embodiments of Umapathi and to include incubation stations which allow mixing of reaction droplets, wherein the mixing occurs by moving fused droplets in patterns through a 3X3 grid, i.e. two dimensional array of planar electrodes, as taught in other embodiments of Umapathi and to include droplet operations to perform different biochemical reactions, including cell free protein expression (e.g. para 0191) as taught in an embodiment of Umapathi and to include the method reagents and steps comprising a first population of droplets comprising template DNA and a second population of droplets comprising in vitro transcription – translation (IVTT) reagents; reaction incubation of two hours at 37°C and detection by fluorescence as taught by Fallah-Araghi et al. as a person of ordinary skill in the art would recognize that these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of method for the cell-free expression of proteins in a digital microfluidic device having a two-dimensional array of planar microelectrodes and having an oil-filled environment.
Therefore, the combined teachings of Umapathi and Fallah-Araghi et al. render obvious the limitations: a method for the cell-free expression of peptides or proteins in a digital microfluidic device having a two-dimensional array of planar microelectrodes; and having an oil-filled or humidified gaseous environment, and moving said droplets using electrowetting-on-dielectric (EWoD) the method comprising: a) taking a first plurality of droplets each having a different nucleic acid template, b) taking a second plurality of droplets each containing a cell-free system having the components for protein expression, c) combining the first plurality of droplets of (a) and the second plurality of droplets of (b) using electrowetting-on-dielectric (EWoD) to produce a third plurality of droplets capable of expressing proteins of different sequences, d) mixing the third plurality of droplets to enable cell-free protein expression, and, e) detecting protein expression within individual droplets.as recited in claim 1.
Furthermore, as Umapathi teaches droplet movement during reaction incubation and Fallah-Araghi et al. teach IVTT reaction incubation of two hours at 37°C, the combined teachings of Umapathi and Fallah-Araghi et al. render obvious claims 2,7, 9 and 24.
Regarding claims 3 and 21:
Claim 3 further describes an alternative of claim 1 that is not required by the claimed invention. Therefore, insofar as claim 3 depends from claim 1, art that meets the requirements of claim 1 also meets claim 3.
Claim 21 depends from claim 3 and further describes an alternative of claim 1 that is not required by the claimed invention.
Therefore, as Umapathi teaches embodiments of electrowetting devices comprising a two plate configuration wherein droplets are sandwiched between the plates in an oil-filled space (e.g. para 0139-0149, pg. 7-8; silicone oil, DuPont Krytox oil, Fluorinert FC-70 or other oil as in para 0149, pg. 7-8; two plate configuration as in para 0220-0221, pg. 11), the combined teachings of Umapathi and Fallah-Araghi et al. render obvious claims 3 and 21.
As Umapathi teaches an electrowetting device comprising an array of tracks of electrode pads, the combined teachings of Umapathi and Fallah-Araghi et al. render obvious the limitation: wherein the electrical signal for the digital microfluidic device is delivered through segmented electrodes as recited in claim 4.
As Umapathi teaches droplets move in an oil carrier fluid, including silicone oil, DuPont Krytox oil, Fluorinert FC-70 or other oil (e.g. para 0139-0149, pg. 7-8), the combined teachings of Umapathi and Fallah-Araghi et al. render obvious claim 5.
Furthermore, as Fallah-Araghi et al. teach droplet- based synthesis of proteins using a population of droplets comprising in vitro transcription – translation (IVTT) reagents, the combined teachings of Umapathi and Fallah-Araghi et al. render obvious claims 10 and 11.
As Umapathi teaches their methods and devices comprise droplet splitting according to user’s choice(e.g. para 0176-0179,pg. 9), the combined teachings of Umapathi and Fallah-Araghi et al. render obvious claim 14.
As Fallah-Araghi et al. teach detection by fluorescence, the combined teachings of Umapathi and Fallah-Araghi et al. render obvious claim 16.
Umapathi, Fallah-Araghi et al. and Cho et al.
Claim(s) 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Umapathi and Fallah-Araghi et al., as applied to claims 1-5,7, 9-11, 14,16, 21 and 24 above, and further in view of Cho et al. ("Droplet-based microfluidic platform for high-throughput, multi-parameter screening of photosensitizer activity." Analytical chemistry 85.18 (2013): 8866-8872; cited in IDS filed 05 September 2024).
The combined teachings of Umapathi and Fallah-Araghi et al. render obvious a method for cell-free protein expression comprising using EWOD with an electrowetting device comprising an array of segmented electrodes in a two plate configuration and droplets that transit through an oil-filled space between the plates.
Furthermore, Umapathi teaches electrowetting devices comprising liquid -liquid-gas interface wherein in a water droplet transits on an oil layer and is surrounded by air or gas(e.g. para 0067-0068, pg. 3; silicone oil, DuPont Krytox oil, Fluorinert FC-70 or other oil as in para 0139-0149, pg. 7-8).
Furthermore, Umapathi teaches components of their devices that control oxygen concentration (e.g. para 0185, pg. 9).
However, the combined teachings of Umapathi and Fallah-Araghi et al. do not expressly teach claims 6 and 8.
Prior to the effective filing date of the claimed invention, Cho et al. teach droplet-based methods are known in the art wherein oxygenated oil is supplemented to the droplets during a reaction (e.g. continuous supply of oxygenated FC-40 oil as in Droplet Incubation and Exposure to Light section, pg. 8868).
Therefore, as both Umapathi and Cho et al. teach methods comprising mediating oxygen concentration associated with reaction droplets, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Umapathi and Fallah-Araghi et al. using an electrowetting device for analysis within droplets in an oil carrier fluid and to include providing a supply of oxygenated oil for droplet-based reactions as taught by Cho et al. as a person of ordinary skill in the art would recognize that these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of method for the cell-free expression of proteins in a digital microfluidic device having a two-dimensional array of planar microelectrodes and having an oil-filled environment.
Therefore, the combined teachings of Umapathi, Fallah-Araghi et al. and Cho et al. render obvious claims 6 and 8.
Umapathi, Fallah-Araghi et al. and Pollack et al.
Claim(s) 15 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Umapathi and Fallah-Araghi et al., as applied to claims 1-5,7, 9-11, 14,16, 21 and 24 above, and further in view of Pollack et al. (US7851184).
The combined teachings of Umapathi and Fallah-Araghi et al. render obvious a method for cell-free protein expression comprising using EWOD with an electrowetting device comprising an array of segmented electrodes in a two plate configuration and droplets that transit through an oil-filled space between the plates.
Furthermore, Umapathi teaches methods using a device comprising electrode pad tracks which induce different droplet manipulations, including droplet movement, merging, mixing and splitting, which are used to perform different biochemical reactions, including cell free protein expression.
However, the combined teachings of Umapathi and Fallah-Araghi et al. do not expressly teach claims 15 and 18.
Prior to the effective filing date of the claimed invention, Pollack et al. teach droplet-based methods using an electrowetting device comprising segmented electrodes wherein droplets comprising detection reagents are merged with reaction product -containing droplets for a detection reaction (e.g. Entire Pollack reference and especially reagents from different sources merge with target droplet as in lines 62-66, col. 28; droplets comprising detection reagents are added separately to reacted droplets as in lines 15-24, col. 30).
Therefore, as both Umapathi and Pollack et al. teach methods comprising merging reagents with target droplets to mediate a reaction, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Umapathi and Fallah-Araghi et al. using electrowetting device for merging droplets in an oil carrier fluid and detecting protein products by fluorescence and to include merging droplets comprising detection reagents with reaction product -containing droplets for a detection reaction as taught by Pollack et al. as a person of ordinary skill in the art would recognize that these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of method for the cell-free expression of proteins in a digital microfluidic device having a two-dimensional array of planar microelectrodes and having an oil-filled environment.
Therefore, the combined teachings of Umapathi, Fallah-Araghi et al. and Pollack et al. render obvious claims 15 and 18.
Umapathi, Fallah-Araghi et al. and Courtois et al.
Claim(s) 22 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Umapathi and Fallah-Araghi et al., as applied to claims 1-5,7, 9-11, 14,16, 21 and 24 above, and further in view of Courtois et al. ("An integrated device for monitoring time‐dependent in vitro expression from single genes in picolitre droplets." ChemBioChem 9.3 (2008): 439-446.).
The combined teachings of Umapathi and Fallah-Araghi et al. render obvious a method for cell-free protein expression comprising using EWOD with an electrowetting device comprising an array of segmented electrodes in a two plate configuration and droplets that transit through an oil-filled space between the plates.
Furthermore, Umapathi teaches methods using a device comprising electrode pad tracks which induce different droplet manipulations, including droplet movement, merging, mixing and splitting, which are used to perform different biochemical reactions, including cell free protein expression.
Furthermore,. Fallah-Araghi et al. teach protein detection by green fluorescence. Furthermore, Fallah-Araghi et al. discuss the work of Courtois et al. comprising in vitro transcription and translation of single green fluorescent protein (GFP) genes and fluorescent detection of the expressed GFP in droplets in microfluidic systems (e.g. Entire Fallah-Araghi reference and especially... IVTT of single green fluorescent protein (GFP) genes and fluorescent detection of the expressed GFP have been demonstrated in picolitre droplets in microfluidic systems...1st para, Introduction section, pg. 883; Results section, pg. 883-885; Experimental section, pg. 888-890).
However, the combined teachings of Umapathi and Fallah-Araghi et al. do not expressly teach claims 22 and 23.
Prior to the effective filing date of the claimed invention, Courtois et al. teach a device and method for detection of protein expression in droplets, wherein the protein is GFP and the method comprises detection of green fluorescence ( e.g. Entire Courtois reference and especially In vitro expression of green fluorescent protein in microdroplets and In vitro expression of GFP from a single DNA template molecule sections, pg. 441-443; Experimental section, pg. 444-445).
Therefore, as Fallah-Araghi et al. discuss the work of Courtois et al. of methods comprising IVTT reactions in droplets, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Umapathi and Fallah-Araghi et al. using electrowetting device for merging droplets in an oil carrier fluid and detecting protein products by fluorescence and to include GFP protein expression and detection of green fluorescence as taught by Courtois et al. as a person of ordinary skill in the art would recognize that these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of method for the cell-free expression of proteins in a digital microfluidic device having a two-dimensional array of planar microelectrodes and having an oil-filled environment.
Therefore, the combined teachings of Umapathi, Fallah-Araghi et al. and Courtois et al. render obvious claims 22 and 23.
Double Patenting
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
U.S. Patent No. 11,821,018
Claims 1-11, 14-16, 18 and 21-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,821,018 in view of in view of Umapathi (US20190262829);Fallah-Araghi et al. ("A completely in vitro ultrahigh-throughput droplet-based microfluidic screening system for protein engineering and directed evolution." Lab on a Chip 12.5 (2012): 882-891; cited in IDS filed 12 August 2022); Cho et al. ("Droplet-based microfluidic platform for high-throughput, multi-parameter screening of photosensitizer activity." Analytical chemistry 85.18 (2013): 8866-8872; cited in IDS filed 05 September 2024); Pollack et al. (US7851184); and Courtois et al. ("An integrated device for monitoring time‐dependent in vitro expression from single genes in picolitre droplets." ChemBioChem 9.3 (2008): 439-446.).
Like the instant invention, claim 1 of U.S. Patent No. 11,821,018 recites a method for cell free protein expression using EWOD with an electrowetting device. Furthermore, claims 2-13 of U.S. Patent No. 11,821,018 recite very similar or identical limitations as recited in the instant set of claims.
Furthermore, the combined teachings of Umapathi and Fallah-Araghi et al. render obvious claims 1-5,7, 9-11, 14,16, 21 and 24. Furthermore, the additional teachings of Cho et al. render obvious claims 6 and 8. Furthermore, the additional teachings of Pollack et al. render obvious claims 15 and 18. Furthermore, the additional teachings of Courtois et al. render obvious claims 22 and 23.
Therefore, it would have been obvious to one skilled in the art to modify a method for cell free protein expression as taught by claim 1 of U.S. Patent No. 11,821,018 by including the features of claims 2-13 of U.S. Patent No. 11,821,018 as well as the teachings of Umapathi; Fallah-Araghi et al.; Cho et al., Pollack et al. and Courtois et al. as a skilled artisan would recognize that these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a method for the cell-free expression of peptides or proteins in a digital microfluidic device having a two-dimensional array of planar microelectrodes and having an oil-filled environment.
Response to the Arguments
Any rejection not reiterated or specifically addressed has been overcome by amendment. New rejections are set forth to address the amended claims.
However, previously cited references teach art relevant to the amended claims and therefore are included in the new rejections.
Regarding Applicants’ arguments that the previously cited art does not meet the requirements of the amended claims: these arguments are not persuasive.
Regarding Applicants’ arguments in reference to surprising results:
See MPEP 716.02.
MPEP 716.02: Allegations of Unexpected Results
Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (differences in sedative and anticholinergic effects between prior art and claimed antidepressants were not unexpected). In In re Waymouth, 499 F.2d 1273, 1276, 182 USPQ 290, 293 (CCPA 1974), the court held that unexpected results for a claimed range as compared with the range disclosed in the prior art had been shown by a demonstration of “a marked improvement, over the results achieved under other ratios, as to be classified as a difference in kind, rather than one of degree.” Compare In re Wagner, 371 F.2d 877, 884, 152 USPQ 552, 560 (CCPA 1967) (differences in properties cannot be disregarded on the ground they are differences in degree rather than in kind); Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (“we generally consider a discussion of results in terms of ‘differences in degree’ as compared to ‘differences in kind’ . . . to have very little meaning in a relevant legal sense”).
As indicated in MPEP 716.02, unexpected results are considered in terms of differences in property that are actually unexpected.
Regarding the instant case, Applicant argues:
“…The inventors "have surprisingly demonstrated that CFPS reagents can be actuated on an
oil-filled EWoD device for hours with minimal surface fouling or biofouling. Actuation
(causing active movement via electrokinesis) during the process of expression also improves the
level of expression over a static system where electrokinesis is not used during the expression
process" (p.13, first para.). It is believed that sealing or using an oil-filled environment prevents
evaporation/ mitigates bio-fouling in CFPS (last ,i of specification).
A further advantage of the claimed invention is that repeated mixing while conducting
CFPS enhances protein synthesis. In this regard, FIG. 3, top panel (copied below) clearly
demonstrates that actuated and mixed droplets had the highest amount of synthesized protein
(A), compared to droplets that were actuated but remained in place (B), and not actuated and not
mixed droplets (C)..…”.
However, as stated in MPEP 716, Applicants’ assertion of unexpected results requires objective evidence , i.e. data, that the results are actually unexpected. See MPEP 716, especially
MPEP 716.01 (a): Objective Evidence of Nonobviousness .
OBJECTIVE EVIDENCE MUST BE CONSIDERED WHEN TIMELY PRESENT Affidavits or declarations, when timely presented, containing evidence of criticality or unexpected results, commercial success, long-felt but unsolved needs, failure of others, skepticism of experts, etc., must be considered by the examiner in determining the issue of obviousness of claims for patentability under 35 U.S.C. 103…
Also: MPEP 716.01( c): Probative Value of Objective Evidence
TO BE OF PROBATIVE VALUE, ANY OBJECTIVE EVIDENCE SHOULD BE SUPPORTED BY ACTUAL PROOF
Objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. See, for example, In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984) ("It is well settled that unexpected results must be established by factual evidence." "[A]ppellants have not presented any experimental data showing that prior heat-shrinkable articles split. Due to the absence of tests comparing appellant’s heat shrinkable articles with those of the closest prior art, we conclude that appellant’s assertions of unexpected results constitute mere argument."). See also In re Lindner, 457 F.2d 506, 508, 173 USPQ 356, 358 (CCPA 1972); Ex parte George, 21 USPQ2d 1058 (Bd. Pat. App. & Inter. 1991).
ARGUMENTS BY APPLICANT CANNOT TAKE THE PLACE OF EVIDENCE
Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
Furthermore, see MPEP 716.02 (b).I. : BURDEN ON APPLICANT TO ESTABLISH RESULTS ARE UNEXPECTED AND SIGNIFICANT …The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance."
In the instant case, Applicant has not provided evidence that mixing droplet contents to provide better reaction yield, i.e. more synthesized product, will establish differences in results that are in fact unexpected and unobvious and of both statistical and practical significance.
Furthermore, regarding Applicants’ arguments in reference to the teaching of Fallah-Araghi et al., these arguments are not persuasive.
Considering amended claim 1:
The step of mixing requires this action “to enable cell free protein expression” but does not expressly require further agitation of the merged droplet.
Considering the Fallah-Araghi et al. reference as a whole, Fallah-Araghi et al. teach merging amplified DNA droplets with droplets containing IVTT expression system and subjecting the merged droplets, which are mixed by virtue of the merging action, to conditions to allow cell free protein expression ( e.g. ... During the 2 hours of incubation at 37 °C the genes were transcribed and translated and, if active b-galactosidase was produced, FDG was converted
to galactose and fluorescein (green fluorescent) by enzymatic hydrolysis... as in 1st para, Coupled in vitro transcription and translation (IVTT) section, pg. 884).Therefore, the teaching of Fallah-Araghi et al. is applied.
The additional arguments rely on the position that a prima facie case was not established in previous rejections. However this was not found persuasive and is not persuasive for the other rejections.
With regards to the rejection on the grounds of non-statutory double patenting, Applicants‘ arguments and the amendment have been fully considered and deemed unpersuasive for the reasons that follow. Applicants have not submitted arguments or documentation (i.e. terminal disclaimer) in response to the double patenting rejection. Therefore, the previous rejection of non-statutory double patenting is maintained.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHANA S KAUP whose telephone number is (571)272-6897. The examiner can normally be reached on M-F 7-10 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, HEATHER CALAMITA can be reached on 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAHANA S KAUP/ Primary Examiner, Art Unit 1684