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 .
Response to Amendment
This action is written in response to applicant’s amendment received on 12/17/25.
Any objection or rejection not reiterated herein has been overcome by amendment.
Claim Rejections - 35 USC § 112 New matter
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
New rejection necessitated by amendment. Claims 1-2, 9-10, 12, 14-16, 22-25, 31-32, 42, 49 and 54-57 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 2 are amended to require where the reaction substrate is unlabelled. The arguments point to support for the claim amendment on p 10 lines 8-19. This section of the specification is discussing existing platforms that use labeled substrates, and there is no mention in the specification of the current invention using unlabeled substrates, simply that there are possible drawbacks associated with the use of labeled substrates.
Claim Rejections - 35 USC § 103
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.
Modified rejection necessitated by amendment. Claims 1, 12, 15, 16, 22-25, 31-32, 49, and 55-57 are rejected under 35 U.S.C. 103 as being unpatentable over Reymond ("Screening systems." White biotechnology (2006): 31-58) and Reymond 2 ("Spectrophotometric enzyme assays for high-throughput screening." Food Technology and Biotechnology 42.4 (2004): 265-269.)
Regarding claims 1, 31-32, and 55-57, Reymond teaches enzyme screening technology (abstract). Reymond teaches microemulsion droplets comprising enzymes and fluorogenic substrates allows very high throughput screening (generating a plurality of droplets) (p37 first partial paragraph). Reymond teaches that epoxide hydrolases (EH) can be screened (p45-46 bridging paragraph). EH are cofactor (redox)-independent enzymes as evidenced by instant specification example 5. Reymond fig 9 teaches that this screening can be performed using EH (target enzyme, fig 9 “1”), a reaction substrate (fig 9 “51”) which forms a target product (fig 9 “54) which interacts with redox cofactor (fig 9 “2. Oxidation”). Raymond teaches that unlabeled reaction substrates can be used and the use of unlabeled reaction substrates is important for industrial biocatalysts (p44 first partial paragraph).
Reymond does not teach a detection reagent comprising a detection enzyme.
Reymond 2 teaches high throughput enzyme screening systems (title and abstract). Reymond 2 teaches that the mechanisms used can be used with epoxide hydrolases (p266-267 “β -Elimination of Umbelliferone” and “Periodate-Coupled Assays for Hydrolases” sections). Reymond 2 teaches that alcohol dehydrogenase (ADH) can be used as a secondary reagent (detection reagent comprising a detection enzyme) (p266 “β-Elimination of Umbelliferone). Reymond 2 teaches that the product produced by the target enzyme (EH) can be acted upon by the ADH (detection enzyme) and NAD+ (redox cofactor) to form a subsequent product (fig 2). The subsequent product can be fluorescent (p266-267 “β -Elimination of Umbelliferone” and “Periodate-Coupled Assays for Hydrolases” sections, figs 3 and 4). Reymond 2 teaches that these are practical solutions and hopes that it finds use in many laboratories (p269 “conclusions).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a detection enzyme of Reymond 2 in the method of Reymond. One of ordinary skill in the art would be motivated to do so because Reymond 2 teaches that these are practical solutions and hopes that it finds use in many laboratories. Further, one of ordinary skill in the art would be motivated to do so because these detection enzymes have been successfully used to screen EH and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. There would be a reasonable expectation of success as both Reymond and Reymond 2 are in the same field of endeavor of enzyme screening of EH.
Regarding claims 12 and 25, Reymond teaches that growing cells can be used (p33-37 “Screening and Selection of Enzyme Activities in Growing Cell Cultures” section).
Regarding claim 15, Reymond teaches surface displayed enzymes can be screened (p33-37 “Screening and Selection of Enzyme Activities in Growing Cell Cultures” section).
Regarding claim 16, Reymond 2 teaches cell supernatants can be used (extracellular) (abstract).
Regarding claim 22, Reymond teaches FACS can be used (p33-37 “Screening and Selection of Enzyme Activities in Growing Cell Cultures” section).
Regarding claim 23, Reymond teaches that enzyme activity can be screened (p32-33 “introduction”).
Regarding claim 24, Reymond teaches the genes encoding the enzymes can be sequenced (p49-50 “Chromatography”).
Regarding claim 49, Raymond teaches enzyme libraries can be screened (abstract).
Claims 2 and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Reymond ("Screening systems." White biotechnology (2006): 31-58) and Reymond 2 ("Spectrophotometric enzyme assays for high-throughput screening." Food Technology and Biotechnology 42.4 (2004): 265-269.) as applied to claims 1, 12, 15 16 22-25 31-32, 49, and 55-57 above, and further in view of Frenz ("Reliable microfluidic on-chip incubation of droplets in delay-lines." Lab on a Chip 9.10 (2009): 1344-1348).
Regarding claim 2, Raymond does not explicitly teach a fluidic device. The droplet composition comprising the enzymes and cofactors is discussed in the rejection of claim 1 above. Raymond teaches that unlabeled reaction substrates can be used and the use of unlabeled reaction substrates is important for industrial biocatalysts (p44 first partial paragraph).
Frenz teaches a microfluidic chip (device) (title). Frenz teaches that this allows for high throughput screening of enzymes (p1344 “introduction”). Frenz teaches that the incubation of droplets is one of the most important and essential steps of microfluidics (abstract). Frenz teaches a design for an incubation chamber comprising multiple incubation chambers coupled with multiple measuring points to monitor reactions over time as the droplets move (continuous flow) (fig 4, p1347-1348 section 3.4 “Measurement of enzyme kinetics”). Frenz teaches that this setup allows the creation of droplet based microfluidic systems for monitoring a wide range of biochemical reactions with increased incubation time (p1348 section 4 “conclusions”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a multiple incubation chamber design of Frenz in the high throughput screening droplets of Raymond and Raymond 2 above. One of ordinary skill in the art would be motivated to do so because these incubation devices have been successfully used to monitor enzyme reactions in a microfluidics system, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. There would be a reasonable expectation of success as both Raymond, Raymond 2 and Frenz are in the same field of endeavor of using high throughput enzyme screening.
Regarding claim 42, Reymond teaches E. coli can be used (p33-37 “Screening and Selection of Enzyme Activities in Growing Cell Cultures” section).
Claim 9, 10, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Reymond ("Screening systems." White biotechnology (2006): 31-58) and Reymond 2 ("Spectrophotometric enzyme assays for high-throughput screening." Food Technology and Biotechnology 42.4 (2004): 265-269.) and Frenz ("Reliable microfluidic on-chip incubation of droplets in delay-lines." Lab on a Chip 9.10 (2009): 1344-1348).as applied to claims 1, 2, 12, 15 16 22-25 31-32, 42, 49, and 55-57 above, and further in view of Galagan (US 11,536,685 B2).
Regarding claims 9 and 10, Raymond does not explicitly teach the use of a reference signal.
Galagan teaches the screening of enzymes (abstract). Galagan teaches the enzymes can be in droplets (column 6 first full paragraph). Galagan teaches that the enzyme activity can be compared to a threshold signal (reference signal) and sorted (isolated) (column 7 lines 42-44). This comparison can be used to determine if a bacteria contains enzymes (one or more characteristics) (column 7 lines 47-54).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a reference signal as taught by Galagan in the screening method of Raymond and Raymond 2 above. One of ordinary skill in the art would be motivated to do so because Galagan teaches this comparison can be used to determine if a bacteria contains enzymes. One of ordinary skill in the art would be motivated to do so because these reference signals have been successfully used to determine enzyme activity and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. There would be a reasonable expectation of success as both Raymond, Raymond 2, and Galagan are in the same field of endeavor of enzyme screening in droplets.
Regarding claim 14, Galagen teaches that isolated cells can be DNA extracted using a Qiagen 27104 kit (column 37 line 15). As evidenced by Qiagen miniprep handbook (see appendix) this kit comprises a lysis step (appendix p11 first full paragraph).
Regarding claim 54, Galagen teaches incubating the bacteria in the drops containing media and are incubated to allow cell growth (increase in number of host cells) prior to addition of AUR (column 37 lines 18-25).
Response to Arguments
Applicant's arguments filed 12/17/25 have been fully considered but they are not persuasive. Applicant argues that examiner has not addressed the limitation “the signal is emitted when the target product is further converted to a subsequent product” (p9-10 bridging paragraph, p11). This was addressed in the non-final rejection mailed on 9/17/25 page4 first partial paragraph in the rejection of claim 1, and is repeated in the rejection of claim 1 above. Specifically “Reymond 2 teaches that the product produced by the target enzyme (EH) can be acted upon by the ADH (detection enzyme) and NAD+ (redox cofactor) to form a subsequent product (fig 2). The subsequent product can be fluorescent (p266-267 “β -Elimination of Umbelliferone” and “Periodate-Coupled Assays for Hydrolases” sections, figs 3 and 4).”
Applicant asserts that none of the molecules are capable of producing a signal without being labeled (p10 first partial paragraph). The cited part of Raymond 2 indicates that compounds can be colorimetric (signal producing without a label) as well (p266-267 “β -Elimination of Umbelliferone” and “Periodate-Coupled Assays for Hydrolases” sections, figs 3 and 4)
Conclusion
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.
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 extension fee 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 TREVOR L KANE whose telephone number is (571)272-0265. The examiner can normally be reached M-F 7:00 am-4:00pm.
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/TREVOR KANE/Examiner, Art Unit 1657
/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657