DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Preliminary Amendments and Status of the Claims
2. The preliminary amendment filed 30 January 2023, in which claims 1-2 were cancelled and new claims 3-19 were added, is acknowledged and entered.
The preliminary amendment filed 12 June 2023, in which the Replacement Drawings were filed, is acknowledged. These drawings are accepted.
The preliminary amendment filed 24 October 2023, in which the title was amended, is acknowledged and entered.
3. Claims 3-19 are under prosecution.
Notice to Comply with Requirements for Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosure.
4. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth below.
Specifically, the application fails to comply with CFR 1.821(d), which states:
(d) Where the description or claims of a patent application discuss a sequence that is set forth in the “Sequence Listing” in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by “SEQ ID NO:” in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application.
The Specification discloses two amino acid sequences in Figure 8. However, none of the sequences are identified by a SEQ ID NO., nor are they included in the Sequence Listing.
For compliance with sequence rules, it is necessary to include the sequence in the “Sequence Listing” and identify them with SEQ ID NO. In general, any sequence that is disclosed and/or claimed as a string of particular bases or amino acids, and that otherwise meets the criteria of CFR 1.821(a), must be set forth in the “Sequence Listing.” See MPEP 2422.03.
5. While the Examiner has made every attempt to check the Specification for sequence compliance, Applicant is required to carefully check the entire Specification for any and all issues regarding sequence compliance.
6. For the response to this Office Action to be complete, Applicant is REQUIRED to comply with the Requirements for Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures. Failure to comply with the Requirements will be considered nonresponsive.
Information Disclosure Statement
7. The Information Disclosure Statement filed 30 January 2023 is acknowledged and has been considered.
It is noted that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
8. The use of trade names or marks used in commerce (including but not necessarily limited to Cy5 in Figure 5 and PicoSurf on page 14), has been noted in this application. Any trade names or marks should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112 and Priority
9. Applicant states that this application is a continuation or divisional application of the prior-filed application. A continuation or divisional application cannot include new matter. Applicant is required to delete the benefit claim or change the relationship (continuation or divisional application) to continuation-in-part because this application contains matter not disclosed in the prior-filed application a discussed in the rejections under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, detailed below.
10. 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.
11. Claims 3-9 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.
This is a new matter rejection necessitated by the amendments.
A. Claim 3 (upon which claims 4-19 depend) recites an “indicator,” and “maintaining the viability” and “analyzing the genome of metabolome” of microbiological objects. A review of both parent Application No. 16,496,595, now U.S. Patent No. 11,604,145 B2; hereafter the “’595 Application) and PCT Application RU/2018/000155 (hereafter the “Parent PCT”) yields no teaching of:
I. Any recitation of an “indicator;”
II. “Maintaining viability;”
III. “Analyzing” a genome; or
IV. Any recitation of a “metabolome.”
B. Claim 8 recites retaining ”viability,” which, as noted above, is not discussed or suggested in either the ‘595 Application or the Parent PCT.
C. Claim 15 recites a ”reporter target cell,” which is not discussed or suggested in either the ‘595 Application or the Parent PCT.
D. Claim 16 recites a ”combination of different fluorescent indicators.” As noted above, “indicators” are not discussed in either the ‘595 Application or the Parent PCT. In addition, a review of both the ‘595 Application and the Parent PCT yields no teaching of an “combination” florescent molecules.
Thus, the limitations above constitute new matter.
12. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly
claiming the subject matter which the applicant regards as his invention.
13. Claims 3-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A. The term “ultrahigh” in claim 3 (upon which claims 4-19 depend) is a relative term which renders the claim indefinite. The term “ultrahigh” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
This term is also present in claim 8.
It is noted that claim 19 recited a “productivity” of 1000-20000 events per second, which is interpreted as being the range of “ultra-high” for that specific claim.
B. Claim 6 is indefinite in the recitation “including,” as it is unclear if the term indicates requiring display libraries or indicates one possible (but not required) embodiment.
C. Claim 8 is indefinite as it is unclear how the cells are “regenerated” if they have retained their “viability.”
For the purposes of examination, the “regenerating” is interpreted as culturing, as culturing results in division of viable cells.
D. The term “high” in claim 9 is a relative term which renders the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
E. Claim 18 is indefinite in the recitation “the chips,” which lacks antecedent basis because claim 3 does not recite any “chip.”
Claim Rejections - 35 USC § 103
14. 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.
15. 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.
16. Claims 3-7, 11-14, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Agresti et al. (U.S. Patent Application Publication No. US 2010/0136544 A1, published 3 June 2010) in combination with Agresti et al. (Proc. Nat. Acad. Sci USA, vol. 107, pages 4004-4009, published 8 February 2010 and Supporting Information, pages 1-5; hereafter “Agresti 2”) and Kwon et al (U.S. Patent Application Publication No. US 2015/0119284 A1, published 30 April 2015).
Regarding claims 3 and 19, Agresti et al. teach methods comprising forming double microfluidic water-in-oil-in-water emulsions (paragraph 0003), wherein the droplets are monodisperse (paragraph 0038) and each droplet encapsulates 1 or more species therein (paragraph 0052), an wherein each droplet has a diameter of 25 micrometers (paragraph 0046). The droplets further comprise fluorescent species (paragraph 0023) and detection of fluorescence (paragraph 0047). Agresti et al. further teach the droplets are isolated using an ultrahigh-throughput method, in the form of FACS, which isolates sub-populations for separate analysis (paragraph 0028). Agresti et al. also teaches genome analysis, in the form of whole genome amplification (paragraphs 0028-0029), and that the sorting is based on a species of interest (paragraph 0053), including enzymes paragraph 0106).
It is noted that the incubating/culturing and regeneration to maintain viability are optional steps, and thus are not specifically required by the instant claim.
Agresti et al. teach ultrahigh-throughput droplet formations of 5000 per second (i.e., claim 19), and that the methods have the added advantage of achieving very rapid coalescence and reaction speeds (paragraph 0085). Thus Agresti et al. teach the known techniques discussed above.
While Agresti et al. teach the sorting is based on a species of interest (paragraph 0053), including enzymes (paragraph 0106) as well as drugs (paragraph 0051, Agresti et al. do not explicitly teach fluorescence generated by the enzymatic activity.
However, Agresti 2 teaches methods comprising formation of droplets and ultra-high throughput screening thereof (Title), wherein the droplets are screened based on enzymatic activity with an indicator, in the form of a fluorogenic substrate for the enzyme (“Results and Discussion”). Agresti 2 further teaches the methods have the added advantage of performing assays with a million fold reduction in cost (Abstract). Thus, Agresti 2 teaches the known techniques discussed above.
Neither Agresti et al. nor Agresti 2 teach the method of double emulsion formation.
However. Kwon et al. teach methods of forming of double microfluidic water-in-oil-in-water emulsion droplets (i.e., microcapsules; Abstract and paragraph 0029). Kwon et al. also the droplets (i.e., microcapsules) are formed by making a first oil-in-water emulsions using a chip with hydrophobic channel, followed by formation of the water-oil-water double emulsion in a hydrophilic channel (paragraphs 0041-0045 and Figure 3). Kwon et al. further teach detection of enzymatic assays, including using indicators (i.e., substrates), and that the methods have the added advantage of allowing drug screening (paragraph 0062). Thus, Kwon et al. teach the known techniques discussed above.
It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of cited prior art to arrive at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantages of:
Achieving very rapid coalescence and reaction speeds as explicitly taught by Agresti et al. (paragraph 0085);
Performing assays with a million fold reduction in cost as explicitly taught by Agresti 2 (Abstract); and
Allowing drug screening as explicitly taught by Kwon et al. (paragraph 0062).
In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined with predictable results because the known techniques of the cited prior art predictably result in useful double emulsions for enzymatic assays.
Regarding claims 4-7 and 12, the method of claim 3 is discussed above. Agresti 2 teaches phenotype libraries (i.e., claim 4; page 4004, column 2), as well as libraries of artificial enzymatic activity, in the form of enzyme mutants (i.e., claim 5), which have different levels of enzymatic activity (i.e., claim 12; Abstract), and display libraries, in the form of yeast cells (i.e., claim 7) displaying enzyme variants on their surfaces (i.e., claim 6; “Results and Discussion”).
In addition, with respect to claim 7, Agresti et al. teach the objects comprise bacterial, yeast, or mammalian cells, which are genetically engineered (paragraph 0055). Thus, it would have been obvious the engineer the cell to have a specific enzyme.
Regarding claim 11, the method of claim 3 is discussed above.
It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
Specifically, Agresti et al. teach the objects are cells (Abstract), as do Agresti 2 (Abstract) and Kwon et al. (paragraph 0028). Cells contain at least one of the claimed enzymes.
In addition, it is noted that the claim does not require the claimed enzymes to be the source of the enzymatic or biocatalytic activity.
Regarding claims 13-14, the method of claim 3 is discussed above. Agresti 2 also teaches the enzyme is horseradish peroxidase, which reacts with hydrogen peroxide and the label AUR (Supporting Information, “Kinetics”). Thus, the fluorescent compound AUR changes its fluorescence both by interacting with the enzyme (i.e., claim 13) and by interacting with a product produced by the enzyme, in the form of the active oxygen species the enzyme generates from hydrogen peroxide (i.e., claim 14).
17. Claims 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Agresti et al. (U.S. Patent Application Publication No. US 2010/0136544 A1, published 3 June 2010) in combination with Agresti et al. (Proc. Nat. Acad. Sci USA, vol. 107, pages 4004-4009, published 8 February 2010 and Supporting Information, pages 1-5; hereafter “Agresti 2”) and Kwon et al (U.S. Patent Application Publication No. US 2015/0119284 A1, published 30 April 2015) as applied to claim 3 above, and further in combination with Wang et al. (U.S. Patent Application Publication No. US 2010/0124759 A1, published 20 May 2010).
Regarding claims 8 and 10, the method of claim 3 is discussed above in Section 16.
While Agresti et al. teach the droplets are isolated using an ultrahigh-throughput method, in the form of FACS, which isolates sub-populations for separate analysis (paragraph 0028), and while Kwon et al. teach the cells are alive after sorting (paragraph 0064), the previously cited prior art does not teach the isolated cells are cultured (i.e., claim 10), which regenerates the cells (i.e., claim 8).
However, Wang et al. teach methods wherein cells are placed in droplets (paragraph 0052), and the droplets are sorted based on the results of an assay (Abstract), including enzymatic assays (paragraph 0011), and where the sorted (i.e., accumulated) cells are cultured (i.e., claims 8 and 10; paragraph 0053). Wang et al. also teach the methods have the added advantage of allowing measurement of clone-specific metabolite concentrations (paragraph 0004) Thus, Wang et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Wang et al. with the previously cited prior art. Because the cells are cultured after isolation, they have remained viable throughout the methods, thus arriving at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantage of allowing measurement of clone-specific metabolite concentrations as explicitly taught by Wang et al. (paragraph 0004). In addition, it would have been obvious to the ordinary artisan that the known techniques of Wang et al. could have been combined with the previously cited prior art predictable results because the known techniques of Wang et al. predictably result in populations of the isolated cells that can be grown and utilized.
18. Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Agresti et al. (U.S. Patent Application Publication No. US 2010/0136544 A1, published 3 June 2010) in combination with Agresti et al. (Proc. Nat. Acad. Sci USA, vol. 107, pages 4004-4009, published 8 February 2010 and Supporting Information, pages 1-5; hereafter “Agresti 2”) and Kwon et al (U.S. Patent Application Publication No. US 2015/0119284 A1, published 30 April 2015) as applied to claim 3 above, and further in combination with Robins (U.S. Patent Application Publication No. US 2014/0322716 A1, published 30 October 2014).
Regarding claim 9, the method of claim 3 is discussed above in Section 16.
Agresti et al. teach the droplets are isolated using an ultrahigh-throughput method, in the form of FACS, which isolates sub-populations for separate analysis (paragraph 0028), and sequencing by standard methods (paragraph 0026).
None of the previously cited prior art teaches the claimed functionally equivalent high throughput sequencing.
However, Robins teaches methods utilizing droplets containing cells (paragraph 0085), wherein the cells are subjected to high throughput sequencing, which has the added advantage of allowing improved ability to determine the number of cells that belong to a specific clone (paragraph 0101). Thus, Robins teaches the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the functionally equivalent high throughput sequencing of Robins to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of allowing improved ability to determine the number of cells that belong to a specific clone as explicitly taught by Robins (paragraph 0101). In addition, it would have been obvious to the ordinary artisan that the known techniques of Robins could have been combined with the previously cited prior art predictable results because the known techniques of Robins predictably result in use of a reliable functionally equivalent sequencing method.
19. Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Agresti et al. (U.S. Patent Application Publication No. US 2010/0136544 A1, published 3 June 2010) in combination with Agresti et al. (Proc. Nat. Acad. Sci USA, vol. 107, pages 4004-4009, published 8 February 2010 and Supporting Information, pages 1-5; hereafter “Agresti 2”) and Kwon et al (U.S. Patent Application Publication No. US 2015/0119284 A1, published 30 April 2015) as applied to claim 3 above, and further in combination with Sprinzl et al. (U.S. Patent Application Publication No. US 2009/0258348 A1, published 15 October 2009).
It is noted that while claim 11 has been rejected as described above, the claim is also obvious using the interpretation outlined below.
Regarding claim 11, the method of claim 3 is discussed above in Section 16.
None of the previously cited prior art teaches esterases.
However, Sprinzl et al. teach methods where protein synthesis is tracked either in cells or droplets (paragraph 0046), wherein it is advantageous to use esterases (paragraph 0155), and that the enzymes have the added advantage of determining the efficacy of in vivo expression systems (paragraph 0013). Thus, Sprinzl et al. teaches the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the functionally equivalent high throughput sequencing of Sprinzl et al. to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of allowing the determination of the efficacy of in vivo expression systems as explicitly taught by Sprinzl et al. (paragraph 0013). In addition, it would have been obvious to the ordinary artisan that the known techniques of Sprinzl et al. could have been combined with the previously cited prior art predictable results because the known techniques of Sprinzl et al. predictably result use of a method of monitoring protein expression.
20. Claims 13 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Agresti et al. (U.S. Patent Application Publication No. US 2010/0136544 A1, published 3 June 2010) in combination with Agresti et al. (Proc. Nat. Acad. Sci USA, vol. 107, pages 4004-4009, published 8 February 2010 and Supporting Information, pages 1-5; hereafter “Agresti 2”) and Kwon et al (U.S. Patent Application Publication No. US 2015/0119284 A1, published 30 April 2015) as applied to claim 3 above, and further in combination with Anderson et al. (U.S. Patent Application Publication No. US 2010/0028926 A1, published 4 February 2014).
It is noted that while claim 13 has been rejected as described above, the claim is also obvious using the interpretation outlined below.
Regarding claims 13 and 16, the method of claim 3 is discussed above in Section 16.
None of the previously cited prior art teaches combinations of different fluorescence indicators (i.e., claim 16).
However, Anderson et al. teach methods wherein different substrates for different enzymatic activities produce different fluorescent product (i.e., claim 16), which results in a change in fluorescence based on the enzyme altering the substrates (i.e., claim 13), and that the methods have the added advantage of allowing detection, identification, and quantification of one or more microorganisms (paragraph 0070). Thus, Anderson et al. teaches the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Anderson et al. to arrive at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantage of allowing detection, identification, and quantification of one or more microorganisms as explicitly taught by Anderson et al. (Paragraph 0070). In addition, it would have been obvious to the ordinary artisan that the known techniques of Anderson et al. could have been combined with the previously cited prior art predictable results because the known techniques of Anderson et al. predictably result in reliable detection of multiple different enzyme activities
21. Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Agresti et al. (U.S. Patent Application Publication No. US 2010/0136544 A1, published 3 June 2010) in combination with Agresti et al. (Proc. Nat. Acad. Sci USA, vol. 107, pages 4004-4009, published 8 February 2010 and Supporting Information, pages 1-5; hereafter “Agresti 2”) and Kwon et al (U.S. Patent Application Publication No. US 2015/0119284 A1, published 30 April 2015) as applied to claim 3 above, and further in combination with Kiel et al. (U.S. Patent Application Publication No. US 2009/0004644 A1, published 1 January 2009).
It is noted that while claim 14 has been rejected as described above, the claim is also obvious using the interpretation outlined below.
Regarding claim 14, the method of claim 3 is discussed above in Section 16.
None of the previously cited prior art teaches changes in fluorescence due to interaction with an enzymatic product.
However, Kiel et al. teach methods wherein aptamers change their fluorescence upon binding to an analyte (paragraph 0006O. Kiel et al. further teach detection of products of enzymatic catalysis using aptamer (paragraph 0088). Thus, it would have been obvious for the aptamer to bind the product of the enzymatic reaction. Kiel et al also teach the aptamers of the methods have the added advantage of precise molecular recognition (paragraph 0005). Thus Kiel et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Kiel et al. to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of allowing precise molecular recognition as explicitly taught by Kiel et al. (paragraph 0005). In addition, it would have been obvious to the ordinary artisan that the known techniques of Kiel et al. could have been combined with the previously cited prior art predictable results because the known techniques of Kiel et al. predictably result in use of reliable fluorescent reporters.
22. Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Agresti et al. (U.S. Patent Application Publication No. US 2010/0136544 A1, published 3 June 2010) in combination with Agresti et al. (Proc. Nat. Acad. Sci USA, vol. 107, pages 4004-4009, published 8 February 2010 and Supporting Information, pages 1-5; hereafter “Agresti 2”) and Kwon et al (U.S. Patent Application Publication No. US 2015/0119284 A1, published 30 April 2015) as applied to claim 3 above, and further in combination with King et al (Lab on a Chip, vol. 7, pages 77-85, published online 29 September 2006).
Regarding claim 15, the method of claim 3 is discussed above in Section 16.
None of the previously cited prior art teaches reporter cells.
However, King et al. teach methods wherein extracellular enzyme products (i.e., transcription factors) are detected by indicators, in the form or reporter cells, whose fluorescence changes because of activation of green fluorescent protein engineered within the reporter cells (i.e., claim 15; Figure 1). King et al. further teach the reporter cells have the added advantage of enabling investigation of dynamic gene expression programs (Abstract). Thus, King et al. teaches the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of King et al. to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of enabling investigation of dynamic gene expression programs as explicitly taught by King et al. (Abstract). In addition, it would have been obvious to the ordinary artisan that the known techniques of King et al. could have been combined with the previously cited prior art predictable results because the known techniques of King et al. predictably result in reliable monitoring of gene expression.
23. Claims 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Agresti et al. (U.S. Patent Application Publication No. US 2010/0136544 A1, published 3 June 2010) in combination with Agresti et al. (Proc. Nat. Acad. Sci USA, vol. 107, pages 4004-4009, published 8 February 2010 and Supporting Information, pages 1-5; hereafter “Agresti 2”) and Kwon et al (U.S. Patent Application Publication No. US 2015/0119284 A1, published 30 April 2015) as applied to claim 3 above, and further in combination with Gunes et al. (U.S. Patent Application Publication No. US 2012/0315313 A1, published 13 December 2012).
Regarding claims 17 and 18, the method of clam 3 is discussed above in Section 16.
Kwon et al. teach the droplets (i.e., microcapsules) are formed by making a first oil-in-water emulsions using a chip with hydrophobic channel, followed by formation of the water-oil-water double emulsion in a hydrophilic channel (paragraphs 0041-0045 and Figure 3).
Agresti et al teach the channel diameters are 25 micrometers (i.e., claim 18; paragraph 0043).
None of the previously cited prior art teaches the functionally equivalent method of using two chips (i.e., claim 17).
However, Gunes et al. teach methods of making w/o/w double emulsions (paragraph 0070), wherein hydrophobic chips are used for making water in oil emulsions, and hydrophilic chips are used to make oil in water emulsions, and that the chips have the added advantage of being commercially available (paragraph 0113). Thus, Gunes et al. teach the known techniques discussed above.
It is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists, and that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the functionally equivalent two chip method of Gunes et al. with the previously cited prior art. The combination would result in the use of two chips having the claimed hydrophobicity and hydrophilicity, which generate the two emulsions of claim 17. The combination would further result in the hydrophobic chip and channel having the proper dimensions for forming the initial single emulsion and the hydrophilic chip and channel having the proper dimensions for forming the final double emulsion, thus arriving at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantage of utilizing commercially available chips as explicitly taught by Gunes et al. (paragraph 0113). In addition, it would have been obvious to the ordinary artisan that the known techniques of Gunes et al. could have been combined with the previously cited prior art predictable results because the known techniques of Gunes et al. predictably result in a functionally equivalent way of forming double emulsions.
Double Patenting
24. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
25. Claims 3-5, 7-8, 10, 12-13, and 15-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,604,145 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to ultrahigh throughput screening, double emulsions, droplet and channel diameters, enzymatic activities, culturing, regenerating, phenotype libraries, artificial activities, etc. Any additional limitations of the ‘145 claims are encompassed by the open claim language “comprising” found in the instant claims.
26. Claims 6, 11, and 14 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,604,145 B2 in combination with Agresti et al. (Proc. Nat. Acad. Sci USA, vol. 107, pages 4004-4009, published 8 February 2010 and Supporting Information, pages 1-5; hereafter “Agresti 2”) based on the citations and rationale provided above.
27. Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,604,145 B2 in combination with Robins (U.S. Patent Application Publication No. US 2014/0322716 A1, published 30 October 2014) based on the citations and rationale provided above.
28. Claim 11 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,604,145 B2 in combination with Sprinzl et al. (U.S. Patent Application Publication No. US 2009/0258348 A1, published 15 October 2009) based on the citations and rational presented above.
29. Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,604,145 B2 in combination with Kiel et al. (U.S. Patent Application Publication No. US 2009/0004644 A1, published 1 January 2009) based on the citations and rationale provided above.
Conclusion
30. No claims is allowed.
31. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert T. Crow whose telephone number is (571)272-1113. The examiner can normally be reached M-F 8:00-4:30.
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Robert T. Crow
Primary Examiner
Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683