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 .
Claims 1, 3-14, 23-25, 48-51 are pending and currently under examination.
Priority
This application 18/036,392 filed on 05/10/2023 is a 371 national phase of PCT//US2021/058809 filed on 11/10/2021, and claims the benefit of provisional U.S. Patent Application No. 63/111,95, filed on 11/10/2020.
The priority date of claims 1 and 24 and their respective dependent claims is determined to be 11/10/2020, the filing date of provisional U.S. Patent Application No. 63/111,95.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because figures are blurred and difficult to read. Figures 8, 11, 12, 20, and 27 are of particularly poor quality. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Specification
The use of terms which are trade names or marks used in commerce (including IIlumina® and Qiagen™ among others), has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears 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 Objections
Claims 1 and 24 are objected to because of the following informalities: Claims 1 and 24 recite the limitation “--ligation of barcoded adaptors to DNA and primer-assisted ligation of the adaptors to cDNA ends)”. It is assumed that the “)” is a typo intended to be “;” or “,”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1, 3-14, 23-25 and 48-51 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.
Claim 1 recites the limitations “cDNA and chromatin cleaved ends” in line 8, “DNA ends” in line 10, “DNA” in line 11, and “cDNA ends” in line 12. The limitation (i) “cDNA and chromatin cleaved ends” in line 8 and (ii) “DNA ends” in line 10, “DNA” in line 11, and “cDNA ends” in line 12 are presented as alternatives. As written, it is unclear which elements are equivalent. For purposes of examination, it is assumed that “chromatin cleaved ends” are the same as the “DNA ends” and “DNA” in lines 10 and 11, while the “cDNA” from line 8 is equivalent to the “cDNA ends” in line 12.
Claim 1 recites the limitation “the adaptors” in lines 11-12. There is insufficient antecedent basis for this limitation in the claim. For examination purposes it is assumed that the limitation is intended to be “the barcoded adaptors”.
Claim 1 recites the limitation "pooling the cells from each reaction well" in line 13. There is insufficient antecedent basis for “each reaction well” in the claim
Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. Claim 1 recites the limitation “pooling the cells from each reaction well” in line 13. The omitted step in claim 1 appears to be a step placing cells in a reaction well. No reaction well is recited before this limitation. Independent claim 1 should clearly delineate all active steps required for performing the claimed methods.
Claims 3-14, and 23 are similarly indefinite because they directly or indirectly depend from claim 1.
Claim 8 recites the limitation "the MNase-digested sites" in line 1. There is insufficient antecedent basis for “MNase-digested sites” in the claim. For purposes of examination, it is assumed that the limitation is intended to refer to the “chromatin cleaved ends” in claim 1.
Claim 13 recites the limitation “comparing the chromatin occupancy and RNA profile from the individual's cells with a chromatin occupancy and RNA profile obtained from a normal individual”. It is unclear what criteria would determine a “normal individual”.
Claim 23 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. Claim 23 recites the limitation “detecting the presence of cancer in the individual using a method comprising subjecting cells from the individual to the method of claim 1”. The omitted steps in claim 23 appear to be steps necessary for detecting cancer. Claim 23 should clearly delineate all active steps required for performing the claimed methods. The steps of claim 23 and the claims it depends from (claim 1) do not specifically result in the claimed ability to detect the presence of cancer.
Claim 24 recites the limitations “the sample” in line 4 and "the cellular heterogeneity of the tumor sample" in line 21. There is insufficient antecedent basis for “the sample” and “the tumor sample” in the claim. For purposes of examination, it is assumed that the limitations are intended to refer to the “solid tumor sample” in the preamble.
Claims 25 and 48-51 are similarly indefinite because they directly or indirectly depend from claim 1.
The term “accurately” in claim 25 is a relative term which renders the claim indefinite. The term “accurately” 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. The limitation "diagnoses stages and nature of the tumor" is rendered indefinite by the use of the term "accurately".
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 11-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Step 1
The claimed invention is directed to the statutory category of a process.
Step 2A, Prong One
The claim is (claims are) taken to be directed to an abstract idea, a judicial exception.
Claim 11 is directed to a method comprising “single cells are resolved by identifying each unique combination of barcodes and indexes”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the identifying step encompasses the mental step of looking at barcodes and making mental judgements.
Claim 12 is directed to a method comprising “using the chromatin occupancy and RNA profile to diagnose or prognose the illness”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the using step encompasses the mental step of looking at sequencing profiles and making mental judgements.
Claim 13 depends from claim 12, and requires the same step of “using the chromatin occupancy and RNA profile to diagnose or prognose the illness”.
Claim 13 is directed to a method comprising “comparing the chromatin occupancy and RNA profile from the individual's cells with a chromatin occupancy and RNA profile obtained from a normal individual”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the comparing step encompasses the mental step of looking at profiling results and making mental judgements.
Step 2A, Prong Two
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception.
While claim 1 recites ” crosslinking cells --; performing chromatin cleavage -- and subjecting the cells to reverse transcription; subjecting the cells to terminal deoxynucleotidyl transferase (TdT)-mediated oligonucleotide addition -- or , subjecting the cells to end repair, deoxyadenosine addition -- and primer-assisted ligation; pooling the cells --; sorting or diluting the pooled cells ; -- amplification steps; and, subjecting the sorted cells to a library construction and sequencing”, these are not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method.
Step 2B
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to ” crosslinking cells --; performing chromatin cleavage -- and subjecting the cells to reverse transcription; subjecting the cells to terminal deoxynucleotidyl transferase (TdT)-mediated oligonucleotide addition -- or , subjecting the cells to end repair, deoxyadenosine addition -- and primer-assisted ligation; pooling the cells --; sorting or diluting the pooled cells ; -- amplification steps; and, subjecting the sorted cells to a library construction and sequencing” are techniques that are routine, conventional, and well-known in the art as demonstrated in the 103 rejection documented below.
Furthermore, the courts have recognized the following laboratory techniques as well-understood, routine, conventional activities in the life science arts when they are claimed in a merely generic manner or as insignificant extra-solution activity:
i. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546;
ii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
iii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
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 (i.e., changing from AIA to pre-AIA ) 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.
Claims 1 and 3-14 are rejected under 35 U.S.C. 103 as being unpatentable over Buenrostro et al. (US 20200248255) in view of Ku et al. (Single- cell chromatin immunocleavage sequencing (scChIC-seq) to profile histone modification. 2019. Nature Methods.16 (4): p. 1-6, on IDS dated 11/01/2023).
Regarding claim 1, Buenrostro teaches a method for analyzing genomic DNA and RNA from single cells, the method comprising crosslinking cells using a fixative (para 59), fragmenting DNA by contacting chromatin within individual cells with a transposase to generate fragmented cellular genomic DNA (para 11); reverse transcribing the mRNA to generate cDNA (para 11); attaching oligonucleotides to the fragmented genomic DNA with the transposase (para 54 and Fig. 1A) and attaching barcoded tags to the DNA during tagmentation (para 80); ligating adapters to cDNA using a oligonucleotide comprising a poly(dT) sequence and a unique molecular identifier (UMI) (i.e. barcode) (para 13); using split and pool strategies (para 11) and amplifying the genomic DNA and cDNA (para 7); generating a library for sequencing (para 56), and profiling chromatin accessibility and mRNA expression (paras 144-149), including joint profiling of chromatin accessibility and transcription (para 34 and Fig. 18).
Buenrostro does not teach (i) end repair, deoxyadenosine addition to the DNA ends, which is followed by T/A ligation of barcoded adaptors to DNA or (ii) profiling chromatin occupancy.
Ku teaches a method of single-cell chromatin immuno-cleavage sequencing comprising cleaving chromatin and ligating adapters to cleaved DNA fragments (p. 1, col. 1). Ku further teaches the method comprises (i) performing end repair, adding 3’ A overhangs and ligating adapters (p. 4, col. 1) and (ii) profiling genome-wide transcription factor binding sites and histone modification (i.e. chromatin occupancy) (p.1, col 1).
Ku states that their method of profiling chromatin occupancy may find broad applications in elucidating chromatin states in rare primary and patient samples (p. 3, col. 2) and that there is a potential association of cellular heterogeneity in gene expression with that in the chromatin state of individual cells in the population (p. 1, col. 1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Buenrostro and Ku to arrive at the instantly claimed invention. The modification would have entailed substituting the chromatin cleavage steps of Ku for the fragmenting DNA by contacting chromatin steps of Buenrostro. One would have been motivated to make the substitution in order to have a method capable of profiling chromatin occupancy instead of accessibility and applying the findings to patient samples. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 3, Ku teaches chromatin cleavage with pA-MNase (p. 323, col. 1).
Regarding claim 4, Ku teaches chromatin cleavage with MNase, an endo-exonuclease (p. 323, col. 1).
Regarding claim 5, Buenrostro teaches reverse transcription is performed in a single cell (i.e. in situ) (paras 54, 160).
Regarding claim 6, Buenrostro teaches reverse transcription using an oligonucleotide comprising a poly(dT) sequence (para 13) and gene-specific primers (i.e. primers that do not anneal to rRNA) (para 88).
Regarding claim 7, Buenrostro teaches a barcode may identify the type of nucleic acids molecules. For example, all DNA molecules may comprise a first common barcode sequence and all RNA molecules or cDNA molecules generated from RNA molecules may comprise a second common barcode sequence (para 93).
Regarding claim 8, Buenrostro teaches cell barcodes were simultaneously ligated to cDNA and chromatin fragments (i.e. chromatin cleaved ends) (para 226).
Regarding claim 9, Buenrostro teaches DNA molecules may comprise a first common barcode (para 93), which reads on barcode adaptors that allow identification of cleaved chromatin.
Regarding claim 10, Buenrostro does not teach the cells are sorted by flow cytometry or by dilution.
Ku teaches cells are sorted using a BD FACSAria III cell sorter (p. 4, col. 2)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Buenrostro and Ku to arrive at the instantly claimed invention. The modification would have entailed further adding the sorting step of Ku. One would have been motivated to sort using the FACS method of Ku in order to have precise control over sorting at the level of a single cell. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 11, Buenrostro teaches barcoding the fragmented genomic DNA and the cDNA within each cell such that the genomic DNA and the cDNA from the same cell receive the same unique barcode sequence (Abstract), attaching one or more barcodes to the fragmented DNA and the cDNA (para 90). Buenrostro further teaches using the unique barcode sequence to identify sequence reads identifying a single cell.
Regarding claim 12, Buenrostro and Ku teach performing the method of claim 1 as described above. Buenrostro also teaches performing the method on an individual (para 48) and providing a diagnosis or prognosis of a condition in a subject (para 8).
Regarding claim 13, Buenrostro does not teach comparing the chromatin occupancy and RNA profile from the individual's cells with a chromatin occupancy and RNA profile obtained from a normal individual.
Regarding claim 14, Buenrostro teaches using the method in cancer research (para 252), which reads on cancer as the condition of the individual.
Claims 23-25 and 48-51 are rejected under 35 U.S.C. 103 as being unpatentable over Buenrostro et al. (US 20200248255) in view of Ku et al. (Single- cell chromatin immunocleavage sequencing (scChIC-seq) to profile histone modification. 2019. Nature Methods.16 (4): p. 1-6, on IDS dated 11/01/2023) as applied to claims 1 and 3-14 above, and further in view of Kennedy et al. (US 20190390253).
Regarding claim 23, Buenrostro and Ku teach performing the method of claim 1 as described above. Buenrostro also teaches performing the method on an individual (para 48) and providing a diagnosis or prognosis of a condition in a subject (para 8), including in cancer (para 252).
Neither Buenrostro nor Ku teach administering to the individual a cancer therapeutic agent.
Kennedy teaches a method for processing nucleic acid populations containing different forms (e.g., RNA and DNA), including epigenetic analysis. Kennedy teaches using the method to diagnose presence of conditions, particularly cancer and select a therapy (par 207). Kennedy further discuses subjects having been treated with chemotherapies (para 176).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Buenrostro and Ku with Kennedy to arrive at the instantly claimed invention. The modification would have entailed interpreting the results from Buenrostro and Ku to identify a condition and selecting an appropriate therapy to administer. One would have been motivated by the benefit of using the data produced by the method to help patients. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 24, Buenrostro teaches a method for analyzing genomic DNA and RNA from single cells, the method comprising crosslinking cells using a fixative (para 59), fragmenting DNA by contacting chromatin within individual cells with a transposase to generate fragmented cellular genomic DNA (para 11); reverse transcribing the mRNA to generate cDNA (para 11); attaching oligonucleotides to the fragmented genomic DNA with the transposase (para 54 and Fig. 1A) and attaching barcoded tags to the DNA during tagmentation (para 80); ligating adapters to cDNA using a oligonucleotide comprising a poly(dT) sequence and a unique molecular identifier (UMI) (i.e. barcode) (para 13); using split and pool strategies (para 11) and amplifying the genomic DNA and cDNA (para 7); generating a library for sequencing (para 56), and profiling chromatin accessibility and mRNA expression (paras 144-149), including joint profiling of chromatin accessibility and transcription (para 34 and Fig. 18).
Buenrostro also teaches using the method to determine the full diversity of cell types and cell states (para 188) and leveraging the naturally occurring heterogeneity within a cell type (para 187) or tissue (para 178) with the method.
Buenrostro does not teach (i) end repair, deoxyadenosine addition to the DNA ends, which is followed by T/A ligation of barcoded adaptors to DNA or (ii) profiling chromatin occupancy.
Ku teaches a method of single-cell chromatin immuno-cleavage sequencing comprising cleaving chromatin and ligating adapters to cleaved DNA fragments (p. 1, col. 1). Ku further teaches the method comprises (i) performing end repair, adding 3’ A overhangs and ligating adapters (p. 4, col. 1) and (ii) profiling genome-wide transcription factor binding sites and histone modification (i.e. chromatin occupancy) (p.1, col 1).
Ku states that their method of profiling chromatin occupancy may find broad applications in elucidating chromatin states in rare primary and patient samples (p. 3, col. 2) and that there is a potential association of cellular heterogeneity in gene expression with that in the chromatin state of individual cells in the population (p. 1, col. 1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Buenrostro and Ku to arrive at the instantly claimed invention. The modification would have entailed substituting the chromatin cleavage steps of Ku for the fragmenting DNA by contacting chromatin steps of Buenrostro. One would have been motivated to make the substitution in order to have a method capable of profiling chromatin occupancy instead of accessibility and applying the findings to patient samples. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Buenrostro teaches biological samples can include whole cells and/or live cells (para 47) and teaches using the method in cancer research (para 252).
However, neither Buenrostro nor Ku teach performing the method on a solid tumor sample.
Kennedy teaches a sample can be a solid tumor sample (para 176). Kennedy also states that the method (processing nucleic acid populations containing different forms (e.g., RNA and DNA), including epigenetic analysis) can be used to determining heterogeneity of a cancer (para 207).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Buenrostro and Ku with Kennedy to arrive at the instantly claimed invention. The modification would have entailed using the solid tumor sample of Kennedy as the sample of Buenrostro and Ku. One would have been motivated to apply the method to a biologically relevant heterogenous tissue such as cancer. Both Buenrostro and Ku were directed towards a method for investigating cellular heterogeneity and stated use of the method in cancer. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 25, neither Buenrostro nor Ku teach the determination of the cellular heterogeneity of the tumor accurately diagnoses stages and nature of the tumor.
Kennedy teaches using results of the method profiling RNA and DNA, including epigenetics, to stage cancer (para 207).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Buenrostro and Ku with Kennedy to arrive at the instantly claimed invention. The modification would have entailed using the data produced by the method of Buenrostro and Ku to characterize tumor cells and stage cancer as taught by Kennedy. One would have been motivated to use the analysis method of Kennedy in order to gain medical benefits from the method. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 48, Buenrostro does not teach chromatin cleavage by one of the claimed elements.
Ku teaches cleaving chromatin with an MNase that is recruited to specific chromatin regions by a specific antibody through protein A–antibody interaction (Ab+PA-MNase) (p. 1, col 1). Ku teaches that this modification allows one to cleave chromatin at specific sites of histone modifications or transcription factors such as H3K4me3 (p. 1, cols. 1 and 2).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Buenrostro and Ku to arrive at the instantly claimed invention. The modification would have entailed using the Ab+PA-Mnase of Ku to create the DNA chromatin fragments of Buenrostro. One would have been motivated by the added benefit of the ability to interrogate particular histone modifications of interest. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 49, Buenrostro teaches reverse transcription is performed in a single cell (i.e. in situ) (paras 54, 160).
Regarding claim 50, Buenrostro teaches reverse transcription using an oligonucleotide comprising a poly(dT) sequence (para 13) and gene-specific primers (i.e. primers that do not anneal to rRNA) (para 88).
Regarding claim 51, Buenrostro teaches a barcode may identify the type of nucleic acids molecules. For example, all DNA molecules may comprise a first common barcode sequence and all RNA molecules or cDNA molecules generated from RNA molecules may comprise a second common barcode sequence (para 93).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA GRAY whose telephone number is (571)272-0116. The examiner can normally be reached Monday-Friday 8-5 with second Fridays off.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, WINSTON SHEN can be reached at (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682