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
Rejections not reiterated in this action are withdrawn.
Claims 1-5, 8-13, 15-16, 19-22, 28-37 are pending.
Priority
This application is a CON of 16/141,901 (09/25/2018, now US 11624062)
16/141,901 has PRO 62/562,684 (09/25/2017)
16/141,901 has PRO 62/562,894 (09/25/2017).
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, 62/562,684 and 62/562,894, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) for one or more claims of this application. For example, claim 1’s step of “in-cell or in-nucleus fragmenting the crosslinked nucleic acid …” does not have support in the provisional documents. The provisional documents have limited disclosure of a fragmentation but not “in-cell”. Specifically, in ‘684 cells are lysed before any fragmentation (‘684 p. 1/63); and ‘894 does not disclose a crosslinked cell at all and any fragmentation that is described is on extracted nucleic acids (‘894 p. 4/62). Thus, one of skill in the art would not recognize Applicant possessed the invention as claimed at the time of filing.
Accordingly, claim 1 and dependent claims 2-5, 8-13, 15-16, 19-22, 28-37 are not entitled to the benefit of the prior application. Thus, the relevant prior art date is that of the filing date 9/25/2018.
Claim Rejections - 35 USC § 112
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.
Claims 28-37 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 28-30 have the language “[t]he method of claim 1 wherein the in-cell or in-nucleus attaching a series of tags” which lacks an antecedent basis and renders the claim indefinite. Dependent claims 31-37 share the indefiniteness and are also rejected.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5, 8-13, 15-16, 19-22, 28-37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Seelig et al. (US20200263234, EFD 2017-09-22, published 2018-09-21).
Regarding claim 1, Seelig teaches:
1. A method to perform single-cell marking of a nucleic acid and/or protein in a sample comprising a plurality of cells, the method comprising: (Abstract; claim 1)
crosslinking a cell from the plurality of cells to provide a crosslinked cell comprising a crosslinked nucleic acid and/or protein material, (claim 1(a): fixing; [0041]: “the methods of labeling nucleic acids in the first cell may comprise fixing the plurality of cells prior to step (a). For example, components of a cell may be fixed or cross-linked such that the components are immobilized or held in place.”)
permeabilizing the crosslinked cell from the plurality of cells or a nucleus thereof, to provide a permeabilized cell or nucleus thereof; (claim 1(a): permeabilizing; [0042])
in-cell or in-nucleus fragmenting the crosslinked nucleic acid and/or protein material to provide molecular complexes each comprising fragmented crosslinked nucleic acid and/or protein material ([0052]; [0062]: “the method may further comprise digesting the DNA with a restriction enzyme prior to step (a)”; [0063]: “one or more restriction enzymes may be used to digest DNA into at least one of blunt end fragments and/or fragments having overhang sequences.”)
in-cell or in-nucleus barcoding nucleic acid and/or protein in the molecular complexes of the permeabilized cell or nucleus thereof, following the in-cell or in-nucleus fragmenting, (Figs. 1, 9, 23; claim 1 (d-k); [0048], [0069]);
to provide an in-cell or in-nucleus single-cell or single-nucleus marked-nucleic acid and/or protein in the molecular complexes of the cell, the nucleic acids and/or proteins barcoded with a single-cell or single-nucleus specific marker (Abstract: “Methods of uniquely labeling or barcoding molecules within a nucleus, a plurality of nuclei, a cell, a plurality of cells”).
Thus, claim 1 is anticipated.
Regarding claim 2-3, Seelig teaches sequential barcoding with tags (Figs. 1, 9, 23; claim 1 (d-k); [0048], [0069]).
Regarding claims 4 and 12, Seelig’s permeabilization and barcoding steps would permeabilize and barcode within the nucleus as claimed.
Regarding claim 5, 8-11, 16 and 19 specifying isolating the nucleus or cell, Seelig teaches applying the technique to “a nucleus” and “a cell” (Abstract; [0098]) as well as manual separation ([0004], Abstract) such that one of skill in the art would at once envisage isolating a single nucleus or cell and apply the technique.
Regarding claim 13 further comprising lysing, Seelig teaches lysing ([0044], claim 48).
Regarding claims 15, and 20-21, Seelig teaches permeabilizing the cell (claim 1(a): permeabilizing; [0042]) and barcoding (Figs. 1, 9, 23; claim 1 (d-k); [0048], [0069]) in a manner that is the same as in the claim.
Regarding claim 22 further comprising lysing, Seelig teaches lysing ([0044], claim 48).
Regarding claim 28, Seelig teaches attaching tags ([(Figs. 1, 9, 23; claim 1 (d-k); [0048], [0069])).
Regarding claim 29, Seelig teaches tagging using nucleic acids bound to antibodies ([0067], Fig. 6).
Regarding claims 30-32 wherein the tags are attached to RNA, Seelig teaches tagging RNA ([0056]-[0060]).
Regarding claim 33 further comprising lysing, Seelig teaches lysing ([0044], claim 48).
Regarding claims 34 and 36, Seelig teaches permeabilizing the cell (claim 1(a): permeabilizing; [0042]) and barcoding (Figs. 1, 9, 23; claim 1 (d-k); [0048], [0069]) in a manner that is the same as in the claim.
Regarding claim 35 and 37 specifying isolating the nucleus or cell, Seelig teaches applying the technique to “a nucleus” and “a cell” (Abstract; [0098]) as well as manual separation ([0004], Abstract) such that one of skill in the art would at once envisage isolating a single nucleus or cell and apply the technique.
Therefore, the claims are anticipated.
Claims 1-4, 11-13, 15, 20-22, 28-34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Seelig et al. (US20160138086).
Seelig teaches a method of labeling nucleic acids within cells with barcodes (Abstract, claim 1) including steps of crosslinking ([0035]), permeabilizing ([0036]), fragmenting with a restriction enzyme ([0056]), and in-cell barcoding ([0026]) with a series of tags ([0047]) by split-pool technique ([0014], [0033], Fig 8), lysed ([0040]), to analyze cDNA and RNA ([0051]-[0055]).
Response to Remarks - 35 USC § 102
Applicant argues that Seelig is not prior art under 35 USC 102. This argument is not persuasive as the relevant prior art date of the current claims is that of 9/25/2018 as detailed in the priority section above which is after Seelig’s non-provisional date of 9/21/2018.
Applicant argues that there is no teaching or suggestion of claim 1’s language “in-cell or in-nucleus fragmenting the crosslinked nucleic acid”. Seelig teaches both crosslinking and fragmenting prior to step (a) ([0041]: “the methods of labeling nucleic acids in the first cell may comprise fixing the plurality of cells prior to step (a). For example, components of a cell may be fixed or cross-linked such that the components are immobilized or held in place.”; [0062]: “the method may further comprise digesting the DNA with a restriction enzyme prior to step (a)”; [0063]: “one or more restriction enzymes may be used to digest DNA into at least one of blunt end fragments and/or fragments having overhang sequences.”) corresponding to the same as in the instant claims. Thus, the argument is not persuasive.
Applicant argues that Seelig has no teaching or suggestion of “in-cell or in-nucleus barcoding” following in-cell or in-nucleus fragmenting and actually “teaches against said features”. This argument is not persuasive because Seelig does clearly teach barcoding of the nucleic acids which occurs after claim 1’s step (a) and thus follows fragmenting (Figs. 1, 9, 23; claim 1 (d-k); [0048], [0069]). Thus, the prior art anticipates the claim. Regarding the alleged “teaching against”, Applicant points to a number of embodiments and argues how none disclose aspects of the claimed invention. This is also not persuasive as teaching away is relevant to obviousness, not anticipation – MPEP 2144.05.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
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