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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-10) in the reply filed on 1/20/2026 is acknowledged.
Claims 1-10 are pending and being examined on the merits.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The disclosure is objected to because of the following informalities:
Paragraph [0002] contains references to color drawings. However, no petition has been filed for the inclusion of color drawings in the application. Therefore, unless a petition is filed, this paragraph should be removed.
Paragraphs [0060-0061 and 00157] contain references to specific colors of beads in Figure 16 (“Orange bead”, “Blue bead”, “Teal bead”). Unless a petition for the inclusion of colored drawings is filed, references to colors in the figures should be removed and a non-color specific identifier should be employed.
Paragraph [0062] reads “Disclose are methods and devices” and should read “Disclosed are methods and devices”.
The last sentence of paragraph [0068] is missing a period.
Appropriate correction is required.
Claim Objections
Claims 1 and 3 are objected to because of the following informalities:
Claim 1, line 8 reads “collecting assay information from the examination area” and should read “collecting assay information from the at least one examination area” to remain consistent claim terminology throughout the claim.
Claim 1, line 19 reads “multi-index barcode” and should read “multi-indexed barcode” to remain consistent claim terminology throughout (consistent with the use of “multi-indexed barcodes” in line 4).
Claim 1, line 24 reads “at least one nucleic acid fragment” and should read “at least one nucleic acid [[fragment]]” to remain consistent throughout the claim.
Claim 3, line 1 reads “wherein the isolating” and should read “wherein[[ the]] isolating”.
Claim 3, lines 4-5 reads “isolation in confined physical geometries comprising aqueous media capped by mechanical”. It appears that a word has been left off, rendering the method of capping unclear.
Appropriate correction is required.
Claim Rejections - 35 USC § 112b - Indefiniteness
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 3 and 8 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 3, lines 4-5 reads “isolation in confined physical geometries comprising aqueous media capped by mechanical”. It appears that a word has been left off, rendering the method of capping unclear. The specification does not provide more explanation of what “capped by mechanical” may mean. Therefore, the scope of the claim is rendered indefinite. Clarification is required.
Claim 8 is directed to the method of claim 1, “wherein the multiple indices of the multi-index barcode comprise at least two of an optical index, an oligonucleotide index, a mass index, a charge index, a size index, a fluorescence index, a chemical index, a shape index, a hardness index, an ionization index, a nucleic acid index, a smell index, and/or an audio index”. It is unclear how indices such as “a hardness index”, “an ionization index”, “a smell index”, and “an audio index” are appended/added to the examination areas. No structures are provided for these indices either in the claim itself or in the specification and therefore the scope of the claim is unclear.
Claim Rejections - 35 USC § 112a – Written Description
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.
Claims 1-10 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 1-6 and 8-10 are rejected for describing a method for analyzing generic cells in a mixture of a plurality of cells. The specific types of cells analyzed by this methodology are not defined until claim 7. The specification lists species of cells applicable to the invention (and thus informs the scope of claims 1-6 and 8-10) as “including mammalian cells, eukaryotic cells, bacterial cells, fungal cells, plant cells, prokaryotic cells, immune cells, cancer cells, antibody secreting cells, genetically modified cells and/or cells of aliens from outer space and new worlds.” (paragraph [0091]). Given that the claims are interpreted in light of the specification, the generic species of “cells” in claim 1 therefore includes cells of aliens from outer space and new worlds. There is no evidence in the art that such a thing exists or would be compatible with the instantly claimed methodology if it did exist. Cells of aliens are not art recognized and therefore do not have adequate written support in this specification. Accordingly, it is deemed that the specification, while providing for the species of “mammalian cells, eukaryotic cells, bacterial cells, fungal cells, plant cells, prokaryotic cells, immune cells, cancer cells, antibody secreting cells, and/or genetically modified cells” (as recited in claim 7), fails to provide adequate written description for the genus of the claims (any cells, including those of “aliens from outer space and new worlds”) and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, has possession of the entire scope of the claimed invention.
Claims 1-10 are rejected for describing multiple types of indices to be used in multi-index barcodes of the invention without providing adequate structural detail as to the nature of said types. Claim 1 recites the inclusion of the generic multi-index barcode. The specification details examples of indices such as oligonucleotide indices, shape indices, fluorescent/optical indices, mass indices, size indices, charge indices, and chemical indices. However, the specification does not provide evidence for the other types of indices (smell indices, audio indices – claim 8; or electrical or radio-frequency indices (paragraph [0077]) as included in the generic scope of “multi-index barcode” in claim 1). No evidence is provided for how these indices would be realized or applied to said method and no structures are provided to indicate that these indices could be used in the method as claimed. Accordingly, it is deemed that the specification, while providing for the structure/species of oligonucleotide, shape, fluorescent/optical, mass, size, charge, and chemical multi-index barcodes, fails to provide adequate written description for the genus of the claims (any type of detectable index, including smell, audio, radio-frequency, etc.) and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 102
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 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 1-10 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Love (Love et al., WO 2019/113457 A1).
Regarding claim 1: Love teaches a method of analyzing cells in a mixture of a plurality of cells wherein a plurality of examination areas is provided which include at least one cell to be analyzed, at least one of a plurality of multi-indexed barcodes, and at least one of a plurality of capture beads (pg 7, ln 19-32; pg 10, ln 25-pg 11, ln 5). Love teaches that multi-index barcodes are in the examination areas and can include a unique nucleic acid spatial barcode attached to a functionalized surface in addition to either a spectrally encoded barcode or a unique stimulus (pg 8, ln 10-14; pg 6, ln 22-30; pg 38, ln 11-15; pg 43, ln 27-43 “co-functionalized surface” or “co-loaded beads”). Love teaches that the plurality of capture beads further comprise a plurality of oligonucleotides (pg 3, ln 13-20). Love teaches performing an assay in the examination arrays and collecting assay information from the examination area (pg 2, ln 16-19; pg 35, ln 10-22; Fig. 6B). Love teaches performing release-and-capture in the at least one examination area, where nucleic acid is released from the at least one cell into the examination area and is captured by at least one of the plurality of oligonucleotides attached to at least one of the plurality of capture beads and at least one of the indices from the multi-indexed barcode in the examination area is released and the index is captured by at least one oligonucleotide attached to the capture bead (pg 7, ln 19-32; pg 8, ln 6; pg 10, ln 25-pg 11, ln 3). Love teaches analyzing the at least one capture bead to identify the captured nucleic acid from the cell and the captured index from the multi-index barcode and generating a molecular-functional profile of the cell (pg 10, ln 25-pg 11, ln 3; pg 19, ln 17-18; pg 37, ln 5-8). Love teaches that the multi-indexed barcode is two indices (spatial barcode/stimulus specific barcode and either a spectrally-encoded barcode or a chemical/stimulus barcode; pg 8, ln 10-14; pg 6, ln 22-30; pg 38, ln 11-15; pg 43, ln 27-43). Love teaches that the oligonucleotides on the capture bead attached to nucleic acids released from the cell and the released index from the multi-indexed barcode (pg 7, ln 19-32; pg 8, ln 6; pg 10, ln 25-pg 11, ln 3).
Regarding claims 2 and 3: Love teaches isolating one or more examination areas from others of the plurality of examination areas by physical isolation which comprises picowell isolation (pg 19, ln 15).
Regarding claim 4: Love teaches that at least two of the plurality of examination areas are fluidically connected (pg 15, ln 18-20).
Regarding claim 5: Love teaches an examination area that is a split examination area, wherein the examination area is split into multiple examination areas (pg 94, ln 10-18; Fig. 22).
Regarding claim 6: Love teaches that two or more of the multiple examination areas in the split examination area are fluidically connected (pg 15, ln 18-20; pg 92, ln 1-2; Fig. 18, 19, and 22).
Regarding claim 7: Love teaches that the plurality of cells can comprise mammalian cells, eukaryotic cells, prokaryotic cells, cancer cells, or bacterial cells (pg 39, ln 13-20).
Regarding claim 8: Love teaches multi-index barcodes wherein the index comprise an oligonucleotide index combined with an optical index, a fluorescence index, a mass index, or a chemical index (pg pg 8, ln 10-14; pg 38, ln 11-15; pg 40, ln 12-14; pg 43, ln 27-28).
Regarding claim 9: Love teaches that the multiple index of the multi-index barcodes are bound to a common substrate wherein the substrate is a solid substrate (e.g., a bead; pg 43, ln 27-28).
Regarding claim 10: Love teaches that the multiple index are bound to the substrate via linkers and that one or more of the linkers are cleavable (pg 38, ln 1-8; pg 40, ln 12-14; pg 43, ln 27-28).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The 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.
Claims 1 and 8-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 11, and 14 of copending Application No. 19/035,214 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to the same limitations. Any additional limitations of '214 claims are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 2-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 4, 11, and 14 of copending Application No. 19/035,214, as applied to claims 1 and 8-10 above, in view of Love (Love et al., WO 2019/113457 A1).
Regarding claim 2 and 3: The claims of ‘214 teach a plurality of examination areas on a biochip. ‘214 does not teach that the examination areas are isolated by physical isolation or further comprise picowell isolation. However, use of picowell isolation for physical isolation of examination areas is known in the art, as taught by Love.
Love teaches isolating one or more examination areas from others of the plurality of examination areas by physical isolation which comprises picowell isolation (pg 19, ln 15).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of ‘214 with the isolated picowells as taught by Love. One would be motivated to do so given the assertion by Love that this enables “massively parallel analysis of large numbers of single cells” (pg 19, ln 5-6). One would have a reasonable expectation of success given that Love is performing a similar methodology of analyzing transcriptomic changes and correlating said information with assay information obtained through observation of the examination areas (pg 10, ln 25-pg 11, ln 3; pg 19, ln 17-18; pg 37, ln 5-8).
Regarding claims 4-6: The claims of ‘214 teach a plurality of examination areas on a biochip. ‘214 does not teach that the examination areas are fluidically connected or comprised of split examination areas that contain multiple examination areas. However, use of fluidically connected examination areas and split examination areas which are also fluidically connected is known in the art, as taught by Love.
Love teaches that at least two of the plurality of examination areas are fluidically connected (claim 4; pg 15, ln 18-20). Love teaches an examination area that is a split examination area, wherein the examination area is split into multiple examination areas (claim 5; pg 94, ln 10-18; Fig. 22). Love teaches that two or more of the multiple examination areas in the split examination area are fluidically connected (claim 6; pg 15, ln 18-20; pg 92, ln 1-2; Fig. 18, 19, and 22).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of ‘214 with the fluidically connected examination areas and split examination areas as taught by Love. One would be motivated to fluidically connect examination areas (both non-split and split) given the teaching by Love that this enables culturing or storing the isolated cells within the arrays themselves (pg 15, ln 9-20). One would be motivated to create split examination areas given the assertion by Love that this allows for multiple examination areas (microarrays) to be processed at one time (pg 94, ln 10-16). One would have a reasonable expectation of success given that Love successfully demonstrates the creation of examination areas that are fluidically connected, and demonstrates designs of split examination areas (Figures 17-22).
Regarding claim 7: The calims of ‘214 teach examining at least one cell of a plurality of cells. ‘214 does not teach that the cells are a specific type of cell (comprise mammalian cells, eukaryotic cells, prokaryotic cells, cancer cells, or bacterial cells). However, useage of these types of cells in a high throughput assay used to determine the biological response of a cell to a perturbation agent is known in the art, as taught by Love.
Love teaches that the plurality of cells can comprise mammalian cells, eukaryotic cells, prokaryotic cells, cancer cells, or bacterial cells (pg 39, ln 13-20).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have used the method of ‘214 with the cell types as taught by Love. One would be motivated to examine, for instance, tumor/cancer cells can be incubated with drugs to determine the effect of said drugs on the cells (pg 43, ln 30-pg 44, ln 4). One would have a reasonable expectation of success given that tumor/cancer cells are commonly used in single-cell RNA sequencing arrays (pg 1, ln 8-30).
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILEY E CASH whose telephone number is (571)272-0971. The examiner can normally be reached Monday-Friday 8:30am-6pm ET.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683