DETAILED ACTION
Status of the Claims
Claims 1-19 and 21-25 are pending.
Claim 20 is cancelled by Applicant.
Claims 1-6, 9-10, 17-18, and 21 are amended.
Claims 22-25 are new.
Claims 1-19 and 21-25 are the subject of this Office Action.
The following Office Action is in response to Applicant’s communication dated 11/11/2025. Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. The following rejection(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Instant application 17/764,804 filed on 03/29/2022 is a 371 national stage entry of PCT/US20/53233 filed on 09/29/2020, which claims priority to U.S. provisional application 62/908,270 filed on 09/30/2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/11/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
New corrected drawings have been submitted and are accepted. Accordingly, the objections to the drawings are withdrawn.
Withdrawn Claim Rejections
The rejections of claims 4, 5, 10, and 18 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the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention are withdrawn in light of amendments made by Applicant to the claims.
The rejection of claim 9 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in light of amendments made by Applicant to the claim.
Maintained Claim Rejections – 35 U.S.C. 103(a)
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 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.
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.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Soumillon et al.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Soumillon et al. (WO 2018/064640 A1, published 04/05/2018, of record).
Regarding claim 21, Soumillon discloses a microfluidic device (e.g., “a microfluidic device having an enclosure containing one or more sequestration pens”, as per ¶0003 and/or Fig. 1-2), comprising 5-50 variable width microchannels (e.g., Fig. 1A shows five microchannels into the sequestration pens), each having (i) an inlet port and an outlet port (e.g., channel 122), (ii) a width of 50-150 µm at the inlet port and at the outlet port (e.g., channel 122 can be 50-1000 µm wide “and the width Wch of the microfluidic channel 122 can be any width within any of the endpoints listed” as per ¶00366), and (iii) a width of 10-50 µm at a region of interest (e.g., width of a connection region 236 at a proximal opening to a sequestration pen 234 can be about 20-500 µm or “any value within any of the endpoints listed” as per ¶00371). Note that in accordance with MPEP 2144.05(I), in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.
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Response to Arguments
The 11/11/2025 remarks argue: not all elements are taught.
Applicant's arguments have been fully considered but they are not persuasive for at least the following reasons.
RE: “Accordingly, the connecting region and proximal opening of Soumillon are located in the sequestration pen and not located within the channel. Therefore, Soumillon does not disclose a variable width microchannel having an inlet port, an outlet port, and a region of interest, let alone having the widths recited in claim 21.”
Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references. As detailed in the rejection above, Soumillon discloses a microfluidic device (e.g., “a microfluidic device having an enclosure containing one or more sequestration pens”, as per ¶0003 and/or Fig. 1-2), comprising 5-50 variable width microchannels (e.g., Fig. 1A shows five microchannels into the sequestration pens), each having (i) an inlet port and an outlet port (e.g., channel 122), (ii) a width of 50-150 µm at the inlet port and at the outlet port (e.g., channel 122 can be 50-1000 µm wide “and the width Wch of the microfluidic channel 122 can be any width within any of the endpoints listed” as per ¶00366), and (iii) a width of 10-50 µm at a region of interest (e.g., width of a connection region 236 at a proximal opening to a sequestration pen 234 can be about 20-500 µm or “any value within any of the endpoints listed” as per ¶00371).
Therefore, the rejection is proper and is maintained.
Modified Double Patenting
Necessitated by Amendments
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
U.S. 12,157,912
Claims 1-19 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 and 28-31 of U.S. Patent No. 12,157,912 (the ‘912 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding present claims 1-2, the claims of the ‘912 patent disclose a nearly identical method of delivering reagents to a region of interest, imaging, and extracting DNA (e.g., as per claims 1, 16-17, and 22-23 of the ‘912 patent).
Regarding present claim 3, the claims of the ‘912 patent disclose further sequencing the cDNA (e.g., as per claim 2 of the ‘912 patent).
Regarding present claim 4, the claims of the ‘912 patent do not disclose the above, wherein the sequencing comprises template switching the cDNAs to add a second PCR handle end sequence at an end opposite from the first PCR handle end sequence, amplifying the cDNAs, producing sequencing constructs via tagmentation, and sequencing the sequencing constructs to produce the cDNA reads, however, such methods and benefits of performing them were well known in the art as of the effectively filed date, for example, as disclosed in Hennig et al. ("Large-scale low-cost NGS library preparation using a robust Tn5 purification and tagmentation protocol." G3: Genes, Genomes, Genetics, 2018, 8(1):79-89).
Regarding present claims 5-6, the claims of the ‘912 patent disclose constructing a spatial molecular expression map (e.g., as per claim 18 of the ‘912 patent).
Regarding present claim 7, the claims of the ‘912 patent does not disclose the claimed method of preparing the FFPE sample for analysis, however, such methods and benefits of performing them were well known in the art as of the effectively filed date, for example, as disclosed in Salmén et al. (Nature protocols, 2018, 13(11), 2501-2534).
Regarding present claims 8-10, the claims of the ‘912 patent disclose the above, wherein the first and/or second microfluidic device is fabricated from PDMS and wherein first and/or second microfluidic device comprises 40 to 60 microchannels with specific measurements (e.g., as per claims 3-4 and 15-16).
Regarding present claim 11, the claims of the ‘912 patent disclose the above, wherein delivery of the first set of barcoded polynucleotides is delivered through the first microfluidic device using a negative pressure system and/or delivery of the second set of barcoded polynucleotides is delivered through the second microfluidic device using a negative pressure system (e.g., as per claim 5 of the ‘912 patent).
Regarding present claim 12, the claims of the ‘912 patent disclose the above, wherein the lysis buffer or denaturation reagents are delivered directly to the tissue section, optionally through a hole in a device clamped to the substrate, wherein the hole is positioned directly above the region of interest (e.g., as per claim 6 of the ‘912 patent).
Regarding present claim 13, the claims of the ‘912 patent disclose the above, wherein the barcoded polynucleotides of the first set comprise a ligation linker sequence, a spatial barcode sequence, and a polyT sequence (e.g., as per claim 7 of the ‘912 patent).
Regarding present claim 14, the claims of the ‘912 patent disclose the above, wherein the barcoded polynucleotides of the second set comprise a ligation linker sequence, a spatial barcode sequence, a unique molecular identifier (UMI) sequence, and a first PCR handle end sequence, optionally wherein the first PCR handle end sequence is terminally functionalized with biotin (e.g., as per claim 8 of the ‘912 patent).
Regarding present claim 15, the claims of the ‘912 patent disclose the above, wherein the first and/or second set of barcoded polynucleotides comprises at least 50 barcoded polynucleotides (e.g., as per claim 10 of the ‘912 patent).
Regarding present claim 16, the claims of the ‘912 patent disclose the above, wherein the binder molecule is an antibody, optionally selected from whole antibodies, Fab antibody fragments, F(ab')2 antibody fragments, monospecific Fab2 fragments, bispecific Fab2 fragments, trispecific Fab3 fragments, single chain variable fragments (scFvs), bispecific diabodies, trispecific diabodies, scFv- Fc molecules, and minibodies (e.g., as per claims 20-21 of the ‘912 patent).
Regarding present claim 17, the claims of the ‘912 patent disclose the above, wherein the nucleic acids of the biological sample are selected from (i) ribonucleic acids (RNAs), optionally messenger RNAs (mRNAs), and (ii) deoxyribonucleic acids (DNAs), optionally genomic DNAs (gDNAs) (e.g., as per claims 11-12 of the ‘912 patent).
Regarding present claim 18, the claims of the ‘912 patent disclose the above, wherein (i) barcoded polynucleotides of the second set are bound to a universal ligation linker, or (ii) the method further comprises delivering to the biological sample a universal ligation linker sequence, wherein the universal ligation linker comprises a sequence complementary to the ligation linker sequence of the barcoded polynucleotides of the first set and comprises a sequence complementary to the ligation linker sequence of the barcoded polynucleotides of the second set (e.g., as per claim 9 of the ‘912 patent).
Regarding present claim 19, the claims of the ‘912 patent disclose the above, wherein the imaging is with an optical or fluorescence microscope (e.g., as per claim 14 of the ‘912 patent).
Regarding present claim 21, the claims of the ‘912 patent disclose a microfluidic device, comprising 5-50 variable width microchannels, each having (i) an inlet port and an outlet port, (ii) a width of 50-150 µm at the inlet port and at the outlet port, and (iii) a width of 10-50 µm at the region of interest (e.g., claims 1 and 16 of the ‘912 patent).
Regarding present claims 22-23, the claims of the ‘912 patent disclose the above, wherein the first and second microfluidic devices each comprise 5-50 variable width microchannels (e.g., as per claims 28-31 of the ‘912 patent).
Regarding present claims 24-25, the claims of the ‘912 patent disclose the above, wherein the width at each inlet port and outlet port is between 10-50% greater than the width at the region of interest (e.g., as per claims 1, 16-17, and 22-23 of the ‘912 patent noting that in accordance with MPEP 2144.05(I), in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists).
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Applicant’s Response
The 11/11/2025 reply includes Applicant’s response to the nonstatutory double patenting rejection of record:
“Applicant will consider filing a terminal disclaimer over the '912 patent rendering this rejection moot upon the finding of otherwise allowable subject matter. Accordingly, withdrawal of the rejection is respectfully requested.”
This request is not the filing of a terminal disclaimer, or filing of a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, as the required response in accordance with MPEP 804 I.B.1.
Applicant’s request is expressly contrary to MPEP 804 I.B.1. (see also MPEP 714.03 and 37 C.F.R. 1.111).
U.S. 18/740,662
Claims 1-19 and 22-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/740,662 (the ‘662 application). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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Applicant’s Response
The 11/11/2025 reply includes Applicant’s response to the nonstatutory double patenting rejection of record:
“Pursuant to MPEP 804 (I)B1, it is requested that the pending provisional double patenting rejection be withdrawn and that the application proceed to allowance. Accordingly, withdrawal of the rejection is respectfully requested.”
This request is not the filing of a terminal disclaimer, or filing of a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, as the required response in accordance with MPEP 804 I.B.1.
Applicant’s request is expressly contrary to MPEP 804 I.B.1. (see also MPEP 714.03 and 37 C.F.R. 1.111).
U.S. 18/926,552
Claims 1-19 and 21-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-40 of copending Application No. 18/926,552 (the ‘552 application). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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Applicant’s Response
The 11/11/2025 reply includes Applicant’s response to the nonstatutory double patenting rejection of record:
“Applicant will consider filing a terminal disclaimer over the '552 patent application upon finding otherwise allowable subject matter in this application rendering this rejection moot. Accordingly, withdrawal of the rejection is respectfully requested.”
This request is not the filing of a terminal disclaimer, or filing of a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, as the required response in accordance with MPEP 804 I.B.1.
Applicant’s request is expressly contrary to MPEP 804 I.B.1. (see also MPEP 714.03 and 37 C.F.R. 1.111).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684