Status of the Claims
Claims 41-47, 55, 58, 61, 68, 70-71, 73-79, and 125 were previously pending.
Claim 46 has been cancelled.
Claims 41-45, 47, 55, 58, 61, 68, 70-71, 73-79, and 125 are currently pending and examined herein.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Election Requirement
The requirement to elect species for the properties of the plurality of wells of claim 47 and a surface the capture probes are disposed on of claim 58 are withdrawn upon further consideration.
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.
The factual inquiries 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.
Frisén et al. and Mimitou et al.
Claims 41, 58, 68, 70-71, 73-79, and 125 are rejected under 35 U.S.C. 103 as being unpatentable over Frisén et al. (US PGPub No: 2019/0203275, cited in IDS of 5/4/23) in view of Mimitou et al. (biorxiv (8 Sept 2020), doi: 10.1101/2020.09.08.286914).
Regarding claim 41, Frisén discloses a method (Fig. 8A) comprising:
(a) providing a substrate comprising a plurality wells (p. 3, ¶ [0025], lines 12-13 and 21-23), wherein a well comprises:
a lysis agent (p. 11, ¶ [0084], lines 14-16)
a surface comprising capture probes (p. 7, ¶ [0059-0066]), wherein a capture probe comprises a spatial barcode (p. 9, ¶ [0070]: “barcode”; p. 5, ¶ [0043]) and a capture domain (p. 12, ¶ [0093]: “target capture moiety”), wherein the capture probes are attached to the surface using bridge amplification (p. 8, ¶ [0065], lines 11-14; ¶ [0066], lines 14-21);
(b) disposing a biological sample into the plurality of wells (p. 10, ¶ [0078], [0084]); and
(c) releasing an analyte (p. 12, ¶ [0097], lines 4-7: “target”) from the sample wherein the analyte binds the capture domain of the capture probe (p. 12, ¶ [0097]).
Therefore, Frisén teaches all limitations of claim 1 except for the analyte capture agent. However, Frisén does foresee the use of an intermediary analyte binding moiety such as a protein or small molecule conjugated to a nucleic acid component (p. 13, ¶ [0102]).
Mimitou discloses analyte capture agents (p. 5, lines 7-24: “antibody:oligo conjugates”) that comprise (Fig. 1b) an analyte binding moiety (antibody), an analyte binding moiety barcode (“Ab barcode”), and an analyte capture sequence (“ATAC bead oligo handle”), where the analyte binds the analyte binding moiety and the analyte capture sequence binds the capture domain (Fig. 1b). Additionally, Mimitou teaches that the approach of using an analyte capture agent intermediary is ideal for multiplexing applications (p. 4, lines 7-10; p. 18, lines 6-8) and that being able to measure the regulation of protein levels provides a new layer of highly sought after information (p. 3, lines 24-29; p. 18, lines 24-27). Furthermore, one of ordinary skill in the art would have a reasonable expectation of success in applying the method of Mimitou to the method of Frisén because it was designed to be compatible with nucleic acid assays (p. 18, lines 6-13) and similarly utilizes capture probes bound to solid supports (Fig. 1b).
Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to incorporate the analyte binding agents of Mimitou with the method of Frisén to produce a method of capturing an analyte on a capture probe via an analyte binding moiety in a plurality of wells, based on the motivation provided by Mimitou to create a multiplexed system that also provides information on protein regulation.
Regarding claim 58, as Frisén discloses that the capture probes are attached to wells in the solid support (p. 6, ¶ [0051]). 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 characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case there is reason to believe that the capture probes of Frisén would be attached to the sides and/or bottom surface of the well as those are the surfaces available for the probes to attach to.
Regarding claims 68, 70-71, and 73, Frisén further discloses that the biological sample is a tissue sample that can be fixed prior to analysis (p. 10-11, ¶ [0084-86]). Additionally, Frisén discloses that the tissue sample can be fresh, frozen (p. 11, ¶ [0085]) or FFPE fixed (p. 11, ¶ [0086], lines 4-6).
Regarding claims 125 and 74-76, Frisén further discloses extending the capture probe using the analyte binding moiety barcode as a template (p. 12, ¶ [0098]), sequencing the analyte moiety barcode and the spatial barcode, and using the sequences to determine the location of the analyte in the sample (p. 12, ¶ [0098], lines 7-12). Frisén also teaches that the sequencing is high-throughput sequencing (p. 14, ¶ [0116]; p. 9 ¶ [0072]).
Regarding claims 77-79, Mimitou discloses that the analyte binding moiety is an antibody or antigen-binding fragment as discussed in regards to claim 41 and that the analyte is an intracellular protein (p. 8-9, “ASAP-seq is compatible with detection of intracellular proteins”).
Frisén et al., Mimitou et al., and Fodor et al.
Claims 42-45, 47, and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Frisén et al. and Mimitou et al. as applied to claims 41, 58, 68, 70-71, 73-79, and 125 above and further in view of Fodor et al. (US PGPub No: 2016/0253584, cited in IDS of 5/4/23).
Frisén teaches a substrate comprising wells as discussed with regards to claim 41, but does not specifically disclose the shape, diameter, nor arrangement of these wells. However, Fodor discloses a substrate that comprises 96 to 5 million wells (p. 19, ¶ 157), that wells can be flat- or round-bottomed (p. 18, ¶ 140, lines 21-23), wells that comprise perimeters that are circularly-shaped, square-shaped, or polyhedral-shaped (p. 17, ¶ 140, lines 2-4), wells with diameters of 5 to 50 μm (p. 18, ¶ 142-143), and center-to-center spacing from about 15 to about 75 μm (p. 19, ¶ 153-154). Fodor additionally teaches that wells can have about the same volume and diameter, necessitating that they could then also have about the same perimeter (p. 18, ¶ 142-143; p. 19, ¶ 150). Fodor also teaches that microwell dimensions are variable and can be easily adapted to different applications (p. 17, ¶ 140). Therefore, Fodor evidences that it is well known in the art to adjust the size, shape, and arrangement of microwells.
As held by decisions in In re Rose, Gardner v. TEC Syst., Inc., and In re Dailey, changes in size, proportion, and shape are considered obvious over prior art if the changes in the claimed device “would not perform differently than the prior art device” (see MPEP § 2144.04(IV)). As the device of Frisén is capable of performing the same function as the device of claim 41, and that, as evidenced by Fodor, the specific dimensions and arrangement of microwells claimed in the instant application were well known in the art, claims 42-45, 47 and 55 are rendered obvious.
Frisén et al., Mimitou et al., and So et al.
Claim 61 is rejected under 35 U.S.C. 103 as being unpatentable over Frisén et al. and Mimitou et al. as applied to claims 41, 58, 68, 70-71, 73-79, and 125 above and further in view of So et al. (US PGPub No: 2018/245142, cited in IDS of 5/4/23).
Frisén and Mimitou disclose all aspects of claim 41, as discussed previously. However, neither discloses that the disposing of the tissue sample into the plurality of wells is performed using pressure applied using a rolling or stamping device.
So discloses the use of a stamping device (Fig. 58A) to dispose a tissue sample using pressure into a plurality of wells for preparation of a spatially addressed library (p. 37, ¶ [0543-4]. So teaches that this is to facilitate “spatial compartmentalization” in order to “limit the diffusion of spatially addressed oligonucleotides (and other reaction components or products) on a tissue section and maintain spatial resolution” (p. 36, ¶ [0530], lines 1-3), providing higher resolution for spatial information than methods where components are able to diffuse freely along the continuous tissue section. Furthermore, So utilizes this device for the preparation of a spatially addressed library in wells using immobilized capture probes, indicating that it would be compatible with the method of Frisén and Mimitou.
Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to apply the stamping device from So to the method of spatial profiling of Frisén and Mimitou, based on the motivation to achieve a higher resolution of spatial information. Furthermore, one of ordinary skill would have had a reasonable expectation of success, given that stamping device of So is used for a similar method as that of Frisén and Mimitou method, specifically capture probe mediated spatial profiling.
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.
US Patent No. 11,592,447
Claims 41, 70-71, 75, 77, and 125 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 7, 23, 24, and 26 of U.S. Patent No. 11592447 in view of Frisén et al. and Prakadan et al. (Nat. Rev. Genet. (2017), 18: 345-361).
Regarding claim 41, claim 1 of the reference patent discloses a method comprising contacting a biological sample with a substrate comprising capture probes, which have spatial barcodes and capture domains. It also discloses the use of analyte capture agents that comprise an analyte binding moiety, an analyte binding moiety barcode, and an analyte capture sequence, as well as an analyte from the sample binding to an analyte capture agent via the analyte binding moiety, and the analyte capture agent binding to a capture probe via the capture domain. Claim 6 further discloses permeabilizing the biological sample. Together, these render obvious all limitations of claim 41 except for that the substrate comprises a plurality of wells and that the analyte is released from the biological sample.
As discussed previously, Frisén discloses a substrate comprising a plurality of wells. Additionally, Prakadan teaches that “a major advantage of nanowells is their operational simplicity and sample effi-ciency” (p. 4 – Nanowells). Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to incorporate the substrate comprising a plurality of wells of Frisén to the method of patent ‘447, based on the motivation provided by Prakadan.
Furthermore, Frisén teaches two general methods for contacting a biological sample with capture probes (p. 12, ¶ [0097], lines 15-30), one being release of an analyte from a biological sample towards the substrate comprising the capture probes. Given that Frisén provides two methods, it would have been obvious to try applying the method of releasing an analyte from the biological sample to the method of patent ‘447, with a reasonable expectation of success.
Regarding claim 77, claim 8 of the reference patent further discloses that the analyte binding moiety is an antibody or an antigen-binding fragment thereof.
Regarding claims 70-71, claims 23-24 of the reference patent further discloses that the biological sample is a tissue sample, wherein the tissue sample is a fixed tissue section.
Regarding claims 125 and 75, claim 26 of the reference patent further discloses sequencing an analyte binding moiety barcode and a spatial barcode and using the sequences to determine the location of the analyte in the sample.
US Patent No. 11,739,381
Claims 41, 70-71, 73, 75, and 125 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, and 13 of U.S. Patent No. 11739381 in view of Frisén et al. and Prakadan et al.
Regarding claim 41, claim 1 of the reference patent discloses a method comprising contacting a biological sample with a substrate comprising capture probes, which have spatial barcodes and capture domains. It also discloses the use of analyte capture agents that comprise an analyte binding moiety, an analyte binding moiety barcode, and an analyte capture sequence, as well as an analyte from the sample binding to an analyte capture agent via the analyte binding moiety, and the analyte capture agent binding to a capture probe via the capture domain. Claim 13 further discloses permeabilizing the biological sample. Together, these render obvious all limitations of claim 41 except for that the substrate comprises a plurality of wells and that the analyte is released from the biological sample. As discussed above, teachings from Frisén and Pradakan render these limitations obvious.
Regarding claims 70-71 and 73, claim 8 of the reference patent further discloses that the biological sample is a tissue sample, wherein the tissue sample is an FFPE tissue sample.
Regarding claims 125 and 75, claim 1 of the reference patent further discloses that the method comprises determining the sequence of the analyte binding moiety barcode and the spatial barcode, thereby determining the spatial location of the analyte in the sample. Claim 16 further discloses that determining the sequence comprises sequencing.
US Patent No. 11,332,790
Claims 41, 70-71, 73, 75-76, and 125 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 19-20, 23, and 28-29 of U.S. Patent No. 11332790 in view of Frisén et al. and Prakadan et al.
Regarding claim 41, claim 1 of the reference patent discloses a method comprising contacting a biological sample with a substrate (“array”) comprising capture probes, which have spatial barcodes and capture domains. It also discloses the use of analyte capture agents (“first and second probes”) that comprise an analyte binding moiety (“sequences that are substantially complementary to the target nucleic acid”), an analyte binding moiety barcode (“sequence of the ligation product”), and an analyte capture sequence (“capture domain sequence”), as well as an analyte from the sample binding to an analyte capture agent via the analyte binding moiety, and the analyte capture agent binding to a capture probe via the capture domain. Claim 23 further discloses permeabilizing the biological sample. Together, these render obvious all limitations of claim 41 except for that the substrate comprises a plurality of wells and that the analyte is released from the biological sample. As discussed above, teachings from Frisén and Pradakan render these limitations obvious.
Regarding claims 70-71 and 73, claims 19 and 20 of the reference patent further disclose that the biological sample is a tissue sample, wherein the tissue sample is an FFPE tissue sample.
Regarding claims 125 and 75-76, claim 1 of the reference patent further discloses determining the sequence of the analyte binding moiety barcode (“sequence of the ligation product”) and the spatial barcode, thereby determining the location of the analyte in the biological sample. Claims 28 and 29 disclose that determining of the sequence comprises high-throughput sequencing (“next-generation sequencing methods”).
Application 18/165,226
Claims 41, 70-71, 73-74, and 125 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of copending Application No. 18165226 in view of Frisén et al. and Prakadan et al.
Regarding claim 41, claim 1 of the reference application discloses a method comprising contacting a biological sample with a substrate (“spatial array”) comprising capture probes, which have spatial barcodes and capture domains. It also discloses the use of analyte (“an RNA”) capture agents (“first and second nucleic acid probes”) that comprise an analyte binding moiety (“a first sequence that is complementary to the RNA”), an analyte binding moiety barcode (“sequence of the ligation product”), and an analyte capture sequence (“a nucleic acid capture sequence”), as well as an analyte from the sample binding to an analyte capture agent via the analyte binding moiety, and the analyte capture agent binding to a capture probe via the capture domain. Claim 6 further discloses permeabilizing the biological sample. Together, these render obvious all limitations of claim 41 except for that the substrate comprises a plurality of wells and that the analyte is released from the biological sample. As discussed above, teachings from Frisén and Pradakan render these limitations obvious.
Regarding claims 70-71 and 73, claim 1 of the reference application further discloses that the biological sample is an FFPE tissue section.
Regarding claims 74 and 125, claim 1 of the reference application further discloses determining the sequence of the spatial barcode and the analyte binding moiety barcode (“sequence of the ligation product”) and determining the location of the analyte in the sample. Additionally, claim 1 teaches extending an end of the capture probe using the analyte binding moiety barcode (“sequence corresponding to the ligation product”) as a template.
This is a provisional nonstatutory double patenting rejection.
Application 18/683,075
Claims 41, 75, and 125 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 78-80 and 87 of copending Application No. 18/683,075 in view of Frisén et al. and Prakadan et al.
Regarding claim 41, claim 78 of the reference application discloses a method comprising contacting a biological sample with a substrate (“an array”) comprising capture probes, which have spatial barcodes and capture domains. It also discloses the use of analyte (“an antigen”) capture agents (“an antigen-binding molecule/nucleic acid conjugate”) that comprise an analyte binding moiety (“an antigen-binding molecule”), an analyte binding moiety barcode (“a sequence encoding an antigen-binding molecule”), and an analyte capture sequence, as well as an analyte from the sample binding to an analyte capture agent via the analyte binding moiety, and the analyte capture agent binding to a capture probe via the capture domain. Claim 87 further discloses permeabilizing the biological sample. Together, these render obvious all limitations of claim 41 except for that the substrate comprises a plurality of wells and that the analyte is released from the biological sample. As discussed above, teachings from Frisén and Pradakan render these limitations obvious.
Regarding claims 75 and 125, claim 78 of the reference application further discloses determining the sequence of the spatial barcode and the analyte binding moiety barcode (“a portion of the sequence of the cDNA”). Claims 79-80 of the reference application disclose using the determined sequences to determine the location of the analyte (“antigen”) in the sample and that the determining comprises sequencing.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/ALEXANDRA OLSON/Examiner, Art Unit 1684
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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