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 2-21 are pending in this application.
This application is a CON of two US Applications which claimed priority to two PCT applications, which claimed priority to two US Provisional Applications. The Examiner has reviewed the prosecution histories of each application. The effective filing date for the pending claims appears to be that of the earliest provisional: 5/22/2020.
Seven IDS statements, citing a total of 2,069 references, have been entered and considered.
Applicant is reminded that it is desirable to avoid the submission of long lists of documents if it can be avoided. As set forth in MPEP 2004, applicant is directed to eliminate clearly irrelevant and marginally pertinent cumulative information. If a long list is submitted, highlight those documents which have been specifically brought to applicant's attention and/or are known to be of most significance. See Penn Yah Boats, Inc. v. Sea Lark Boats, Inc., 359 F.Supp. 948, 175 USPQ 260 (S.D. Fla. 1972), aft'd, 479 F.2d 1338, 178 USPQ 577 (5th Cir. 1973), cert. denied, 414 U.S. 874 (1974). But cf. Molins PLC v. Textron Inc., 48 F.3d 1172, 33 USPQ2d1823 (Fed. Cir. 1995). Applicant has cited more than 2000 references, many of which are not clearly relevant to the claimed invention. Applicant is cautioned against burying material references and the appearance of inequitable conduct in this application.
The drawings as filed are suitable for examination.
The abstract of the disclosure is objected to because the pending claims are drawn to a system, while the abstract is a single sentence describing an intended method. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 11, 16 are objected to because of the following informalities:
In claim 11, the Latin phrase “in situ” should be italicized.
Claim 16 appears to be a duplicate of claim 8.
Appropriate correction is required.
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.
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.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3, 4, 12-15, 18-21 are rejected 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.
With respect to claims 3-4, the analyte is not a part of the system. It is part of the intended use of the system, but none of the parts of the system clearly comprise an analyte.
With respect to claim 12, this modifies an intended use of the computer component but does not further limit the system or the computer component itself.
With respect to claims 13-15, these claims directed to a second analysis of a second analyte are directed to further use of the system, and do not modify or limit the system itself, or its components.
With respect to claims 18-21, these claims, directed to analyzing a tissue section at different time points, with different treatment of a subject with an agent, et al. are all directed to further intended uses of the system which fail to modify the system itself, or its components.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claims 2-21 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.
The metes and bounds of claim 2 are unclear as to how the system components are connected, such that each intended use of each component can be carried out, and the intended correlational analysis can be performed. The system has the intended use of “for performing temporal analysis in a tissue section” however the system itself does not change over time, and no analytical steps are performed in a positive active set of method steps or instructions that could theoretically represent temporal analysis.
The metes and bounds of claims 3-4 are unclear, in that the tissue sample of component a) of claim 2 does not clearly recite an analyte.
The metes and bounds of claim 10 are entirely unclear as to how this modifies the system of claim 2. Claim 2, directed to a system, does not set forth an ordered series of method steps which may have been able to be modified as recited “prior to obtaining the image of the tissue section.” The system comprises an imager. The tissue section of component a) could possibly be further modified to comprise a stained tissue section, without the temporal requirement, however this interpretation cannot be read into the claims. Further in claim 2, it is unclear how the “electrical field” is generated, as no specific component appears able to provide the field. It is suggested that the component required be recited.
The metes and bounds of claims 13-16 are unclear as to how the system is modified by these limitations. The system itself does not comprise instructions to carry out any second analysis, and the intended use of the system to analyze a second analyte do not change the system itself.
With respect to claim 17, this claim is unclear in its entirety as the components of claim 2 are not steps that can be repeated at different time points. It is entirely unclear how to implement these limitations. This also applies to claims 18-21, which require different time points, treatment of a subject with an agent, and stages of disease or age, all of which fall outside the bounds of the system, and do not further limit that system.
It is suggested the claims be clearly amended to recite the system components and perhaps include a non-transitory computer-readable-media comprising instructions to carry out particular method steps, when executed by a processor.
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.
Claim(s) 2-16 is/are rejected under 35 U.S.C. 102a1 as being anticipated by Frisen (US 2019/0203275 A1, published 7/4/2019).
Frisen discloses systems comprising components, for analysis of an analyte in a biological specimen.
With respect to claim 2 component a), Frisen teaches providing a tissue section, including healthy or diseased tissues, at least at [0020, 0028, 0044, 0081, 0084, 0088-0091 et al.].
“[0028] As used herein, the term “biological specimen” is intended to mean one or more cell, tissue, organism or portion thereof.”
“[0044] As used herein, the term “tissue” is intended to mean an aggregation of cells, and, optionally, intercellular matter. Typically the cells in a tissue are not free floating in solution and instead are attached to each other to form a multicellular structure. Exemplary tissue types include muscle, nerve, epidermal and connective tissues.”
With respect to claim 2, component b) Frisen provides barcoded arrays, which can contact the tissue, and comprise fiducial markers that can be optically encoded, at least at [arrays: 0008, 0009, 0019, 0025, 0056, et al; barcodes: 0006-0008, 0027, 0043, 0047, 0070, 0102, et al; markers: 0108].
With respect to claim 2, component c) Frisen provides imaging components to obtain images at least at [0104-0106].
With respect to claim 2 component d) Frisen provides migration of the analyte to the array in the flow cell system. The tissue section is treated, then applied to the barcoded array, and the flow cell provides the environment by which the analyte (mRNA) migrates to the barcoded array, which appears to encompass an electrical field. (Examples I-IV).
With respect to claim 2 component e) Frisen provides a sequencing instrument at least at [0018, 0019, 0072-0076].
With respect to claim 2, component f) Frisen provides correlation of location to sequence such as at [0097, 0107, Fig 3, 5, 7-8].
With respect to claims 3-4, Frisen discloses analytes which can be nucleic acids, such as DNA or RNA, or mRNA at [0026, 0038]
With respect to claim 5, Frisen discloses flow cells, throughout.
With respect to claim 6-7, Frisen discloses using healthy or disease tissue section at [0090].
With respect to claims 8 and 16, Frisen discloses a plurality of capture probes which comprise spatial barcodes and a capture domain at least at [0008, Fig 7-8, 0045, 0058-0060, 0064, 0093 et al.]
With respect to claim 9, the analyte can bind the capture domain directly. [0008, Fig 7-8, 0045, 0058-0060, 0064, 0093 et al.]
With respect to claim 10 the tissue section can be stained with fluorescent tags, as shown at least at: [0104, 0107]
With respect to claim 11, sequencing, such as Sequencing by Synthesis and NGS are disclosed as set forth above.
With respect to claim 12, correlation of gene expression with a spatial barcode is disclosed at [0097, 0107, Fig 3, 5, 7-8].
With respect to claims 13-14, Frisen discloses other analytes such as proteins at [0038].
With respect to claim 15-16, this embodiment is met when the target is a protein as identified above.
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 17-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Frisen (US 2019/0203275 A1) as applied to claims 2-15 above, in view of Gierahn (WO2019/113457 A1; PTO-1449).
Frisen teaches the system of claims 2-16 as set forth above. Claims 17-21 are directed to a further intended use of the system, to repeat an analysis, or to analyze the tissue in the presence/ absence of an agent, and has further limitations to the subject providing the tissue.
Frisen et al. teach a method for identifying a location and abundance of an analyte in a biological sample comprising the steps:
(a) contacting the biological sample with a substrate comprising a spatial barcode and a capture domain (parag. 8),
(b) recording intracellular gene expression of a nucleic acid located in a perfusion chamber comprising a gasket and a substrate and a plurality of apertures (parags. 19-20, 25, 51, 92 and 94),
(c) hybridizing the analyte to the capture probe (parags. 38, 71 and 77),
(d) extending the capture probe using the analyte as a template (parag. 9 and Fig. 1),
(e) amplifying the extended capture probe (parags. 8 and 24); and
(f) determining all or part of the sequence of the spatial barcode, all or part of the sequence of the analyte and identifying the location and abundance of the analyte in the biological sample (parags. 6, 7, 20 and 22).
Frisen does not teach:
(i) also using a drug for screening.
(i) Regarding the use of a drug in the perfusion chamber in claims 18-21, Gierahn et al. teach a method of identifying a location and abundance of an analyte in a biological sample and further screening a drug’s interaction with the sample using a spatial barcode (pg. 35 lines 9-27, pg. 40 lines 12-16 and pg. 93 lines 14-28).
Specifically, Gierahn teaches:
“The well-based biological analysis platform, also referred to as Seq-well, facilitates the
creation of barcoded single-cell sequencing libraries from thousands of single cells using devices that contain 10,000-1,000,000 or more wells of micron dimensions and picoliter volumes preloaded with barcoded transcript-capture beads. Cells are simply applied to the top surface of the array and drop into the wells by gravity within minutes. This simplified loading scheme enables Seq-well to capture nearly 100% of cells applied to the surface of the device. Key to the robust capture of single cell transcriptomes by Seq-well is the attachment of a semi- permeable membrane to the array surface after cell loading (as disclosed in published PCT Application No. PCT/US17/13791), enabling facile buffer exchange within the wells for cell lysis and RNA hybridization while retaining biologic macromolecules (e.g., DNA, RNA, and protein) for capture.” (pg. 1 lines 8-18).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to combine the teachings of Frisen regarding a method for identifying a location and abundance of an analyte in a biological sample with the teachings of Gierahn who teaches a method for identifying a location and abundance of an analyte in a biological sample and that their method can be used to screen for drug interactions to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Gierahn teaches that using a method with a spatial barcode can also empower the screening multiple test compounds for rare phenotypes.
There would have been a reasonable expectation of success that the spatial barcode and method of Frisen could also screen test compounds, since Gierahn teaches a method utilizing a spatial barcode to screen nucleic acids in a cell sample and also screen for test compounds.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
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 2-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11,624,086. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are drawn to systems, comprising components to carry out the same methods. System claims were not examined or restricted in the parent application.
Claims 2-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,866,767. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are drawn to systems, comprising components to carry out the same methods. System claims were not examined or restricted in the parent application.
Claims 2-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-23 of U.S. Patent No. 12,249,085. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are drawn to systems, comprising components to carry out the same methods.
Claim s 2-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 85-104 of copending Application No. 18/746,646 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to systems, comprising computers, imagers, tissue sections, barcoding arrays , sequencers et al.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY K ZEMAN whose telephone number is 5712720723. The examiner can normally be reached on 8am-2pm M-F. Email may be sent to mary.zeman@uspto.gov if the appropriate permissions have been filed.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry Riggs can be reached on 571 270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY K ZEMAN/ Primary Examiner, Art Unit 1686
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