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 .
This application is a continuation of 17/531093, now US patent 11827935 claiming benefit of 63/115916, filed on 11/19/2020.
Specification
The use of the term TWEEN™ which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Although the specification has been carefully reviewed it is incumbent on applicants to review the contents for all marks. Correction is required.
Information Disclosure Statement
Applicants submitted 77 pages of information disclosure statements, consisting of 1,649 citations. The IDS statements are in compliance with 37 CFR 1.97 through 1.98 and have been considered to the extent allowed by US Patent rules. The number of references cited and the dates of submission are as follows:
59 pages submitted on 12/05/2023 consisting of 1372 citations
5 pages submitted on 03/05/2024 consisting of 85 citations
3 pages submitted on 06/20/2024 consisting of 46 citations
3 pages submitted on 09/18/2024 consisting of 41 citations
3 pages submitted on 12/12/2024 consisting of 23 citations
3 pages submitted on 03/13/2025 consisting of 36 citations
4 pages submitted on 06/10/2025 consisting of 46 citations
Status of the Claims
Claim 1 has been canceled by preliminary amendment received on 01/06/2025. Claims 2-21 are pending and are under consideration.
Claim interpretation
Prior to analysis of the art, the claims must be construed. As noted in MPEP 2111, citing Phillips v. AWH Corp., 415 F.3d l303, 75 USPQ2d l321 (Fed. Cir. 2005), "During patent examination, the pending claims must be 'given their broadest reasonable interpretation consistent with the specification.' ".
As pointed out in In re Mott, 190 U.S.P.Q. 536 (CCPA 1975), "Claims must be given broadest reasonable construction their language will permit in ex parte prosecution, and applicant who uses broad language runs the risk that others may be able to support the same claim with a different disclosure."
The breath of the phrase “capture probe on an array” varies in the art. A capture probe array is considered an ordered arrangement of immobilized, short, synthetic oligonucleotide probes to capture, isolate, and detect specific, complementary DNA or RNA sequences from a complex. Capture probes are recognition element to test the nucleotide sequence of target deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) in the sample solution by using DNA or RNA hybridization.
The terms “Barcode” and “UMI” in the art are used interchangeably. These are short, often random nucleotides sequences added to individual DNA or RNA sequences to tag the sequences for identification.
“Splint Oligonucleotides” (also referred to as “bridge oligonucleotides”) are short, synthetic, single-stranded DNA or RNA molecules used as a template to bridge two separate nucleic acid strands (RNA or DNA), in close proximity for enzymatic ligation.
The term “backbone” as used herein refers to a nucleotide backbone which forms the structural framework for the nucleic acid helix. It acts as the outer rails of the DNA ladder comprising deoxyribose sugars and 3’ to 5’ phosphodiester bonds or in the case of RNA, ribose sugar.
“Restriction enzymes” are proteins which act as molecular scissors to cut double stranded DNA at short specific sequences. There are many different types of restriction enzymes including types I- through V. A transposase enzyme is a type of restriction enzyme in that it cuts at specific sequences but in addition acts to insert the sequence at another site.
The term “a first portion that is complementary to a first sequence of an extended capture probe; a second portion that is complementary to a second sequence of the extended capture probe”. The term “complementary” does not have a fixed meaning in the art, however, the instant specification describes it as “a polymer core and a detectable label coupled thereto” (para. 5), and as “a polymer core and a plurality of nucleotide moieties attached thereto” (para. 8). An embodiment of polymer-nucleotide conjugate is shown in Fig. 28 (para. 50). Thus, the broadest reasonable interpretation of the term “polymer-nucleotide complex”, when read in light of the specification, is a construct comprising a polymer core with nucleotides moieties and a detectable label attached thereto.
Claims Rejected under 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.
Claims 2-17 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 2 recites the limitations "(a) hybridizing the analyte in a biological sample to a capture probe on an array, wherein the capture probe comprises a spatial barcode and a capture domain and "(b) extending the capture probe using the analyte as a template, thereby generating an extended capture probe, and generating a second stand comprising a sequence that is complementary to (i) the analyte or a complement thereof and (ii) the spatial barcode or complement thereof, wherein the second strand is generated using a second strand synthesis primer".
It is not clear from the claim or the specification what comprise the metes and bounds of the second strand synthesis primer (Fig.2 part 206) from the nucleic acid extension reaction (Fig. 2 part 203).
Since the capture probe comprises a sequence that hybridizes to the analyte and is extended, the 3' end of the analyte, if it is bound to the capture probe, could also be extended, in the opposite direction, to generate a sequence complementary to the spatial barcode. The claims do not indicate that such a reaction is prevented from occurring, as the sequence representing the spatial barcode could readily serve as a template if the 3' end of the analyte hybridizes to it. As seen in Figure 2, a second strand synthesis primer is hybridized to the extended capture probe (Fig. 2, parts 204 and 206), and the primer is extended to generate the second strand that includes a sequence of the analyte or a complement thereof and the sequence of the spatial barcode or complement thereof (Fig 2, part 207). If the method is intended to be performed in this manner, then a unique second strand synthesis primer would necessarily be required for each different analyte since it must hybridize to a complement of the analyte sequence generated by extension of the capture probe using the analyte as a template. The specification, however, only references the phrase “second strand synthesis primer” in reference to Figure 2. There is no discussion in the specification as to the metes and bounds of what would comprise such a primer, nor the parameters required to make it work 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 1-20 of U.S. Patent No.11,827935. Although the claims at issue are not identical, they are not patentably distinct from each other. Issued claim 1 recites steps a through g of instant claim 2, while the instant application recites steps a through f. The steps in both are identical wherein the method in the issued patent is drawn to “A method of determining location of an analyte in a biological sample, the method comprising, while the instant claim merely recites “A method comprising:” The claims differ in step g which recites; and (g) determining all or part of the sequence of the amplified second strand to determine the location of the analyte in the biological sample which is an inherent feature of the instant claim. Furthermore, all of the subsequent claims are all dependent from claim 2 and do not correct the noted deficiency.
Prior Art rejections
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.
23. Claims 18-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by So et al. (US20180245142) because 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.
So et al. teach a composition comprising an array of a plurality probes. The spatial mapping of nucleic acid on an array comprising a first capture probe (2310) and a second capture probe 2310b. Capture probes 2310 include a cleavable domain 2315, an SBS primer region 2320, a spatial address (aka a spatial barcode) region 2325, a unique molecular identifier (UMI) 2330, and a capture region 2335 and a bridge or splint oligonucleotide (2340 90262) used in amplification). In addition, the array of So et al. teach the use of a UMI region 2330a, which comprises a unique sequence for capture probe 2310a; and a gene-specific capture region 2335a, which is specific for the 3' end of a mRNA molecule and the at 2345 and 2340 a splint oligonucleotide region which comprises a first and second portion. Capture probe 2310b comprises cleavable sequence 2315; SBS primer region 2320b, which comprises a SBS12 sequence; spatial address region 2325b, which comprises a unique spatial address region for the Y dimension; UMI region 2330b. So et al. teach the composition also includes RCA primers and DNA polymerase ([0121, and Table 1) and the use of ligase (0621) and restriction enzymes (0595). A backbone sequence (AKA containing phosphodiester bonds) is taught at [0114] along with an extension to form a nucleic acid sequence.
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Accordingly, So et al. anticipates the claimed invention.
Conclusion
No claim is allowed.
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/GARY BENZION/Supervisory Patent Examiner, Art Unit 1681