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 .
Claim Interpretation
Attention is directed to MPEP 904.01 [R-08.2012].
The breadth of the claims in the application should always be carefully noted; that is, the examiner should be fully aware of what the claims do not call for, as well as what they do require. During patent examination, the claims are given the broadest reasonable interpretation consistent with the specification. See In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997). See MPEP § 2111 - § 2116.01 for case law pertinent to claim analysis.
It is noted with particularity that narrowing limitations found in the specification cannot be inferred in the claims where the elements not set forth in the claims are linchpin of patentability. In re Philips Industries v. State Stove & Mfg. Co, Inc., 186 USPQ 458 (CA6 1975). While the claims are to be interpreted in light of the specification, it does not follow that limitations from the specification may be read into the claims. On the contrary, claims must be interpreted as broadly as their terms reasonably allow. See Ex parte Oetiker, 23 USPQ2d 1641 (BPAI, 1992). In added support of this position, attention is directed to MPEP 2111 [R-11.2013], where, citing In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-51 (CCPA 1969), is stated:
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.
Additionally, attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Attention is also directed to MPEP 2111.02 II [R-07.2022]. As stated herein:
II. PREAMBLE STATEMENTS RECITING PURPOSE OR INTENDED USE
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The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "'extraneous' limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation")… (Emphasis added)
Attention is directed to MPEP 2111 [R-10.2019]. As stated therein:
During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1). (Emphasis added).
Attention is directed to MPEP 2173.04 [R-10.2019]. As stated therein:
Breadth of a claim is not to be equated with indefiniteness. In re Miller, 441 F.2d 689, 169 USPQ 597 (CCPA 1971); In re Gardner, 427 F.2d 786, 788, 166 USPQ 138, 140 (CCPA 1970) ("Breadth is not indefiniteness."). A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined. But a claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear. For example, a genus claim that covers multiple species is broad, but is not indefinite because of its breadth, which is otherwise clear. But a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim). (Emphasis added)
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.
Claims 52-54 are rejected under 103 as being unpatentable over McCloskey et al. (2019) (McCloskey et al., Ligase-Mediated Threose Nucleic Acid Synthesis on DNA Templates ACS Synth Biol., 2019 Feb 15;8(2):282-286. doi: 10.1021/acssynbio.8b00511. Epub 2019 Jan 14) in view of Frisen et al. (Frisen et al., WO 2018/091676 Al, publication date 05/24/2018).
McCloskey et al. (2019) teach that “Ligases are a class of enzymes that catalyze the formation of phosphodiester bonds between an oligonucleotide donor with a 5' terminal phosphate and an oligonucleotide acceptor with a 3' terminal hydroxyl group. Here, we wished to explore the substrate specificity of naturally occurring DNA and RNA ligases to determine whether the molecular recognition of these enzymes is sufficiently general to synthesize alternative genetic polymers with backbone structures that are distinct from those found in nature. We chose threose nucleic acid (TNA) as a model system, as TNA is known to be biologically stable and capable of undergoing Darwinian evolution. Enzyme screening and reaction optimization identified several ligases that can recognize TNA as either the donor or acceptor strand with DNA. Less discrimination occurs on the acceptor strand indicating that the determinants of substrate specificity depend primarily on the composition of the donor strand. Remarkably, T3 and T7 ligases were able to join TNA homopolymers together, which is surprising given that the TNA backbone is one atom shorter than that of DNA. In this reaction, the base composition of the ligation junction strongly favors the formation of A-T and A-G linkages. We suggest that these results will enable the assembly of TNA oligonucleotides of lengths beyond what is currently possible by solid-phase synthesis and provide a starting point for further optimization by directed evolution” (See abstract).
McCloskey et al. (2019) teach that “Broad Screen for TNA Ligase Activity. 1 μM of dyelabeled acceptor oligonucleotide (DNA P1 or TNA P1), 1 μM of phosphorylated donor oligonucleotide (DNA P2 or TNA P2), 1 μM of DNA splint were added to a total of 10 μL of reaction volume with 1× of the buffers provided by NEB for each ligase” (See left column, page 285), and “Mass Spectrometry Validation. 1 μM of TNA P1A, 1 μM of TNA P3T, and 1 μM of complementary template (DNA splint 2) were mixed in a solution containing 1× of T3/
T7 buffer” (See right column, page 285)
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Figure 2. Initial screen of ligases and conditions. (a) Sequence and schematic illustration of the nicked duplex substrate.
McCloskey et al. (2019) do not explicitly teach a ligase-mediated nucleic acid synthesis on a splint DNA templates in the context of “generating the special array” recited in step (d) of claim 52.
Frisen et al., teach that “The present invention relates to methods for spatial tagging of nucleic acid molecules in a biological specimen and in particular to a method comprising: (a) providing a solid substrate on which multiple species of capture probes are immobilized such that each species occupies a distinct position on the solid substrate, wherein said probes are for a primer extension reaction and wherein each species of said capture probes comprise a nucleic acid molecule comprising: (i) a cleavage domain for releasing the capture probe from the surface of the solid substrate, (ii) a positional domain that corresponds to the position of the capture probe on the solid substrate, and ( iii) a capture domain; (b) contacting said solid substrate with a biological specimen; and ( c) releasing said capture probes from the surface of the solid substrate under conditions that allow nucleic acids of the biological specimen to hybridize to the capture domain in said capture probes and simultaneously and/or subsequently extending said capture probes using the nucleic acid molecules hybridized to the capture probes as extension templates to produce extended probes thereby spatially tagging the nucleic acids of the biological specimen, wherein step (c) comprises contacting said solid substrate with an aqueous reaction mixture comprising: (i) a polymerase enzyme capable of extending said capture probes using the nucleic acid molecules hybridized to the capture probes as extension templates; and (ii) means for releasing said capture probes from the surface of the solid substrate” (See Abstract; emphasis added).
Frisen et al., teach that “Spatial genomic and transcriptomic methods utilize nucleic acid probes immobilized to a solid substrate (e.g. an array) to capture nucleic acids (DNA or RNA) from a biological specimen and subsequently tag said nucleic acids (e.g. with a nucleic acid "barcode" sequence) based on their location within the biological specimen (see e.g. WO 2012/140224 herein incorporated by reference). The "tagged" nucleic acids are subsequently released from the solid substrate and analyzed to generate information about the localization, distribution and/or expression of genes, or indeed about the localization or distribution of any genomic variation (not necessarily in a gene) in a biological specimen, such as a tissue sample (See page 1). (Emphasis added)
Frisen et al., teach that “the capture domain may be selected or designed to bind (or put more generally may be capable of binding) selectively or specifically to the particular nucleic acid, e.g. RNA, it is desired to detect or analyse. For example the 10 capture domain may be selected or designed for the selective capture of mRNA. As is well known in the art, this may be on the basis of hybridisation to the poly-A tail of mRNA. Thus, in a preferred embodiment the capture domain comprises a poly-T oligonucleotide, i.e. a series of consecutive deoxythymidine residues linked by phosphodiester bonds, which is capable of hybridizing to the poly-A tail of mRNA” (page 28). (Emphasis added)
Frisen et al., teach that “In embodiments where the capture domain comprises a sequence specific for a particular target gene or group of genes it may be desirable to synthesize the capture probes on the solid substrate directly, e.g. using ligation reactions. In particular, it may be useful to synthesize the capture domain of the capture probe on the solid substrate directly. For instance, a solid substrate may be provided comprising capture probes immobilized by their 5' end in which the capture domain is replaced with a universal domain that is common to all of the probes on the solid substrate (such probes may be viewed as a positional domain oligonucleotide). The substrate is contacted with one or more ligation helper probes that comprise 5' to 3': (i) a domain that is complementary to a sequence at the 5' of the capture domain; and (ii) a domain that is complementary to a universal domain in the probes immobilized on the solid substrate, under conditions that allow the ligation helper probe to hybridize to the probes immobilized on the solid substrate. The substrate is also contacted with one or more species of probe containing a capture domain (such probes may be viewed as a capture domain oligonucleotide), wherein the probes comprise 5' to 3': (i) a domain that is complementary to a sequence at the 5' of the helper probe; and (ii) a capture domain comprising a sequence specific for a particular target gene, under conditions that allow the probes comprising the capture domain to hybridise to the helper probes (See pages 28-29). (Emphasis added)
In view of the above presentation, it would have been quite obvious to one of ordinary skill in the art to have adapted the method of McCloskey et al. (2019) to include features disclosed by Frisen et al., for to do so would enabled on to not just detect nucleic acids of interest, but to also identify their location “spatial analysis” of the tissue section via the spatial array of Frisen et al.
In view of the above presentation and in the absence of convincing evidence to the contrary, claims 52-54 are rejected under 103 as being unpatentable over McCloskey et al. (2019) (McCloskey et al., Ligase-Mediated Threose Nucleic Acid Synthesis on DNA Templates ACS Synth Biol., 2019 Feb 15;8(2):282-286. doi: 10.1021/acssynbio.8b00511. Epub 2019 Jan 14) in view of Frisen et al. (Frisen et al., WO 2018/091676 Al, publication date 05/24/2018).
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.
Claim 52 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,649,485 (Date of Patent 05/16/2023, US application 17/212,681) in view of McCloskey et al. (2019) (McCloskey et al., Ligase-Mediated Threose Nucleic Acid Synthesis on DNA Templates ACS Synth Biol., 2019 Feb 15;8(2):282-286. doi: 10.1021/acssynbio.8b00511. Epub 2019 Jan 14) in view of Frisen et al. (Frisen et al., WO 2018/091676 Al, publication date 05/24/2018).
Claim 1 of U.S. Patent No. 11,649,485 is copied below.
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See above for the basis of the rejection as it pertains to the disclosure of Frisen et al.
As evidenced above claim 1 of U.S. Patent No. 11,649,485 is to “a method of generating a spatial array”, and Frisen et al., teach how to make and use a spatial array. Given such, the aspect of Claim 1 being to “a method of generating an array for spatial analysis of nucleic acids in a tissue section would have been quite obvious. Given such detailed disclosure and claims, claim 52 of the instant application is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,649,485 (Date of Patent 05/16/2023, US application 17/212,681) in view of McCloskey et al. (2019) (McCloskey et al., Ligase-Mediated Threose Nucleic Acid Synthesis on DNA Templates ACS Synth Biol., 2019 Feb 15;8(2):282-286. doi: 10.1021/acssynbio.8b00511. Epub 2019 Jan 14) in view of Frisen et al. (Frisen et al., WO 2018/091676 Al, publication date 05/24/2018).
Claim 52 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,545,949 (Date of Patent 02/10/2026, US application 17/312,714) in view of McCloskey et al. (2019) (McCloskey et al., Ligase-Mediated Threose Nucleic Acid Synthesis on DNA Templates ACS Synth Biol., 2019 Feb 15;8(2):282-286. doi: 10.1021/acssynbio.8b00511. Epub 2019 Jan 14) in view of Frisen et al. (Frisen et al., WO 2018/091676 Al, publication date 05/24/2018).
Claim 1 of U.S. Patent No. 12,545,949 is copied below.
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See above for the basis of the rejection as it pertains to the disclosure of Frisen et al.
In view of the detailed teachings, it would have been quite obvious to develop a method for generating the array that is used in the claimed methods. Given such, and in the absence of convincing evidence to the contrary, claim 52 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,545,949 (Date of Patent 02/10/2026, US application 17/312,714) in view of McCloskey et al. (2019) (McCloskey et al., Ligase-Mediated Threose Nucleic Acid Synthesis on DNA Templates ACS Synth Biol., 2019 Feb 15;8(2):282-286. doi: 10.1021/acssynbio.8b00511. Epub 2019 Jan 14) in view of Frisen et al. (Frisen et al., WO 2018/091676 Al, publication date 05/24/2018).
Allowable Subject Matter
Claims 55-69 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682
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