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 .
DETAILED ACTION
1. Applicant’s election without traverse of group I (claims 1-18) in the reply filed on August 6, 2026 is acknowledged. With reference to the Applicant’s arguments drawn to kit claim 19 reciting instructions for performing the method, examining claim 19 together with group I claims would not be a search burden, the arguments have been fully considered and found unpersuasive because claim 19 is drawn to a product and instructions for performing the method indicates mere instructions to use the kit. Further, as indicated in the previous office action both groups are distinct as shown by their different classification and each group requires different searches. The issues are not same for each group in terms of 35 USC 112 and 101 statutes. For all the above, restriction for examination purposes as indicated is deemed proper.
Status of the Application
2. Claims 1-18 are considered for the examination. Claims 19-20 are withdrawn from further consideration as being drawn to nonelected group.
Priority
3. This application filed on May 13, 2024 is a DIV of US 17/406,824 filed on August 19, 2021, now US patent 11,981,958 which claims priority benefit of US 63/068,146 filed on August 20, 2020.
Informalities
4. The following informalities are noted:
(i) Claims 1-18 recite “RTL probe’. Expanding the term ‘RTL’ at least for the first time that it appears in the claim is suggested. Appropriate correction is required.
Nucleotide and/or Amino Acid Sequence Disclosures
5. This application contains disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821. (a) Nucleotide and/or amino acid sequences, as used in 1.821 through 1.825, are interpreted to mean an unbranched sequence of 4 or more amino acids or an unbranched sequence of 10 or more nucleotides.
(i) Nucleotide and/or amino acid sequences appearing in the drawings (Fig. 9A, 9B) are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Appropriate correction is required.
Claim objections
6. The claims are objected to because of the following informalities:
Claim 18 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 7. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
7. 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.
A. Claims 17 is 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 17 recites the limitation "the ligated probe" in line 7. There is insufficient antecedent basis for this limitation in the claim. The limitation is unclear and indefinite because claim 12 upon which claim 17 depends lack support for said limitation and it is unclear what the limitation is referring to.
B. Claims 1-18 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. Claims 1-18 recite ‘a first RTL probe and a second RTL probe’. The specification lacks any definition for ‘RTL’. The metes and bounds of the claims are unclear and indefinite because it is not clear if the RTL refers to an oligonucleotide, padlock probe or any other sequence.
Claim Rejections - 35 USC § 102
8. 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.
Claims 1-16 and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nilsson et al. (WO 2019/068880).
Note: DNA target is interpreted as genomic DNA and RTL probes are interpreted as padlock probes, iLock probes or oligonucleotides.
Nilsson et al. teach a method of claim 1 and 8, for determining the abundance and/or location of a genomic DNA (gDNA) analyte or a genetic variant in a biological sample, the method comprising: (a) contacting the biological sample with a substrate comprising a plurality of capture probes, wherein a capture probe of the plurality comprises a spatial barcode and a capture domain (page 16, line 31 to line 34 on page 19, page 52, line 14 to line 10 on page 54, page 48, line 24 to line 3 on page 50, page 31, line 26 to line 15 on page 32); (b) contacting the biological sample with a first RTL probe and a second RTL probe, wherein the first RTL probe and the second RTL probe are substantially complementary to adjacent sequences of the gDNA analyte, and wherein the second RTL probe comprises a 5' FLAP (page 16, line 31 to line 34 on page 19, page 52, line 14 to line 10 on page 54, page 48, line 24 to line 3 on page 50, page 31, line 26 to line 15 on page 32); (c) hybridizing the first RTL probe and the second RTL probe to the gDNA analyte (page 16, line 31 to line 34 on page 19, page 52, line 14 to line 10 on page 54, page 48, line 24 to line 3 on page 50, page 31, line 26 to line 15 on page 32); (d) cleaving the second RTL probe, thereby releasing the 5' FLAP (page 16, line 31 to line 34 on page 19, page 52, line 14 to line 10 on page 54, page 48, line 24 to line 3 on page 50, page 31, line 26 to line 15 on page 32); (e) hybridizing the 5' FLAP to the capture domain (page 16, line 31 to line 34 on page 19, page 52, line 14 to line 10 on page 54, page 48, line 24 to line 3 on page 50, page 31, line 26 to line 15 on page 32); and (f) determining (i) all or a part of the sequence of the 5' FLAP, or a complement thereof, and (ii) all or a part of the sequence of the spatial barcode, or a complement thereof, and using the determined sequence of (i) and (ii) to identify the abundance and/or location of the gDNA analyte in the biological sample (page 16, line 31 to line 34 on page 19, page 52, line 14 to line 10 on page 54, page 48, line 24 to line 3 on page 50, page 31, line 26 to line 15 on page 32).
With reference to claim 2, Nilsson et al. teach that the first RTL probe and the second RTL probes are DNA probes (page 4, line 3-8, page 5, line 27-33).
With reference to claim 3, Nilsson et al. teach that the 5' FLAP comprises a first barcode sequence, wherein the first barcode sequence comprises a sequence that identifies the first RTL probe, the second RTL probe, the gDNA analyte, or any combination thereof (page 31, line 26 to line 15 on page 32, page 11, line 17-29).
With reference to claim 4, 14-16, Nilsson et al. teach that the 5' FLAP comprises (i) a functional sequence, wherein the functional sequence is a primer sequence, and (ii) a capture probe binding domain, wherein the capture probe binding domain comprises a homopolymeric sequence (universal/common sequence) or a poly(A) sequence (page 31, line 26 to line 15 on page 32, page 11, line 17-29 table 4).
With reference to claim 5, Nilsson et al. teach that the cleaving of the second RTL probe comprises providing an endonuclease, wherein the endonuclease cleaves a portion of the first RTL probe, a portion of second RTL probe, the 5' FLAP of the second RTL probe, or any combination thereof (page 12, line 9-35).
With reference to claim 6, Nilsson et al. teach that the determining step comprises sequencing all or part of the 5' FLAP (page 32, line 8-15).
With reference to claims 7 and 18, Nilsson et al. teach that the biological sample is a formalin-fixed, paraffin- embedded (FFPE) sample (page 48, line 9-23).
With reference to claim 9-11, Nilsson et al. teach that the genetic variant is a single nucleotide polymorphism (SNP) or a nucleotide point mutation, or wherein the genetic variant comprises at least two, at least three, at least four, at least five, or more genetic variants, wherein the first RTL probe comprises a sequence that is substantially complementary to a sequence 3' to the genetic variant, or at least one nucleotide that is complementary to a wild-type sequence of the genetic variant or the second RTL probe comprises a sequence substantially complementary to a sequence 5' to the genetic variant, and/or a nucleotide that is complementary to the genetic variant (page 17, line 11-29).
With reference to claim 12, Nilsson et al. teach that the 5' FLAP further comprises a nucleotide that is complementary to the genetic variant (page 16, line 29 to line 29 on page 17).
With reference to claim 13, Nilsson et al. teach that 13, the first RTL probe and the second RTL probe are capable of forming an invasive cleavage structure in the presence of the genetic variant (page 11, line 34 to line 35 on page 12). For all the above the claims are anticipated.
Claim Rejections - 35 USC § 103
8. 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.
Claims 1-18 are rejected under 35 U.S.C. 103 as being unpatentable over Nilsson et al. (WO 2019/068880) in view of Frisen et al. (US 2019/0017106).
Nilsson et al. teach a method for detecting a genetic variant in a gDNA analyte as discussed above in section 7. However, Nilsson et al. did not specifically teach blocking moiety on capture probe binding domain to detect genetic variant.
Frisen et al. teach a method for detecting analytes in a sample, wherein the method comprises localized detection of genomic DNA comprising contacting DNA molecules with capture probes immobilized on a substrate comprising a positional domain (barcode) and a capture domain, extending or ligating to obtain tagged DNA molecules, releasing tagged DNA and analyzing the sequence of the released DNA molecules to detect spatial expression of genes in the sample wherein capture probes comprise poly A tail sequence, and modify capture domain of the capture probes with a blocking moiety to block 3’ of the capture probe and to avoid addition of poly-A sequences to the 3’ end of the probes, wherein the blocking domain comprises a capture domain comprising poly-U or poly Tand releasing the capture domain by denaturation (para 0145-0150, 0301-0302, 0340-0341, para 0024-0036).
It would have been prima facie obvious to one skilled in the art before the effective filing date of the invention to modify the method of Nilsson et al. with blocking moiety as taught by Frisen et al. to develop a sensitive method for detecting a genomic variant in a DNA target. The ordinary person skilled in the art would have motivated to combine the method of Nilsson et al. with the blocking moiety on capture probes as taught by Frisen et al. and have a reasonable expectation of success that the combination would improve the sensitivity of detecting a genetic variant in a sample because Frisen et al. explicitly taught blocking capture probe domain avoids addition of poly-A tail to the free 3’ end of the capture probes and are protected from being extended (para 0145-0150, 0301) and such a modification of the method is considered obvious over the cited prior art.
Double Patenting
9. 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 1-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 and 11-18 of U.S. Patent No. 11,981,958 (hereafter the ‘958).
Note: The following rejection is made because elected method claims are within the scope of the claims in the patent ‘958.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims 1-18 are entirely within the scope of the claims 1-9 and 11-18 of the patent ‘958. Specifically, the method steps in claims 1-18 comprising contacting the biological sample with a substrate comprising a plurality of capture probes wherein the capture probes comprises a spatial barcode and a capture domain; contacting the biological sample with a first and a second RTL probe complementary to adjacent sequences of the gDNA analyte, hybridizing the first and second RTL probes to the gDNA analyte, cleaving the second RTL probe, thereby releasing the 5’ flap , hybridizing the 5’flap to the capture domain and determining all or part of the sequence of the 5’flap or complement thereof, (ii) all or a part of the sequence of the spatial barcode, or a complement thereof, and using the determined sequence of (i) and (ii) to identify the abundance and/or location of the gDNA analyte in the biological sample are within the scope of the claims 1-9 and 11-18 of the patent ‘958. The only difference is that the claims in the patent ‘958 disclose a first and a second probe which are obvious over the first and a second RTL probes and are coextensive in scope.
Conclusion
No claims are allowable.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681
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