DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Please note that the examiner for this application has changed. Please address future correspondence to Robert T. Crow (Art Unit 1683) whose telephone number is (571) 272-1113.
Election/Restrictions
3. Applicant’s election of Group I in the reply filed on 15 September 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 15 September 2025.
Claims 1-15 are under prosecution.
Information Disclosure Statement
4. The Information Disclosure Statements filed 21 May 2024 and 22 September 2025 are acknowledged and have been considered.
It is noted that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
5. The use of trade names or marks used in commerce (including but not necessarily limited to tSMS), has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear 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.
Notice to Comply with Requirements for Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosure.
6. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth below.
Specifically, the application fails to comply with CFR 1.821(d), which states:
(d) Where the description or claims of a patent application discuss a sequence that is set forth in the “Sequence Listing” in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by “SEQ ID NO:” in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application.
7. Table 2 discloses peptide sequences. However, none of the sequences are identified by a SEQ ID NO.
For compliance with sequence rules, it is necessary to include the sequence in the “Sequence Listing” and identify them with SEQ ID NO. In general, any sequence that is disclosed and/or claimed as a string of particular bases or amino acids, and that otherwise meets the criteria of CFR 1.821(a), must be set forth in the “Sequence Listing.” See MPEP 2422.03.
While the Examiner has made every attempt to check the Specification for sequence compliance, Applicant is required to carefully check the entire Specification for any and all issues regarding sequence compliance.
For the response to this Office Action to be complete, Applicant is REQUIRED to comply with the Requirements for Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures. Failure to comply with the Requirements will be considered nonresponsive.
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 1-15 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.
A. Claim 1 (upon which claims 2-15 depend) is indefinite in each of the following:
I. The multiple recitations of “the second surface primer” starting in line 2 of (b). Line 2 of (a) recites “a second surface primer,” and the last line of (a) also recites “a second surface primer.” Thes, the claim encompasses two different second surface primers, and renders the remaining recitations of “the second surface primer:” indefinite as there can be more than one.
II. The term “sequencing” as found in line 1 of (b) and line 1 of (d), as the steps merely recite primer extension, but no active sequencing steps.
For the purposes of examination, the claimed “sequencing” is interpreted as merely extending the primers as claimed.
B. Claims 2-5, 7-12, and 15 are indefinite in the recitation “step (a)” claims 2 and 15, which lacks antecedent basis because claim 1 does not recite any “step.”
C. Claims 2-5 and 7-12 are indefinite in the recitation “the second surface oligonucleotide” in claim 2, as the second surface oligonucleotide is not generated until (b).
For the purposes of examination, the “second surface oligonucleotide” is interpreted as the second surface primer.
D. Claim 5 is indefinite in the recitation “the one or more dihydroxylation reagent comprises a single reagent comprising OsO4.” It is unclear how a reagent can “comprise” a single regent “comprising” anything due to the multiple recitations of open claim language.
E. Claims 10-11 are indefinite in the recitation “step (d)” claim 10, which lacks antecedent basis because none of claims 1 or 8-9 recite any “step.”
Claim Rejections - 35 USC § 103
10. 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.
11. 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.
12. Claims 1-2, 6-7, and 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Kawashima et al. (U.S. Patent Application Publication No. US 2005/0100900 A1, published 12 May 2005) and Lui et al. (U.S. Patent Application Publication No. US 2012/0208194 A1, published 16 August 2012).
Regarding claim 1, Kawashima et al. teach methods comprising providing a surface having a first surface bound oligonucleotide bound thereto via the 5’ end (paragraph 0125) and having a first polynucleotide template (Figure 1A (b) and paragraphs 0109-0117) with a free 3’ end attached thereto (paragraphs 0037-0042). The surface comprises a second surface primer that the polynucleotide template hybridizes to at its 3’ end (Figure 1A(g)). The second surface primer is then extended using the second surface primer and a portion of the first polynucleotide template to generate the structure comprising a first read sequence as claimed in (b) of the instant claim (Figure 1A (g)-(h)), thereby “sequencing” the first polynucleotide template as discussed above.
Kawashima et al. further teach cleaving the obtained structure at a portion of the first polynucleotide template using a restriction endonuclease to produce the claimed structure (Figure 12B(c)-(d) and paragraphs 0171-0173); it is noted that the “5’ portion” interpreted as any portion of the first polynucleotide template that is upstream from the free 3’ end.
Kawashima et al. also teach Figure 13A(a), which shows a bound extended first surface oligonucleotide having a sequence bound thereto, which is analogous to the hybridized second polynucleotide template, wherein the primer is extended to form a read region (i.e., the claimed second read region; Figure 13A(b)), thereby sequencing at least a portion of the second polynucleotide template as discussed above.
Kawashima et al. also teach the process is repeated to provide amplified immobilized molecules (Abstract) and repetition of the extension with least one extended molecule (paragraph 0024), and that the methods have the added advantage of being useful for many different purposes, including gene expression (Abstract). Thus, Kawashima et al. teach the known techniques discussed above.
In addition, Liu et al. methods comprising providing surface having immobilized extended DNA molecules hybridized to cleavable primers (Figure 2(b) which is analogous to Figure 12B(c) of Kawashima et al.), wherein the primer is cleaved and sequence by extension and stand displacement (Figure 2 and paragraph 0030), and that the methods have the added advantage of maximizing the efficiency of sequencing reactions (paragraph 0015). Thus, Liu et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Kawashima et al. and Liu et al. to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of being useful form many different purposes, including gene expression as explicitly taught by Kawashima et al. (Abstract) and maximizing the efficiency of sequencing reactions as explicitly taught by Liu et al. (paragraph 0015). In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined with predictable results because the known techniques of the cited prior art predictably result in useful methods for sequencing nucleic acids.
Regarding claim 2, the method of claim 1 is discussed above. Kawashima et al. teach a fourth polynucleotide template complementary to and hybridized to the first polynucleotide template and covalently bound to the 3’ end of the second surface primer and hybridized to a portion of the first surface oligonucleotide; namely, because the claimed fourth polynucleotide template is attached at the 3’ end of the second primer, the fourth polynucleotide template is merely a portion of the 3’ end of the second surface primer. Kawashima et al. teach the second surface primer is extend all the way to the end of the first surface primer through the first surface oligonucleotide (e.g., Figure 10A(a). Liu et al also teach an analogous extended structure (Figure 2). Liu et al. teach both primers are modified for cleavage (paragraph 0149); thus, it would have been obvious to cleave both the first surface oligonucleotide(which is a primer) and the second surface primer, thereby generating the claimed structure.
Regarding claim 6, the method of claim 1 is discussed above. Kawashima et al. teach both immobilized primers retain hybridized portions of the cleaved and extended molecules (e.g., Figure 12B(d)). Thus, cleavage of both primers as taught by Liu et al. results in the instantly claimed structure.
Regarding claim 7, the method of claim 2 is discussed above. Liu et al. teach strand displacement to extend the second surface primer, which creates the fourth polynucleotide (Figure 2 and paragraphs 0030 and 0091).
It is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, counsel’s mere arguments cannot take the place of evidence in the record.
Regarding claim 12, the method of claim 2 is discussed above. Kawashima et al. teach washing after denaturation (paragraph 0165). Liu et al. also teach washing (paragraphs 0209-0210) and denaturation (Abstract).
It is reiterated that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record.
Regarding claim 13, the method of claim 1 is discussed above. Liu et al. teach cleavage comprises removing an excisable base (i.e., uridine), and generating a free 3’ hydroxyl at the end (paragraph 0030). It is noted that while the claim 13 recites removing a “second” excisable base, only claim 3 recites a first excisable base, and claim 13 does not depend upon claim 3. Thus, claim 13 only requires removal of one excisable base.
It is reiterated that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record.
Regarding claims 14 and 15, the method of claim 1 is discussed above. Kawashima et al. teach washing after cleavage (i.e., claim 14; paragraph 0165) treating the surface with and exonuclease (i.e., claim 15; paragraph 0166). Liu et al. also teach washing (paragraphs 0209-0210).
It is reiterated that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record.
13. Claims 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Kawashima et al. (U.S. Patent Application Publication No. US 2005/0100900 A1, published 12 May 2005) and Lui et al. (U.S. Patent Application Publication No. US 2012/0208194 A1, published 16 August 2012) as applied to claim 2 above, and further in view of Wu et al. (U.S. Patent Application Publication No. US 2019/0352327 A1, published 21 November 2019).
Regarding claims 3-5, the method of claim 2 is discussed above in Section 12.
While Liu et al. teach cleavage comprises cleavage, in the form of removing an excisable base (i.e., uridine) and generating a free 3’ hydroxyl at the end (paragraph 0030), neither Kawashima et al. nor Lui et al. teach use of a dihydroxylation reagent.
However, Wu et al. teach methods wherein bridged (i.e., clustered) immobilized polynucleotides are cleaved (abstract and Figure 1) using the dihydroxylation reagent osmium tetroxide (i.e., claims 3 and 5, paragraphs 0246-0247), Wu et al. also teach the use of allyl-T as a cleavage site (i.e., claim 4; paragraph 0019), and that the methods have the added advantage of being an effective alternative method of cleavage (paragraph 0007). Thus, Wu et al. teach the known techniques discussed above.
It is reiterated that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Wu et al. with Kawashima et al. and Liu et al. to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of utilizing an effective alternative method of cleavage as explicitly taught by Wu et al. (paragraph 0007). In addition, it would have been obvious to the ordinary artisan that the known techniques of Wu et al. could have been combined with the cited prior art with predictable results because the known techniques of Wu et al. predictably result in useful methods for cleaving nucleic acids.
14. Claims 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Kawashima et al. (U.S. Patent Application Publication No. US 2005/0100900 A1, published 12 May 2005) and Lui et al. (U.S. Patent Application Publication No. US 2012/0208194 A1, published 16 August 2012) as applied to claim 2 above, and further in view of Ma et al. (U.S. Patent Application Publication No. US 2003/0134349 A1, published 17 July 2003).
Regarding claims 8-11, the method of claim 2 is discussed above in Section 12.
Kawashima et al. teach the molecules are DNA and RNA molecules (paragraph 0031), and Liu et al. teach RNA (i.e., ribonucleotides; paragraph 0023).
While Liu et al. also teach polynucleotides with flaps (e.g., Figure 2), neither Kawashima et al. nor Liu et al. teach a flap nuclease.
However, Ma et al. teach methods wherein cleavage of flaps (i.e., removal of nucleotides; claim 8) is performed with an enzyme having flap nuclease activity (i.e., claim 9) in the form of an operably linked construct (i.e., chimera) of the nuclease and a DNA polymerase (i.e., claim 10; paragraph 0132). Ma et al. teach the polymerase is derived from Taq DNA polymerase or the flap activity is derived from FEN-1 (i.e., claim 11; paragraph 0101), and that the methods have the added advantage of allowing direct detection and quantitation of nucleic acids (Abstract). Thus, Ma et al. teach the known techniques discussed above.
It is reiterated that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Ma et al. with Kawashima et al. and Liu et al. to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of allowing direct detection and quantitation of the nucleic acids as explicitly taught by Ma et al. (Abstract). In addition, it would have been obvious to the ordinary artisan that the known techniques of Ma et al. could have been combined with the cited prior art with predictable results because the known techniques of Ma et al. predictably result in useful methods for cleaving nucleic acids.
Conclusion
15. No claim is allowed.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert T. Crow whose telephone number is (571)272-1113. The examiner can normally be reached M-F 8:00-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Robert T. Crow
Primary Examiner
Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683