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 .
Election/Restrictions
2. Applicant’s election with traverse of Group I (claims 1, 66, 68, 70, 72 and 74, as well as newly added dependent claims 76-93) in the reply filed on 5/19/2026 is acknowledged. The traversal is based on applicant’s allegation that the Office has not shown a serious burden would be required to examine Groups I and IV together. This is not found persuasive because page 6 (see paragraph 7) of the previous Office action specifically indicated that there would be a serious search burden if restriction were not required. To set the record more clearly, since Groups I and IV belong to different classifications (i.e., Group I is classified in C12Q 1/6869, whereas Group IV is classified in C12Q 1/6855) and recite divergent subject matters (i.e., Group I requires a “sequencing” step, whereas Group IV does not require such; Group IV requires a step of “determining the number of amplicon duplicates”, whereas Group I does not require such), each of them would require a different field of search under a different classification, as well as searching for different features by employing different search queries. Thus, the restriction requirement is still deemed proper and is therefore made FINAL.
3. Claims 1 and 66-93 are pending in the application. Claims 67, 69, 71, 73 and 75 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 66, 68, 70, 72, 74 and 76-93 are currently under examination.
Claim Objections
4. Claims 74 and 93 are objected to because of the following informalities:
Claim 74, lines 1-2: “each of the nonrandom oligonucleotide species” should be changed to “each of the nonrandom oligonucleotide adapter species” for more clarity.
Claim 93: the wherein clause should be changed to “wherein the .
Appropriate correction is required.
Claim Rejections - 35 USC § 112
5. 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.
6. Claims 1, 66, 68, 70, 72, 74 and 76-93 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.
(1). Claim 1 recites “a ratio of the double-stranded nucleic acid template species to double-stranded or partially double-stranded nonrandom oligonucleotide adapter species is greater than 1,000 to 1” in step (a). It is unclear whether the recited “ratio” refers to a ratio of the numbers of the two types of species, or a ratio of the mass or molar amounts of the two types of species, or a ratio of the concentrations of the two types of species. Claims 76-85, each of which depends from claim 1, are also rejected for the same reason.
In the interest of compact prosecution and for purposes of current examination, the recitation “a ratio of the double-stranded nucleic acid template species to double-stranded or partially double-stranded nonrandom oligonucleotide adapter species is greater than 1,000 to 1” in step (a) of claim 1 is being interpreted as “a ratio of the number of the double-stranded nucleic acid template species to the number of the double-stranded or partially double-stranded nonrandom oligonucleotide adapter species is greater than 1,000 to 1”.
(2). Claim 66 recites “a ratio of double-stranded nucleic acid template species to the first polynucleotide species is greater than 1,000 to 1” in lines 10-11. It is unclear whether the recited “ratio” refers to a ratio of the numbers of the two types of species, or a ratio of the mass or molar amounts of the two types of species, or a ratio of the concentrations of the two types of species. Claims 68, 70, 72, 74 and 86-93, each of which depends from claim 66, are also rejected for the same reason.
In the interest of compact prosecution and for purposes of current examination, the recitation “a ratio of double-stranded nucleic acid template species to the first polynucleotide species is greater than 1,000 to 1” in lines 10-11 of claim 66 is being interpreted as “a ratio of the number of the double-stranded nucleic acid template species to the number of the first polynucleotide species is greater than 1,000 to 1”.
(3). Claim 66 recites the limitation “the first polynucleotide species” in line 10. There is insufficient antecedent basis for this limitation in the claim.
(4). Claim 86 recites the limitation “the second polynucleotide species”. There is insufficient antecedent basis for this limitation in the claim.
In addition, claim 86 also recites “the first polynucleotide species” which seems to find support in line 10 of claim 66 (from which claim 86 depends). However, the limitation “the first polynucleotide species” in line 10 of claim 66 does not have antecedent basis as discussed above.
Double Patenting
7. 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.
8. Claims 1, 66, 68, 70, 72, 74 and 76-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 and 30-41 of U.S. Patent No. 11,352,662. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-15 and 30-41 of U.S. Patent No. 11,352,662 teach or render obvious all the features as recited in instant claims 1, 66, 68, 70, 72, 74 and 76-93.
Specifically, claim 1 of U.S. Patent No. 11,352,662 teaches all the steps and elements required by instant claim 1, and claim 30 of U.S. Patent No. 11,352,662 teaches all the steps and elements required by instant claim 66. In addition, the other features as recited in dependent claims 68, 70, 72, 74 and 76-93 are also taught or rendered obvious by claims 1-15 and 30-41 of U.S. Patent No. 11,352,662.
Claim Rejections - 35 USC § 102
9. 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 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.
10. 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.
11. Claims 1, 76-82 and 84-85 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wong et al. (article titled “Multiplex Illumina Sequencing Using DNA Barcoding”, Curr. Protoc. Mol. Biol. 2013, 101:7.11.1-7.11.11, published online January 2013).
Regarding claim 1
Wong et al. teach, throughout the whole document, a method for determining a sequence of nucleotides for one or more nucleic acid templates in a nucleic acid sample, wherein the nucleic acid templates are of different double-stranded nucleic acid template species, the method comprising: (a) contacting the double-stranded nucleic acid templates with a predetermined discrete set of double-stranded or partially double-stranded nonrandom oligonucleotide adapter species under ligation conditions (see Figure 7.11.1), thereby generating nonrandom oligonucleotide adapter-ligated nucleic acid templates, wherein: there are 999 or fewer (e.g., 96) double-stranded or partially double-stranded nonrandom oligonucleotide adapter species (see Table 7.11.2 and the “Barcode design and selection” section); a ratio of the number of the double-stranded nucleic acid template species to the number of the double-stranded or partially double-stranded nonrandom oligonucleotide adapter species is greater than 1,000 to 1 (The method of Wong et al. is for multiplex sequencing, wherein multiple samples are uniquely tagged with short identifying sequences known as barcodes, pooled, and then sequenced together in a single lane (see Abstract). According to Wong et al., the method is especially suitable for sequencing experiments involving organisms with small genomes (see Abstract), such as yeasts with small genomes (see the first paragraph under “INTRODUCTION”). In the method of Wong et al., each genomic DNA sample to be included in the multiplex sequencing is first sheared to generate fragments of “100 to 500 bp” (see the “Size of input DNA material” section in page 7.11.9). As evidenced by Horecka et al. (Yeast 2000, 16:967-970), the size of yeast genome is about 12 Mb (see page 967, column 2, paragraph 2; page 968, column 2, last paragraph). When a yeast genomic DNA sample is sheared to generate fragments of 100 to 500 bp, the number of unique fragments (i.e., nucleic acid template species) generated would be at least 24,000 (i.e., 12[Symbol font/0xB4]106/500). Thus, the ratio of the number of the double-stranded nucleic acid template species to the number of the double-stranded or partially double-stranded nonrandom oligonucleotide adapter species is at least 24,000 to 1 for the method of Wong et al.); (b) amplifying the adapter-ligated nucleic acid templates, thereby generating amplicons (see Figure 7.11.1); and (c) sequencing all or a portion of each amplicon, thereby determining the sequence of the double-stranded nucleic acid templates in the nucleic acid sample (see Figure 7.11.1 description: “DNA libraries are then ready for mixing and Illumina sequencing”. Also see steps 21 and 22 as listed in page 7.11.6).
Regarding claim 76
The method according to Wong et al., wherein the sequences of the double-stranded or partially double-stranded nonrandom oligonucleotide adapter species are non-degenerate (see Tables 7.11.1 and 7.11.2).
Regarding claim 77
The method according to Wong et al., wherein amplifying the nonrandom oligonucleotide adapter-ligated nucleic acid templates generates double-stranded amplicons, and sequencing comprises sequencing all or a portion of each strand of the amplicons (see Figure 7.11.1 and the corresponding description paragraphs).
Regarding claim 78
The method according to Wong et al., wherein the nonrandom oligonucleotide adapter-ligated nucleic acid templates are amplified by a process comprising exponential amplification (e.g., PCR) (see Figure 7.11.1; page 7.11.10, the “Number of PCR cycles for amplification” section).
Regarding claim 79
The method according to Wong et al., wherein each adapter-ligated nucleic acid template comprises one nonrandom oligonucleotide adapter at a first end and a standard sequencing adapter at a second end, or wherein the each of the adapter-ligated nucleic acid templates comprises a first nonrandom oligonucleotide adapter at a first end and a second nonrandom oligonucleotide adapter at a second end (see Figure 7.11.1).
Regarding claim 80
The method according to Wong et al., wherein the nucleic acid templates are sheared double-stranded DNA templates (see page 7.11.9, the “Size of input DNA material” section).
Regarding claim 81
The method according to Wong et al., comprising blunt-ending the nucleic acid templates before contacting the nucleic acid templates with the nonrandom oligonucleotide adapter species (see Figure 7.11.1).
Regarding claim 82
The method according to Wong et al., wherein the nonrandom oligonucleotide adapter species comprise a blunt end (see Figure 7.11.1).
Regarding claim 84
The method according to Wong et al., comprising providing a base call, wherein each base call represents a single nucleotide located at a single nucleotide position in the nucleic acid template (see Figure 7.11.1; page 7.11.6, steps 21 and 22. The sequencing data would provide a base call for each single nucleotide position in the nucleic acid template.).
Regarding claim 85
The method according to Wong et al., wherein the double-stranded nucleic acid templates or the partially double-stranded nonrandom oligonucleotide adapter species comprise a ligation linker (see Figure 7.11.1).
Claim Rejections - 35 USC § 103
12. 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 of this title, 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.
13. 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.
14. Claim 83 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (article titled “Multiplex Illumina Sequencing Using DNA Barcoding”, Curr. Protoc. Mol. Biol. 2013, 101:7.11.1-7.11.11, published online January 2013) as applied to claim 1 above, and further in view of Schmitt et al. (US 2015/0044687 A1).
Wong et al. teach the method of claim 1 as discussed above. According to Wong et al., sequencing all or a portion of each amplicon is performed using a sequencer (e.g., Illumina sequencer) (see Abstract; Figure 7.11.1), which generates thousands to millions of sequence reads (see page 7.11.9, column 1, paragraph 1; page 7.11.10, column 1, paragraph 2). Wong et al. do not specifically disclose the use of the method for detecting a single nucleotide alteration or a single nucleotide alteration that is present at a frequency of 5 percent or lower.
However, Schmitt et al. teach that such sequencing method may be used for detecting a single nucleotide alteration or a single nucleotide alteration that is present at a frequency of 5 percent or lower (see paragraphs [0006] and [0089]; Example 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the sequencing method of Wong et al. for detecting a single nucleotide alteration or a single nucleotide alteration that is present at a frequency of 5 percent or lower per the teaching of Schmitt et al., because such (or similar) sequencing method had already been used in the art for detecting a single nucleotide alteration or a single nucleotide alteration that is present at a frequency of 5 percent or lower. In addition, combining prior art elements according to known methods to yield predictable results is considered prima facie obvious (see MPEP 2143.I.A). Given the teachings of the prior art and the level of the ordinary skilled artisan at the time of the application’s effective filing date, it must be considered, absent evidence to the contrary, that said skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Conclusion
15. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAIJIANG ZHANG whose telephone number is (571)272-5207. The examiner can normally be reached Monday - Friday, 8:30 am - 5 pm.
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/KAIJIANG ZHANG/Primary Examiner, Art Unit 1684
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