DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
2. Applicant's election of species in the reply filed on 4/3/2026 is acknowledged. However, the species election requirement as set forth in the Office action dated 10/6/2025 has been withdrawn in view of applicant’s amendment to claim 39 and cancellation of claims 40-65.
3. Claims 39 and 66-87 are currently pending and under examination.
Priority
4. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e), 120, 121, or 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
None of the prior-filed applications provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for claims 39 and 66-87 of this application. Specifically, none of the prior-filed applications provide support for the combination of features involving the use of a “reference sequence” as recited in step (d) of independent claim 39 (i.e., “(d) for each of a plurality of the cypher-target nucleic acid complexes: (i) comparing the first-strand sequencing reads and second-strand sequencing reads to a reference sequence to identify one or more sequence correspondences to the reference sequence; (ii) analyzing the one or more sequence correspondences to identify a sequence variation; and (iii) identifying the sequence variation as a true mutation or an artifact mutation, wherein a true mutation is a sequence variation relative to the reference sequence that is consistent between the first strand sequencing reads and second strand sequencing reads, and wherein an artifact mutation is a sequence variation relative to the reference sequence that is not consistent between the first strand sequencing reads and second strand sequencing reads”). In fact, such combination of features involving the use of a “reference sequence” was also not described in the disclosure as filed on 8/25/2021. Thus, instant claims 39 and 66-87 are not entitled to the benefit of any of the prior-filed applications, and therefore the effective filing date for instant claims 39 and 66-87 is 4/3/2026 (when amended claim 39 and new claims 66-87 were first presented).
Double Patenting
5. A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
6. Claims 39 and 66-87 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 39-61 of copending Application No. 17/464,341 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Claim Rejections - 35 USC § 112
7. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
8. Claims 39 and 66-87 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 39 has been amended to recite “(d) for each of a plurality of the cypher-target nucleic acid complexes: (i) comparing the first-strand sequencing reads and second-strand sequencing reads to a reference sequence to identify one or more sequence correspondences to the reference sequence; (ii) analyzing the one or more sequence correspondences to identify a sequence variation; and (iii) identifying the sequence variation as a true mutation or an artifact mutation, wherein a true mutation is a sequence variation relative to the reference sequence that is consistent between the first strand sequencing reads and second strand sequencing reads, and wherein an artifact mutation is a sequence variation relative to the reference sequence that is not consistent between the first strand sequencing reads and second strand sequencing reads” (emphasis provided). However, no support for such newly added combination of features involving the use of a “reference sequence” as recited in step (d) could be found in the disclosure as filed. Since claims 66-87 depend from claim 39, these claims also require the same newly added feature(s) that lacks support in the disclosure as filed.
Applicants submit that “[s]upport for the amendments and new claims can be found throughout the application as originally filed” (see page 6 of applicant’s submission filed on 4/3/2026).
The original disclosure has been thoroughly reviewed, but no support for the newly added combination of features involving the use of a “reference sequence” as recited in step (d) of claim 39 could be found. In fact, the specification does not mention the use of any “reference sequence”, let alone the use of a “reference sequence” in the particular way as specified in step (d) of claim 39 as currently presented.
Applicants are reminded that it is their burden to show where the specification supports any amendments to the disclosure. See MPEP 714.02, paragraph 5, last sentence and also MPEP 2163.06.I.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application.” MPEP 2163.06 further notes: When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicants should therefore specifically point out the support for any amendments made to the disclosure.
Claim Rejections - 35 USC § 102
9. The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
10. Claims 39 and 66-87 are rejected under pre-AIA 35 U.S.C. 102(b) and 102(e) as being anticipated by Salk et al. (US 10,760,127 B2).
Regarding claim 39
Salk et al. teach a method of sequencing DNA, the method comprising: (a) attaching cypher polynucleotides (e.g., adapters) to double-stranded DNA fragments to generate double-stranded cypher-target nucleic acid complexes, wherein the cypher polynucleotides comprise bar codes (e.g., barcodes) selected from a plurality of distinct bar code sequences (e.g., barcode sequences); (b) amplifying original strands of the cypher-target nucleic acid complexes to produce a plurality of cypher-target amplification products from first strands and complementary second strands of the cypher-target nucleic acid complexes; (c) sequencing the cypher-target amplification products to produce a plurality of first-strand sequencing reads and a plurality of second-strand sequencing reads; and (d) for each of a plurality of the cypher-target nucleic acid complexes: (i) comparing the first-strand sequencing reads and second-strand sequencing reads to a reference sequence to identify one or more sequence correspondences to the reference sequence; (ii) analyzing the one or more sequence correspondences to identify a sequence variation; and (iii) identifying the sequence variation as a true mutation (e.g., true variant) or an artifact mutation (e.g., a processing error or a site of DNA damage), wherein a true mutation is a sequence variation relative to the reference sequence that is consistent between the first strand sequencing reads and second strand sequencing reads, and wherein an artifact mutation is a sequence variation relative to the reference sequence that is not consistent between the first strand sequencing reads and second strand sequencing reads (see claims 1-2).
Regarding claim 66
The method according to Salk et al., wherein: (a) the artifact mutation is a processing error or a site of DNA damage; (b) comparing the first-strand sequencing reads and second-strand sequencing reads to the reference sequence comprises comparing the first-strand sequencing reads to the second-strand sequencing reads; and (c) the method further comprises: (i) identifying nucleotide bases that are not consistent between the first strand sequencing reads and second strand sequencing reads; and (ii) identifying nucleotide bases that are consistent between the first strand sequencing reads and second strand sequencing reads (see claim 2).
Regarding claim 67
The method according to Salk et al., wherein prior to comparing the first-strand sequencing reads and second-strand sequencing reads to the reference sequence, the method comprises grouping the first-strand sequencing reads and second-strand sequencing reads based on at least the bar code sequences (see claims 3 and 18).
Regarding claim 68
The method according to Salk et al., further comprising generating an error-corrected sequence for a plurality of the cypher-target nucleic acid molecules, wherein each error-corrected sequence comprises nucleotide bases at which the first-strand sequencing reads and second-strand sequencing reads are in agreement (see claim 4).
Regarding claim 69
The method according to Salk et al., further comprising comparing the error-corrected sequence to the reference sequence, and identifying a mutation occurring at a particular position in the error-corrected sequence as a true mutation (see claim 5).
Regarding claim 70
The method according to Salk et al., further comprising comparing the error corrected sequence to the reference sequence and identifying a mutation type of the true mutation (see claim 6).
Regarding claim 71
The method according to Salk et al., wherein the mutation type is a transition, a substitution, an insertion, or a mutation of a single nucleotide (see claim 7).
Regarding claim 72
The method according to Salk et al., further comprising identifying a nucleotide sequence at a particular position in the error-corrected sequence as a true nucleotide sequence (see claim 8).
Regarding claim 73
The method according to Salk et al., wherein the true nucleotide sequence comprises a true mutation relative to the reference sequence (see claims 5 and 8).
Regarding claim 74
The method according to Salk et al., wherein: (a) comparing the first-strand sequencing reads and second-strand sequencing reads to the reference sequence comprises comparing the first-strand sequencing reads to the second-strand sequencing reads; and (b) the method further comprises identifying non-complementary bases between the first-strand sequencing reads and the second-strand sequencing reads as experimental errors or sites of DNA damage (see claims 3 and 9).
Regarding claim 75
The method according to Salk et al., wherein amplifying original strands comprises amplifying original strands via bridge amplification, emulsion amplification, nano-ball amplification, or PCR amplification (see claim 10).
Regarding claim 76
The method according to Salk et al., wherein the double-stranded DNA fragments comprise a deaminated cytosine (see claim 11; column 29, lines 35-39).
Regarding claim 77
The method according to Salk et al., wherein the method further comprises enzymatically treating the double-stranded DNA molecules to repair damaged ends thereof prior to the attaching (see claim 11; column 3, lines 53-55; column 15, lines 6-11).
Regarding claim 78
The method according to Salk et al., wherein the cypher-target nucleic acid complexes subjected to the amplifying step comprise double-stranded DNA fragments that range in size from 100 to 1,000 nucleotides (see Example 1).
Regarding claim 79
The method according to Salk et al., wherein the cypher-target nucleic acid complexes subjected to the amplifying step comprise double-stranded DNA fragments that range in size from 150 to 500 nucleotides (see Example 1).
Regarding claim 80
The method according to Salk et al., further comprising providing a sample comprising the double-stranded DNA fragments from a patient tissue (see claims 15, 23 and 25).
Regarding claim 81
The method according to Salk et al., wherein prior to comparing the first-strand sequencing reads and second-strand sequencing reads to a reference sequence, the method comprises grouping the first-strand sequencing reads and second-strand sequencing reads based on at least the bar code sequences (see claim 18).
Regarding claim 82
The method according to Salk et al., wherein the double-stranded DNA fragments were generated by nuclease cleavage (see claim 17).
Regarding claim 83
The method according to Salk et al., wherein the nuclease is a restriction endonuclease (see column 13, lines 59-62; column 14, lines 11-22).
Regarding claim 84
The method according to Salk et al., further comprising grouping the first-strand sequencing reads and second-strand sequencing reads for a particular cypher-target nucleic acid complex based on at least a bar code sequence (see claim 18; Figure 1).
Regarding claim 85
The method according to Salk et al., wherein prior to sequencing, the method further comprises purifying a plurality of cypher-target nucleic acid complexes, wherein the purified cypher-target nucleic acid complexes comprise nucleic acid molecules that map to specific genomic regions (see claim 20).
Regarding claim 86
The method according to Salk et al., wherein the double-stranded DNA fragments range in size from 100 to 1,000 nucleotides (see column 22, lines 45-48).
Regarding claim 87
The method according to Salk et al., wherein the double-stranded DNA fragments range in size from 150 to 500 nucleotides (see column 22, lines 45-48).
Conclusion
11. 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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KAIJIANG ZHANG/Primary Examiner, Art Unit 1684
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