DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed October 20, 2025. Currently, claims 1, 4, 10, 13-16, 18, 19, 26-27, 31-32, 36-38, and 42-45 are pending. Claims 26-27, 31-32, 36, 43-45 have been withdrawn as drawn to non-elected subject matter.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow. This action is made FINAL.
Any objections and rejections not reiterated below are hereby withdrawn.
Election/Restrictions
Applicant's election of Group I, claims 1, 4, 10, 13-16, 18, 19, 27-38, and 42, EGFR and L858R, in the paper filed February 28, 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 § 818.03(a)).
Claims 26-27, 31-32, 36, 43-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application is a 371 of PCT/CN2019/119684, filed November 20, 2019 and claims priority to CN 201811402300.7, filed November 21, 2018.
It is noted no translation of the foreign priority document has been filed.
Drawings
The drawings are acceptable.
Claim Rejections - 35 USC § 112- Second Paragraph
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.
Claims 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 pre-AIA the applicant regards as the invention.
Claim 18-19 are directed to a cell comprising the reference DNA comprising a mixture of a DNA fragment 1 and a DNA fragment 2. Claim 19 provides the reference DNA exist in homozygous state. It is unclear how the reference DNA may exist in homozygous state if the claim requires fragment 1 and fragment 2. Clarification is required.
Regarding claims 38, 42, the claim requires the content percentage of the DNA fragment 1 and the DNA fragment 2 is 0.01% to 99.9%; 10%, 25% or 50%.... It is unclear whether each of the fragments are 0.01% to 99.9% and if so it is unclear how the percentage can be greater than 100%. Furthermore, the claim lists percentages within the range which do not appear to limit the claim. It is unclear what each of these percentages refers to and how they limit the claim.
Claim Rejections - 35 USC § 112-4th Paragraph
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 16 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 16 has been amended to require the spike-in reference DNA is a spike-in reference standard DNA. This limitation does not appear to limit Claim 1 in any way since Claim 1 already requires a spike-in DNA. The claims are identical in scope. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
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.
Claim(s) 1, 4, 16, 37 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bui et al. (Plant Methods, Vol. 5, No. 1, January 2009).
Bui teaches two double stranded DNA fragments that comprise a mutation and a mismatch. Bui teaches there may be a mismatch at the penultimate position and the SNP position.
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With respect to Claim 4, the mutation and the X2 base are 1bp between the positions.
With respect to Claim 16, the claim only recites an intended use. The DNA may be used for this purpose.
Response to Arguments
The response traverses the rejection. The response asserts Bui discloses primers for distinguishing Arabidopsis SNPs which is not mutations associated with disease outcome, diagnosis and/or treatment. This argument has been considered but is not convincing because Bui teaches SNPs are the most abundant form of DNA polymorphisms and serve as the most valuable molecular marker for research and application including detection of risk associated alleles and crop breeding. The SNPs are indispensable for genotyping progeny of genetic crosses, discriminating between mutant alleles from wild type alleles (page 2, col 1). Thus, Bui teaches the SAP method may be used for mutations associated with disease occurrence or diagnosis.
The response further argues Bui does not disclose the spike-in DNA mixture of DNA fragment 1 and 2. The recitation “spike-in reference DNA” is a statement of intended use. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Thus for the reasons above and those already of record, the rejection is maintained.
Claim(s) 1, 4, 10, 16, 37-38 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guo et al. (US 5,780,233, July 14, 1998).
Guo teaches a DNA fragment that comprising an artificial altered base X2 and differs from the DNA fragment 1 only in that it does not comprise the defined base X1 mutation. Gup teaches a DNA fragment with two artificial mismatches and one true mismatch.
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Response to Arguments
The response traverses the rejection. The response asserts Guo relates to a method for hybridizing an oligonucleotide probe to target to distinguish a first control target nucleic acid from a second variant nucleic acid target that differs from the control target. This argument has been reviewed. Guo teaches detecting sequence variations in DNA including investigating point mutations in the B-globin gene.
The response argues Guo does not disclose the spike-in DNA mixture of DNA fragment 1 and 2. The recitation “spike-in reference DNA” is a statement of intended use. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Thus for the reasons above and those already of record, the rejection is maintained.
Newly amended Claim(s) 1, 4, 16, 18, 19, 37-38, 42 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ristow et al. (New England J. of Medicine, Vol. 339, No. 14, pages 953-959, October 1998).
Ristow teaches sequence analysis of a cloned DNA fragment from an obese subject with a mutation in the peroxisome-Proliferator-Activated Receptor Y2 gene. Figure 2 illustrates the different sequences. Ristow teaches a PCR primer was constructed by changing a nucleotide 3 bp upstream of the putative mutation to introduce a new restriction site which, when coupled with the mutation, generated a site for restriction enzyme HindII when the mutant allele was present.
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Ristow teaches cloning and sequencing found a heterozygous mutation at nucleotide 344, Pro115Gln, associated with obesity and type 2 diabetes. Ristow teaches an artificial mutation of serine at position 114 was introduced and evaluated for phosphorylation. The sequences were added to a construct and used for retrovirus-mediated, stable transfection of NIH 3T3 fibroblasts.
Claim Rejections - 35 USC § 103
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.
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 1, 4, 13-16, 37-38, 42 are rejected under 35 U.S.C. 103 as being unpatentable over Xiang et al. (Oncology Letters, Vol. 10, pages 1293-1296, 2015) in view of Newton (Nucleic Acids Research, Vol. 17, No. 7, pages 1989).
Xiang teaches two double stranded nucleic acid sequences, one with the mutant base X1 and one with the normal base X1. Xiang teaches performing ARMS analysis of the L858R EGFR mutation associated with lung cancer. ARMS method relies upon two primers with the different mutant and normal alleles. Figure 3 illustrates EGFR mutations were identified using the ARMS method over many cycles and generated several double stranded molecules.
Xiang does not teach adding an artificial altered base X2 into the ARMS primer.
However, Newton teaches point mutations in DNA may be analyzed using amplification refractory mutation system (ARMS). Newton teaches introducing additional deliberate mismatches near the 3’ end of appropriate primers ameliorates the problem of no amplification is allowed to proceed. Newton illustrates introducing artificial altered bases 7, 5 and 3 nucleotides from the 3’ end to destabilize and deliberately introduce the mismatch. These primers demonstrated increased specificity (page 2511-2512).
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention to have deliberately introduced a mismatch 3, 5 or 7 bases from the 3’ end of the ARMS primers of Xiang to destabilize the primers and increase specificity, as taught by Newton. The ordinary artisan would have modified the ARMS primers for EGFR taught by Xiang that are designed to include a mutant or normal X1 base and include an artificial altered base X2 for the explicit reasons provided by Newton.
Response to Arguments
The response traverses the rejection. The response argues Xiang nor Newton disclose the spike-in DNA mixture of DNA fragment 1 and 2. The recitation “spike-in reference DNA” is a statement of intended use. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Thus, for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable over the art.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Lin et al. (J. of Molecular Diagnostics, Vol. 20, No. 3, May 2018) teaches generating quality control materials for clinical molecular genet testing using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated endonuclease Cas9. The CRISPR/Cas9 system was used to generate genome-engineered cell lines harboring target mutations. Lin further teaches artificial mutations were confirmed by both Sanger sequencing and amplification refractory mutation system (abstract).
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Figure 1 illustrates the EGFR L858R mutation. Supplemental Table S1 illustrates introduced variants. EGFR-3SNP donor illustrates 3 introduced variants. Lin teaches the DNA was placed in cells by cell culture and transfection.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng (Winston) Shen can be reached on (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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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
January 28, 2026