DETAILED ACTION
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 .
The claim set dated 9/13/2023 is under consideration.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-6, 9, 10, 12, 14, 15, 17, 19, 20, 24, 26, 28, 30, 32, 33 and 35) in the reply filed on 12/16/2025 is acknowledged.
Claim 37 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 12/16/2025.
Applicant’s election without traverse of the species: A) a viral nucleic acid; B) n/a; and C) calibrator probe - SEQ ID NO: 1 and indicator probe - SEQ ID NO: 2, in the reply filed on 12/16/2025 is acknowledged.
SEQ ID NOs: 1 and 2 are specific for RRDR. For species A, applicant had an opportunity to elect bacterial amplified nucleic acids, in particular RRDR (claim 10), but elected viral nucleic acids, which do not read on the use of SEQ ID NO: 1 and SEQ ID NO: 2. Thus, in view of the election of a viral nucleic acid, the election of SEQ ID NO: 1 and 2 is not applicable, similar to species “B” being “n/a”.
Claims 10, 12, 24, 26 and 28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/16/2025. The election of a “viral nucleic acid” does not encompass the alternatives of claims 10 and 12. The election of a “viral nucleic acid” does not read on the use SEQ ID NOs: 1 and 2, which target bacterial nucleic acid sequences as encompassed by claims 24, 26 and 28.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout 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 or cited on any submitted IDS, they have not been considered.
Drawings
High resolution copies of the drawings may be accessed via PAIR/Patent Center Retrieval using the Supplemental Content tab.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
#1 – Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). In Tables 1 and 2, nucleotide sequences are disclosed that are not identified with their assigned SEQ ID NOs.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The use of terms, such as Cy™ and TexasRed®, which are trade names or marks used in commerce, 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.
Claim Interpretation
The claim set includes “optional” limitations. Claim scope is not limited by claim language that makes optional but does not require particular elements. MPEP 2111.04.
Claim Rejections - 35 USC § 112
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.
Claims 1, 2, 3, 4, 5, 6, 9, 14, 15, 17, 19, 20, 30, 32, 33 and 35 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.
Regarding claim 1, the term “sufficiently” is a relative term which renders the claim indefinite. The term “sufficiently” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear if a probe comprising a sequence that is 95% complementary to a sequence of the amplified target nucleic acid is encompassed by the claim but not one that is 90% complementary to the sequence of the amplified target nucleic acid. Alternatively, it is unclear if a probe comprising a sequence that is 90% complementary to a sequence of the amplified target nucleic acid is encompassed by the claim but not one that is 85% complementary to the sequence of the amplified target nucleic acid.
Furthermore, based on one set of conditions used in the incubating step, an indicator probe may be “sufficiently” complementary to a sequence of an amplified target nucleic acid for hybridization to occur, but under a different set of conditions used in the incubating step, the same indicator probe may not be “sufficiently” complementary to the sequence of the amplified target nucleic acid for hybridization to occur. Thus, the same probe is and is not encompassed by those of claimed method. It is noted the conditions broadly encompassed by the “incubating” step are sufficient for hybridizing of calibrator probe to the amplified target nucleic acid, but may or not be sufficient for the hybridization of the indicator probe.
Claims 2, 3, 4, 5, 6, 9, 14, 15, 17, 19, 20, 30, 32, 33 and 35 depend from claim 1 and are rejected for the same reason.
Regarding claim 1, the claim recites “a score value determined from the signal from the first detectable label and the signal from the second detectable label”. Based on the use of the passive voice, it is unclear if the claim requires an active method step of “determining a score value from the signal from the first detectable label and the signal from the second detectable label”.
Alternatively, the reference to a “score value determined” lacks proper antecedent basis as no active method step is set forward that results in “determining a score value”.
Claims 2, 3, 4, 5, 6, 9, 10, 14, 15, 17, 19, 20, 30, 32, 33 and 35 depend from claim 1 and are rejected for the same reason.
Regarding claim 2, it is unclear if the claim requires an active method step of “determining a score value comprising a Z-score”, which is set forth in the claim.
Regarding claim 5, the phrase “e.g.”, which is equivalent to "for example", renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 32, the claim states “one or more additional primers”. It is unclear if the claim implicitly requires both “a primer” and at least one more “additional primer”.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, 4, 6, 9, 14, 15, 17, 19, 20, 30, 32, 33, and 35 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Andre (US 2021/0189486 A1).
Regarding claims 1 and 4, Andre teaches “incubating” in a partition a plurality of probe sets corresponding to a plurality of target regions (para. 7), wherein each probe set of the plurality of probe sets comprises (para. 8):
a drop-off probe as an “indicator probe” comprising a drop-off label or “second detectable label” and an oligonucleotide drop-off sequence or “third nucleic acid sequence” that is complementary to a wildtype sequence or “fourth nucleic acid sequence” at a target region corresponding to the respective probe set (para. 9); and
a reference probe as an “calibrator probe” comprising a reference label or “first detectable label” and an oligonucleotide reference sequence or “first nucleic acid sequence” complementary to a wildtype sequence or “second nucleic acid sequence” at an adjacent reference region upstream or downstream to the target region corresponding to the respective probe set (para. 10).
The partition further includes an amplicon as an “amplified target nucleic acid” (para. 11).
Andre further teaches the reference label and a drop-off label of each probe set of the plurality of probe sets are detectable via different detection channels (para. 11).
The incubation is under conditions for hybridization to occur because Andre detects the hybridization (para. 11).
Andre teaches detecting the labels of the probes (para. 11).
Andre teaches “determining the absence or the presence of the mutation” by using the detected signals in the plurality of partitions from the hybridization of reference probes to amplicons comprising wildtype sequences at the reference regions and using detected signals from the hybridization of drop-off probes of the plurality of probe sets to amplicons comprising wildtype sequences at the target regions.
Andre teaches expected “score values” or “predetermined threshold values”: 1) detection of a signal from a reference label and a signal from a drop-off label in a probe set indicates a wildtype sequence at the target region corresponding to the probe set; and 2) detection of a signal from a reference label but no signal from a drop-off label in a probe set indicates a mutant sequence at the target region corresponding to the probe set. See para. 11. Thus, deviation from these “score values” indicates the absence of a mutation or the presence of the mutation.
Regarding claim 3, as noted above, Andre teaches expected “score values”: 1) detection of a signal from a reference label and a signal from a drop-off label in a probe set indicates a wildtype sequence at the target region corresponding to the probe set; and 2) detection of a signal from a reference label but no signal from a drop-off label in a probe set indicates a mutant sequence at the target region corresponding to the probe set. See para. 11. These “scores” are based on the “absolute value” of signals from two probes when binding to “negative control samples” without the mutation and “positive control samples” with the mutation.
Regarding claim 6, Andre teaches the mutations may be insertion, deletions or single mutations (para. 113, 618).
Regarding claim 9, Andre teaches the nucleic acid target are derived from viruses (para. 226).
Regarding claim 14, Andre teaches the probes have a length of 30-40 nucleotides (para. 178).
Regarding claim 15 and 17, Andre teaches probes may include modified nucleotides, including LNA (para. 178).
Regarding claim 19, Andre teaches the probe labels are fluorescent labels (para. 185).
Regarding claims 20 and 30, Andre teaches the probes are molecular beacons, each having a quencher and a fluorophore (para. 176).
Regarding claim 32, Andre teaches the partition includes “additional” primers and a DNA polymerase (para. 33-35).
Regarding claim 33, Andre teaches amplifying the target nucleic acid using isothermal techniques (para. 117).
Regarding claim 35, Andre teaches real-time detection of probe signals (para. 205) or at an end point (para. 184).
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
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.
Claim(s) 2 and 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Andre (US 2021/0189486 A1) in view of Evans (US 2022/0088003 A1).
Regarding claims 2 and 5, Andre teaches “incubating” in a partition a plurality of probe sets corresponding to a plurality of target regions (para. 7), wherein each probe set of the plurality of probe sets comprises (para. 8):
a drop-off probe as an “indicator probe” comprising a drop-off label or “second detectable label” and an oligonucleotide drop-off sequence or “third nucleic acid sequence” that is complementary to a wildtype sequence or “fourth nucleic acid sequence” at a target region corresponding to the respective probe set (para. 9); and
a reference probe as an “calibrator probe” comprising a reference label or “first detectable label” and an oligonucleotide reference sequence or “first nucleic acid sequence” complementary to a wildtype sequence or “second nucleic acid sequence” at an adjacent reference region upstream or downstream to the target region corresponding to the respective probe set (para. 10).
The partition further includes an amplicon as an “amplified target nucleic acid” (para. 11).
Andre further teaches the reference label and a drop-off label of each probe set of the plurality of probe sets are detectable via different detection channels (para. 11).
The incubation is under conditions for hybridization to occur because Andre detects the hybridization (para. 11).
Andre teaches detecting the labels of the probes (para. 11).
Andre teaches “determining the absence or the presence of the mutation” by using the detected signals in the plurality of partitions from the hybridization of reference probes to amplicons comprising wildtype sequences at the reference regions and using detected signals from the hybridization of drop-off probes of the plurality of probe sets to amplicons comprising wildtype sequences at the target regions.
Andre teaches expected “score values” or “predetermined threshold values”: 1) detection of a signal from a reference label and a signal from a drop-off label in a probe set indicates a wildtype sequence at the target region corresponding to the probe set; and 2) detection of a signal from a reference label but no signal from a drop-off label in a probe set indicates a mutant sequence at the target region corresponding to the probe set. See para. 11. Thus, deviation from these “score values” indicates the absence of a mutation or the presence of the mutation.
Andre does not teach the additional elements specific to claims 2 and 5.
However, Evans teaches that z-scores were known and they are calculated using the equation in Table 2 and comparing them to a threshold Table 3.
It would have been prima facie obvious to the ordinary artisan at the time of filing to have modified the method of Andre by using the Z-score and the comparison to determine whether not the mutation is present. The modification has a reasonable expectation of success as it merely requires swapping data analysis methods in order to reach a conclusion about a sample.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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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 at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682