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 claims dated 11/14/2025 are under consideration.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-10, in the reply filed on 11/14/2025 is acknowledged. The traversal is on the ground(s) that it would not be unduly burdensome to perform a search on all the claims in the present application. This is not found persuasive because a burden does exist regarding the search and consideration of all the claims. A burden exists because:
(a) the inventions have acquired a separate status in the art in view of their different classification;
(b) the inventions have acquired a separate status in the art due to their recognized divergent subject matter;
(c) the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries);
(d) the prior art applicable to one invention would not likely be applicable to another invention; and/or
(e) the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
The requirement is still deemed proper and is therefore made FINAL.
Priority
The present application claims priority to US provisional application 63/329,786 (filed 4/11/2022).
Priority is recognized.
Information Disclosure Statement
The listing of references in the specification of 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, they have not been considered.
Specification
The disclosure is objected to because of the following informalities: the specification on p. 3 in line 25 recites “sample as” rather than “sample as”.
Appropriate correction is required.
The disclosure is objected to because of the following informalities: the specification uses the term “Trychophyton” and “Trichophyton” in reference to the same element. It is suggested a single term consistently be used.
Appropriate correction is required.
The use of terms that are trade names or marks used in commerce, such as Jublia®, Kerydin®, Joe™ and Cy5™, 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. While some of the trade names/marks include a proper symbol, not all of them do.
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 Objections
Claim 10 is objected to because of the following informalities: the claim recites “Trychophyton” rather than “Trichophyton”. Appropriate correction is required.
Claim Interpretation
Claim 4 includes an element that is optionally included as part of the method. Claim scope is not limited by claim language that makes optional but does not require steps to be performed. 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 3, 4, 6 and 7 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 3, the claims recites “the reaction mixture” in line 1 of part “ii”. The recitation lacks proper antecedent basis as the claim fails to previously set forth or describe “a reaction mixture”. Amending the claim to depend from claim 2 may aid in overcoming this rejection.
Regarding claim 4, the claims recites “the reaction mixture” in line 1 of part “ii”. The recitation lacks proper antecedent basis as the claim fails to previously set forth or describe “a reaction mixture”. Amending the claim to depend from claim 2 may aid in overcoming this rejection.
Regarding claim 6, it is unclear based on the use of the passive voice if the claim requires an active method step of “obtaining the sample from a human”.
Regarding claim 7, it is unclear based on the use of the passive voice if the claim requires an active method step of “obtaining the sample from a human”.
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) 1, 2, 5, 6 and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rajagopal (WO 2020/051521 A1) and Whitcombe (Clinical Chemistry. 1998. 44(5):918-923).
Regarding claim 1, Rajagopal teaches a method involving the hybridizing of a “tailed primer”, e.g., an allele specific primer with a universal tail (Fig. 1) or target specific primer with universal binding motifs (Fig. 5), to a sample comprising genomic locus having wild-type copies and mutant copies with a “point mutation” (Fig. 1).
The “tailed primer” includes a target complementary sequence that is fully complementary to the target site of the mutant and a 5’ tail that is not complementary to the genomic locus (Fig. 1 and 5).
Rajagopal teaches extending the “tailed primer” using the genomic locus as a template (Fig. 1 and 5).
Rajagopal teaches detecting the “extension product” using qPCR that includes:
a “forward primer” that hybridizes with a complement of the 5’ tail of the “tailed primer” (Fig. 5b);
a “reverse primer” that hybridizes with the “opposite strand” in the form of the “extension product” that is downstream of the site to which the “tailed primer bound” (Fig. 5a); and
a “hydrolysis probe” that hybridizes with the target complementary sequence of the “tailed primer” and to the 5’ tail (Fig. 5b). See also, paras. 9 and 24, 62, 107; and Fig. 1C.
Rajagopal teaches the probes have lengths of 20, 30, 40 or 50 nucleotides (para. 103). Rajagopal further teaches 50% of the probe is complementary to a target nucleic acid (para. 105). In embodiments in which the probe hybridizes to the target complementary sequence of the “tailed primer” and to the 5’ tail, as noted above, and has a length of 20, 30, 40 or 50 nucleotides, the probe would have 10, 15, 20 or 25 bases that are complementary to the target nucleic acid and 10, 15, 20 or 25 nucleotides that are complementary to the 5’ tail, respectively.
Rajagopal does not specifically teach the target complementary sequences includes a 3’ terminal nucleotide that base pairs with a point mutation.
However, Whitcombe teaches an assay that is analogous to that of Rajagopal in Fig. 1.
Whitcombe teaches the nucleotide at the 3’ terminus of a “tailed primer” is specific for a mutation (Table 1, BRCA2 variant primers).
It would have been prima facie obvious to the ordinary artisan at the time of filing that the nucleotide complementary to the mutation to be detected in the method of Rajagopal may be placed at the 3’ terminus of the tailed primer based on the teachings of Whitcombe. One would be motivated to use the positioning of Whitcombe because Rajagopal is silent regarding the placement of the nucleotide complementary to the mutated nucleotide. The modification has a reasonable expectation of success as Whitcombe demonstrates that such positioning is known and applicable in a method that is substantially similar to that of Rajagopal.
Regarding claim 2, Rajagopal teaches combining the above noted primers and probes with a polymerase and nucleotides in a reaction vessel and thermocycling it without opening the reaction vessel or adding additional reagents as all required elements for extension, amplification and detection are provided from the start. See paras. 75, 76-79, 85-122.
Regarding claim 5, Rajagopal teaches primers and probes may be of various lengths encompassed by the length limitations of claim 5. The ordinary artisan would have been able to design primers encompassed by the present claim. For example, the use of primers and probes with a length of 25 bases is suggested by Rajagopal (para. 90, 92, 93 and 103).
Regarding claim 6, Rajagopal is silent regarding the source of the sample other than it is from a subject.
Whitcombe teaches that samples from human subjects were known. It would have been prima facie obvious to the ordinary artisan that samples from human may be used in the method of Rajagopal.
Regarding claim 7, Rajagopal is silent regarding the source of the sample other than it is from a subject.
Whitcombe teaches that samples from human subjects were known. It would have been prima facie obvious to the ordinary artisan that samples from human may be used in the method of Rajagopal.
Rajagopal further teaches the target nucleic acid is from a pathogen (para. 80 and 81).
Claim(s) 8, 9, 10 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rajagopal (WO 2020/051521 A1) and Whitcombe (Clinical Chemistry. 1998. 44(5):918-923) as applied to claims 1 and 7 above and in further view of Rudramurthy (Antimicrobial Agents and Chemotherapy. 2018. 62(5):e02522-17).
Regarding claims 8, 9, 10 and 16, the combination of Rajagopal and Whitcombe renders obvious the elements of claims 1 and 7 as described above and as required by claims 8, 9, 10 and 16.
The combination does not specifically render obvious the additional elements specific to claims 8, 9, 10 and 16.
However, Rudramurthy teaches variants that occur in squalene epoxidase gene of Trichophyton associated with terbinafine were known.
Regarding claim 8, Rudramurthy teaches mutations in the squalene epoxidase gene at positions T1189C (F397L) and L393F were known and associated with antibiotic resistance (p. 2 and 6 of 9).
Regarding claim 9, Rudramurthy teaches the pathogen is the fungus Trichophyton contained within a human sample (p. 7 of 9).
Regarding claim 10, Rudramurthy teaches samples with various MIC (Fig. 2). The lower the MIC the ratio of wild-type to mutant skews to the wild-type copies and the higher the MIC the ratio of wild-type to mutant skews to the mutant copies. Thus, the samples of Rudramurthy render obvious the ratio of claim 10.
Regarding claim 16, Rudramurthy teaches mutations in the squalene epoxidase gene at positions T1189C (F397L) and L393F were known and associated with antibiotic resistance (p. 2 and 6 of 9).
It would have been prima facie obvious to the ordinary artisan at the time of invention to have modified the method of Rajagopal in order to detect the known mutations characterized by Rudramurthy. The modification would involve designing primer and probes that recognize the F397L and L393F mutations in the squalene epoxidase gene. The primers as modified by Whitcombe would have 3’ termini that recognize the mutated base resulting in the F397L and L393F mutations rendering obvious the tailed primers of claim 16 having a sequence that is identical to the 3’ end of SEQ ID NO: 5 or 7. The modification has a reasonable expectation as it involves designing known primers to recognize known sequences according to conventional design practices.
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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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682
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