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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on July 7, 2026 is acknowledged. The traversal is on the grounds that the referenced art in the Restriction mailed on April 8, 2026 does not anticipate or render obvious the claimed invention. This argument has been considered, but is deemed moot in view of the below obviousness rejection.
The requirement is still deemed proper and is therefore made FINAL.
Claims 9-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on July 7, 2026.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The IDS received on January 29, 2024 is proper and is being considered by the Examiner.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because the drawings filed on January 29, 2024 are poor in quality and the texts therein are not clearly legible. For example, see Figure 2 and Figure 3, and the x-/y- axis descriptions and values. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
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The Office also notes that Figure 5 does not match its description found on pages 46-48. On page 48 of the specification, the three reactions which are depicted by the figure should contain: 1) 104 B subtilis; 2) 102 E. coli; and 3) 104 B. subtilis and 102 E. coli) (see below):
Figure 5, however, though unclear, appears to disclose that the third reaction contains 106 B. subtilis and 103 E. coli, which is erroneous.
Correction is required.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 2, line 28, for example). Applicant is required to peruse the specification and delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The specification is further objected to for failing to comply with the Sequence Rules. On page 36, Table 1 contains a plurality of nucleotide sequences which are not identified by their respective SEQ ID Numbers. The Table 1 contains what appears to be termed, “Id”. If this is referencing to SEQ ID Numbers, amendment is suggested to this effect.
In addition, page 44 discloses nucleotide sequences of primers (see lines 27-30), which are not accompanied by their respective SEQ ID Numbers.
Applicants’ must peruse the specification amend all such references to nucleotide sequences with their respective SEQ ID Numbers as necessary.
Failure to comply will result in Applicants’ Amendment being deemed non-responsive.
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 1-8 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.
Claim 1 is indefinite for reciting the phrase, “given thermal cycle of a reaction mixture comprising one or more probes”. This is because the claim recites that the thermal cycler is configured for utilizing “at least two fluorescence probes”. Therefore, it is confusing whether the subject-phrase is referring to these at least two fluorescence probes, or one of more probes (which need not be fluorescence bearing) entirely different. For the purpose of prosecution, the former interpretation is assumed.
Claim 1 also recites the phrase, “the presence of one of more nucleic acid sequences”. There is an insufficient antecedent basis for this limitation in the claim.
Claim 1 is also indefinite for reciting the phrase, “at least two measurements carried out during at least some of the thermal cycles” because it is unclear whether the two measurements are carried out in at least each cycle of the of the thermal cycles, that is, at least two measurements occur at a single cycle and this occurrence occurs some of the many cycles; or at least two measurements are carried out in some of the thermal cycles, which typically occurs in any thermal cycles as measurements are typically made once a cycle, and therefore, more than one measurement is made in some of the cycles. The former interpretation is made.
Claim 2recites trademarked reagents, such as QUASR and QZyme. The usage of trademark in a claim renders the claim indefinite as the product identified solely by its trademarked name does not define the product but the source of the product, where the product may change over time while retaining the same tradename, such as Coke®.
Claim 2 is also indefinite for using an improper transitional language (i.e., comprising) to define a Markush group of elements. MPEP 2173.05(h) clearly discusses that a Markush Group, “is a closed group of alternatives, i.e., the selection is made from a group ‘consisting of’ (rather than ‘comprising’ or ‘including’) the alternative members.”
Claims 3 and 4 are indefinite because the claims define the attributes of reagents which are not actively required in the claims. This is because claims 3 and 4 depend from claim 1, and claim 1 recites that the device comprises a thermal cycler configured to perform a series of thermal cycles within an in vitro nucleic acid amplification reagent containing at least two fluorescence probes. The thermal cycler having a simple reaction chamber is configured to perform the reaction with any reagents therein and therefore, claims 3 and 4 do not further limit the device structurally, or if they do, it is unclear just exactly what such limitations are.
Claims 2-8 are indefinite by way of their dependency on claim 1.
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.
Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Chakravorty et al. (Journal of Clinical Microbiology, 2017, vol. 55, issue 1, pages 183-198; IDS ref) in view of Carrick et al. (US 2007/0111246 A1, published May 17, 2007).
A product is solely defined by the physical elements actively required by the claims. Their intended usages are not given patentable weight, absent said intended usages necessary confer a physical limitation.
As discussed above, present claims do not actively require the presence of any amplification reagents which includes inter alia, at least two fluorescence probes combining a quencher and a fluorophore that specifically target a distinct nucleic acid sequence that emit overlapping fluorescent wavelengths.
Regarding claim 1, Chakravorty et al. teach a method of performing a multiplex-PCR (“10-color, eightplex PCR”, page 185, 1st paragraph), which involves a thermal cycler (as the assay is multiplex PCR), a light sensor (“same excitation light-emitting diodes, filters, and detectors contained in a GeneXpert MTB/RIF instrument”, page 187, 1st column), and an analyzer that quantifies the amount of target nucleic acids being assayed (“our assay would be able to correctly determine the drug resistance of genotype of even small quantities of M. tuberculosis against a large NTM background”, page 190, bottom paragraph).
Chakravorty et al. teach the usage of a large Stokes shift dyes that excite at different wavelengths, but emit at the same wavelength (thus overlapping):
“We have leveraged new large-Stokes-shift fluorophores …” (page 193)
“We sought to further increase the multiplexing by developing what we have termed off-axis fluorophores that produce a larger Stokes shift … These proprietary off-axis fluorophores have excitation spectra similar to of on-axis fluorphores, but their unique combination of excitation and emission spectra enabled us to assign each one to a distinct channel that distinguished them from on-axis fluorophores. Large Stokes-shift fluorophores CF7 (which excites blue and emits yellow), CF8 (which excites green and emits orange), CF9 (which excites blue and emits orange), and CF10 (which excites green and emits IR) … were created” (page 185, 2nd paragraph)
Chakravorty et al. also teach that the light sensor is configured to measure radiation emitted by fluorophores in fluorescence wavelength range (as evidenced above, measurement of the each fluorophore necessarily requires that more than one measurement is made per cycle).
With regard to claims 2 and 3, while the claims do not actively require the presence of the reagents, Chakravorty et al. employs molecular beacons (see above, also “[w]e also developed … quenching molecules with sufficient spectral overlap to efficiently quench all of the new fluorophores, allowing us to incorporate … into molecular beacon probes”, page 185).
With regard to claim 4, the reagents are not actively required.
Although Chakravorty et al. teach that their analyzer is configured to determine, for each respective fluorescence probe1, a value representative of a concentration in modified state (when signal is produced from SMB), the artisans are silent in that the analyzer determines this value based on the fluorescence measured as a function of time (claim 1, in-part).
Chakravorty et al. do not teach the usage of a matrix system (claim 5), that solves one matrix system per group of fluorescence probes (claim 6), using a minimization algorithm (claim 7), or applying gradient decent or neural network (claim 8).
Carrick et al. teach a method of performing a real-time PCR amplification reaction wherein the artisans teach the evaluation of a graph which measures the fluorescence against time (“preferred embodiments, software or machine-executable instructions for performing an algorithm can be loaded or otherwise held in a memory component of a freestanding computer, or in a memory component of a computer linked to a device used for monitoring, preferably as a function of time, the amount of product undergoing analysis … monitoring the amount of amplicon present in a reaction mixture as a function of time.”, section [0093]; also “software that correlates a feature of a growth curve representing the quantity of amplified copies of the nucleic acid of interest as a function of time, as detected by the detector, to the number of copies of nucleic acid of interest present in a test sample”, section [0095]).
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 combine the teachings of Chakravorty et al. with the teachings of Carrick et al. and knowledge available in the art, thereby arriving at the invention as claimed.
As discussed above, Chakravorty et al. already teach a method of performing and quantifying multiple targets in a PCR reaction utilizing dyes that have an overlapping emission spectra. While Chakravorty et al. did not explicitly teach that their analyzer arrived at a value (or amount of target present in the sample) based on measured fluorescence as a function of time, Carrick et al. teach that quantification of target nucleic acids in an amplification reaction is derived from data produced from measured fluorescence against time (see above).
In addition, Carrick et al. explicitly teach the usage of computer software which is routinely applied for calculating and arriving at the quantification value.
Therefore, one ordinary skill in the art would have been motivated to combine the teachings of Chakravorty et al. with the teachings of Carrick et al. to utilize an alternatively known means of calculating the amount of target nucleic acids in a sample based on fluorescence vs. time, as doing so would have yielded the same predictable outcome (as evidenced by Carrick et al.), utilizing generally known means of computerized algorithms as suggested by Carrick et al., widely encompassing matrix systems, or neural network, or minimization algorithm, as also recited generically in the claims.
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YOUNG J KIM/Primary Examiner
Art Unit 1637 September 21, 2026
/YJK/
1 Although the claims do not explicitly require the presence of any amplification reagents, such as probes, the method fluorescence produced in Chakravorty et al.’s method involves probes (SMB, Sloppy Molecular Beacon).
Prosecution Insights