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 .
Status of Claims
Cancelled: 3, 15, 16, 19, 26
Examined Herein: 1, 2, 4-14, 17, 18, 20-25, 27
Priority
Priority to PRO 63/025,852 filed on 5/15/2020 is acknowledged.
Drawings
The drawings filed on 5/14/2021, 6/1/2021, and 6/26/2021 are accepted.
Withdrawn Rejections
The rejection of claims 11, 21, and 27 rejected under 35 U.S.C. 112(b) and 35 U.S.C. 112(d) is hereby withdrawn in view of Applicant’s amendments to claim 11, 21, and 27, which replaces the phrase “the fluorophore comprises” with “the fluorophore is,” thereby rendering the rejection moot. [Reply 11/14/2025, Page 8]
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.
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.
Claims 1, 2, 4-6, 8-14, 18, 20, 22-25, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Mukherjee (Detection of oxidative stress-induced carbonylation in live mammalian cells, 3/20/2015, Free Radical Biology and Medicine, 84:11-21), in view of Schill (4-Trifluoromethyl-Substituted Coumarins with Large Stokes Shifts: Synthesis, Bioconjugates, and Their Use in Super-Resolution Fluorescence Microscopy, 11/7/2013, Chemistry-A European Journal, Volume 19, Issue 49).
With respect to claim 1, Mukherjee discloses a method of detecting carbonylated biomolecules in a sample comprising carbonylated polypeptides (proteins), lipids, or nucleic acids (DNA) in living cells, comprising;
Incubating the living A549 cells with a fluorophore, 7-hydrazinyl-4-methyl-coumarin,
reacting the fluorophore with the carbonylated biomolecule of the sample to couple the fluorophore to the biomolecules through a hydrazone linkage;
Illuminating the conjugated fluorophore with a diode 405 nm laser;
and detecting the fluorophore by imaging illumination of the fluorophore reacted with the carbonylated biomolecule via a fluorimeter or confocal microscopy. [Page 12, Col. 1, Paragraph 3-5 and Page 12, Col. 2, Paragraph 7 and Page 13, Col. 1, Paragraph 2-6 and Page 13, Col. 2, Paragraph 2-4 and Page 18, Figure 6]
With respect to claim 5, Mukherjee discloses the fluorophore has a fluorescent emission peak which shifts as a result of the hydrazone linkage and the carbonylated biomolecules are within living cells. [Page 14, Col. 1, Paragraph 4 and Page 14, Col. 2, Paragraph 1-3 and Page 15, Figure 2]
With respect to claim 27, Mukherjee discloses the fluorophore is 7-hydrazinyl-4-methyl-coumarin. [Page 12, Col. 1, Paragraph 3 & 5 and Page 18, Figure 6]
With respect to claim 8, Mukherjee discloses a method of detecting carbonylated biomolecules in a sample comprising living cells, comprising;
Incubating the sample, which comprises living A549 cells and the carbonylated biomolecules, with a fluorophore, 7-hydrazinyl-4-methyl-coumarin, conjugated to the carbonylated biomolecules through a hydrazone linkage;
Illuminating the conjugated fluorophore with a diode 405 nm laser;
and detecting the conjugated fluorophore by imaging fluorescent emissions via a fluorimeter or confocal microscopy, wherein the conjugated fluorophore has an emission spectrum peak shifted with respect to the fluorophore and is detected by fluorescent imaging of the shifted spectrum emission peak over an area comprising the cells. [Page 12, Col. 1, Paragraph 3 & 5 and Page 12, Col. 2, Paragraph 7 and Page 13, Col. 1, Paragraph 1-4 and Page 13, Col. 2, Paragraph 1-4 and Page 14, Col. 2, Paragraph 2-3 and Page 15, Figure 2 and Page 18, Figure 6]
With respect to claim 4, Mukherjee discloses the conjugated fluorophore comprises 7-hydrazinyl-4-methyl-coumarin hydrazone. [Page 12, Col. 1, Paragraph 3 & 5 and Page 18, Figure 6]
With respect to claim 6, Mukherjee discloses the fluorophore is conjugated to the carbonylated biomolecule through a hydrazone linkage. [Page 14, Col. 2, Paragraph 2-3, and Page 15, Figure 2]
With respect to claim 10, Mukherjee discloses the sample comprise living A549 cells and the method further comprises exposing the living cells to a drug, hydrogen peroxide, prior to said incubating. [Page 18, Figure 6] Additionally, Mukherjee discloses the carbonylated biomolecules result from reactive oxygen species caused by metabolism of the drug by the living cells. [Page 18, Col. 2, Paragraph 1] Furthermore, Mukherjee discloses detecting comprises quantifying free radical-induced oxidative damage to the living cells from the drug. [Page 18, Col. 2, Paragraph 1-2 – Page 19, Col. 1, Paragraph 1]
With respect to claim 11, Mukherjee discloses the fluorophore is 7-hydrazinyl-4-methyl-coumarin. [Page 12, Col. 1, Paragraph 3 & 5 and Page 18, Figure 6]
With respect to claim 12-13, Mukherjee discloses the conjugated fluorophore is illuminated at a first wavelength, 405 nm, and said detecting comprises detecting the fluorescent emissions at a second wavelength, 420 nm or 475 nm, concurrent with fluorescent imaging of a distinct fluorophore, resazurin, at a different wavelength, 570 nm, from the second wavelength. [Page 13, Col. 1, Paragraph 7 – Col. 2, Paragraph 1-2]
With respect to claim 14, Mukherjee discloses the sample comprises living A549 cells, and said incubating comprises providing a multi-well plate having a plurality of wells. Each well or subset, which contains living cells, are treated with a different drug treatment, CH or 0.5% PB. [Page 13, Col. 1, Paragraph 7 – Col. 2, Paragraph 1-2]
With respect to claim 18, Mukherjee discloses the detection of the conjugated fluorophore occurs about 30 minutes after the commencement of said incubating. [Page 18, Figure 6]
With respect to claim 20, Mukherjee discloses the detecting comprises imaging unwashed living A549 cells using confocal microscopy. [Page 18, Figure 6]
With respect to claim 22, Mukherjee discloses the fluorophore has a fluorescent emission peak which shifts as a result of the hydrazone linkage. [Page 14, Col. 1, Paragraph 4 - Col. 2, Paragraph 1-3, and Page 15, Figure 2]
With respect to claim 23, Mukherjee discloses the sample comprises fixed cells and the carbonylated biomolecules are detected by imaging within the fixed cells. [Page 12, Col. 1, Paragraph 2, Page 14, Col. 1, Paragraph 2, Page 20, Col. 2, Paragraph 2]
With respect to claim 24, Mukherjee discloses further comprising analyzing the detected fluorophore based on a level of carbonylation of biomolecules, to assess a toxic insult to the cells. [Page 16, Col. 2, Paragraph 4 and Page 18, Col. 1, Paragraph 1]
Mukherjee does not disclose the fluorophore, 7-hydrazinyl 4-methyl coumarin, comprises a trifluoro group, to form 7-hydrazinyl 4-trifluoromethyl coumarin.
However, with respect to claim 1, 2, 4, 8, 9, 11, 17, 25, and 27, Schill discloses a trifluoro (CF3) group, especially at the 4-position of coumarin fluorophores, increases photostability. Schill discloses the introduction of a strong electron acceptor, a perfluoroalkyl group, at C-4 provides a pronounced redshift of the absorption and fluorescence bands and, because the bathofluoric shift is expected to be larger, increase the Stokes shifts. Schill further discloses a trifluoromethyl group at the 4-position of coumarin reduces the bleaching coefficient of a dye by about 20% and increases the Stokes shift (compared with the 4-unsubstituted derivative). [Schill, Page 16558, Col. 1, Paragraph 2-3]
Modifying the method disclosed by Mukherjee by replacing the methyl group at the 4-position of the fluorophore 7-hydrazinyl 4-methyl coumarin, with a trifluoromethyl group to form 7-hydrazinyl 4-trifluoromethyl coumarin, results in the method of claim 1 and 8.
In which case, with respect to claim 11 and 27, Mukherjee and Schill discloses the fluorophore is 7-hydrazinyl 4-trifluoromethyl coumarin.
With respect to claim 2, Mukherjee and Schill discloses the fluorophore is 7-hydrazinyl 4-trifluoromethyl coumarin. 7-hydrazinyl 4-trifluoromethyl coumarin has a limit of detection in cell lysate of 89 nM.
With respect to claim 4, Mukherjee and Schill discloses the conjugated fluorophore is 7-hydrazinyl 4-trifluoromethyl coumarin hydrazone.
With respect to claim 9 and 25, Mukherjee and Schill discloses the fluorophore is 7-hydrazinyl 4-trifluoromethyl coumarin. 7-hydrazinyl 4-trifluoromethyl coumarin has a quantum yield of greater than 0.1 in 0.5% DMSO in phosphate buffered water at pH 7.0.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Mukherjee by replacing the methyl group at the 4-position of the fluorophore 7-hydrazinyl 4-methyl coumarin, with a trifluoromethyl group to form 7-hydrazinyl 4-trifluoromethyl coumarin and have a reasonable expectation of success. Mukherjee discloses a method comprising conjugating carbonylated biomolecules to a fluorophore, 7-hydrazinyl 4-methyl coumarin. Schill discloses coumarin fluorophores may be modified by introducing a trifluoro group the C-4 position. So, Mukherjee discloses a coumarin fluorophore and Schill discloses such a fluorophore may be modified by introducing a CF3 group at the C-4 position. Thus, the combined teachings of Mukherjee and Schill suggests the fluorophore, 7-hydrazinyl 4-methyl coumarin, disclosed by Mukherjee may be modified by introducing a CF3 group at the C-4 position. Therefore, it is reasonable to expect the method disclosed by Mukherjee may be modified by replacing the methyl group at the 4-position of the fluorophore 7-hydrazinyl 4-methyl coumarin, with a trifluoromethyl group to form 7-hydrazinyl 4-trifluoromethyl coumarin. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. In the instant case, Mukherjee discloses a coumarin fluorophore and Schill discloses a trifluoro (CF3) group, especially at the 4-position of coumarin fluorophores increases photostability, provides a pronounced redshift of the absorption and fluorescence bands, increases the Stokes shifts, and reduces the bleaching coefficient of a dye by about 20%. [Schill, Page 16558, Col. 1, Paragraph 2-3] Thus, one would be motivated by the expectation that replacing the methyl group at the 4-position of the fluorophore 7-hydrazinyl 4-methyl coumarin, with a trifluoromethyl group to form 7-hydrazinyl 4-trifluoromethyl coumarin could increase photostability, provide a pronounced redshift of the absorption and fluorescence bands, increase the Stokes shifts, and reduce the bleaching coefficient of a dye by about 20%.
Claims 1, 2, 4-14, 17, 18, 20-25, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Mukherjee and Schill, as applied to claim 1, 2, 4-6, 8-14, 18, 20, 22-25, and 27 above, and further in view of Weiss (US 2007/0020690 A1, Published 1/25/2007) and Bissell (Some 7-substituted-4-(trifluoromethyl)coumarins, 7/1/1981, Journal of Chemical & Engineering Data, Volume 26, Issue 3).
With respect to claim 1 and 8, Mukherjee and Schill disclose the teachings above.
Mukherjee and Wang do not disclose the fluorophore is 7-alkoxyamine 4-trifluoromethyl coumarin.
However, with respect to claim 1, 7, 8, 17, and 21, Weiss discloses fluorophores can contain reactive functionalities including hydrazine or alkoxyamine, which are suitable for coupling oxidized biomolecules such as serine or threonine. [Weiss, 0011]
Also, with respect to claim 1, 7, 8, 17, and 21, Bissell discloses the spectral properties of 7-substited 4-trifluoromethyl coumarins, wherein 7-hydroxy is substituted with 7-methoxy, 7-methyl, 7-amlno, 7-(ethylamino), 7-(benzylamino), 7-anllino, 7-(acetyl), 7-benzoyl, 7-bromoacetyl, and others. [Bissell, Abstract] Bissell discloses it is advantageous to be able to control optical properties such as ultraviolet absorption maxima or fluorescence excitation and emission maxima of 7-hydroxy and 7-amino coumarins by suitable alterations in their structures. [Bissell, Page 348, Col. 1, Paragraph 2]
Modifying the method disclosed by Mukherjee and Schill by substituting the 7-substituent of the fluorophore 7-hydrazinyl 4-trifluoromethyl coumarin with alkoxyamine to form 7-alkoxyamine 4-trifluoromethyl coumarin, results in the method of claim 1 and 8.
In which case, with respect to claim 17 and 21, Mukherjee, Schill, Weiss, and Bissell disclose the fluorophore is 7-alkoxyamine 4-trifluoromethyl coumarin.
With respect to claim 7, Mukherjee, Schill, Weiss, and Bissell disclose the fluorophore is 7-alkoxyamine 4-trifluoromethyl coumarin, which forms oximes linkages. Thus, the fluorophore is conjugated to the carbonylated biomolecule through an oxime linkage.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Mukherjee and Schill by substituting the 7-substituent of the fluorophore 7-hydrazinyl 4-trifluoromethyl coumarin with alkoxyamine to form 7-alkoxyamine 4-trifluoromethyl coumarin and have a reasonable expectation of success. Mukherjee and Schill disclose a method comprising conjugating carbonylated biomolecules to a fluorophore, 7-hydrazinyl 4-trifluoromethyl coumarin. Weiss discloses hydrazine and alkoxyamine are both reactive moieties contained by fluorophores and are suitable for coupling oxidized biomolecules such as serine or threonine. Furthermore, Bissell discloses altering the 7-substituent in the base structure of 7-substited 4-trifluoromethyl coumarins is advantageous to control optical properties such as ultraviolet absorption maxima or fluorescence excitation and emission maxima thereof. So, Mukherjee and Schill disclose a fluorophore, 7-hydrazinyl 4-trifluoromethyl coumarin, Weiss discloses with respect to such a fluorophore, alkoxyamine, like hydrazinyl, is a reactive moiety capable of coupling oxidized biomolecules, and Bissell discloses altering the 7-substituent in the base structure of 7-substited 4-trifluoromethyl coumarins is advantageous. Thus, the combined teachings of Mukherjee, Schill, Weiss, and Bissell suggests altering the 7-substituent in 7-hydrazinyl 4-trifluoromethyl coumarin, by substituting hydrazinyl for another reactive moiety, alkoxyamine, is a routine and advantageous modification. Therefore, it is reasonable to expect the method disclosed by Mukherjee and Schill by substituting the 7-substituent of the fluorophore 7-hydrazinyl 4-trifluoromethyl coumarin with alkoxyamine to form 7-alkoxyamine 4-trifluoromethyl coumarin. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. In the instant case, Mukherjee discloses a 7-substited 4-trifluoromethyl coumarin fluorophore and Bissell discloses altering the 7-substituent in the base structure of 7-substited 4-trifluoromethyl coumarins is advantageous to be able to control optical properties such as ultraviolet absorption maxima or fluorescence excitation and emission maxima thereof. [Bissell, Page 348, Col. 1, Paragraph 2] Thus, one would be motivated by the expectation that by substituting the 7-substituent of 7-hydrazinyl 4-trifluoromethyl coumarin, with alkoxyamine, to form 7-alkoxyamine 4-trifluoromethyl coumarin, the optical properties of the fluorophore may be controlled.
Response to Arguments
Applicant's arguments filed 11/14/2025 have been fully considered but they are not persuasive.
Applicant asserts “A POSITA would be well aware that modifications made to optimize photophysical properties (e.g., by adding a strong EWG like -CF3) can, and often do, have profound and detrimental effects on a molecule's chemical reactivity. The Examiner provides no reason why a POSITA, whose primary goal must be to preserve the essential nucleophilic reactivity of Mukherjee's probe, would be motivated to make a substitution taught only for optical benefits, especially when that substitution would be expected to destroy the probe's chemical function.” [Remarks 11/14/2025, Page 13-14]
Applicant’s arguments are not persuasive because the Examiner has provided a valid reason to combine the references of Mukherjee and Schill. Mukherjee discloses a method comprising employing a coumarin fluorophore and Schill discloses modifying a coumarin fluorophore by introducing a CF3 group at the C-4 position to improve photostability and fluorescence properties.
Moreover, Applicant has not provided evidence that the proposed modification would destroy the probe’s chemical function. Arguments presented by applicant cannot take the place of evidence in the record. Accordingly, Applicant’s assertion, in the absence of evidence, is merely speculative.
Applicant asserts “A POSITA, applying these principles, would have inevitably concluded that replacing Mukherjee's 4-CH3 (EDG) with Schill's 4-CF3 (EWG) would be detrimental for the probe's chemical function. The 4-CF3 group would enhance the "pull" of then-system, promoting the delocalization of the Nl lone pair and pulling its electron density away from the nitrogen. This deactivation is confirmed by quantitative data, which shows the pKa of the 7-amino group plummets to -0.10, rendering it "practically non-basic". A POSIT A would thus have concluded that the Nl nitrogen of the 4-CF3 derivative would be a very poor substrate, exhibiting attenuated reactivity and rendering it chemically inert and useless for Mukherjee's purpose of spontaneous carbonyl detection. This is not a lack of a reasonable expectation of success; it is a strong, scientifically-grounded teaching away from the Examiner's proposed combination.” [Remarks 11/14/2025, Page 14-15]
Applicant’s arguments are not persuasive because a reference teaches away when it criticizes, discredits, or otherwise discourages the solution claimed. Nothing in the prior art teaches that the N1 nitrogen of the 4-CF3 derivative would be a very poor substrate exhibiting attenuated reactivity. Moreover, nothing in the prior art teaches that the proposed modification would have resulted in an ‘inoperable’ probe as asserted by the Applicant. Applicant’s remarks constitute a theoretical discussion of potential effects of the 4-CF3-substituted probe. However, Applicant has not provided evidence demonstrating that the proposed modification would render the probe inoperable. Arguments presented by applicant cannot take the place of evidence in the record. Accordingly, Applicant’s assertion, in the absence of evidence, is merely speculative.
Applicant asserts “The Expected Result: An inert, non-reactive probe (i.e., "attenuated reactivity"). The Unexpected Result: The 4-CF3-substituted probe ("TFCH") is not only reactive, but is 10-fold more sensitive than Mukherjee's 4-methyl probe ("CH"). Mukherjee et al. The specification and supporting data show that TFCH can be used at a concentration of 2 μM, which is 1110th the concentration required for the CH-based assay. Furthermore, the hydrazone product ("TFCZ") has a Limit of Detection (LOD) of -89 nM, an order of magnitude lower than the prior art. This quantitative, 10-fold improvement in sensitivity is a classic and powerful demonstration of unexpected results. The 4-CF3 group, which was expected to reduce reactivity, surprisingly resulted in a probe with vastly superior sensitivity for its intended chemical reaction.” [Remarks 11/14/2025, Page 15-16]
Nothing in the prior art teaches that the N1 nitrogen of the 4-CF3 derivative would be a very poor substrate exhibiting attenuated reactivity or that the proposed modification would have resulted in an ‘inoperable’ probe as asserted by the Applicant. Accordingly, the Examiner questions whether, in the absence of such teachings, a POSITA would conclude “the expected result” to be an inert, non-reactive probe. Moreover, any observed improvement in detection sensitivity may reasonably be attributed to the improved photostability and optical properties taught by Schill. Nonetheless, the observed improvement in detection sensitivity is not unexpected. Wang discloses a -CF3 group is used to improve the sensitivity and operational ability of a 7-substiuent coumarin. [Page 211, Col. 2, Paragraph 1] Thus, the proposed modification would expectedly exhibit superior sensitivity. Therefore, Applicant has not demonstrated that the alleged unexpected results are actually greater than expected.
*Wang (Chromogenic and fluorescent ‘‘turn-on’’ chemodosimeter for fluoride based on F-sensitive self-immolative linker, 2016, Chinese Chemical Letters 27, 211-214).
Applicant asserts “A POSITA, having been taught away by the chemically-sound analysis of the Nl position, would have had no reason to investigate this alternative, more subtle mechanism. The discovery that the N2 nitrogen remains reactive and that the 4-CF3 group concurrently enhances optical properties without destroying this N2 reactivity is the core of the invention. This discovery could only be made through inventive experimentation, not by a routine combination of prior art. The Examiner's rejection, which works backward from the Applicant's successful invention, is therefore based on impermissible hindsight.” [Remarks 11/14/2025, Page 16]
Applicant’s assertion hinges on the idea that a POSITA would have been taught away from investigating the N2 nitrogen based on the analysis of the N1 nitrogen. However, nothing in the prior art teaches that the N1 nitrogen of the 4-CF3 derivative would be a very poor substrate exhibiting attenuated reactivity. Accordingly, nothing in the prior art would have necessitated or led a POSITA to investigate an alternative mechanism. Applicant’s arguments rely on assumptions of what a POSITA would conclude, even in the absence of any teaching from the prior art to form a basis for these assumptions. Arguments presented by applicant cannot take the place of evidence in the record. Accordingly, Applicant’s assertion, in the absence of evidence, is merely speculative.
Moreover, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. The motivation to modify the method disclosed by Mukherjee does not rely on any information gleaned from Applicant’s disclosure. Rather, the motivation is explicitly taught by Schill.
Applicant asserts “This rejection is tainted by the same impermissible hindsight as the primary rejection. It improperly assumes the 4-CF3 coumarin backbone is an obvious starting point for a POSITA seeking to detect carbonyls. As established in Section B.3, this backbone is, in fact, non-obvious for this purpose, as the art strongly teaches away from its use.” [Remarks 11/14/2025, Page 17]
The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. Thus, the inventor may pursue a different goal, consider different mechanisms, or have a different starting point than what is taught or suggested by Mukherjee and Schill. It is not necessary that the inventor’s and the prior art’s path to the claimed invention align.
Furthermore, the motivation to modify the method disclosed by Mukherjee does not rely on any information gleaned from Applicant’s disclosure. Rather, the motivation is explicitly taught by Schill.
Applicant asserts “This extensive list of other substituents, compiled by one skilled in the art, would suggest to a POSITA that these specific reactive groups are not synthetically feasible, stable, or useful on this backbone, thereby constituting a "teaching away" by omission.” [Remarks 11/14/2025, Page 18]
Teaching away is a teaching that criticizes, discredits, or otherwise discourages the solution claimed. The prior art’s mere disclosure of more than one alternative does not constitute teaching away and “teaching away by omission” is not a standard set forth by the MPEP.
Applicant asserts “A POSITA, having concluded from basic chemical principles that the 4-CF3 group deactivates the 7-position (Nl) for hydrazines, would have every reason to believe it would also deactivate the 7-position for the electronically similar alkoxyamines. A general teaching of equivalency is irrelevant when the entire class of 7-nucleophilic-N compounds is expected to fail.” [Remarks 11/14/2025, Page 18]
Applicant’s arguments regarding the expected failure of the entire class of 7-nucleophilic-N compounds is speculative, as it relies on assumptions regarding what a POSITA would conclude, even in the absence of any teaching from the prior art to form a basis for these assumptions.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618