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 .
Drawings
The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the plurality of spectrophotometers (claims 7, 17 and 33), and the fluorescence and absorbance measurement arrangement combination (claims 11, 18 and 29), must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
Claims 6, 16, 26, 28 and 32 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor, or a joint inventor, regards as the invention.
Each of claims 6, 16 and 26 are indefinite at least because:
a) the term “order” is not defined; and
b) the limitation “is selectable” lacks venue insofar as the claim does not tie the function of selecting to a structure of the claimed invention; as such, it is unclear whether the selecting function is in fact required by the claim.
Claims 28 and 32 are each indefinite at least because the limitation does not make sense. The skilled artisan appreciates the fact that the excitation wavelength or wavelength band is determined by the particular fluorophore that is intended to be excited. The fluorophores are selected based at least on the chemical factors involved in the sample and whether the spectrophotometer is sensitive to the fluorescence wavelength(s). As such, the skilled artisan recognizes that the excitation wavelength of the light source is not dependent on any operational characteristic of the spectrophotometer. One of ordinary skill is unable to determine what is intending to be claimed. Therefore, the meets and bounds of the claim cannot be ascertained.
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 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.
Claims 1-3, 5-10, 22, 23 and 25-28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Atzler (US 2013/0119277 A1).
Regarding claim 1, Atzler discloses a system (Figs.1b, 3, 16 and 17), including:
a) a light source 502 arranged to transmit an excitation light to a container 17 including a sample 512;
b) a neutral density filter stack apparatus 506 positioned between the light source 502 and the container 17, where the neutral density filter stack apparatus includes a plurality of neutral density filters (par.0149);
c) a spectrophotometer 514, 516 arranged to measure fluorescence of one or more fluorophores 14 in the sample 16 in the container 17; and
d) a computing device 520 configured to characterize the liquid sample 16 over a dynamic range using the measured fluorescence (par.0150).
With respect to claim 2, Atzler further discloses that the neutral density filter stack apparatus 506 is coupled to the light source 502 (Figs.3 and 16).
With respect to claim 3, Atzler further discloses that the neutral density filter stack apparatus 506 includes a frame and a plurality of slots for removably receiving therein the plurality of neutral density filters (par.0137; also see an example of a frame with slots for receiving attenuation filters in Fig.12).
With respect to claim 5, Atzler further discloses that each of the plurality of neutral density filters has a different optical density (par.0149).
With respect to claim 6, Atzler further discloses that an order of the plurality of neutral density filters is selectable (the filters exist in the apparatus, as such, they were “selected” and have an “order”).
With respect to claim 7, Atzler further discloses that the spectrophotometer is a plurality of spectrophotometers (Fig.3).
With respect to claim 8, Atzler further discloses that the computing device 520 is programmed to control positioning of the plurality of neutral density filters between the light source 502 and the container 17 (Fig.17).
With respect to claim 9, Atzler further discloses that the computing device 520 is programmed to select which of the plurality of neutral density filters are positioned between the light source 502 and the container 17 (Fig.17).
With respect to claim 10, Atzler further discloses an import device 518 capable of reading and importing measurements from the spectrophotometer 514, 516 (Fig.16).
Regarding claim 22, Atzler discloses a neutral density filter stack apparatus 506 for modulating an intensity of a light source (Figs.1a, 3, 12 and 16), including:
a) a frame 258;
b) a plurality of slots of the frame 258; and
c) a plurality of neutral density filters 268, 270 insertable into the plurality of slots of the frame 258; where
d) the frame is positionable between a light source 502 and a container 17 (Fig.16; the additional limitations are directed to an intended use that does not structurally distinguish the claimed invention over the prior art; the claim is directed to the filter stack apparatus and does not positively set forth a light source or a sample container).
With respect to claim 23, Atzler further discloses that the frame is coupled to the light source (at least optically; also presumably housed within the cartridge 10 or 80 and thus mechanically coupled to the light source at least indirectly, see par.0133; additionally, since the claim is directed to the neutral density filter stack apparatus, none of the other structures are positively set forth as part of the invention. As such, these limitations are directed to an intended use that does not structurally distinguish the claimed invention over the prior art).
With respect to claim 25, Atzler further discloses that each of the plurality of neutral density filters has a different optical density (par.0149).
With respect to claim 26, Atzler further discloses that an order of the plurality of neutral density filters is selectable (the filters exist in the apparatus, as such, they were “selected” and have an “order”).
Regarding claim 27, Atzler discloses a method for carrying out fluorescence measurements on a liquid sample 16 over a selectable dynamic range (Figs.16 and 17); including:
a) dispensing the liquid sample 16 into a container 17, where the liquid sample includes one or more fluorophores 14;
b) inserting a neutral density filter stack 506 between a light source 502 and the container 17, where the neutral density filter stack 506 includes a plurality of neutral density filters (par.0149);
c) exciting the liquid sample 16 with the light source 502, where an intensity of the light source 502 is modulated by the neutral density filter stack 506 (Fig.17);
d) measuring with a spectrophotometer 514, 516 fluorescence of the liquid sample 16 in the container 17 to obtain a plurality of fluorescence measurements over a selectable dynamic range (Fig.17); and
e) determining one or more characteristics of the liquid sample 16 using the plurality of fluorescence measurements (par.0003).
With respect to claim 28, Atzler further discloses that an excitation band used to elicit one or more emissions of the one or more fluorophores is selected based on operational characteristics of the spectrophotometer 514 , 516 (at least indirectly based on fluorophore selection, see 35 USC 112(b) rejection above).
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 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.
Claims 11-13, 15-21 and 29-35 are rejected under 35 U.S.C. 103 as being unpatentable over Atzler in view of Muller (US 5,804,384).
Regarding claim 11, Atzler discloses a system (Figs.16 and 18; pars.0151-0152), including:
a) a light source 502 or 702 arranged to transmit an excitation light to a container 17 including a liquid sample 16;
b) a neutral density filter stack apparatus 506 or 706 positioned between the light source 502 or 702 and the container 17, where the neutral density filter stack apparatus includes a plurality of neutral density filters (par.0149);
c) a spectrophotometer 514, 516 arranged to measure fluorescence of one or more fluorophores in the liquid sample 16, and a photodetector 712 arranged to measure absorbance of one or more chromophores; and
d) a computing device 520, 720 configured to characterize the liquid sample 16 over a dynamic range using the measured absorbance and measured fluorescence (par.0003).
Further regarding claim 11, Atzler does not specifically disclose that the absorbance is measured with a spectrophotometer. Atzler teaches a photodiode detector with no means of wavelength specificity.
Muller teaches the practice of using spectrophotometry in order to measure the absorbance of one or more chromophores (col.15, lines 17-23). In this manner, the chromophores are accurately identified and measured.
It would have been obvious to one of ordinary skill in the art at the time of the invention for Atzler to arrange a spectrophotometer to measure the absorbance of one or more chromophores, as taught by Muller, in order to improve the accuracy and precision of the measurement.
With respect to claim 12, Atzler further discloses that the neutral density filter stack apparatus 506, 706 is coupled to the light source 502, 702 (Figs.16 and 18).
With respect to claim 13, Atzler further discloses that the neutral density filter stack apparatus 506, 706 includes a frame and a plurality of slots for removably receiving therein the plurality of neutral density filters (par.0137; also see an example of a frame with slots for receiving attenuation filters in Fig.12).
With respect to claim 15, Atzler further discloses that each of the plurality of neutral density filters has a different optical density (par.0149).
With respect to claim 16, Atzler further discloses that an order of the plurality of neutral density filters is selectable (the filters exist in the apparatus, as such, they were “selected” and have an “order”).
With respect to claim 17, Atzler further discloses that the spectrophotometer is a plurality of spectrophotometers (Fig.3).
With respect to claim 18, the combination of Atzler and Muller results in an absorbance spectrophotometer (as taught by Muller, see claim 11) and a separate fluorimeter 514, 516 (Atzler, Fig.16). Given the modularity of the cartridges as taught by Atzler, Atzler may accommodate multiple configurations of separate spectrophotometer arrangements (par.0152).
It would have been obvious to one of ordinary skill in the art at the time of the invention for Atzler to have the absorbance spectrophotometer for improved chromophore measurements, as taught by Miller, and a separate fluorimeter in order to efficiently accommodate the multimodal measurement system, as taught by Atzler.
With respect to claim 19, Atzler further discloses that the computing device 520 is programmed to control positioning of the plurality of neutral density filters between the light source 502 and the container 17 (Fig.17).
With respect to claim 20, Atzler further discloses that the computing device 520 is programmed to select which of the plurality of neutral density filters are positioned between the light source 502 and the container 17 (Fig.17).
With respect to claim 21, Atzler further discloses an import device 518 capable of reading and importing measurements from the spectrophotometer 514, 516 (Fig.16).
Regarding claim 29, Atzler discloses a method for carrying out absorbance and fluorescence measurements on a liquid sample 16 over a selectable dynamic range (Figs.16-19; pars.0151-0152), including:
a) dispensing the liquid sample 16 into a container 17, where the liquid sample includes one or more chromophores 14 and one or more fluorophores 14;
b) inserting a neutral density filter stack 506, 706 between a light source 502, 702 and the container 17, where the neutral density filter stack 506, 706 includes a plurality of neutral density filters (par.0149);
c) exciting the liquid sample 16 with the light source 502, 702 where an intensity of the light source 502, 702 is modulated by the neutral density filter stack 506, 706 (Figs.17 and 19);
d) measuring with a spectrophotometer 514, 516 fluorescence of the liquid sample 16 in the container 17 to obtain a plurality of fluorescence measurements over a selectable dynamic range (Fig.17); and
e) determining one or more characteristics of the liquid sample 16 using the plurality of fluorescence measurements (par.0003).
Further regarding claim 29, Atzler does not specifically disclose that the absorbance is measured with a spectrophotometer. Atzler teaches a photodiode detector with no means of wavelength specificity (Figs.1c, 7, 8 and 18).
Muller teaches the practice of using spectrophotometry in order to measure the absorbance of one or more chromophores (col.15, lines 17-23). In this manner, the chromophores are accurately identified and measured.
It would have been obvious to one of ordinary skill in the art at the time of the invention for Atzler to arrange a spectrophotometer to measure the absorbance of one or more chromophores, as taught by Muller, in order to improve the accuracy and precision of the measurement.
With respect to claim 30, both Atzler and Muller teach that the step of determining includes using multiple spectral features of either or both of the fluorescence measurements and the absorbance measurements.
With respect to claim 31, it would have been obvious to one of ordinary skill in the art at the time of the invention that the one or more chromophores are selected to have absorbance characteristics sufficiently distinct from the excitation and emission characteristics of the one or more fluorophores in order to be able to know which one is being detected, as is known in the art.
With respect to claim 32, Atzler further discloses that an excitation band used to elicit one or more emissions of the one or more fluorophores is selected based on operational characteristics of the spectrophotometer 514 , 516 (at least indirectly based on fluorophore selection, see 35 USC 112(b) rejection above).
With respect to claim 33, Atzler further discloses that the spectrophotometer is a plurality of spectrophotometers (Fig.3).
With respect to claim 34, it would have been obvious to one of ordinary skill in the art at the time of the invention that the liquid sample 16 in the container 17 be excited at a first wavelength, the absorbance measurements may be carried out at a second wavelength, and the fluorescence measurements may be carried out at a third wavelength, in order for the separate measurements to be distinguishable from one another, as known in the art.
With respect to claim 35, it would have been obvious to one of ordinary skill in the art at the time of the invention to have two or more chromophore concentrations, if there are two or more aspects of the sample to be measured, and as long as their spectral characteristics do not overlap, as known in the art.
Claims 4 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Atzler, as applied to claims 1 and 21 above, respectively, in view of Petisce (US 2025/0102423 A1).
With respect to claims 4 and 24, Atzler does not specifically disclose that the plurality of neutral density filters have the same optical density. Atzler teaches the common practice of providing a series of neutral density filters with different optical densities (par.0149).
Petisce teaches the practice of providing different optical densities in a stack of neutral density filters by providing filters of the same optical density separate and together in order to achieve the desired attenuation (a 50% filter, and a sandwich of two 50% filters to achieve 25% transmittance, par.0072).
It would have been obvious to one of ordinary skill in the art at the time of the invention for Atzler to have the plurality of neutral density filters have the same optical density in order to achieve the desired attenuation, as taught by Petisce, as a functionally-equivalent means of achieving the desired attenuation.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Atzler and Muller, as applied to claim 11 above, in view of Petisce (US 2025/0102423 A1).
With respect to claim 14, Atzler does not specifically disclose that the plurality of neutral density filters have the same optical density. Atzler teaches the common practice of providing a series of neutral density filters with different optical densities (par.0149).
Petisce teaches the practice of providing different optical densities in a stack of neutral density filters by providing filters of the same optical density separate and together in order to achieve the desired attenuation (a 50% filter, and a sandwich of two 50% filters to achieve 25% transmittance, par.0072).
It would have been obvious to one of ordinary skill in the art at the time of the invention for Atzler to have the plurality of neutral density filters have the same optical density in order to achieve the desired attenuation, as taught by Petisce, as a functionally-equivalent means of achieving the desired attenuation.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure (see attached PTO-892 unless otherwise stated):
Yonggang (GB) teaches a fluorescence spectrometer with selected neutral density filter stacks for optimizing the excitation beam intensity according to the desired fluorescence detection sensitivities;
Modlin (US) teaches the common practice of using spectrophotometry to measure both fluorescence and absorbance (Figs.5 and 6; pars.0084-0085; also see Figs.7 and 15 and par.0160); and
The remaining prior art teaches various aspects of using neutral density filters in fluorescence spectroscopy.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THOMAS R ARTMAN whose telephone number is (571)272-2485. The examiner can normally be reached Monday-Thursday 10am-6:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Makiya can be reached on 571.272.2273. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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THOMAS R. ARTMAN
Primary Examiner
Art Unit 2884
/THOMAS R ARTMAN/ Primary Examiner, Art Unit 2884