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 .
Response to Arguments
Applicant’s arguments with respect to claim 1 have been considered but are moot in view of a new grounds of rejection necessitated by the amendments to the claims.
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 1-6, 11-15, and 18-23 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 recites the limitation "the detection signal" in the last line. There is insufficient antecedent basis for this limitation in the claim. Prior lines of the claim recite “detection signals output by the detection unit” but this is not sufficient antecedent basis as it would be unclear which one of the plurality is being referred to in the “the detection signal” limitation. Prior lines of the claim also recite “a removal process for removing an overlapping portion of a wavelength range of a plurality of types of light from the detection signal corresponding to each light”; however, this limitation appears to be presented in the alternative to the limitation containing the “the detection signal” limitation in the last line (“wherein the data processing unit is further configured to execute at least one of a correction process for correcting a dark current of the detection unit, a removal process for removing an overlapping portion of a wavelength range of a plurality of types of light from the detection signal corresponding to each light, or a conversion process for converting the detection signal output as a voltage signal into an intensity of light.”). Therefore, sufficient antecedent basis is not present for the limitation “the detection signal” in the last line of the claim.
Claim 5 recites the limitation "the mounting unit" in line 4. There is insufficient antecedent basis for this limitation in the claim. The base claims from which claim 5 depends do not recite a mounting unit.
Claim 20 recites the limitation “the detection signal” in the last line. There is insufficient antecedent basis for this limitation in the claim for the same reasons discussed in regard to claim 1, above.
Dependent claims are rejected for the same reason(s) as the base claim(s) upon which they depend.
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 1-2, 6, 12-15, 18-20, and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Sato et al. (Microcirculation-on-a-Chip: A Microfluidic Platform for Assaying Blood- and Lymphatic-Vessel Permeability) in view of Can et al. (US Patent Application Publication 2009/0245611).
Regarding claim 1, Sato et al. discloses a measurement system (Abstract) comprising:
a flow channel device (called microfluidic device) (Abstract) including a first flow channel (Abstract) (p. 3 para. 3) (Fig. 1, p. 4), a second flow channel having a communicating portion that communicates with at least part of the first flow channel (Abstract) (p. 3 para. 3-4) (Fig. 1, p. 4), and a cell sheet in which a plurality of cultured cells are arranged in such a manner that the cells are bound to each other and which partitions between the first flow channel and the second flow channel at the communicating portion (Abstract) (p. 3 para. 3-p. 5 para. 1, p. 14 para. 3) (Fig. 1, p. 4); and
a measurement device (comprising fluorescence microscope) (p. 7 para. 2-4) including:
a detection unit that includes at least one excitation light source (excitation light is produced and therefore it is taken that at least one excitation light source is necessarily present) (p. 7 para. 2-3), and that is configured to optically distinguish and detect a leakage state of each of a plurality of types of tracers of an evaluation liquid (p. 6 para. 4-p. 7 para. 4) (Fig. 7, p. 13), the tracers having different sizes (p. 6 para. 4) and leaking out from the first flow channel into the second flow channel through a defect occurring in the cell sheet (p. 6 para. 4-p. 7 para. 4, p. 12 para. 2-p. 14 para. 1), the evaluation liquid being used for evaluation of barrier properties of the cell sheet and containing the plurality of types of tracers in a mixed state (p. 6 para. 4-p. 7 para. 4, p. 12 para. 2-p. 14 para. 1); and
a data processing unit that is coupled to the detection unit and is configured to perform data processing on detection signals output by the detection unit (images derived from detection signals output by the detection unit are generated by software and therefore it is taken that a data processing unit is necessarily present to execute the software) (p. 7 para. 2-4) (Fig. 1, p. 8).
Sato et al. does not expressly teach wherein the data processing unit is further configured to execute at least one of a correction process for correcting a dark current of the detection unit, a removal process for removing an overlapping portion of a wavelength range of a plurality of types of light from the detection signal corresponding to each light, or a conversion process for converting the detection signal output as a voltage signal into an intensity of light.
However, Sato et al. discloses wherein the measurement device is configured to supply excitation light to induce fluorescence of material within the flow channel device such that images can be obtained based on detected fluorescence intensity (p. 7 para. 2-p. 8 para. 1, p. 15 “fluorescence micrographs”) (Fig. 2, p. 8).
Can et al. discloses that the presence of dark current contributed by a detection unit is a known issue that arises during fluorescence microscopy analysis of cells and that it is desirable to remove the dark current (para. 1-7). To this end, Can et al. further discloses a system comprising a data processing unit configured to execute a correction process for correcting a dark current of a detection unit (Abstract, para. 21-27).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the data processing unit disclosed by Sato et al. to be further configured to execute a correction process for correcting a dark current of the detection unit, as Can et al. discloses that it was known in the art to use a processor execute such a process during fluorescence measurement to improve results, and the skilled artisan would have been motivated to enhance the utility of the measurement system by correcting for dark current issues.
Regarding claim 2, Sato et al. discloses wherein each of the plurality of tracers is a fluorescent tracer which emits fluorescence having a different wavelength range (the tracers comprise TRITC-dextran and Lucifer Yellow, p. 6 para. 4; these are tracers which emit fluorescence having a different wavelength, see Millipore Sigma comparison chart which is cited herein as an evidentiary reference), and wherein the detection unit detects a plurality of types of fluorescence emitted by each of the plurality of types of tracers (p. 6 para. 4-p. 7 para. 4).
Regarding claim 6, Sato et al. discloses wherein the leakage state that the detection unit is configured to detect includes a change in a leakage amount over a period of time (p. 6 para. 4, p. 12 para. 2-p. 13 para. 1) (Fig. 7, p. 13).
Regarding claim 12, Sato et al. discloses wherein the cell sheet is cultured on a support (p. 4 para. 1-p. 5 para. 1) (Fig. 1, p. 4).
Regarding claim 13, Sato et al. discloses the plurality of types of tracers, as set forth above, and further discloses wherein TRITC-dextran is used as a large tracer and Lucifer Yellow is used as a small tracer (p. 6 para 4, p. 8 para. 1) in order to study the behavior of leakage of different materials through the cell sheet (p. 8 para. 1-p. 13 para. 1).
Sato et al. is silent as to wherein a particle size of each of the plurality of types of tracers is within a range of 1 nm or more and 100 µm or less.
Nonetheless, it has been held that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, when the particular parameter is recognized as a result-effective variable (MPEP §2144.05). Sato et al. discloses general conditions for a size of the tracers and the skilled artisan would clearly recognize that particle size impacts function during a leakage study (p. 3 para. 3, p. 6 para 4, p. 8 para. 1). Therefore, it would have been obvious to one of ordinary skill in the art to discover an optimum or workable range for the particle size of each of the plurality of types of tracers by routine experimentation.
Regarding claim 14, Sato et al. discloses the plurality of types of tracers, as set forth above, and further discloses wherein TRITC-dextran is used as a large tracer and Lucifer Yellow is used as a small tracer (p. 6 para 4, p. 8 para. 1) in order to study the behavior of leakage of different materials through the cell sheet (p. 8 para. 1-p. 13 para. 1).
Sato et al. is silent as to wherein the plurality of types of tracers include a tracer having a particle size on the order of 1 nm to several hundreds of nm and a tracer having a particle size on the order of 1 µm to several tens of µm.
Nonetheless, it has been held that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, when the particular parameter is recognized as a result-effective variable (MPEP §2144.05). Sato et al. discloses general conditions for a size of the tracers and the skilled artisan would clearly recognize that particle size impacts function during a leakage study (p. 3 para. 3, p. 6 para 4, p. 8 para. 1). Therefore, it would have been obvious to one of ordinary skill in the art to discover an optimum or workable range for the particle size of each of the plurality of types of tracers, including a large size tracer and a small size tracer, by routine experimentation.
Regarding claim 15, Sato et al. discloses a supply mechanism for supplying the evaluation liquid to the first flow channel (p. 3 para. 6, p. 6 para. 4).
Regarding claim 18, Sato et al. discloses wherein the measurement device further comprises an optical element configured to separate light of a plurality of wavelengths (called dichroic mirror) (p. 7 para. 2) and a light receiving section configured to receive the light separated by the optical element (the measurement unit comprises a fluorescence microscope that obtains images via light that passes through the dichroic mirror and therefore it is taken that the measurement unit necessarily comprises a light receiving section as claimed) (p. 7 para. 2-4).
Regarding claim 19, Sato et al. discloses wherein the data processing unit is configured to process the detection signals and to derive the leakage state of each of the plurality of types of tracers (p. 7 para. 2-4) (p. 12 para. 2-p. 13 para. 1) (Fig. 7, p. 13).
Regarding claim 20, Sato et al. discloses wherein the data processing unit is further configured derive a concentration of each of the plurality of types of tracers leaked out from the first flow channel to the second flow channel based on the detection signal output by the detection unit (p. 7 para. 2-4) (p. 12 para. 2-p. 13 para. 1) (Fig. 7, p. 13).
Regarding claim 22, Sato et al. discloses wherein the support is a permeable membrane (p. 3 para. 3).
Regarding claim 23, Sato et al. discloses wherein the permeable membrane has pores having a diameter of 1 µm (falls within the claim range) (p. 3 para. 3).
Claims 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Sato et al. (Microcirculation-on-a-Chip: A Microfluidic Platform for Assaying Blood- and Lymphatic-Vessel Permeability) in view of Can et al. (US Patent Application Publication 2009/0245611) as applied to claim 1, above, and in further view of Kei et al. (US Patent Application Publication 2019/0049343).
Regarding claim 3, Sato et al. discloses wherein the at least one light source irradiates each of the plurality of types of tracers with excitation light that excites fluorescence (p. 7 para. 2-4), and wherein the measurement device further comprises a dichroic mirror block (p. 7 para. 2) and a light receiving section configured to receive the fluorescence emitted by the tracers (the measurement unit comprises a fluorescence microscope that receives the fluorescence so as to obtain images and therefore it is taken that the measurement unit necessarily comprises a light receiving section) (p. 7 para. 2-4).
Sato et al. does not expressly teach an optical filter configured to separate the plurality of types of florescence and a light receiving section configured to receive the fluorescence separated by the optical filter.
Kei et al. discloses a system for analyzing a biological sample via fluorescence observation (Abstract, para. 22-25), the system comprising at least one light source configured to irradiate a microplate containing the sample so as to excite fluorescence (para. 28). Kei et al. discloses wherein “The fluorescence wavelength emitted from the sample is various” (para. 29). To address this, Kei et al. discloses wherein the system comprises an optical filter comprising a dichroic mirror (235) wherein the optical filter is configured to separate different wavelengths of emitted fluorescence, e.g., to send specific wavelengths to respective detectors (238a, 238b) (para. 28-29) (Fig. 1, sheet 1 of 9).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the system disclosed by Sato et al. to comprise an optical filter configured to separate the plurality of types of fluorescence and a light receiving section configured to receive the fluorescence separated by the optical filter, based on the teachings of Kei et al., in order to handle a plurality of emitted fluorescence wavelengths for simultaneous and/or separate processing thereof.
Regarding claim 4, Sato et al. discloses wherein the detection unit includes an excitation light source and a light receiving section, wherein each of the plurality of types of tracers emits fluorescence having a different wavelength range, as set forth above.
Sato et al. does not expressly teach only one excitation light source, wherein the light receiving section is provided for each of the plurality of types of fluorescence.
However, Kei et al. discloses a system for analyzing a biological sample via fluorescence observation, as discussed above, wherein the system comprises only one excitation light source (239) (para. 28) (Fig. 1, sheet 1 of 9) and the light receiving section is provided for each of the plurality of types of fluorescence (respective detectors 238a and 238b receive respective emission wavelengths separated by the optical filter as discussed above, each detector has a receiving section) (para. 26-29) (Fig. 1, sheet 1 of 9).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the system disclosed by Sato et al. to comprise only one excitation light source wherein the light receiving section is provided for each of the plurality of types of fluorescence, based on the teachings of Kei et al., as the skilled artisan would have been motivated to adopt a configuration known in the art to be suitable for handling various emission wavelengths.
Regarding claim 5, Sato et al. in view of Kei et al. teaches the one excitation light source, as set forth above. Sato et al. discloses wherein the excitation light source irradiates, with excitation light, a position that is downstream from a leakage point of tracer leaking out from the communicating portion, in the flow channel device, such that the excitation light is incident only on the second flow channel (p. 6 para. 4) (Fig. 1, p. 4).
As to the limitation of the flow channel device mounted on the mounting unit, this limitation is indefinite as discussed in the 35 U.S.C. 112(b) rejection above, and as the claim does not positively require that the system comprises a mounting unit, the limitation does not introduce a patentable distinction over the prior art. Nonetheless, Sato et al. discloses that the flow channel device is mounted on a fluorescence microscope (p. 4 para. 4-p. 7 para. 4) and therefore it is taken that the flow channel device is mounted on a mounting device such as a microscope stage during irradiation with excitation light.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Sato et al. (Microcirculation-on-a-Chip: A Microfluidic Platform for Assaying Blood- and Lymphatic-Vessel Permeability) in view of Can et al. (US Patent Application Publication 2009/0245611) as applied to claim 1, above, and in further view of Jing et al. (US Patent Application Publication 2019/0352589).
Regarding claim 11, Sato et al. discloses wherein the data processing unit is configured to generate measurement data representing the leakage state, including a change in leakage amount over time (p. 7 para. 2-4) (Fig. 7, p. 13).
Sato et al. is silent as to the system further comprising an output control unit configured to receive measurement data representing the leakage state from the data processing unit and to output the leakage state to a display unit in real time.
Jing et al. discloses a system for measuring parameters of a biological sample (Abstract), the system comprising a processor configured to handle measurement data (para. 67-68). Jing et al. discloses using a display to output measurement data in real time (para. 72) and further discloses a remote computer configured to receive measurement data (para. 72).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the system disclosed by Sato et al. to further comprise an output control unit, such as a remote computer, configured to receive the measurement data representing the leakage state from the data processing unit and to output the leakage state to a display in real time, as Jing et al. discloses that such techniques were known in the art, and the skilled artisan would have been motivated to display real time measurement data remotely to allow an operator to monitor system function from a remote location.
Allowable Subject Matter
Claim 21 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOLLY KIPOUROS whose telephone number is (571)272-0658. The examiner can normally be reached M-F 8.30-5PM.
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/HOLLY KIPOUROS/Primary Examiner, Art Unit 1799
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