DETAILED ACTION
The Applicant’s response, received 08 September 2025 has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 the Claims
Claims 1-19 are pending.
Claims 1-7 and 12-16 are withdrawn.
Claims 8-11 and 17-19 are rejected.
Applicant is advised that should claim 11 be found allowable, claim 19 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Priority
Claims 8-11 and 17-19 are given the benefit of priority to Foreign Application No. PCT/JP2019/006078, filed 19 February 2019.
Therefore, the effective filing date of the claimed invention is 19 February 2019.
Claim Rejections - 35 USC § 112
The amendment received 08 September 2025 has been fully considered, however after further consideration, the rejection of claims 8-11 and 17-19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, in the Office action mailed 18 April 2025 is maintained with modification in view of the amendment.
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 8-11 and 17-19 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 8 is indefinite for reciting “measuring, by a processor, cell viability of cells from the subject after irradiating and calculating, by the processor, an intracellular protoporphyrin IX accumulation based on the cell viability” because it is not clear as to whether the processor performs the measuring of cell viability and the calculating of an intracellular protoporphyrin IX accumulation using an algorithm (e.g., Specification, page 17, para. [0043], line 24 to page 18, lines 1-4), or alternatively if the processor is used to control an external device that performs the measuring, e.g., a fluorescence detection high-performance liquid chromatograph method and a flow cytometer (e.g., Specification, page 11, para. [0030], lines 16-19; and page 14, para. [0038], lines 14-20). This limitation is interpreted to mean using an algorithm to perform the measuring and calculating steps with data generated using the aforementioned external device(s).
Claims 9-11 and 17-19 are indefinite for depending from claim 8 and for failing to remedy the indefiniteness of claim 8.i
Claims 11 and 19 are indefinite for reciting “determining a plurality of times of light irradiation” because it is not clear as to whether the plurality of times refers to the clock time when light irradiation occurs, or alternatively the number of instances of light irradiation that occurs. This limitation is interpreted to mean “instances” of light irradiation.
Response to Arguments
The Applicant’s arguments/remarks received 08 September 2025 have been fully considered, but are not persuasive.
The Applicant states on page 7 of the Remarks that independent claim 8 has been amended to recite “measuring, by a processor, cell viability of cells from the subject after irradiating and calculating, by the processor, an intracellular protoporphyrin IX accumulation based on the cell viability” and accordingly requests withdrawal of the rejection.
These arguments/remarks are not persuasive, because the amendment does not remedy the indefiniteness of the claim, as discussed in the above rejection.
Claim Rejections - 35 USC § 101
The amendment received 08 September 2025 has been fully considered, however after further consideration, the rejection of claims 8-11 and 17-19 under 35 U.S.C. 101 in the Office action mailed 18 April 2025 is maintained with modification in view of the amendment.
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 8-11 and 17-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite: (a) mental processes, i.e., concepts performed in the human mind (e.g., observation, evaluation, judgement, opinion); and (b) mathematical concepts (e.g., mathematical relationships, formulas or equations, mathematical calculations).
Subject matter eligibility evaluation in accordance with MPEP 2106.
Eligibility Step 1: Step 1 of the eligibility analysis asks: Is the claim to a process, machine, manufacture or composition of matter?
Claims 8-11 and 17-19 are directed to a method (i.e., a process) for determining light irradiation conditions in photodynamic therapy.
Therefore, these claims are encompassed by the categories of statutory subject matter, and thus satisfy the subject matter eligibility requirements under step 1.
[Step 1: YES]
Eligibility Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in Prong Two whether the recited judicial exception is integrated into a practical application of that exception.
Eligibility Step 2A Prong One: In determining whether a claim is directed to a judicial exception, examination is performed that analyzes whether the claim recites a judicial exception, i.e., whether a law of nature, natural phenomenon, or abstract idea is set forth or described in the claim.
Independent claim 8 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
measuring cell viability of cells (i.e., mental processes and mathematical concepts);
calculating an intracellular protoporphyrin IX accumulation based on the cell viability (i.e., mental processes and mathematical concepts); and
prior to initiation of a next therapy, determining a light irradiation energy density and a 5-aminolevulinic acid dose using a predetermined relational expression based on the measured intracellular accumulation of protoporphyrin IX (i.e., mental processes and mathematical concepts).
Dependent claims 9, 10, 11, 17, 18, and 19 further recite the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas, as noted below.
Dependent claim 9 further recites:
wherein said relational expression is determined based on a regression curve representing a correlation among three condition parameters of a cell viability (Y), an intracellular protoporphyrin IX accumulation (X), and a light irradiation energy density (P) (i.e., mental processes and mathematical concepts).
Dependent claims 10 and 17 further recite:
wherein said relational expression includes a lookup table illustrating a relationship among the protoporphyrin IX accumulation (X) and the light irradiation energy density (P) (i.e., mental processes and mathematical concepts).
Dependent claims 11, 18, and 19 further recite:
determining a plurality of times of light irradiation when the measured protoporphyrin IX accumulation is less than a predetermined value (i.e., mental processes and mathematical concepts).
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification. As noted in the foregoing section, the claims are determined to contain limitations that can practically be performed in the human mind with the aid of a pen and paper (e.g., determining a plurality of times of light irradiation when the measured protoporphyrin IX accumulation is less than a predetermined value) and therefore recite judicial exceptions from the mental process grouping of abstract ideas. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas (e.g., determining a light irradiation energy density and a 5-aminolevulinic acid dose using a predetermined relational expression based on the measured intracellular accumulation of protoporphyrin IX) are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind.
Therefore, claims 8-11 and 17-19 recite an abstract idea.
[Step 2A Prong One: YES]
Eligibility Step 2A Prong Two: In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP 2106.04(d)). A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements are analyzed to determine if the abstract idea is integrated into a practical application (MPEP 2106.04(d)(I); MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d)(III)).
The judicial exceptions identified in Eligibility Step 2A Prong One are not integrated into a practical application because of the reasons noted below.
Dependent claims 9-11 and 17-19 do not recite any elements in addition to the judicial exception, and thus are part of the judicial exception.
The additional elements in independent claim 8 include:
a processor;
irradiating a subject with a light source providing light having a light intensity to inactivate cells with protoporphyrin IX accumulation after an administration of 5-aminolevulinic acids to the subject; and
adjusting the light intensity of the light for the next therapy, based on the light irradiation density.
The additional element of a processor (claim 8) invokes a computer and/or computer-related components merely as tools for use in the claimed process, and therefore is not an improvement to computer functionality itself, or an improvement to any other technology or technical field, and thus, does not integrate the judicial exceptions into a practical application (see MPEP 2106.04(d)(1)).
The additional element of irradiating a subject with a light source providing light having a light intensity to inactivate cells with protoporphyrin IX accumulation after an administration of 5-aminolevulinic acids to the subject (claim 8) is merely a pre-solution activity of gathering data for use in the claimed process – a nominal addition to the claims that does not meaningfully limit the claims, and therefore does not add more than insignificant extra-solution activity to the judicial exceptions (MPEP 2106.05(g)).
The additional element of adjusting the light intensity of the light for the next therapy, based on the light irradiation density (claim 8) amounts to no more than a recitation of the words “apply it” (MPEP 2106.05(f) because the claim does not actually recite any additional elements that apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exceptions (MPEP 2106.04(d)). Furthermore, the step of “adjusting the light intensity of the light for the next therapy” (emphasis added) is an intended use of the adjusted light intensity, and does not actually recite a limitation that applies or uses a recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition (MPEP 2106.04(d)(2)).
Thus, the additionally recited elements merely invoke a computer and/or computer related components as tools; and/or amount to insignificant extra-solution activity; and/or mere instructions to apply an exception; and/or do not effect a particular treatment or prophylaxis for a disease or medical condition; and as such, when all limitations in claims 8-11 and 17-19 have been considered as a whole, the claims are deemed to not recite any additional elements that would integrate a judicial exception into a practical application, and therefore claims 8-11 and 17-19 are directed to an abstract idea (MPEP 2106.04(d)).
[Step 2A Prong Two: NO]
Eligibility Step 2B: Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they amount to significantly more than the judicial exception (MPEP 2106.05A i-vi).
The claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exception(s) because of the reasons noted below.
Dependent claims 9-11 and 17-19 do not recite any elements in addition to the judicial exception(s).
The additional elements recited in independent claims 1, 29, and 30 and dependent claim 14 are identified above, and carried over from Step 2A Prong Two along with their conclusions for analysis at Step 2B. Any additional element or combination of elements that was considered to be insignificant extra-solution activity at Step 2A Prong Two was re-evaluated at Step 2B, because if such re-evaluation finds that the element is unconventional or otherwise more than what is well-understood, routine, conventional activity in the field, this finding may indicate that the additional element is no longer considered to be insignificant; and all additional elements and combination of elements were evaluated to determine whether any additional elements or combination of elements are other than what is well-understood, routine, conventional activity in the field, or simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, per MPEP 2106.05(d).
The additional element of a processor (claim 8) is conventional (see MPEP at 2106.05(b) and 2106.05(d)(II) regarding conventionality of computer components and computer processes).
The additional elements of irradiating a subject with a light source providing light having a light intensity to inactivate cells with protoporphyrin IX accumulation after an administration of 5-aminolevulinic acids to the subject (claim 8); and adjusting the light intensity of the light for the next therapy, based on the light irradiation density (claim 8); are conventional. Evidence for the conventionality is shown by Shafirstein et al. (“Interstitial Photodynamic Therapy – A Focuses Review.” Cancers, 2017, Vol. 9, No. 12, pp. 1-14, newly cited in view of the amendment).
Shafirstein et al. reviews interstitial photodynamic therapy (Title; and Abstract) and discusses various studies of photodynamic therapy using 5-ALA-induced protoporphyrin IX accumulation in cancer patients (e.g., page 9, para. 2; and throughout). Shafirstein et al. further discusses treatment planning software that performs an initial calculation of the light dose and determines effective attenuation coefficients, and thereafter, at specific intervals the light is interrupted and a monitoring evaluation test is performed and tissue optical properties are obtained, enabling one to determine the effective attenuations and update the light dose (page 4, para. 2).
Therefore, when taken alone, all additional elements in claims 8-11 and 17-19 do not amount to significantly more than the above identified judicial exception(s). Even when evaluated as a combination, the additional elements fail to transform the exception(s) into a patent-eligible application of that exception. Thus, claims 18-11 and 17-19 are deemed to not contribute an inventive concept, i.e., amount to significantly more than the judicial exception(s) (MPEP 2106.05(II)).
[Step 2B: NO]
Response to Arguments
The Applicant’s arguments/remarks received 08 September 2025 have been fully considered, but are not persuasive.
The Applicant states on page 8 (para. 2) of the Remarks that amended independent claim 8 demonstrates an integration of the alleged judicial exception into a practical application, and that the claims recite, inter alia, irradiating a subject with a light source providing light at a first intensity, determining cell viability of cells from the subject and determining an intracellular protoporphyrin IX accumulation, determining a light irradiation density and a 5-aminolevulinic acid dose using a predetermined relational expression based on the measured intracellular protoporphyrin IX accumulation, and adjusting the light intensity of the light for the next therapy based on the light irradiation density.
These arguments/remarks are not persuasive, at least because the claims do not recite the limitation “providing light at a first intensity” in addition to the reasons provided in the above rejection in regard to the judicial exceptions not being integrated into a practical application.
The Applicant summarizes elements of the eligibility analysis under Step 2A Prong 2 on page 8 (para. 3) of the Remarks and states (para. 4) that amended independent claim 8 recites particular improvements to methods related to photodynamic therapy. The Applicant further states that the independent claim irradiates a subject at a first light intensity, performs measurements to determine conditions for a next therapy (e.g., a 5-aminolevulinic acid dose and a light irradiation density), and adjusts a light intensity of a light source for the next therapy. The Applicant further states that the claims provide specific, practical, and technical solutions for analyzing cells from a subject following a first irradiation and adjusting light intensity parameters for a next therapy. The Applicant further states that the present invention further provides specificity and meaningful limits with regard to its structure and method of operation, and therefore, under Step 2A, Prong 2 the claims demonstrate practical applications of the alleged exception and cannot be considered to be directed to an abstract idea.
These arguments are not persuasive, because as noted and discussed in the above rejection, amended claim 8 does not recite any additional elements that apply, rely on, or use the judicial exception(s) in a manner that imposes a meaningful limit on the judicial exceptions. The additional element of irradiating a subject with a light source providing light having a light intensity to inactivate cells with protoporphyrin IX accumulation after an administration of 5-aminolevulinic acids to the subject is a step in the process of gathering data for use in the claimed process (e.g., using the data in the relational expression step), and the additional element of adjusting the light intensity of the light for the next therapy, based on the light irradiation density, amounts to no more than a recitation of the words “apply it” (MPEP 2106.05(f) because the claim does not actually recite any additional elements that apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exceptions (e.g., the light source does not actually use the adjusted light intensity) (MPEP 2106.04(d)). Furthermore, the step of “adjusting the light intensity of the light for the next therapy” (emphasis added) is an intended use of the adjusted light intensity, and does not actually recite a limitation that applies or uses a recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition (MPEP 2106.04(d)(2)).
The Applicant states on page 9 (para. 2) of the Remarks that under Step 2B the claims recite elements that amount to significantly more than any purported abstract idea, and that as discussed above, the present claims provide specific technical improvements to determining light irradiation conditions for photodynamic therapy by analyzing cell viability and specific cell characteristics following a first administration of light, determining how to modify the therapy, and executing a next therapy with an adjusted light intensity. The Applicant further states that the claimed invention solves, for example, data assessment and efficiency issues, and provides a sophisticated, computer-assisted method to collect cell information following light therapies, and update personalized treatment based on the collected data, and as such, the specific limitations recited in the claims, when considered in combination, present improvements in the related art, add specific limitations other than what is well-understood, routine and conventional in the field and recite significantly more than any alleged abstract idea.
These arguments are not persuasive, because first, Step 2B asks: Does the claim recite additional elements that amount to significantly more than the judicial exception? Answering this question, as noted and discussed in the above rejection, requires first identifying whether there are any additional elements (features/limitations/steps) recited in the claim beyond the judicial exception(s), and then evaluating those additional elements individually and in combination to determine whether they contribute an inventive concept (i.e., amount to significantly more than the judicial exception(s)). As shown in the above rejection, the only additional elements identified in independent claim 8 are:
a processor;
irradiating a subject with a light source providing light having a light intensity to inactivate cells with protoporphyrin IX accumulation after an administration of 5-aminolevulinic acids to the subject; and
adjusting the light intensity of the light for the next therapy, based on the light irradiation density.
As discussed in the above rejection, these additional elements, when evaluated individually and in combination, do not amount to significantly more than the above identified judicial exception(s), and thus, are deemed to not contribute an inventive concept, i.e., amount to significantly more than the judicial exception(s).
Claim Rejections - 35 USC § 103
The amendment received 08 September 2025 has been fully considered, however after further consideration, the rejection of claims 8-11 and 17-19 under 35 U.S.C. 103 in the Office action mailed 18 April 2025 is maintained with modification in view of the amendment.
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.
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.
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.
Claims 8-11 and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Jones et al. (US 2011/0270056, as cited in the Office action mailed 18 April 2025) in view of Tyrrell et al. (Cancers, 2019 (Published 10 January), Vol. 11, Issue 72, pp. 1-14, as cited in the Office action mailed 18 April 2025).
Jones et al. shows the determination of photodynamic therapy (PDT) treatment parameters (Title) and a photodynamic therapy system and methods to determine the amount (concentration) of a photosensitizer agent present in the target tissue, and that the system may also determine light dosimetry parameters based on the amount of the photosensitizer in the tissue (Abstract).
Tyrrell et al. shows regression analysis of protoporphyrin IX measurements obtained during dermatological photodynamic therapy (Title); and that photodynamic therapy (PDT) is a light activated drug therapy that can be used to treat a number of dermatological cancers and precancers (Abstract).
Regarding independent claim 8, Jones et al. further shows that in many circumstances undesirable tissue is removed from internal structures of a patient, for example pre-cancerous or cancerous tissue, and that one example of a technique for the removal of undesirable tissue is photodynamic therapy, which is a “drug and light” therapy that involves the combined effect of a photosensitizer agent and the delivery of laser light to result in ablation of the target tissue (para. [0004]). Jones et al. further shows a flowchart illustrating an example process by which a processor may determine the amount of photosensitizer agent in target tissue (para. [0014]; FIGS. 6A-6B); and a flowchart illustrating an example process by which a processor may determine light dosimetry parameters based on the amount of photosensitizer agent in the target tissue (para. [0015]; FIG. 7). Jones et al. further shows specific examples of photosensitizers including aminolevulinic acid (ALA; para. [0024]: NOTE: ALA is the precursor to protoporphyrin IX (PpIX); and an equation for determination of light dosimetry parameters based on photosensitizer content showing a relationship between administered light dose in units of J/cm and the photosensitizer tissue content in mg/kg (para. [0052]) and that light dosimetry parameters may be determined based on the photosensitizer concentration in the target tissue (para. [0054]).
Further regarding independent claim 8, Jones et al. further shows illuminating target tissue of a patient containing a concentration of a photosensitizer with one or more wavelengths suitable for fluorescence excitation of the photosensitizer (para. [0007]); and that if the photosensitizer concentration is less than a threshold concentration, the light dose (intensity and/or duration) may be adjusted to improve the effects of the PDT when delivered (para. [0055]).
Regarding claim 9, Jones et al. shows a relational expression representing a correlation among the condition parameters of photosensitizer accumulation, and light irradiation energy density (para. [0052]).
Regarding claims 10 and 17, Jones et al. shows that once relationships between parameters are determined (e.g., para. [0036] & FIG. 5) a lookup table or other data structure may be generated, stored in a memory or other storage device, and used as an index to determine the photosensitizer concentration in the target tissue (paras. [0037] & [0048]). Jones et al. further shows an equation depicting a relationship between a photosensitizer and light irradiation energy density (para. [0052]).
Regarding claims 11, 18, and 19, Jones et al. shows that the photosensitizer concentration may be compared to one or more threshold concentrations, e.g., if the photosensitizer concentration is less than a first threshold concentration, additional photosensitizer may be introduced to the target tissue to improve the effects of the PDT when delivered, and as another example, if the photosensitizer concentration is less than a third threshold concentration, the light dose (intensity and/or duration) may be adjusted to improve the effects of the PDT when delivered (para. [0055]); and that the one or more threshold concentrations may be the same or different (para. [0055]) and that the thresholds may be predefined thresholds (para. [0056]).
Jones et al. does not show that the photosensitizer is protoporphyrin IX (PpIX; claims 8-11 and 17-19); or measuring cell viability of cells from the subject after irradiating (claim 8); or that the relational expression is determined based on a regression curve and includes cell viability as one of the condition parameters (claim 9); or that the lookup table illustrates a relationship among the protoporphyrin IX accumulation and the light irradiation energy density (claims 10 and 17).
Regarding claims 8-11 and 17-19, Tyrrell et al. shows that clinical protoporphyrin IX (PpIX) fluorescence data were obtained using a pre-validated, non-invasive imaging system during routine methyl aminolevulinate (MAL)-PDT treatment of 172 patients with licensed dermatological indications (Abstract).
Further regarding independent claim 8, Tyrrell et al. shows in vivo studies have also indicated a positive correlation between PpIX photobleaching and cellular damage, and that PpIX photobleaching particularly during the first minute of irradiation, is also strongly correlated to oxygen consumption during dermatological MAL-PDT, and simple observation of PpIX photobleaching can act as a surrogate for the photodynamic reaction in progress (as the production of singlet oxygen by MAL-PDT interacts with PpIX to produce a non PDT active photoproduct) (page 11, para. 1) (i.e., the generation of singlet oxygen can be measured as a direct correlate to cell viability and thus the success of the PDT).
Regarding claim 9, Tyrrell et al. shows that linear and logistic regressions were employed to model any relationships between variables that may have affected PpIX accumulation and/pr PpIX photobleaching during irradiation and thus clinical outcome at three months (Abstract); PpIX photobleaching during the first treatment was concluded to be an excellent predictor of clinical outcome across all lesion types (Abstract); that in vivo studies have indicated a positive correlation between PpIX photobleaching and cellular damage (i.e., cell viability), and therefore simple observation of PpIX photobleaching can be used as a surrogate for the photodynamic reaction in progress (as the production of singlet oxygen by MAL-ODT interacts with PpIX to produce a non PDT active photoproduct; page 11, para. 1).
Regarding claims 10 and 17, Tyrrell et al. shows protoporphyrin IX (PpIX) as the photosensitizer (Title; Abstract; and throughout); and further shows that there is a relationship between PpIX levels and the applied light dose (e.g., it may be possible to improve outcomes in patient who accumulate high PpIX levels prior to irradiation but then experience relatively low photobleaching during irradiation, by extending the light delivery period to increase the light dose applied if substantial PpIX levels remain at the end of the standard light deliver period (page 10, para. 1)).
Therefore, 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 modify Jones et al. by incorporating the methods of Tyrrell et al. One of ordinary skill in the art would have been motivated to combine the method of Jones et al. with the method of Tyrrell et al. because both Jones et al. and Tyrrell et al. relate to photodynamic therapy and show that providing an improvement of efficacy is required to widen its application (Jones et al. at para [0005]; and Tyrrell et al. at Abstract). This modification would have had a reasonable expectation of success because both Jones et al. and Tyrrell et al. are directed to methods related to determining the amount of a photosensitizer agent present in a target tissue in relation to other condition parameters (e.g., light dosimetry, or photobleaching as a surrogate for cell viability during irradiation).
Furthermore, with regard to independent claim 8, one of ordinary skill in the art would have been motivated to combine the method of Jones et al. with the method of Tyrrell et al. because Jones et al. shows a specific example of a photosensitizer that includes aminolevulinic acid (ALA; which is a precursor for protoporphyrin IX) and Tyrrell et al. shows using protoporphyrin IX, and further shows that protoporphyrin IX is the photosensitizer most commonly used in dermatological photodynamic therapy (page 2, para. 1).
With regard to claim 9, one of ordinary skill in the art would have been motivated to combine the method of Jones et al. with the method of Tyrrell et al. because Jones et al. shows that both protoporphyrin IX accumulation and photobleaching are important indicators of treatment success and that anything that adversely affected them had the potential to reduce treatment efficacy (page 2, para. 2), because protoporphyrin IX accumulation and photobleaching are correlated (FIG. 1; i.e., higher PpIX concentration correlates with photobleaching as a surrogate for cellular damage), and Jones et al. shows methods for determining the amount of photosensitizer agent present in the target tissue in relation to other variables such as light dosimetry (paras. [0017] & [0052]).
With regard to claims 10 and 17, one of ordinary skill in the art would have been motivated to combine the method of Jones et al. with the method of Tyrrell et al. because Jones et al. shows that once a relationship between the amount of a photosensitizer agent and other parameters has been determined, a lookup table or an equation can be saved to computer memory and accessed by a processor for determining the photosensitizer concentration in the target tissue during photodynamic therapy (para. [0037]), and Tyrrell et al. shows that any number of parameters might influence the photodynamic therapy, and thus may also affect treatment efficacy (page 10, para. 1).
Response to Arguments
The Applicant’s arguments/remarks received 08 September 2025 have been fully considered, but are not persuasive.
The Applicant presents the amendments to independent claim 8 on pages 9-10 of the Remarks and states (page 10, middle) that the PDT system of Jones determines the light irradiation conditions based on the concentration of photosensitizer in tissue, however, Jones merely uses a simple proportional relationship or lookup table and fails to teach or disclose the relationship with cell viability and intracellular protoporphyrin (PpIX) accumulation, and that specifically, Jones does not teach or disclose determining a light irradiation density and a 5-aminolevulinic acid dose using “a predetermined relation expression based on the measured intracellular accumulation of protoporphyrin IX, and adjusting the light intensity…based on the light irradiation density” as recited in claim 8, and further that Tyrell, likewise, does not teach or disclose the above feature of claim 8, and therefore claim 8 is patentably distinct.
These arguments are not persuasive, because as shown in the above rejection, the combination of references show the limitations recited in amended independent claim 8, i.e., Jones shows an equation for determination of light dosimetry parameters based on photosensitizer content showing a relationship between administered light dose in units of J/cm and the photosensitizer tissue content in mg/kg (para. [0052]) and that light dosimetry parameters may be determined based on the photosensitizer concentration in the target tissue (para. [0054]); further shows illuminating target tissue of a patient containing a concentration of a photosensitizer with one or more wavelengths suitable for fluorescence excitation of the photosensitizer (para. [0007]); and still further, shows that if the photosensitizer concentration is less than a threshold concentration, the light dose (intensity and/or duration) may be adjusted to improve the effects of the PDT when delivered (para. [0055]). Tyrell shows that PpIX photobleaching can act as a surrogate for the photodynamic reaction in progress, i.e., a measure of cell viability. Therefore, 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 modify Jones et al. by incorporating the methods of Tyrrell et al., as discussed in the above motivation statements.
Conclusion
No claims are allowed.
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.
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/S.W.B./Examiner, Art Unit 1687
/Joseph Woitach/Primary Examiner, Art Unit 1687