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 .
Claims 1, 6, and 7 have been amended.
Claims 1, 3, 6-9, 11-12, 26-34 are pending.
Claims 2, 4, 5, 10, and 13-25 are cancelled.
Claims 26-34 are added
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/02/2026 has been entered.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 6-9, 11-12, 26-34 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2 and 4 of U.S. Patent No. US11285223B2 in view of SINGH (US 10,086,072 B2)The patent teaches, a method for assessing gut function in a subject in need thereof, comprising the steps of:
establishing a baseline of the patient comprising:
administering an effective amount of a composition for assessing gut function, the composition comprising a fluorescent challenge molecule, wherein the fluorescent challenge molecule is not substantially absorbed by a healthy gut (claim 1), wherein the composition is administered orally (claim 2) which reads on enterally administering a first dosage of a composition comprising a fluorescent tracer
irradiating the fluorescent challenge molecule absorbed by the subject's gut with non-ionizing radiation, wherein the radiation causes the fluorescent challenge molecule to fluoresce and detecting the fluorescence of the fluorescent challenge molecule (claim 1), which reads on measuring, via fluorescence, a first amount of the administered dose that can be found outside the gut over a period of time; and
Note, the recitation of “calculating a baseline total percentage of the administered dose recovered” appears to be a mental step.
the detected fluorescence of the fluorescent challenge molecules is measured over time (claim 4), which reads on treating the patient for the digestive disease or the pre-disease state since time can be considered a treatment.
Note the recitation of “comparing the second total percentage of the administered dose recovered to (i)the baseline total percentage of the administered dose recovered and (ii) a mean recovery value of a normal population”, “classifying the patient as having mucosal healing when the second total percentage of the administered dose recovered is less than the baseline of the patient and less than or equal to two standard deviations above the mean recovery value of the normal population” appear to be mental steps.
The patent does not teach measuring again after treatment and maintaining or reducing treatment after the measurements are taken.
SINGH teaches a method of monitoring therapeutic efficiency in an individual receiving therapy having inflammatory bowel disease (IBD), wherein the IBD comprises Crohn's disease, the method comprising: (a) measuring the levels of an array of mucosal healing markers in a sample from the individual at a plurality of time points over the course of therapy; (b) applying a statistical algorithm to the level of the one or more markers determined in step (a) to generate a mucosal healing index; (c) comparing the individual's mucosal healing index to that of a control, wherein the control is an endoscopic score; ( d) determining whether the therapy is appropriate for the individual to promote mucosal healing; and ( e) administering an appropriate therapy (claim 1). Determination of whether a patient should continue therapy or not can be assessed (column 3, paragraph 1). The measurements can be taken prior to therapy with a therapeutic and/or during the course of therapy (column 5, paragraph 6). This allows an assessment of disease induction as well as disease progression and resolution (column 2, paragraph 1). Selecting an appropriate therapy comprises maintaining, increasing, or decreasing a subsequent dose of the course of therapy for the subject (column 6, paragraph 1). In the case of disease resolution, treatment can be stopped so as to avoid the expense and potential toxicity of chronic maintenance therapy in those who have a low risk of recurrence (column 28, paragraph 1).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate measuring the patient again after treatment and adjusting the treatment as needed. The person of ordinary skill in the art would have been motivated to make those modifications, because it allows an assessment of disease induction as well as disease progression and resolution and in the case of disease resolution, treatment can be stopped so as to avoid the expense and potential toxicity of chronic maintenance therapy in those who have a low risk of recurrence, and reasonably would have expected success because both references are in the same field of endeavor, such as assessing gut function in patient.
The references do not specifically teach the dosage concentration as claimed by the Applicant. The dosage concentration is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal dosage concentration in order to best achieve desired results, such as having the appropriate concentration needed for detection due to the photoactive agent employed or the area to be examined. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the dosage concentration would have been obvious at the time of Applicant’s invention.
Claims 1, 3, 6-9, 11-12, 26-34 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. US11077211B2 in view of SINGH (US 10,086,072 B2).
The patent teaches, a method for assessing gut function in a human subject in need thereof, the method comprising the steps of:
establishing a baseline of the patient comprising:
orally administering to the subject an effective amount of a composition comprising two fluorescent challenge molecules, wherein the first fluorescent challenge molecule is not substantially absorbed by a healthy gut, and wherein the second fluorescent challenge molecule is substantially absorbed by a healthy gut into the subject's gut (Claim 1), which reads on enterally administering a first dosage of a composition comprising a fluorescent tracer
irradiating the composition absorbed by the subject's gut with non-ionizing radiation, wherein the radiation causes the composition to fluoresce and detecting the fluorescence of the fluorescent challenge molecules in the composition (claim 1), which reads on measuring, via fluorescence, a first amount of the administered dose that can be found outside the gut over a period of time; and
Note the recitation of “calculating a baseline total percentage of the administered dose recovered” appears to be a mental step.
the detected fluorescence of the fluorescent challenge molecules is measured over time (claim 5), which reads on treating the patient for the digestive disease or the pre-disease state since time can be considered a treatment.
Note the recitation of “comparing the second total percentage of the administered dose recovered to (i)the baseline total percentage of the administered dose recovered and (ii) a mean recovery value of a normal population”, “classifying the patient as having mucosal healing when the second total percentage of the administered dose recovered is less than the baseline of the patient and less than or equal to two standard deviations above the mean recovery value of the normal population” appear to be mental steps.
The patent does not teach measuring again after treatment and maintaining or reducing treatment after the measurements are taken.
SINGH teaches a method of monitoring therapeutic efficiency in an individual receiving therapy having inflammatory bowel disease (IBD), wherein the IBD comprises Crohn's disease, the method comprising: (a) measuring the levels of an array of mucosal healing markers in a sample from the individual at a plurality of time points over the course of therapy; (b) applying a statistical algorithm to the level of the one or more markers determined in step (a) to generate a mucosal healing index; (c) comparing the individual's mucosal healing index to that of a control, wherein the control is an endoscopic score; ( d) determining whether the therapy is appropriate for the individual to promote mucosal healing; and ( e) administering an appropriate therapy (claim 1). Determination of whether a patient should continue therapy or not can be assessed (column 3, paragraph 1). The measurements can be taken prior to therapy with a therapeutic and/or during the course of therapy (column 5, paragraph 6). This allows an assessment of disease induction as well as disease progression and resolution (column 2, paragraph 1). Selecting an appropriate therapy comprises maintaining, increasing, or decreasing a subsequent dose of the course of therapy for the subject (column 6, paragraph 1). In the case of disease resolution, treatment can be stopped so as to avoid the expense and potential toxicity of chronic maintenance therapy in those who have a low risk of recurrence (column 28, paragraph 1).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate measuring the patient again after treatment and adjusting the treatment as needed. The person of ordinary skill in the art would have been motivated to make those modifications, because it allows an assessment of disease induction as well as disease progression and resolution and in the case of disease resolution, treatment can be stopped so as to avoid the expense and potential toxicity of chronic maintenance therapy in those who have a low risk of recurrence, and reasonably would have expected success because both references are in the same field of endeavor, such as assessing gut function in patient.
The references do not specifically teach the dosage concentration as claimed by the Applicant. The dosage concentration is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal dosage concentration in order to best achieve desired results, such as having the appropriate concentration needed for detection due to the photoactive agent employed or the area to be examined. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the dosage concentration would have been obvious at the time of Applicant’s invention.
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 28-30 and 32-34 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.
Regarding claim 28, given the broadest reasonable interpretation of the claims, the boundaries of the percentage ratio in claim 28, are unclear because it is conditional (e.g. only practice if the threshold indicates that the percentage ratio is less than or equal to a threshold selected from 40%, 50%, or 60%, the treatment is continued, reduced or stopped). Thus, the scope remains unclear as to whether the step of adjusting the treatment should be performed if the percentage ratio is above 40%, 50%, or 60%.
Regarding claim 30, given the broadest reasonable interpretation of the claims, the boundaries of the percentage ratio in claim 30, are unclear because it is conditional (e.g. only practice if the threshold indicates that the percentage ratio is greater than a threshold selected from 40%, 50%, or 60%, a second intervention is needed). Thus, the scope remains unclear as to whether the step of adjusting the treatment should be performed if the percentage ratio is below 40%, 50%, or 60%.
Regarding claim 32, given the broadest reasonable interpretation of the claims, the boundaries of the percentage ratio in claim 32, are unclear because it is conditional (e.g. only practice if the threshold indicates that the percentage ratio is less than or equal to a threshold selected from 100%, 150%, or 200%). Thus, the scope remains unclear as to whether the step of maintaining or reducing the treatment should be performed if the percentage ratio is above 100%, 150%, or 200%.
Regarding claim 33, given the broadest reasonable interpretation of the claims, the boundaries of the percentage ratio in claim 33, are unclear because a threshold under 40%, 50%, or 60%. would also be under 100%, 150% and 200%. So it is unclear which action should be taken, stopping, reducing or maintaining treatment.
The dependent claims fall therewith.
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 (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.
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.
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 1, 6-9, 11, 12, 26-28, and 30-34 are rejected under 35 U.S.C. 103 as being unpatentable over DORSHOW (US 2015/0147277A1) in view of SINGH (US 10,086,072 B2).
Regarding claim 1, DORSHOW teaches a method for assessing gut function, specifically the health of the gut (page 1, paragraph 0012) comprising:
establishing a baseline of the patient comprising:
orally administering a composition comprising a fluorescent molecule that is not substantially absorbed by a healthy gut (claims 8 and 9), which reads on enterally administering a first dosage of a composition comprising a fluorescent tracer
The fluorescence is then measured by irradiating the composition absorbed by the subject's gut with non-ionizing radiation, wherein the radiation causes the composition to fluoresce (claim 8), which reads on measuring, via fluorescence, a first amount of the administered dose that can be found outside the gut over a period of time; and
The gut function is assessed in the subject based on the detected fluorescence (claim 8), Gut function is assessed by comparing the detected fluorescence of the fluorescent challenge molecule that is not substantially absorbed by a healthy gut to the fluorescent challenge molecule that is substantially absorbed by a healthy gut (page 4, paragraph 0052), which reads on calculating a baseline total percentage of the administered dose recovered;
The detected fluorescence of the fluorescent challenge molecules is measured over time (claim 14), which reads on treating the patient for the digestive disease or the pre-disease state since time can be considered a treatment.
measuring gut permeability of the patient after treatment comprising:
The composition can be administered in multiple doses (page 6, paragraph 0083), which reads on enterally administering a second dosage of the composition comprising the fluorescent tracer;
The fluorescence is then measured by irradiating the composition absorbed by the subject's gut with non-ionizing radiation, wherein the radiation causes the composition to fluoresce (claim 8), which reads on measuring, via fluorescence, a second amount of the administered dose that can be found outside the gut over a period of time; and
The gut function is assessed in the subject based on the detected fluorescence (claim 8), Gut function is assessed by comparing the detected fluorescence of the fluorescent challenge molecule that is not substantially absorbed by a healthy gut to the fluorescent challenge molecule that is substantially absorbed by a healthy gut (page 4, paragraph 0052), which reads on calculating a second total percentage of the administered dose recovered;
The composition is given orally in a dosage of 6 mg/kg (figure 3).
Additional disclosures: This method can be used to determine response to treatments (paragraph 0028). Common gut issues associated with gut permeability are Crohn’s disease and ulcerative colitis (Page 1, paragraph 3). The dosage of the composition may vary depending upon the particular integrated photoactive agent employed, the areas to be examined, the equipment employed in the clinical procedure, and the efficacy of the treatment achieved (paragraph 0083). DORSHOW teaches that the dose is used to achieve an effect diagnostic objective (page 6, paragraph 0083).
DORSHOW does not teach maintaining or reducing treatment in response to the classification of having mucosal healing.
SINGH teaches a method of monitoring therapeutic efficiency in an individual receiving therapy having inflammatory bowel disease (IBD), wherein the IBD comprises Crohn's disease, the method comprising: (a) measuring the levels of an array of mucosal healing markers in a sample from the individual at a plurality of time points over the course of therapy; (b) applying a statistical algorithm to the level of the one or more markers determined in step (a) to generate a mucosal healing index; (c) comparing the individual's mucosal healing index to that of a control, wherein the control is an endoscopic score; ( d) determining whether the therapy is appropriate for the individual to promote mucosal healing; and ( e) administering an appropriate therapy (claim 1). Determination of whether a patient should continue therapy or not can be assessed (column 3, paragraph 1). The measurements can be taken prior to therapy with a therapeutic and/or during the course of therapy (column 5, paragraph 6). This allows an assessment of disease induction as well as disease progression and resolution (column 2, paragraph 1). Selecting an appropriate therapy comprises maintaining, increasing, or decreasing a subsequent dose of the course of therapy for the subject (column 6, paragraph 1). In the case of disease resolution, treatment can be stopped so as to avoid the expense and potential toxicity of chronic maintenance therapy in those who have a low risk of recurrence (column 28, paragraph 1).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate maintaining or reducing treatment in response to the classification of having mucosal healing. The person of ordinary skill in the art would have been motivated to make those modifications, because once an assessment of disease progression and resolution is determined therapy can either be stopped or continued. If the disease is still present, therapy can be continued whereas if the disease has been resolved unnecessary treatment is no longer needed so as to avoid the expense and potential toxicity of chronic maintenance therapy, and reasonably would have expected success because the references are in the same field of endeavor, such as methods of determining gut health for Crohn’s disease and DORSHOW teaches that the method taught can be used to determine response to treatments.
Note with regard to claim 1, the recitation of “calculating a baseline total percentage of the administered dose recovered”, “calculating a second total percentage of the administered dose recovered”, “comparing the second total percentage of the administered dose recovered to (i) the baseline total percentage of the administered dose recovered and (ii) a mean recovery value of a normal population” and “classifying the patient as having mucosal healing when the second total percentage of the administered dose recovered is less than the baseline of the patient and less than or equal to two standard deviations above the mean recovery value of the normal population” appear to be mental steps. It would also have been obvious to include these mental steps in order to determine the dose recovered and/or to more clearly perform the method of the prior art.
With regard to claim 6, the recitation of “classifying the patient as likely not having mucosal healing” appears to be a mental step.
Regarding claim 7, SINGH teaches determining whether the therapy is appropriate for the individual to promote mucosal healing; and administering an appropriate therapy (claim 1).
Regarding claim 8, SINGH teaches that assessment of healing can be taken at multiple time points including at week 1, up to week 100 (column 5, paragraph 6).
Regarding claim 9, DORSHAW teaches the method is used for Crohn’s disease (Page 1, paragraph 3). SINGH also teaches the method is for Crohn’s disease (claim 1).
Regarding claims 11 and 12, DORSHAW teaches the fluorescent molecule used is 3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]carbamoyl}pyrazine (paragraph 0042).
Regarding claim 26, the references do not specifically teach the dosage concentration as claimed by the Applicant. The dosage concentration is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal dosage concentration in order to best achieve desired results, such as having the appropriate concentration needed for detection due to the photoactive agent employed or the area to be examined. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the dosage concentration would have been obvious at the time of Applicant’s invention.
Regarding claim 27, SINGH teaches that a negative predictive value can be calculated which shows the probability that an individual is not having the predicted therapeutic response to therapy (column 54, paragraph 2). A positive predictive value can be calculated which shows the probability that an individual is having the predicted therapeutic response to therapy (column 54, paragraph 3). These values can be used to select/optimize a treatment option (column 54, paragraph 4). Furthermore, the recitation of “calculating a percentage ratio of the second total percentage of the administered dose recovered to the baseline total percentage of the administered dose recovered” appears to be a mental step.
Regarding claims 28 and 30, in Ex parte Schulhauser, Appeal 2013-007847 (PTAB April 28, 2016) for an analysis of contingent claim limitations in the context of both method claims and system claims. In Schulhauser, both method claims and system claims recited the same contingent step. When analyzing the claimed method as a whole, the PTAB determined that giving the claim its broadest reasonable interpretation, “[i]f the condition for performing a contingent step is not satisfied, the performance recited by the step need not be carried out in order for the claimed method to be performed” (quotation omitted). Schulhauser at 10. When analyzing the claimed system as a whole, the PTAB determined that “[t]he broadest reasonable interpretation of a system claim having structure that performs a function, which only needs to occur if a condition precedent is met, still requires structure for performing the function should the condition occur.” Schulhauser at 14. Therefore "[t]he Examiner did not need to present evidence of the obviousness of the [ ] method steps of claim 1 that are not required to be performed under a broadest reasonable interpretation of the claim (e.g., instances in which the electrocardiac signal data is not within the threshold electrocardiac criteria such that the condition precedent for the determining step and the remaining steps of claim 1 has not been met);" however to render the claimed system obvious, the prior art must teach the structure that performs the function of the contingent step along with the other recited claim limitations. Schulhauser at 9, 14.
In the instant case, the prior art, SINGH, teaches a structure that performs the function of the contingent steps (i.e. negative and positive predictive values that can be used to select/optimize a treatment option (column 54, paragraph 4). The selection of treatment includes optimizing dosage (increase or decrease) or changing treatment to a different drug (column 75, paragraph 3).
Regarding claim 31, SINGH teaches that selecting an appropriate therapy comprises maintaining, increasing, or decreasing a subsequent dose of the course of therapy for the subject (column 6, paragraph 1).
Regarding claim 32, SINGH teaches that selecting an appropriate therapy comprises maintaining, increasing, or decreasing a subsequent dose of the course of therapy for the subject (column 6, paragraph 1). Note the recitation of “calculating a percentage ratio of the second total percentage of the administered dose recovered to an average total percentage of the administered dose recovered in a normal population” appears to be a mental step. The conditional limitation is discussed in the above rejection of claims 28 and 30.
Regarding claim 33, DORSHOW teaches a method for assessing gut function, specifically the health of the gut (page 1, paragraph 0012) comprising:
establishing a baseline of the patient comprising:
orally administering a composition comprising a fluorescent molecule that is not substantially absorbed by a healthy gut (claims 8 and 9), which reads on enterally administering a first dosage of a composition comprising a fluorescent tracer
The fluorescence is then measured by irradiating the composition absorbed by the subject's gut with non-ionizing radiation, wherein the radiation causes the composition to fluoresce (claim 8), which reads on measuring, via fluorescence, a first amount of the administered dose that can be found outside the gut over a period of time; and
The gut function is assessed in the subject based on the detected fluorescence (claim 2), Gut function is assessed by comparing the detected fluorescence of the fluorescent challenge molecule that is not substantially absorbed by a healthy gut to the fluorescent challenge molecule that is substantially absorbed by a healthy gut (page 4, paragraph 0052), which reads on calculating a baseline total percentage of the administered dose recovered;
The detected fluorescence of the fluorescent challenge molecules is measured over time (claim 7), which reads on treating the patient for the digestive disease or the pre-disease state since time can be considered a treatment.
measuring gut permeability of the patient after treatment comprising:
The composition can be administered in multiple doses (page 6, paragraph 0083), which reads on enterally administering a second dosage of the composition comprising the fluorescent tracer;
The fluorescence is then measured by irradiating the composition absorbed by the subject's gut with non-ionizing radiation, wherein the radiation causes the composition to fluoresce (claim 8), which reads on measuring, via fluorescence, a second amount of the administered dose that can be found outside the gut over a period of time;
The gut function is assessed in the subject based on the detected fluorescence (claim 8), Gut function is assessed by comparing the detected fluorescence of the fluorescent challenge molecule that is not substantially absorbed by a healthy gut to the fluorescent challenge molecule that is substantially absorbed by a healthy gut (page 4, paragraph 0052), which reads on calculating a second total percentage of the administered dose recovered;
Note, the recitation of “calculating a percentage ratio of the second total percentage of the administered dose recovered to an average total percentage of the administered dose recovered in a normal population” appears to be a mental step. Furthermore SINGH, as discussed above, does teach calculating positive and negative predictive values.
Note, regarding the recitation of “reducing or stopping the treatment when the percentage ratio is less than or equal to a threshold selected from 40%, 50%, or 60%;maintaining or reducing the treatment when the percentage ratio is less than or equal to a threshold selected from about 100%, about 150%, and about 200%”, the conditional limitations are discussed above. Furthermore, SINGH teaches a structure that performs the function of the contingent steps (i.e. negative and positive predictive values that can be used to select/optimize a treatment option (column 54, paragraph 4). The selection of treatment includes optimizing dosage (increase or decrease) or changing treatment to a different drug (column 75, paragraph 3).
Regarding claim 34, SINGH teaches that selecting an appropriate therapy comprises maintaining, increasing, or decreasing a subsequent dose of the course of therapy for the subject (column 6, paragraph 1). Note the recitation of “calculating a percentage ratio of the second total percentage of the administered dose recovered to an average total percentage of the administered dose recovered in a normal population” appears to be a mental step.
Claims 1, 3, 6-9, 11, 12, 26-28, and 30-34 are rejected under 35 U.S.C. 103 as being unpatentable over DORSHOW (US 2015/0147277A1) and SINGH (US 10,086,072 B2) in further view of DORSHOW 2 (Transdermal fluorescence detection of a dual fluorophore system for noninvasive point-of-care gastrointestinal permeability measurement. Biomedical Optics Express. 2019.).
DORSHOW and SINGH teach Applicant’s invention as discussed above. DORSHAW further teaches the fluorescence is detected by irradiating the composition absorbed by the subject's gut with non-ionizing radiation, wherein the radiation causes the composition to fluoresce (claim 1) and is detected transcutaneously (claim 6).
DORSHOW and SINGH do not teach measuring fluorescence transdermally.
Regarding claim 3, DORSHOW 2 teaches a method for measuring gut function, via measuring the gastrointestinal integrity (abstract). A fluorescence composition is administered, excited and measured transdermally or transcutaneously (Page 5105, paragraph 5 and page 5106, paragraph 2).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate measuring the fluorescence transdermally. The person of ordinary skill in the art would have been motivated to make those modifications, because measuring transdermally or transcutaneously are functional equivalents of measuring fluorescence, and reasonably would have expected success because the references are in the same field of endeavor, measuring fluorescence to determine gut integrity.
Claims 1, 3, 6-9, 11, 12, 26-28, and 30-34 are rejected under 35 U.S.C. 103 as being unpatentable over DORSHOW (US 2015/0147277A1), SINGH (US 10,086,072 B2) and DORSHOW 2 (Transdermal fluorescence detection of a dual fluorophore system for noninvasive point-of-care gastrointestinal permeability measurement. Biomedical Optics Express. 2019.) in further view of HANES (Getting Off Prednisone: Lowering Your Dose to Reduce Withdrawal. Right Care. 2020.).
DORSHOW, SINGH and DORSHOW 2 teach Applicant’s invention as discussed above.
DORSHOW, SINGH and DORSHOW 2 do not teach that stopping treatment involves weaning the patient off medication. SINGH teaches that prednisone can be one of the treatments provided (column 56, paragraph 2).
Regarding claim 29, HANES teaches that when a patient wants to stop taking prednisone, they should taper off (page 2, paragraph 2), which reads on weaning off the patient. Tapering off reduces the risk of withdrawal symptoms which can include body aches, dizziness, extreme fatigue, loss of appetite, nausea, and weakness (page 2, paragraph 3).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate tapering off/weaning off a patient of medication. The person of ordinary skill in the art would have been motivated to make those modifications, because it reduces the risk of withdrawal symptoms such as body aches and dizziness, and reasonably would have expected success because SINGH teaches that one of the treatments that can be provided is prednisone and further teaches that medication can be decreased or stopped.
Response to Arguments
Applicant argues, neither patent requires treating the patient between first and second tracer administrations, nor does either patent require re-administering a tracer after treatment for purposes of determining therapeutic efficacy. Neither patent requires calculating a "total percentage of administered dose recovered" at two separate time points and performing a dual comparison to both a patient-specific baseline and a normal population mean. Neither patent discloses or claims a two-standard-deviation statistical threshold relative to a normal population to define mucosal healing. Critically, neither patent requires modifying therapy -- such as maintaining or reducing a treatment -- in response to a quantified permeability determination. The earlier patents are directed to measuring gut permeability or gut function. They do not claim a therapeutic decision algorithm, do not require classification of mucosal healing using population-based statistical boundaries, and do not require active therapeutic modification in response to that classification. The present claims therefore introduce additional substantive limitations that change the character of the invention from a measurement method to a treatment management method. The newly added dependent claims further reinforce this distinction.
The examiner does not find the argument persuasive because as discussed above, SINGH teaches taking measurements can be taken prior to therapy with a therapeutic and/or during the course of therapy which allows an assessment of disease induction as well as disease progression and resolution. In the case of disease resolution, treatment can be stopped so as to avoid the expense and potential toxicity of chronic maintenance therapy in those who have a low risk of recurrence. The recitation of “calculating” appears to be a mental step.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate measuring the patient again after treatment and adjusting the treatment as needed. The person of ordinary skill in the art would have been motivated to make those modifications, because it allows an assessment of disease induction as well as disease progression and resolution and in the case of disease resolution, treatment can be stopped so as to avoid the expense and potential toxicity of chronic maintenance therapy in those who have a low risk of recurrence, and reasonably would have expected success because both references are in the same field of endeavor, such as assessing gut function in patient.
Additionally, only the broadest claim on the application, in the instant case, claim 1, needs to be rejected for a double patenting rejection to hold. The dependent claims are not needed for the double patenting rejection.
Applicant argues, that instant claim 1 is not merely a method of measuring gut
permeability. It is a closed-loop, statistically defined treatment management method that ties
quantified permeability data to a specific therapeutic action. None of the cited references disclose
or suggest this framework.
The examiner does not find the argument persuasive because as discussed above DORSHOW and SINGH teach the method steps as claimed. Additionally, SINGH teaches using the data to select a specific therapeutic action. Additionally, calculating appears to be a mental step.
Applicant argues, the references do not teach or suggest establishing a patient-specific baseline prior to treatment treating a digestive disease and then re-administering the tracer after treatment, calculating a total percentage of the administered dose recovered pre- and post-treatment, comparing post-treatment permeability to both a patient baseline and a statistically defined normal population mean, applying a two-standard-deviation statistical threshold relative to a normal population, classifying mucosal healing based on that dual statistical comparison, or maintaining or reducing treatment in response to that classification. Dorshow is fundamentally a permeability measurement technology reference and does not teach or suggest a therapeutic decision protocol tied to statistical population thresholds. The Examiner's position effectively converts any measurement method into a treatment management method without evidentiary support. The Examiner has not identified, and the cited art does not disclose, any teaching that mucosal healing can or should be defined as permeability within two standard deviations of a normal population.
The examiner does not find the argument persuasive because SINGH teaches using gut measurements to assess healing and selecting a modification to treatment, such as reducing treatment, based on the measurements. Additionally, calculating and classifying appear to be a mental steps.
Applicant argues, for dosage the "result-effective variable" doctrine to apply, the prior art must recognize that the parameter affects the result in a predictable way. Dorshow does not identify mg/kg dosage as affecting the ability to classify mucosal healing relative to statistical thresholds, nor is there any teaching that permeability resolution, baseline comparability, or population threshold analysis is optimized by adjusting dosage within the claimed range.
The examiner does not find the argument persuasive because DORSHOW teaches the composition is given orally in a dosage of 6 mg/kg. Additionally, DORSHOW teaches that the dose is used to achieve an effect diagnostic objective and the dosage of the composition may vary depending upon the particular integrated photoactive agent employed, the areas to be examined, the equipment employed in the clinical procedure, and the efficacy of the treatment achieved.
Applicant argues, newly added claims 27-34 introduce additional layers of quantitative therapeutic decision-making, including calculation of a percentage ratio of post-treatment recovery to baseline, application of defined thresholds such as 40%, 50%, or 60%, maintenance, reduction, stopping, or intervention based on those thresholds, weaning, and comparison to 100%, 150%, or 200% of a normal population value. None of the cited references disclose or suggest this structured, multi-threshold decision tree. The cited references do not teach ratio-based treatment management or tiered therapeutic consequences tied to quantitative permeability thresholds.
The examiner does not find the argument persuasive because as discussed above, SINGH teaches SINGH, teaches a structure that performs the function of the contingent steps (i.e. negative and positive predictive values that can be used to select/optimize a treatment option (column 54, paragraph 4). The selection of treatment includes optimizing dosage (increase or decrease) or changing treatment to a different drug (column 75, paragraph 3).
Applicant argues, the examiner effectively assumes that permeability equals mucosal healing, that permeability should be compared to a statistical normal population, that two standard-deviations define healing, and that therapy should be modified accordingly. These elements originate from Applicant's disclosure, not from the cited art.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, 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. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, as discussed above, DORSHOW teaches the same method steps as claimed by applicant including administering a fluorescent composition, such as 3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]carbamoyl}pyrazine, that can be found outside the gut over a period of time and SINGH teaches using these measurements to determine positive and negative values that corelate to the efficacy of treatment. These measurements then in turn are used to select a modification of treatment.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL HARTLEY can be reached at (571) 272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.L.M./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
Prosecution Insights