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 .
Claim Objections
Claims 2 and 6 are objected to because the claims are not full sentence as they do not end with a period. The MPEP, in section 608.01(m), states: “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995).”
Appropriate action required.
Claim Rejections - 35 USC § 101
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 1-14, 17-18, 58, and 75 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claims 1-18 are drawn to methods and a non-transitory computer readable storage media device, which is/are statutory categories of invention (Step 1: YES).
Independent claim 1 recites (i) prior to treatment with a therapeutic agent, (a) providing a patient-reported outcome (PRO) questionnaire; (b) recording each episode of dysphagia, at the time the episode occurs, for a period of at least about two weeks using the PRO questionnaire; and (iii) recording, using the PRO questionnaire, each episode of dysphagia, at the time each episode occurs, while the patient is being treated, wherein dysphagia over a two week period of time while the patient is being treated is reduced compared to the dysphagia prior to treatment.
Independent claim 58 recites (a) provide a questionnaire to a patient, wherein the questionnaire comprises: at least one input to record episode-based dysphagia events; wherein said input records: (i) at least one question determining the severity of the dysphagia event as the event occurs; (ii) at least one question determining the pain associated with the dysphagia event, as the event occurs; and (ii) at least one question determining the discomfort associated with the dysphagia event, as the event occurs; and (b) apply an algorithm to answers to said questions to determine a score calculated over 1-21 days, wherein the algorithm comprises: scoring the at least one severity question from 0 to 10; scoring the at least one pain question from 0 to 10; scoring the at least one discomfort question from 0 to 10; summing the scores of all the questions presented in the questionnaire; and calculating the daily average score; (c) evaluating the evaluating the daily score against a treatment range; and (d) if the daily score falls within a treatment range, instruct the administration of a therapeutic agent.
Independent claim 75 (a) providing a PRO questionnaire to a patient, wherein the PRO questionnaire comprises: (i) at least one question determining the severity of the dysphagia event, as the event occurs; (ii) at least one question determining the pain associated with the dysphagia event, as the event occurs; and (ii) at least one question determining the discomfort associated with the dysphagia event, as the event occurs; and (b) applying an algorithm to answers to said questions to determine a score calculated over 1-21 days, wherein the algorithm comprises: scoring the at least one severity question from 0 to 10; scoring the at least one pain question from 0 to 10; scoring the at least one discomfort question from 0 to 10; summing the scores of all the questions presented in the questionnaire; and calculating the daily average score; (c) evaluating the evaluating the daily score against a treatment range; and (d) administering a therapeutic agent to the patient when the daily average score falls within the treatment range.
The respective dependent claims 2-14 and 17-18, but for the inclusion of the additional elements specifically addressed below, provide recitations further limiting the invention of the independent claim(s).
Said recited limitations, as drafted, under their broadest reasonable interpretation, cover certain methods of organizing human activity, as reflected in the specification, which states that having a (patient-reported outcome) “PRO assessment used in the methods disclosed herein improves on current assessments by providing a real-time assessment of patient symptoms by including an episode-based diary” (see: specification paragraph 86). If a claim limitation, under its broadest reasonable interpretation, covers managing personal behavior or relationships or interactions between people, then it falls within the “Certain Methods of Organizing Human Activity” grouping of abstract ideas. The present claims cover certain methods of organizing human activity because they address a problem where, “[b]ecause the symptoms of EoE overlap with GERD and other inflammatory conditions, diagnosis of EoE and treatment is difficult” (see: specification paragraph 4), so “[t]here exists a need in the art for accurate methods of recording episodes of dysphagia and treating dysphagic diseases such as EoE based on thereon” (see: specification paragraph 5). Accordingly, the claims recite an abstract idea(s) (Step 2A Prong One: YES).
This judicial exception is not integrated into a practical application. The claims are abstract but for the inclusion of the additional elements including “via a digital processing device…” (claim 1), “non-transitory computer readable storage media device encoded with a computer program including instructions executable by a digital processing device…instructions configured to…instructions configured to…via the digital processing device…the device is configured to…” (claim 58), and “via a digital processing device…via the digital processing device…” (claim 75), which are additional elements that are recited at a high level of generality (e.g., the “digital processing device” is employed though no more than a statement than functions are performed “via” said device or that said device is “configured” to perform functions; the “non-transitory computer readable storage media device encoded with a computer program” is executable by a digital processing device to perform functions through no more than a statement than that “instructions” are “configured to” perform said functions) such that they amount to no more than mere instruction to apply the exception using generic computer elements. See: MPEP 2106.05(f).
The claims recite the additional elements of “(c) measuring esophageal eosinophils in the patient; then (ii) treating the patient with a therapeutically effective amount of a therapeutic agent for at least two weeks” (claim 1), “wherein the therapeutic agent is a corticosteroid, a proton pump inhibitor (PPI), or an antibody” (claim 4), “wherein the corticosteroid is budesonide, fluticasone, flunisolide, ciclesonide, mometasone, beclomethasone, or tixocortol, or a salt, ester, solvate, polymorph, or prodrug thereof” (claim 5), “wherein the PPI is omeprazole, lansoprazole, dexlansoprazole, esomeprazole, pantoprazole, or rabeprazole” (claim 6), “wherein the antibody is an IL-4, IL-5, or IL-13 antibody” (claim 7), “wherein the antibody is benralizumab, mepolizumab, dupilumab, RPC-4046” (claim 8), “wherein the esophageal eosinophils are measured by obtaining a biopsy” (claim 9), “wherein the biopsy is an endoscopy” (claim 10), “measuring esophageal eosinophils in the patient after the patient has been treated with the therapeutic agent for at least two weeks” (claim 12), “wherein after step (iii) the patient continues treatment with the therapeutic agent at the same dose as used in step (ii)” (claim 17), and “after step (iii), the method further comprises administering a dose of the therapeutic agent which is decreased by at least about 5%” (claim 18), which are nominal or tangential addition to the abstract idea(s) and amount to extra-solution activity concerning mere data gathering. The addition of an insignificant extra-solution activity limitation does not impose meaningful limits on the claim such that is it not nominally or tangentially related to the invention. In the claimed context, these claimed additional elements are incidental to the performance of the recited abstract idea(s) as outlined in the recitations above. See: MPEP 2106.05(g).
The combination of these additional elements is no more than mere instructions to apply the exception using generic computer elements and limitations directed toward extra-solution activity. Accordingly, even in combination, these additional elements do not integrate the abstract idea(s) into a practical application because they do not impose any meaningful limits on practicing the abstract idea(s). Accordingly, the claims are directed to an abstract idea(s) (Step 2A Prong Two: NO).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As discussed above with respect to integration of the abstract idea(s) into a practical application, using the additional elements to perform the abstract idea(s) amounts to no more than mere instructions to apply the exception using generic components. Mere instructions to apply an exception using generic components cannot provide an inventive concept. See MPEP 2106.05(f).
Further, the claimed additional elements directed toward extra-solution activity, identified above, are not sufficient to amount to significantly more than the judicial exception because they are generic components that are configured to perform well-understood, routine, and conventional activities previously known to the industry. See: MPEP 2106.05(d). Said additional elements are recited at a high level of generality and provide conventional functions that do not add meaningful limits to practicing the abstract idea(s). The originally filed specification supports this conclusion:
Paragraph 8, where “In some embodiments, the therapeutic agent is a corticosteroid, a proton pump inhibitor (PPI), or an antibody, e.g., any therapeutic agent described herein. In some embodiments, the corticosteroid is budesonide, fluticasone, flunisolide, ciclesonide, mometasone, beclomethasone, or tixocortol, or a salt, ester, solvate, polymorph, or prodrug thereof. In some embodiments, the PPI is omeprazole, lansoprazole, dexlansoprazole, esomeprazole, pantoprazole, or rabeprazole. In some embodiments, the antibody is an IL-4, IL-5, or IL-13 antibody. In some embodiments, the antibody is benralizumab, mepolizumab, dupilumab, RPC-4046.”
Paragraph 93, where “In some embodiments, the PRO assessment is used for monitoring the effect of various treatments for dysphagia, including but not limited to, diet changes, proton pump inhibitors (PPI), dilating strictures, or therapeutic agents (e.g. corticosteroids, such as fluticasone propionate or biologics)…”
Paragraph 102, where “In addition to the PRO assessment and the methods of using the same as described herein, the treatment of gastrointestinal inflammation may also be measured by any means known in the art. For example, tests used to evaluate patients with esophageal inflammation such as EoE include, but are not limited to, biopsies, evaluation of symptoms (e.g. through patient reported outcome (PRO) or physician questionnaire), quality of life measurements, determination of Dysphagia-Free-Days in a patient, endoscopy (e.g. EREFS), esophageal compliance and/or improvement in esophageal remodeling (e.g. using a suitable diagnostic test such as EndoFLIP (available from Crospon Inc.), evaluation of biomarkers, decrease in peak eosinophil count, decrease in food impaction, and/or histology.”
Paragraph 132, where “In some embodiments, histology scores are measured prior to initiating treatment according to the present methods. In some embodiments, histology scores are measured at least two weeks after initiating treatment according to the present methods. In some embodiments, histology scores are measured prior to initiating treatment according to the present methods, and at least two weeks after initiating such treatment.”
Paragraph 138, where “…determining the number of episodes of dysphagia over a period of time, e.g., about two weeks…”
Paragraph 149, where “…In some embodiments, the disclosure provides for a therapeutic agent (as described herein e.g. a corticosteroid or antibody) for use in a method of treating dysphagia...”
Paragraph 151, where “In some embodiments, the therapeutic agents disclosed herein are co-administered with one or more corticosteroids. Suitable corticosteroids include, but are not limited to hydrocortisone, prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, etc. or mineralocorticoid potencies (e.g., alsosterone), budesonide, fluticasone, flunisolide, ciclesonide, mometasone, beclomethasone, tixocortol and salts, or esters and mixtures thereof.”
Paragraph 152, where “In some embodiments, therapeutic agents disclosed herein are co-administered with one or more proton pump inhibitors (PPI). Suitable PPIs include, but are not limited to, omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, and esomeprazole. In some embodiments the PPI is administered at high doses.”
Paragraph 163, where “The therapeutic agents disclosed herein may be administered in any appropriate dose and using any therapeutic agent. While one of skill in the art can determine the desirable dose in each case…”
The claims recite the additional elements directed to pre-solution and post-solution activity, as recited and indicated above, each of which amount to extra-solution activity. The specification (e.g., as excerpted above) does not indicate that the additional element(s) provide anything other than well‐understood, routine, and conventional functions when claimed in a merely generic manner (as they are presently). See: MPEP 2106.05(g).
Further, the concepts of receiving or transmitting data over a network, such as using the Internet to gather data, storing and retrieving information in memory, determining the level of a biomarker in blood by any means (the claimed measuring), and immunizing a patient against a disease (the claimed treating) have been identified by the courts as well-understood, routine, and conventional activities. See: MPEP 2106.05(d)(II).
Further, the additional elements that are nominal or tangential addition to the abstract idea(s) and amount to extra-solution activity are demonstrated to be widely prevalent or in common use in the following publications:
U.S. Patent Application Publication 2016/0213681 (para 4);
U.S. Patent Application Publication 2017/0199191 (para 3);
U.S. Patent Application Publication 2014/0163389 (para 3);
U.S. Patent Application Publication 2016/0152718 (abstract, para 5, 9-10, 22-23, 34, 39, 42, and 53-54);
U.S. Patent Application Publication 2015/0017176 (abstract, para 9-10, 22-23, 34, 39, 42, and 53-54);
U.S. Patent Application Publication 2016/0078186 (para 101, 174, 16-18, 87, 101, 142, 174, and 181-182);
U.S. Patent Application Publication 2019/0040126 (paragraph 16-18, 87, and 142);
WO 2018/035393A1 (abstract, para 11, 16, 56, 167, 187, 210, 222-223, 231, 425-426); and
de Rooij, W.E., Dellon, E.S., Parker, C.E. et al. Pharmacotherapies for the Treatment of Eosinophilic Esophagitis: State of the Art Review. Drugs 79, 1419–1434 (2019) (abstract).
Viewing the limitations as an ordered combination, the claims simply instruct the additional elements to implement the concept described above in the identification of abstract idea(s) with routine, conventional activity specified at a high level of generality in a particular technological environment. Hence, the claims as a whole, considering the additional elements individually and as an ordered combination, do not amount to significantly more than the abstract idea(s) (Step 2B: NO).
Dependent claim(s) 2-14 and 17-18, when analyzed as a whole, considering the additional elements individually and/or as an ordered combination, are held to be patent ineligible under 35 U.S.C. 101 because the additional recited limitation(s) fail(s) to establish that the claim(s) is/are not directed to an abstract idea(s) without significantly more. These claims fail to remedy the deficiencies of their parent claims above, and are therefore rejected for at least the same rationale as applied to their parent claims above, and incorporated herein.
As per claims 19 and 20, the limitations of “wherein the patient is treated with the decreased dose of the therapeutic agent for at least the period of time during which the number of episodes of dysphagia are reduced as determined via the PRO questionnaire” (claim 19) and “…the method further comprises administering the same dose as in step (ii)” (claim 20), when considered in ordered combination with the limitations of the claims from which they depend, provide significantly more than the abstract idea(s). If these limitations and the limitations of the claims from which they depend were properly incorporated into their respective independent claim, said independent claim would be rendered statutory.
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 58 and 75 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 pre-AIA the applicant regards as the invention.
As per claims 58 and 75, the claims each teach two “(ii)” limitations under section “(a)”, and it is unclear as to if these are meant to be alternatives or a singular limitation or something altogether different.
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.
Claim(s) 1-14 and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication 2016/0078186 to Hill in view of U.S. Patent Application Publication 2019/0040126 to Radin.
As per claim 1, Hill teaches a method of managing eosinophilic esophagitis (EoE) in a patient in need thereof (see: Hill, abstract, a daily patient questionnaire, the questionnaire; para (0006), the patient has dysphagia associated with eosinophilic esophagitis; (0171), To demonstrate that an oral budesonide solution (OBS) induces, over a 12-week course of therapy: ... a symptom response as measured by the Dysphagia Symptom Questionnaire (DSQ)), comprising:
(i) prior to treatment with a therapeutic agent (see: Hill, para (0174). Patients were given a placebo for a 4-week period to establish a Baseline for the co-primary endpoint determinations),
(a) providing, via a digital processing device (abstract, computer-based systems, software, and methods of using the same including a daily patient questionnaire.), a patient-reported outcome (PRO) questionnaire (see: Hill, Title, A PATIENT-REPORTED OUTCOME MEASURE OF DYSPHAGIA PATIENTS WITH EOSINOPHILIC ESOPHAGITIS);
(b) recording each episode of dysphagia, at the time the episode occurs, for a period of at least about two weeks using the PRO questionnaire (see: Hill, para (0189), A paper-based 4-question DSQ (see FIG. 21) was converted into an electronic format for hand-held devices.; Fig. 21, 02 "Since you work up this morning, has food gone down slowly or been stuck in your throat."), for a period of at least about two weeks using the PRO questionnaire (see: Hill, para (0174), a Final Treatment Period Evaluation at week 16; paragraph 86 and 93, is met by 14 day period of time); and
(c) measuring esophageal eosinophils in the patient (see: Hill, para (0176), 93 randomized EoE subjects 11-40 years old with >15/HPF at two levels of the esophagus and persistent dysphagia after 4 week blinded placebo Baseline period);
then (ii) treating the patient with a therapeutically effective amount of a therapeutic agent for at least two weeks (see: Hill, para (0174), Patients were then divided into 2 groups, one receiving OBS treatment and the other continued placebo for a 12-week period; paragraph 86 and 93, is met by 14 day period of time); and
(iii) recording, using the PRO questionnaire, each episode of dysphagia, at the time each episode occurs, while the patient is being treated (see: Hill, para (0174), a Final Treatment Period Evaluation at week 16.; abstract, a daily patient questionnaire), wherein dysphagia over a period of time while the patient is being treated is reduced compared to the dysphagia prior to treatment (see: Hill, para (0194), The proportion of subjects who were overall responders, which is defined as a reduction in the DSQ Score of >30% from Baseline to the Final Treatment Period Evaluation and a peak eosinophil count of <6/HPF across all available esophageal levels at the Final Treatment Period Evaluation (week 16), is shown in FIG. 24).
Hill teaches a 16 week period, which meets a period of for at least two weeks, but fails to teach wherein dysphagia over a period of time while the patient is being treated is reduced compared to the dysphagia prior to treatment for a two week period; however, Radin teaches that a parameter is quantified at baseline and at one or more time-points after administration of the pharmaceutical composition of the present invention, such that an EoE-related parameter may be measured at day 14 or at the end of week 2, where pharmaceutical composition administration may include or exceed up to two weeks (see: Radin, paragraph 54, 66, 99, 124, and 155).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the period of time as taught by Hill to be a two week period of time as taught by Radin with the motivation of determining whether the EoE-related parameter has "improved" (see: Radin, paragraph 64-66).
As per claim 2, Hill and Radin teach the invention as claimed, see discussion of claim 1, and further teach:
wherein recording in step (i)(b) comprises recording one or more of: incidence of an episode of dysphagia; duration of dysphagia, severity of dysphagia pain caused by dysphagia; discomfort of dysphagia (see: Hill, Fig. 21, Q2 "Since you work up this morning, has food gone down slowly or been stuck in your throat.");
As per claim 3, Hill and Radin teach the invention as claimed, see discussion of claim 1, and further teach:
wherein recording in step (iii) comprises recording one or more of: incidence of an episode of dysphagia, duration of dysphagia, severity of the episode of dysphagia, time and date of administering treatment (see: Hill, Fig. 21, Q2 "Since you work up this morning, has food gone down slowly or been stuck in your throat.").
As per claim 4, Hill and Radin teach the invention as claimed, see discussion of claim 1, and further teach:
wherein the therapeutic agent is a corticosteroid, a proton pump inhibitor (PPI), or an antibody (see: Hill, para 174, patients were then divided into 2 groups, one receiving OBS (Oral Budesonide Solution) treatment and the other continued placebo for a 12-week period).
As per claim 5, Hill and Radin teach the invention as claimed, see discussion of claim 4, and further teach:
wherein the corticosteroid is budesonide, fluticasone, flunisolide, ciclesonide, mometasone, beclomethasone, or tixocortol, or a salt, ester, solvate, polymorph, or prodrug thereof (see: Hill, para 174, Patients were then divided into 2 groups, one receiving OBS (Oral Budesonide Solution) treatment and the other continued placebo for a 12-week period).
As per claim 6, Hill and Radin teach the invention as claimed, see discussion of claim 4, and further teach:
wherein the PPI is omeprazole, lansoprazole, dexlansoprazole, esomeprazole, pantoprazole, or rabeprazole (see: Hill, para 101, the therapy comprises orally administering to the patient an effective amount of a proton pump inhibitor (PPI), e.g., omeprazole, lansoprazole, dexlansoprazole, esomeprazole, pantoprazole, or rabeprozol).
As per claim 7, Hill and Radin teach the invention as claimed, see discussion of claim 4, and further teach:
wherein the antibody is an IL-4, IL-5, or IL-13 antibody (see: Radin, paragraph 16, 55, and 114, is met by the IL-4/IL-13, IL-5 inhibitor such as an antibody).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the treatment as taught by Hill to include the IL-4/IL-13, IL-5 inhibitor such as an antibody as taught by Radin with the motivation of treating or inhibiting or preventing active eosinophilic esophagitis in a subject, including humans (see: Radin, paragraph 18).
As per claim 8, Hill and Radin teach the invention as claimed, see discussion of claim 7, and further teach:
wherein the antibody is benralizumab, mepolizumab, dupilumab, RPC-4046 (see: Radin, paragraph 16-18, 87, and 142, is met by dupilumab).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the treatment as taught by Hill to include dupilumab as taught by Radin with the motivation of treating or inhibiting or preventing active eosinophilic esophagitis in a subject, including humans (see: Radin, paragraph 18).
As per claim 9, Hill and Radin teach the invention as claimed, see discussion of claim 1, and further teach:
wherein the esophageal eosinophils are measured by obtaining a biopsy (see: Hill, paragraph 181-182, biopsy, and Table 8-9, endoscopy).
As per claim 10, Hill and Radin teach the invention as claimed, see discussion of claim 9, and further teach:
wherein the biopsy is an endoscopy (see: Hill, Table 8-9, endoscopy).
As per claim 11, Hill and Radin teach the invention as claimed, see discussion of claim 1, and further teach:
wherein the patient has an esophageal eosinophil count of ≥15 per high-power field (HPF) (see: Hill, paragraph 176, with > 15/HPF).
As per claim 12, Hill and Radin teach the invention as claimed, see discussion of claim 1, and further teach:
measuring esophageal eosinophils in the patient after the patient has been treated with the therapeutic agent for at least two weeks (see: Radin, paragraph 54, 66, 99, 124, and 155, is met by a parameter is quantified at baseline and at one or more time-points after administration of the pharmaceutical composition of the present invention, such that an EoE-related parameter may be measured at day 14 or at the end of week 2, where pharmaceutical composition administration may include or exceed up to two weeks).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the period of time as taught by Hill to be a two week period of time as taught by Radin with the motivation of determining whether the EoE-related parameter has "improved" (see: Radin, paragraph 64-66).
As per claim 13, Hill and Radin teach the invention as claimed, see discussion of claim 11, and further teach:
wherein the patient is a histological non-responder (see: Radin, paragraph 7-9, 40, 42, and 114, is met by patient characteristics such as patients that are unresponsive or resistant to prior treatment, non-responsive or resistant to prior therapy).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the patient information as taught by Hill to include patient characteristics that include unresponsive or resistant to prior treatment, non-responsive or resistant to prior therapy as taught by Radin with the motivation of selecting a patient with moderate-to-severe EoE and administering a
therapeutically effective amount of a pharmaceutical composition (see: Radin, paragraph 8 and 40).
As per claim 14, Hill and Radin teach the invention as claimed, see discussion of claim 12, and further teach:
wherein the patient has an esophageal eosinophil count of ≤15 per high-power field (HPF) (see: Hill, paragraph 176-177, with > 15/HPF, eosinophil count of <6/HPF across all available esophageal levels at the Final Treatment Period Evaluation).
As per claim 17, Hill and Radin teach the invention as claimed, see discussion of claim 1, and further teach:
wherein after step (iii) the patient continues treatment with the therapeutic agent at the same dose as used in step (ii) (see: Hill, paragraph 175, 10 mL/dose given twice daily in Treatment Period).
As per claim 18, Hill and Radin teach the invention as claimed, see discussion of claim 1, and further teach:
after step (iii), the method further comprises administering a dose of the therapeutic agent which is decreased by at least about 5% (see: Radin, paragraph 55 and 101, is met by the IL-4/IL-13 pathway inhibitor is administered the subject at a decreasing dose over time, and the amount in the initial, secondary and/or tertiary doses varies from one another (e.g., adjusted down as appropriate) during the course of treatment, and the first amount (initial dose) is 1.5x the second amount (secondary dose)).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the does as taught by Hill to include a decreasing dose over time such as the initial does being 1.5x the secondary dose as taught by Radin with the motivation of providing a therapeutically effective amount of a pharmaceutical composition in combination with a background therapeutic regimen a subject is on (see: Radin, paragraph 55).
As per claim 19, Hill and Radin teach the invention as claimed, see discussion of claim 18, and further teach:
wherein the patient is treated with the decreased dose of the therapeutic agent for at least the period of time during which the number of episodes of dysphagia are reduced as determined via the PRO questionnaire (see: Radin, paragraph 55 and 101, is met by the IL-4/IL-13 pathway inhibitor is administered the subject at a decreasing dose over time, and the amount in the initial, secondary and/or tertiary doses varies from one another (e.g., adjusted down as appropriate) during the course of treatment, and the first amount (initial dose) is 1.5x the second amount (secondary dose)).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the does as taught by Hill to include a decreasing dose over time during the course of treatment as taught by Radin with the motivation of providing a therapeutically effective amount of a pharmaceutical composition in combination with a background therapeutic regimen a subject is on (see: Radin, paragraph 55).
As per claim 20, Hill and Radin teach the invention as claimed, see discussion of claim 19, and further teach:
wherein if the number of episodes of dysphagia increases while the patient is receiving the decreased dose, as determined via the PRO questionnaire, the method further comprises administering the same dose as in step (ii) (see: Radin, paragraph 55 and 101, is met by the IL-4/IL-13 pathway inhibitor is administered the subject at a constant dose, or at an increasing dose, or at a decreasing dose, over time, and the amount in the initial, secondary and/or tertiary doses varies from one another (e.g., adjusted down as appropriate) during the course of treatment).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the does as taught by Hill to include a constant dose, or at an increasing dose, or at a decreasing dose, over time, adjust as appropriate during the course of treatment, as taught by Radin with the motivation of providing a therapeutically effective amount of a pharmaceutical composition in combination with a background therapeutic regimen a subject is on (see: Radin, paragraph 55).
Claim(s) 58 and 75 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication 2016/0078186 to Hill.
As per claim 58, Hill teaches a non-transitory computer readable storage media device encoded with a computer program including instructions executable by a digital processing device for treating dysphagia in a patient in need thereof (see: Hill, paragraph 38, 108, 115, and 117), comprising
(a) instructions configured to provide a questionnaire to a patient, wherein the questionnaire comprises: at least one input to record episode-based dysphagia events (see: Hill, Fig. 1-3, paragraph 37 and 51-53 and 58 is met by patient questionnaire comprising questions to elicit input form a patient);
wherein said input records: (i) at least one question determining the severity of the dysphagia event as the event occurs (see: Hill, Fig. 5, and paragraph 37, 55-56, 62, and 64-65, is met by a question for determining whether the patient had difficulty swallowing solid food);
(ii) at least one question determining the pain associated with the dysphagia event, as the event occurs (see: Hill, Fig. 7, and paragraph 37, 55-56, and 68-69, is met by a question for determining the amount of pain the patient experienced while swallowing food, including a pain scale of 1 to 10); and
(ii) at least one question determining the discomfort associated with the dysphagia event, as the event occurs (see: Hill, Fig. 6, and paragraph 37, 55-56, and 65-67, is met by question for determining what action the patient took to correct or relieve difficulty swallowing food); and
(b) instructions configured to apply via the digital processing device an algorithm to answers to said questions to determine a score calculated over 1-21 days, wherein the algorithm comprises (see: Hill, paragraph 37, 86, and 93, is met by applying an algorithm to answers to one or more of said questions to determine a score, where an algorithm comprises numeric elements assigned to each answer option to one or more questions of a questionnaire, and a wide range of time periods for daily scores including 1-21 days):
scoring the at least one severity question (see: Hill, paragraph 37, 86, 91, and 94-95, is met by said score illustrates severity, where answer options for question determining whether the patient had difficulty swallowing solid food);
scoring the at least one pain question (see: Hill, paragraph 37, 86, 91, and 94-95, is met by said score illustrates severity, where answer options for determining the amount of pain a patient experienced when swallowing food are based on the severity of the pain);
scoring the at least one discomfort question (see: Hill, paragraph 37, 86, 91, and 94-95, is met by said score illustrates intensity, where answer options for determining what action the patient took to correct or relieve difficulty swallowing food are assigned numeric elements based on the severity of the action);
summing the scores of all the questions presented in the questionnaire (see: Hill, paragraph 86 and 91, is met by a daily score is the sum of the numeric elements for the selected answer option for each question); and
calculating the daily average score (see: Hill, paragraph 93, is met by a daily average score such as sum of daily scores divided by number of days, where a wide range of time periods for daily scores are possible, including 1-21 days);
(c) evaluating the evaluating the daily score against a treatment range (see: Hill, paragraph 37 and 98-104, is met by said score illustrates suitability of a patient for a particular therapy for dysphagia, where the average daily score above or below a threshold indicates suitability of a patient for a particular therapy); and
(d) if the daily score falls within a treatment range, the device is configured to instruct the administration of a therapeutic agent (see: Hill, paragraph 37, 98-104, and 108, is met by said score illustrates suitability of a patient for a particular therapy for dysphagia such as a one pharmacologic agent, where the average daily score is used in therapy such as a treatment, and communicate information for display to a patient, caregiver, or healthcare provider).
Hill fails to specifically teach scoring the questions from 0 to 10; however, Hill does teach scoring the questions by assigning other numeric elements to the answers including numeric elements up to 10 (see: Hill, paragraph 94-95), and it would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the scoring to include numeric elements from 0 to 10, as claimed, with the motivation of optionally tuning to focus on dysphagia symptom severity or detecting differences or changes in dysphagia symptom severity (see: Hill, paragraph 94).
Additionally or alternately, the range from 0 to 10 is considered similar to the ranges applied by Hill (see: Hill, paragraph 37, 86, 91, and 94-95), such that it would have been obvious to one of ordinary skill in the art at the time the intention was filed to expect similar results (see: MPEP, 2144.05, I).
As per claim 75, Hill teaches a method for treating dysphagia in a patient in need thereof, comprising
(a) providing, via a digital processing device (see: Hill, paragraph 38, 108, 115, and 117, abstract, computer-based systems, software, and methods of using the same including a daily patient questionnaire), a PRO questionnaire to a patient (see: Hill, Title, A PATIENT-REPORTED OUTCOME MEASURE OF DYSPHAGIA PATIENTS WITH EOSINOPHILIC ESOPHAGITIS),
wherein the PRO questionnaire comprises: (i) at least one question determining the severity of the dysphagia event, as the event occurs (see: Hill, Fig. 5, and paragraph 37, 55-56, 62, and 64-65, is met by a question for determining whether the patient had difficulty swallowing solid food);
(ii) at least one question determining the pain associated with the dysphagia event, as the event occurs (see: Hill, Fig. 7, and paragraph 37, 55-56, and 68-69, is met by a question for determining the amount of pain the patient experienced while swallowing food, including a pain scale of 1 to 10); and
(ii) at least one question determining the discomfort associated with the dysphagia event, as the event occurs (see: Hill, Fig. 6, and paragraph 37, 55-56, and 65-67, is met by question for determining what action the patient took to correct or relieve difficulty swallowing food); and
(b) applying, via the digital processing device, an algorithm to answers to said questions to determine a score calculated over 1-21 days, wherein the algorithm comprises (see: Hill, paragraph 37, 86, and 93, is met by applying an algorithm to answers to one or more of said questions to determine a score, where an algorithm comprises numeric elements assigned to each answer option to one or more questions of a questionnaire, and a wide range of time periods for daily scores including 1-21 days):
scoring the at least one severity question (see: Hill, paragraph 37, 86, 91, and 94-95, is met by said score illustrates severity, where answer options for question determining whether the patient had difficulty swallowing solid food);
scoring the at least one pain question (see: Hill, paragraph 37, 86, 91, and 94-95, is met by said score illustrates severity, where answer options for determining the amount of pain a patient experienced when swallowing food are based on the severity of the pain);
scoring the at least one discomfort question from (see: Hill, paragraph 37, 86, 91, and 94-95, is met by said score illustrates intensity, where answer options for determining what action the patient took to correct or relieve difficulty swallowing food are assigned numeric elements based on the severity of the action);
summing the scores of all the questions presented in the questionnaire (see: Hill, paragraph 86 and 91, is met by a daily score is the sum of the numeric elements for the selected answer option for each question); and
calculating the daily average score (see: Hill, paragraph 93, is met by a daily average score such as sum of daily scores divided by number of days, where a wide range of time periods for daily scores are possible, including 1-21 days);
(c) evaluating the evaluating the daily score against a treatment range (see: Hill, paragraph 37 and 98-104, is met by said score illustrates suitability of a patient for a particular therapy for dysphagia, where the average daily score above or below a threshold indicates suitability of a patient for a particular therapy); and
(d) administering a therapeutic agent to the patient when the daily average score falls within the treatment range (see: Hill, paragraph 37, 98-104, and 108, is met by said score illustrates suitability of a patient for a particular therapy for dysphagia such as a one pharmacologic agent, where the average daily score is used in therapy such as a treatment, and communicate information for display to a patient, caregiver, or healthcare provider).
Hill fails to specifically teach scoring the questions from 0 to 10; however, Hill does teach scoring the questions by assigning other numeric elements to the answers including numeric elements up to 10 (see: Hill, paragraph 94-95), and it would have been obvious to one of ordinary skill in the art at the time the invention was filed to modify the scoring to include numeric elements from 0 to 10, as claimed, with the motivation of optionally tuning to focus on dysphagia symptom severity or detecting differences or changes in dysphagia symptom severity (see: Hill, paragraph 94).
Additionally or alternately, the range from 0 to 10 is considered similar to the ranges applied by Hill (see: Hill, paragraph 37, 86, 91, and 94-95), such that it would have been obvious to one of ordinary skill in the art at the time the intention was filed to expect similar results (see: MPEP, 2144.05, I).
Conclusion
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/ROBERT A SOREY/Primary Examiner, Art Unit 3626