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 .
Application Status
The preliminary amendment filed on 10/18/2024 is acknowledged. Claims 1-4, 6-8, 11-17, 20-24, 26 and 28-30 are currently pending and under consideration.
Information Disclosure Statement
The information disclosure statement filed on 11/26/2024 and 10/09/2025 is acknowledged and has been considered except where lined through.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 11 is objected to because of the following informalities: Claim 11 recites the phrase “or about” twice in a row.
Claims 8, 21-23, 26 and 28-30 recite acronyms which have not been previously defined. Appropriate correction is required.
Claim Interpretation
The Examiner is interpreting the claims in the following manner:
-Deudomperidone is being interpreted also be interchangeable with “d4-domperidone” and “CIN-102” (see specification, paragraph 0035).
-The various test used to characterize the patient population and/or determine the efficacy of the treatment such as GEBT and ANMS GCSI-DD are known in the art and appear to be associated with measurements useful for the diagnosis/prognosis of gastroparesis (see paragraphs 0044 and 0046 of the specification). It is noted that while these two measurements characterize the patient population and efficacy of the treatment, the Examiner recognizes that the claims do not specifically require an active step of measuring these two scores.
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 8, 12 and 26 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.
Regarding claims 8 and 12, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 26, the claim recite the phrases “the pulse rate (PR) interval” and “the QRS interval”. However, there is no recitation of these two limitations recited in claim 1. As such, claim 26 lacks antecedent basis for the phrases.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 3-4, 6, 11, 13-17, 23-24, 26 and 28 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2020086947A1 to Cindome Pharma Inc (2020-04-30, IDS), referred to herein as Cindome.
Cindome teach pharmaceutical formulations comprising d4-domperidone having the formula
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and a method of treating gastroparesis or nausea and/or vomiting associated with gastroparesis comprising administration to a patients a formulation comprising d4-domperidone (abstract). With regards to the patients, Cindome teaches that the patient is a human. With regards to the pharmaceutical formulation, Cindome teaches that the pharmaceutical formulation contain about 1 to about 50 mg of d4-domperidone (Paragraph 00039). For example, Cindome teaches formulations comprising 10 mg of d4-domperidone which are suitable for oral administration as a tablet or capsule (paragraph 00074 and 00075).
Regarding the “results” limitations of claim 14-17, 23-24, 26 and 28, the instant limitations appear to be directly correlated with the administration of d4-domperidone to a patient having gastroparesis in the amount claimed. Accordingly, since the prior art teaches administration of the claimed compound to the claimed patient population in the claimed about, such limitations appear to be met by the prior art teachings. See MPEP 2112.01 and 2111.02.
Claim(s) 1, 3-4, 6, 11, 14-17, 23-24 and 28-30 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pearce et al. (US 10,266,516B2, 2019-04-23).
Pearce et al. teach a method of treating a disorder that is gastroparesis or nausea that is associated with gastroparesis in a patient in need thereof, comprising administering to a patient a formulation comprising d4-domperidone, wherein the amount is 5mg to 100 mg of d4-domperidone (see claims 1-4 and 7-14).
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.
Claim(s) 2, 12 and 29-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO2020086947A1 to Cindome Pharma Inc (2020-04-30, IDS), as applied to claims 1, 3-4, 6, 11, 13-17, 23-24, 26 and 28 above, in view of NCT04026997 version 10 (“A Phase 2 Study of CIN-102 in Adults With Idiopathic and Diabetic Gastroparesis”, ClinicalTrials.gov, 2021-03-09).
Cindome teach pharmaceutical formulations comprising d4-domperidone having the formula
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and a method of treating gastroparesis or nausea and/or vomiting associated with gastroparesis comprising administration to a patients a formulation comprising d4-domperidone (abstract). With regards to the patients, Cindome teaches that the patient is a human. With regards to the pharmaceutical formulation, Cindome teaches that the pharmaceutical formulation contain about 1 to about 50 mg of d4-domperidone (Paragraph 00039). For example, Cindome teaches formulations comprising 10 mg of d4-domperidone which are suitable for oral administration as a tablet or capsule (paragraph 00074 and 00075).
Cindome does not specifically teach that the patients is suffering from idiopathic or diabetic gastroparesis or that the formulation is administered twice daily or that the amount is 30 mg or 60 mg of d4-domperidone.
NCT04026997 teaches a randomized, double-blind, placebo-controlled study to evaluate the safety, efficacy, pharmacokinetics, and dose Response of oral CIN-102 in adults with idiopathic and diabetic gastroparesis (Official Title). With regards to the dose, NCT04026997 teaches three dosing protocols that will be used, dose 1, dose 2 and dose 3 giving in the form of tablets by mouth twice daily for 14 days (see Arms and Interventions). Moreover, NCT04026997 teaches that the primary outcome measured will be change from baseline in gastric emptying and secondary outcomes will be change from baseline in gastric emptying terminal phase elimination half life, change from baseline in ANMS GCSI-DD total scores and change from baseline in ANMS GCSI-DD subscale scores (Outcome Measures). With regards to the adults, NCT04026997 teaches that the adults have a current diagnosis of idiopathic or diabetic gastroparesis OR documented delayed gastric emptying and presence of moderate to severe nausea (Eligibility).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by Cindome to treat patients suffering from idiopathic and diabetic gastroparesis with d4-domperidone, e.g. CIN-102, in view of the teachings of NCT04026997. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
- NCT04026997 teaches evaluating the safety, efficacy, pharmacokinetics, and dose response of oral CIN-102 in adults with idiopathic and diabetic gastroparesis.
Moreover, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to optimize the 10 mg dose of d4-domperidone taught by Cindome in the method of treating patients suffering from gastroparesis with d4-domperidone, e.g. CIN-102, in view of the teachings of NCT04026997. One would have been motivated to make such an optimization, with a reasonable expectation of success because:
- NCT04026997 teaches a study using three different doses given twice a day to determine the safety, efficacy, pharmacokinetics, and dose response of oral CIN-102.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Claim(s) 7-8 and 21-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO2020086947A1 to Cindome Pharma Inc (2020-04-30, IDS) in view of NCT04026997 version 10 (“A Phase 2 Study of CIN-102 in Adults With Idiopathic and Diabetic Gastroparesis”, ClinicalTrials.gov, 2021-03-09, as applied to claims 1-4, 6, 11-17, 23-24, 26 and 28-30 above) in further view of Sarosiek et al. (Clinical Gastroenterology and Hepatology 2022; 20:e452-e464, IDS).
The combination of Cindome and NCT04026997 have been discussed above and incorporated herein.
The combination does not specifically teach the clinical or “baseline” characteristics of the patients suffering from gastroparesis prior to treatment with d4-domperidone.
Sarosiek et al. discuss the results of a dynamic cohort study on the effect of domperidone therapy on gastroparesis symptoms (Title). Regarding the study, Sarosiek et al. teach that the study was designed to investigate the patients who enrolled in 2 long-term perspective studies which enrolled patients with documented diabetic and idiopathic gastoparesis, as well as patients with typical GP symptoms but normal gastric emptying (Page e453, 2nd column, Study data). Specifically, Sarosiek et al. disclose the baseline characteristics, including the clinical characteristics, of patients at enrollment and at initiation of domperidone during follow up:
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(see e456, Table 1).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by the combination so as to obtain baseline information of the patient by using the various tests available at the time the application was filed in view of the teachings of Sarosiek et al.. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-The specification teaches that techniques such as GEBT and ANMS GCSI-DD are known in the art and appear to be associated with measurements useful for the diagnosis/prognosis of gastroparesis; and
-In view of the teachings of Sarosiek et al, it is typical to obtain clinical characteristics prior to administration of a therapeutic agent.
It is noted that a review of the specification does not appear to identify anything special about this specific patient population and its correlation to the efficacy of the drug. Moreover, the teachings of the specification appear to be a clinical trial and similar to the teachings of Sarosiek et al, it is an effort to gather clinical characteristics which are used as a baseline for comparisons later. In the instant case, Applicants appear to be using a different test to identify a baseline for those test and the patient populations appear to be the same.
Claim(s) 2, 12-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pearce et al. (US 10,266,516B2, 2019-04-23), as applied to claims 1, 3-4, 6, 11, 14-17, 23-24 and 28-30 above, in view of NCT04026997 version 10 (“A Phase 2 Study of CIN-102 in Adults With Idiopathic and Diabetic Gastroparesis”, ClinicalTrials.gov, 2021-03-09).
Pearce et al. teach a method of treating a disorder that is gastroparesis or nausea that is associated with gastroparesis in a patient in need thereof, comprising administering to a patient a formulation comprising d4-domperidone, wherein the amount is 5mg to 100 mg of d4-domperidone (see claims 1-4 and 7-14).
Pearce et al. does not specifically teach that the patients is suffering from idiopathic or diabetic gastroparesis or that the formulation is administered twice daily.
NCT04026997 teaches a randomized, double-blind, placebo-controlled study to evaluate the safety, efficacy, pharmacokinetics, and dose Response of oral CIN-102 in adults with idiopathic and diabetic gastroparesis (Official Title). With regards to the dose, NCT04026997 teaches three dosing protocols that will be used, dose 1, dose 2 and dose 3 giving in the form of tablets by mouth twice daily for 14 days (see Arms and Interventions). Moreover, NCT04026997 teaches that the primary outcome measured will be change from baseline in gastric emptying and secondary outcomes will be change from baseline in gastric emptying terminal phase elimination half life, change from baseline in ANMS GCSI-DD total scores and change from baseline in ANMS GCSI-DD subscale scores (Outcome Measures). With regards to the adults, NCT04026997 teaches that the adults have a current diagnosis of idiopathic or diabetic gastroparesis OR documented delayed gastric emptying and presence of moderate to severe nausea (Eligibility).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by Pearce et al. to treat patients suffering from idiopathic and diabetic gastroparesis with d4-domperidone, e.g. CIN-102, in view of the teachings of NCT04026997. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
- NCT04026997 teaches evaluating the safety, efficacy, pharmacokinetics, and dose response of oral CIN-102 in adults with idiopathic and diabetic gastroparesis.
Moreover, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to optimize the 10 mg dose of d4-domperidone taught by Pearce et al. in the method of treating patients suffering from gastroparesis with d4-domperidone, e.g. CIN-102, in view of the teachings of NCT04026997. One would have been motivated to make such an optimization, with a reasonable expectation of success because:
- NCT04026997 teaches a study using three different doses given twice a day to determine the safety, efficacy, pharmacokinetics, and dose response of oral CIN-102.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Claim(s) 7-8 and 21-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pearce et al. (US 10,266,516B2, 2019-04-23) in view of NCT04026997 version 10 (“A Phase 2 Study of CIN-102 in Adults With Idiopathic and Diabetic Gastroparesis”, ClinicalTrials.gov, 2021-03-09, as applied to claims 1-4, 6, 11-17, 23-24, 26 and 28-30 above) in further view of Sarosiek et al. (Clinical Gastroenterology and Hepatology 2022; 20:e452-e464, IDS).
The combination of Pearce et al. and NCT04026997 have been discussed above and incorporated herein.
The combination does not specifically teach the clinical or “baseline” characteristics of the patients suffering from gastroparesis prior to treatment with d4-domperidone.
Sarosiek et al. discuss the results of a dynamic cohort study on the effect of domperidone therapy on gastroparesis symptoms (Title). Regarding the study, Sarosiek et al. teach that the study was designed to investigate the patients who enrolled in 2 long-term perspective studies which enrolled patients with documented diabetic and idiopathic gastoparesis, as well as patients with typical GP symptoms but normal gastric emptying (Page e453, 2nd column, Study data). Specifically, Sarosiek et al. disclose the baseline characteristics, including the clinical characteristics, of patients at enrollment and at initiation of domperidone during follow up:
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(see e456, Table 1).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by the combination so as to obtain baseline information of the patient by using the various tests available at the time the application was filed in view of the teachings of Sarosiek et al.. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-The specification teaches that techniques such as GEBT and ANMS GCSI-DD are known in the art and appear to be associated with measurements useful for the diagnosis/prognosis of gastroparesis; and
-In view of the teachings of Sarosiek et al, it is typical to obtain clinical characteristics prior to administration of a therapeutic agent.
It is noted that a review of the specification does not appear to identify anything special about this specific patient population and its correlation to the efficacy of the drug. Moreover, the teachings of the specification appear to be a clinical trial and similar to the teachings of Sarosiek et al, it is an effort to gather clinical characteristics which are used as a baseline for comparisons later. In the instant case, Applicants appear to be using a different test to identify a baseline for those test and the patient populations appear to be the same.
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.
At least Claims 1, 3-4, 6, 11, 14-17, 23-24 and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1, 4, 5-6, 20-21 and 23-24 of U.S. Patent No. 12514852B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the method of treating a disorder that is gastroparesis or nausea that is associated with gastroparesis in a patient in need thereof, comprising orally administering to a patient a formulation comprising d4-domperidone, wherein the amount is 5mg to 20 mg of d4-domperidone overlaps in scope with the instantly claimed method.
Note: US Patent 12514852B2 is a 371 of WO2020086947A1. Accordingly, the obviousness rationale setforth above can also be applied to claims 2, 7-8, 12, 21-22 and 29-30 using US Patent 12514852B2 for WO2020086947A1 as an NSDP.
At least Claims 1, 3-4, 6, 11, 14-17, 23-24 and 28-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1-4 and 7-14 of U.S. Patent No. 10590110B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the method of treating a disorder that is gastroparesis or nausea that is associated with gastroparesis in a patient in need thereof, comprising administering to a patient a formulation comprising d4-domperidone, wherein the amount is 5mg to 100 mg of d4-domperidone overlaps in scope with the instantly claimed method.
Note: The obviousness rationale setforth above can also be applied claims 2, 7-8, 12 and 21-22 using US Patent 10590110B2 as an NSDP.
Conclusion
Therefore, No Claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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BRANDON J. FETTEROLF, PHD
Primary Patent Examiner
Art Unit 1626
/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
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