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 .
Status of the Claims
Claims 1, 6-7, 11-42 are pending.
Priority
This application filed on 09/25/2024, claims priority to U.S. provisional application Nos:
1) 63/668, 377, filed on 07/08/2014;
2) 63/650,360, filed on 05/21/2024;
3) 63/634,306, filed on 04/15/2024; and
4) 63/589,729, filed on 10/12/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/25/2024, 01/16/2025 and 06/24/2026, were in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The IDS documents were considered. A signed copy of Form PTO-1449 is enclosed herewith.
Claim Rejections - 35 USC § 102
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.
Claims 1-2, 6-7, 11-13, 32-36, 38, 40-42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gilleen et al (hereinafter “Gilleen”, Psychopharmacology, 2021, 238, 1279-1289).
Applicants’ invention is directed to a method for treating:
i) a neuropsychiatric disorder (independent claims 1 and 6); or
ii) negative symptoms of schizophrenia (independent claim 2),
in a patient in need thereof, comprising administering to the patient, an effective amount of tilivapram, zatolmilast, roflumilast, or a pharmaceutically acceptable salt thereof, and one or more antipsychotic agents.
Applicants disclose the term “an effective amount” as referring to an amount sufficient to accomplish a stated purpose (see ¶ 0062 of the specification). Accordingly, for the purpose of examination, an amount of tilivapram, zatolmilast, roflumilast, or a pharmaceutically acceptable salt thereof, and one or more antipsychotic agents, that is employed in order to generate the desired therapeutic outcome, is included in the interpretation of “an effective amount”.
Regarding claims 1-2, 6-7, 11-13, 15, 32-36, 38, 40-42, Gilleen teaches a method for treating cognitive impairment in patients suffering from schizophrenia comprising administering roflumilast (a PDE 4 inhibitor) and olanzapine (an antipsychotic agent, see claim 11) to the patients (see, e.g., abstract, “Method” section on pages 1281-1284, Table 1 and discussions therein). The cognitive impairment was measured using HVLT-R and the positive and negative syndrome scale for schizophrenia (PANSS, see pages 1282-1285 and 1288).
Claims 1-2, 15-16 and 28-42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Prickaerts et al (hereinafter “Prickaerts”, U.S. Pub. No. 20150051254, published 02/19/2015).
Regarding claims 1-2, Prickaerts (see claim 1) teaches:
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Regarding claims 15-16, Prickaerts discloses that administration can be orally or transdermally (see ¶ 0106).
Regarding claims 28-31, Prickaerts discloses cognitive impairment associated with Parkinson’s disease (see ¶ 0013).
Regarding claims 32-35, 38, 40 and 42, Prickaerts discloses cognitive impairment associated with schizophrenia (see discussions above).
Regarding claim 36, Prickaerts discloses MCI (see ¶ 0013).
Regarding claim 37, Prickaerts discloses cognitive impairment due to ADHD (see ¶ 0013).
Regarding claim 39, Prickaerts discloses cognitive impairment due to depression (see ¶ 0013).
Regarding claim 41, Prickaerts (see ¶ 0149), discloses determining cognitive impairment based on computerized cognitive battery, a validated tool for measuring the cognitive impairment in humans. The battery will consist of: VLT, Spatial Memory Task (SMT), Stroop Task, and Bond- Lader Visual Analogue Scales (BL-VAS).
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.
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.
Claims 6, 13-14 and 23-27 are rejected under 35 U.S.C. 103 as being unpatentable over Gilleen (Psychopharmacology, 2021) as applied to claims 6 and 13 above, and in view of Etkin et al (hereinafter “Etkin”, U.S. Pub. No. 20220226302, published 07/21/2022) as evidenced by Schlicker et al (hereinafter “Schlicker”, Naunyn-Schmiedeberg’s Arch Pharmacol, 1996, 353, 290-294).
The limitations of claims 6 and 13 as well as the corresponding teachings of Gilleen are described above, and are hereby incorporated into the instant rejections.
The invention of claims 14 and 23-27 depend from claim 13, however, claims 14 and 23-27 differs slightly from claim 13 in that claims 14 and 23-27 require transdermal administration.
Although Gilleen teaches orally administering a combination of roflumilast (a PDE4 inhibitor) and olanzapine (an antipsychotic agent), Gilleen differs slightly from the claimed invention only insofar as Gilleen is not explicit in disclosing transdermal administration.
However, the claimed inventions would have been obvious over Gilleen, because at the time of the instant invention, it was known in the art that a combination of a PDE4 inhibitor and an antipsychotic agent can be administered transdermally. For example, Etkin discloses that a combination of a PDE4 inhibitor and an antipsychotic agent (e.g., H3 antagonist) can be administered transdermally can be orally or transdermally (see, e.g., abstract, ¶s 0009, 0064, 0071-0073). Similar to Gilleen (see discussions above), Etkin relates to use of a combination of a PDE4 and an antipsychotic agent (e.g., H3 antagonist) for the treatment of psychiatric and neurological disorders (see, e.g., ¶ 0002).
Olanzapine is an H3 antagonist, as evidenced by Schlicker, who discloses Olanzapine as an H3 antagonist (see page 293 and Table 1).
Accordingly, at the time of the instant invention, one skilled in the art would have envisaged a method for treating cognitive impairment in a subject in need thereof, with transdermal administration of a combination of a PDE4 inhibitor (e.g., roflumilast) and an antipsychotic agent (e.g., olanzapine), in the disclosures of Gilleen and Etkin as evidenced by Schlicker. A person skilled in the art would have had a reasonable expectation that the transdermal administration of the combination, would treat psychiatric and neurological disorders.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
Regarding claims 23 and 25-27, the requirement that the method of claim 14 results in the outcomes recited in claims 23 and 25-27, is not given any patentable weight because each of the clause is simply expressing the intended result of a process positively recited. Please see Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003). Since Gilleen and Etkin as evidenced by Schlicker, combine to disclose the method of claim 14 (see discussions above), the method of Gilleen and Etkin as evidenced by Schlicker, must necessarily produce the same outcomes of recited in claims 23 and 25-27, because each of the recited outcomes is a natural process that flows from the subject and the transdermally administered composition. Please see MPEP, 2111.04.
Regarding claim 24, the recited dosing schedule is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art. The dose(s) administered and the duration of administration (e.g., over at least 2 hours), will be determined in accordance with factors distinctive to a subject in need thereof, such as age, weight, general state of health and other characteristics, which can influence therapeutic efficacy.
It is noted that no criticality has been demonstrated in the specification with regard to the recited dosing schedule.
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 1 and 17-22 are rejected under 35 U.S.C. 103 as being unpatentable over Prickaerts (U.S. Pub. No. 20150051254) as applied to claim 1 above, and in view of Fenton et al (hereinafter “Fenton”, WO9504045, published 02/09/1995).
The limitations of claim 1 as well as the corresponding teachings of are Prickaerts described above, and are hereby incorporated into the instant rejections.
The invention of claims 17-22 depend from claim 1, however, claims 17-22 differs slightly from claim 1 in that claims 17-22 require tilivapram.
Tilivapram (AVE8112) is also known in the art as 4-(cyclopropylmethoxy)-N-(3,5-dichloro- 1-oxidopyridin-4-yl)-5-methoxypyridine-2-carboxamide or 4-(cyclopropylmethoxy)-N-(3,5-dichloro-1-oxido-4-pyridyl)-5-methoxypyridine-2-carboxamide (see ¶ 0054 of the specification):
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Although Prickaerts teaches a method for treating a neuropsychiatric disorder with a PDE4 inhibitor (roflumilast), Prickaerts differs slightly from the claimed invention only insofar as Prickaerts is not explicit in disclosing tilivapram as a PDE4 inhibitor.
However, the claimed inventions would have been obvious over Prickaerts, because at the time of the instant invention, tilivapram was known in the art as a PDE4 inhibitor. For example, Fenton (see, e.g., page 30, lines 35-36, pages 123-124) teaches tilivapram as a PDE4 useful in treating a disease condition in which the therapeutic intervention is at PDE4 inhibition (see, e.g., page 2, lines 27-35 and page 10, lines 9-16).
Accordingly, at the time of the instant invention, one skilled in the art would have envisaged a method for treating a neuropsychiatric disorder in a subject in need thereof, with a PDE4 inhibitor (e.g., tilivapram), in the disclosures of Prickaerts and Fenton. A person skilled in the art would have had a reasonable expectation that the administration of the PDE4 inhibitor (e.g., tilivapram), would treat a neuropsychiatric disorder in the subject.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
Regarding claims 17-22, Prickaerts discloses that a PDE4 inhibitor can be administered orally and transdermally (see discussions above).
Regarding claims 19 and 22, each of the recited ranges is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art. For example Fenton (see page 123), states:
“The dose employed will be determined by the physician, and depends upon the desired therapeutic effect, the route of administration and the duration of the treatment, and the condition of the patient. In the adult, the doses are generally from about 0.001 to about 50, preferably about 0.001 to about 5, mg/kg body weight per day by inhalation, from about 0.01 to about 100, preferably 0.1 to 70, more especially 0.5 to 10 mg/kg body weight per day by oral administration, and from about 0.001 to about 10, preferably 0.01 to 1, mg/kg body weight per day by intravenous administration. In each particular case, the doses will be determined in accordance with the factors distinctive to the subject to be treated, such as age, weight, general state of health and other characteristics which can influence the efficacy of the medicinal product.”
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Conclusion
No claim is allowable.
If Applicants should amend the claims, a complete and responsive reply will clearly identify where support can be found in the disclosure for each amendment. Applicants should point to the page and line numbers of the application corresponding to each amendment, and provide any statements that might help to identify support for the claimed invention (e.g., if the amendment is not supported in ipsis verbis, clarification on the record may be helpful). Should the Applicants present new claims, Applicants should clearly identify where support can be found in the disclosure.
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
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S LUNDGREN can be reached on 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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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/ Supervisory Patent Examiner, Art Unit 1629
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