DETAILED ACTION
This office action is in response to applicant’s filing dated August 20, 2025.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of claims
Claims 1 – 19 are pending in the instant application.
Election/Restrictions
Applicant’s election of species:
Compound 6E of formula
PNG
media_image1.png
111
211
media_image1.png
Greyscale
and
opioid agonist morphine in the reply filed on August 20, 2025 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 3, 4, 6, 7, 13, and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 20, 2025.
The claims under consideration in the present office action are claims: 1, 2, 5, 8 – 12, 14 – 17 and 19, as being drawn to elected species, compound 6E and opioid agonist morphine.
Priority
The present application Is a CON of U.S. Application No.16/191,119, filed November 14, 2018, which is a CON of 14/960,750, filed December 7, 2015, now abandoned, which is a DIV of U.S. Application No.13/835,607, filed March15,2013, now issued as U.S. Patent No. 9,220,715, which claims the benefit of U.S. Provisional Patent Application No.61/643,611, filed May 7, 2012, and U.S. Application No.13/835,607 is a CIP of U.S. Application No.13/290,868, filed November 7, 2011, which claims the benefit of U.S. Provisional Patent Application No.61/411,431, filed November 8, 2010, and claims the benefit of U.S. Provisional Patent Application No.61/411,437, filed November 8, 2010, and claims the benefit of U.S Provisional Patent Application No.61/482,994, filed May 5, 2011.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on November 17, 2022 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
Acknowledgement is made of the drawings received on August 31, 2022. These drawings are accepted.
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 pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1, 2 and 5 are rejected under pre-AIA 35 U.S.C. 102(a) and (b) as being anticipated by Barlow et al (US 2007 /0208029 A1, cited in IDS, filed 11/17/2022, hereinafter Barlow).
Instant claims are drawn to a method of treating an addiction to an addictive agent, such as an opioid agonist morphine, comprising administering to a subject in need thereof an effective amount of a selective phosphodiesterase 7 (PDE7) inhibitor.
Barlow teaches a method of treating diseases, disorders, and conditions of the central and/or peripheral nervous systems (CNS and PNS, respectively), by administering a PDE agent (page 10, [0094]), wherein administering a PDE agent stimulate neurogenesis, wherein PDE agent is a PDE7 inhibitor, wherein the patient’s decreased neurogenesis condition e.g. drug addiction (page 9, [0084]) is due to the anti-neurogenic effects of an opiate like morphine (page 9, [0082]).
Thus, teachings of Barlow anticipate the method of instant claims 1, 2 and 5.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained through the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 8 – 12, 14 – 17 and 19 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Barlow et al (US 2007 /0208029 A1, cited in IDS, filed 11/17/2022) in view of Inoue et al (US 2009/0131413 A1, cited in IDS, filed 11/17/2022, hereinafter Inoue).
Regarding claims 1, 12 and 14, drawn to a method of treating an addiction to an addictive agent, such as an opioid agonist morphine, comprising administering to a subject in need thereof an effective amount of a selective phosphodiesterase 7 (PDE7) inhibitor, wherein the PDE7 selective inhibitor has molecular weight of less than 450g/mol and is a compound of formula 6, such as 6E
PNG
media_image1.png
111
211
media_image1.png
Greyscale
. Barlow teaches a method of treating diseases, disorders, and conditions of the central and/or peripheral nervous systems (CNS and PNS, respectively), by administering a PDE agent (page 10, [0094]), wherein administering a PDE agent stimulate neurogenesis, wherein PDE agent is a PDE7 inhibitor, wherein the patient’s decreased neurogenesis condition e.g. drug addiction (page 9, [0084]) is due to the anti-neurogenic effects of an opiate like morphine (page 9, [0082]).
Barlow does not teach where PDE7 inhibitor is a compound of formula 6E.
However, Inoue teaches a compound 369
PNG
media_image1.png
111
211
media_image1.png
Greyscale
(page 178, Table 120), where the compound possess potent and selective PDE 7 inhibiting effect. The compound 369 of Inoue has a molecular weight 432.58 g/mol (873541-44-7 Substance Detail | CAS SciFinder).
Thus, since Barlow teaches a method of treating of patient’s conditions such as drug addiction caused by use of morphine, by administering a selective PDE7 inhibitor, and Inoue teaches a compound, such as compound 369, acting as a selective PDE7 inhibitor, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to try to apply a known PDE7 inhibitor to the known method of treatment of patients having inhibited neurogenesis due to the exposure to morphine, since the prior art teaches PDE7 inhibitors are effective agents to treat said conditions. The one of ordinary skills would be motivated to do so in search of an effective method of treatment of patients having addiction to drug such as addiction to morphine with the reasonable expectation of success.
Regarding claims 8 and 9, drawn to a method where PDE7 inhibitory agent has an IC50 for inhibiting PDE7A and/or PDE7B activity of less than about 1 µM, or less than about 100 nM.
Barlow teaches PDE inhibitors, such as PDE7 inhibitors, individually having IC50 values of less than about 1 μM, or less than about 0.1 μM or lower (page 5, [0043]). The IC50 value 0.1 μM is equal to 100nM, when converted into nM units. Inoue teaches compound 369, having IC50 value of PDE7 inhibiting activity equal to 0.024 µM (page 18, Table 4). The IC50 value of 0.024 µM, taught by Inoue, is equal to 24nM. Thus, IC50 values taught by prior art within the ranges of instant claims. MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003). MPEP 2131.03 (I) states: "If the prior art discloses a point within the claimed range, the prior art anticipates the claim." UCB, Inc. v. Actavis Labs. UT, Inc., 65 F.4th 679, 687, 2023 USPQ2d 448 (Fed. Cir. 2023).
Regarding claims 10 and 11, drawn to a method where the agent has IC50 for inhibiting PDE7A activity and the IC50 for inhibiting PDE7B activity is less than one-tenth of the IC50 for inhibiting the activity of any other PDE enzyme from the PDE1-6 and PDE8-11 enzyme families, or where the agent has IC50 for inhibiting PDE7A activity and the IC50 for inhibiting PDE7B activity is less than one-fiftieth of the IC50 for inhibiting the activity of any other PDE enzyme from the PDE1-6 and PDE8-11 enzyme families.
Barlow teaches the method where a PDE agent such as PDE7 inhibitor exhibit "isozyme-selective" activity, where PDE agent is active against one or more enzyme within a PDE family and substantially inactive against one or more other enzyme of PDE family (page 15, [0137]). Isozyme-selectivity can be measured as the ratio of IC50 for a target PDE:IC50 for a non-target PDE, wherein PDE agent has an isozyme selectivity that is less than about 1: 10, or less than about 1:50 (page 5, [0044]). Inoue teaches compounds selectively inhibiting PDE 7, where selectivity is more than 10 times compared to other phosphodiesterase (PDE) (page 16, [0488]). As an example, Inoue demonstrate inhibiting effect of PDE7 inhibitors on PDE4. The PDE7 inhibitor compound 369 has IC50 value 7.6 μM of PDE 4 inhibiting effect, which concentration is about 316 times higher than that of PDE 7 inhibiting effect (0.024 μM) (page 18, Table 4). The exemplary result of inhibiting effect of PDE7 inhibitor on PDE4, shown by Inoue, lays within the claimed ranges. MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003). MPEP 2131.03 (I) states: "If the prior art discloses a point within the claimed range, the prior art anticipates the claim." UCB, Inc. v. Actavis Labs. UT, Inc., 65 F.4th 679, 687, 2023 USPQ2d 448 (Fed. Cir. 2023).
Regarding claims 15 – 17 and 19, drawn to a method of preventing a subject from becoming addicted, or reducing the likelihood that a subject will become addicted, to an addictive therapeutic opioid agonist such as morphine, comprising providing to a subject in need thereof an addictive therapeutic opioid agonist (morphine) and an effective amount of a selective PDE7 inhibitor, wherein the PDE7 inhibitor is compound of formula 6, such as compound of formula 6E
PNG
media_image1.png
111
211
media_image1.png
Greyscale
.
Barlow teaches a method to treat or prevent decreases in neurogenesis e.g. drug addiction, drug rehabilitation, and/or prevention of relapse into addiction, due to use of an opioid receptor agonist, such as morphine. The method comprises the administration of a PDE agent, such as PDE7 inhibitor (page 9, [0084]). Barlow teaches the method of treating, where PDE agent, such as PDE7 inhibitor is administered to a subject or person, where the subject or person is about to be administered morphine. A PDE agent is administered to a subject before, simultaneously with, or after the subject is administered morphine ( page 2, [0016]).
Barlow does not teach the method where the PDE7 inhibitor is claimed compound of formula 6, such as compound of formula 6E.
However, Inoue teaches a compound 369
PNG
media_image1.png
111
211
media_image1.png
Greyscale
(page 178, Table 120), where the compound possess potent and selective PDE 7 inhibiting effect.
Thus, since Barlow teaches a method of treating or preventing a drug addiction, by administering to a subject in need a therapeutically effective amount of PDE7 inhibitor, where PDE7 inhibitor is administered to a patient before, simultaneously with, or after the patient is administered morphine, Inoue teaches a compound 369, which structure is identical to the structure of claimed compound 6E, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to try to apply a known PDE7 inhibitor to the known method to arrive at claimed invention with the reasonable expectation of success. Especially, since prior art teaches PDE7 inhibitors are effective agents to treat or prevent drug addiction in a patient undergoing treatment with morphine.
Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
Claims 1, 2, 5, 8 – 12, 14 – 17 and 19 are rejected. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELENA V VISHNYAKOVA whose telephone number is (571)272-3781. The examiner can normally be reached 7:30am - 5pm ET.
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, DEIRDRE (RENEE) Claytor can be reached at (571)272-8394. 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.
/E.V.V./ Examiner, Art Unit 1691
/SAVITHA M RAO/ Primary Examiner, Art Unit 1691