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 .
Priority
This application filed 01/25/2024 Claims Priority from provisional application 63481635, filed 01/26/2023.
Information Disclosure Statement
Applicant has not submitted an information disclosure statement (IDS).
Claim status
Claims 1-16 are currently pending and hereby examined on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 1 is directed to a method of treating. Embodiments of the specification disclose that “treating" refers to administering the composition to a subject for therapeutic purposes and/or for
prevention [0029]. For prevention, the specification discloses ‘prophylactic or preventative treatment measures or reducing the onset of a condition or disease’ ([0029], lines 1-2). For therapeutic, the specification discloses ‘ameliorating, decreasing, reducing, inhibiting, suppressing, limiting, controlling, or preventing occurrence, frequency, severity, progression, or duration of a disease or condition, or consequences of the disease or condition in a subject ([0035] lines 6-9).
Claim 14 is directed to a method of treating. As noted above, ‘prevention’ is disclosed in the embodiments of the specification.
While the instant specification is enabling for administering the composition to a subject, for therapeutic purpose, the specification is not enabling for a method of treating encompassing prevention in claims 1 and 14. This is a scope of enablement rejection.
As stated in § MPEP 2164.01(a), “there are many factors to consider when determining whether
there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is ‘undue’. These factors include, but are not limited to:
1. The breadth of the claims;
2. The nature of the invention;
3. The state of the prior art;
4. The level of skill in the art;
5.The level of predictability in the art;
6. The amount of direction provided by the inventor;
7. The presence or absence of working examples;
8. The quantity of experimentation needed to make or use the invention based on the
disclosure.
See in re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The eight Wands
factors are applied to claims 1-16 as follows:
The breadth of the claims and the nature of the invention
Claims 1-16 are directed to a method of treatment, wherein, the method of treatmentencompasses prevention, in a subject population in need thereof, comprising administering the composition. The specification does not provide evidence that a subject in need of prevention, of traumatic brain injury (TBI), as recited in claim 1 or TBI with PTSD as recited in claim 14, is administered the composition, wherein prevention entails ‘prophylactic or preventative treatment measures, or reducing the onset of a condition or disease’’ ([0029], lines 1-2). Accordingly, claims 1-16 are unduly broad with respect to treating TBI and TBI with PTSD combined.
The State of the Prior Art
It is noted that there is prior art that teaches the composition in the treatment of
subject with TBI and TBI with PTSD combined (see Yacoub et al., Pharmacology & Therapeutics 231 (2022) 107982). There is no prior art for the prevention aspect, in view of the definition of ‘treating’, as disclosed in the specification.
The Level of Skill in the Art
Practitioners in this art (physicians, pharmacologists) would presumably be highly skilled in the art for generating compositions with the treatment properties as claimed.
The Level of Predictability in the Art
It is noted that the therapeutic art it unpredictable, requiring each embodiment to be
individually assessed for physiological activity. The amount of guidance or direction needed to enable
the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). This is because it
is not obvious from the disclosure, of a specific method of treatment of subject comprising prevention ofsymptoms. In the instant case, the
specification does not demonstrate prevention in a subject, of TBI or TBI with PTSD, treatment regimen for prophylaxis, or reduction in the onset of a condition or disease.
Without any experimentation demonstrating the claimed treatment, the level of unpredictability
remains high. Therefore, it is unpredictable that the composition will function in the treatment method
as claimed.
The amount of Direction Provided by the Inventor and The Presence or Absence of
Working Examples
The instant specification does not provide adequate guidance with regard to the method of
Treatment or subject population requiring the treatment. Applicant’s limited disclosure is noted but is not sufficient to justify claiming the composition for therapeutic purpose, broadly. Absent a reasonable a priori expectation of success for using , NOR agonists and antagonists, one skilled in the art would have to extensively test the NOP receptor agonists and antagonists, determine an effective dose on a subject
suffering TBI and PTSD, ascertain amelioration of symptoms, clinical benefit, etc. Since each prospective
embodiment, and indeed future embodiments as the art progresses, would have to be empirically
tested, and those which initially failed tested further, an undue amount of experimentation would be
required to practice the invention as it is claimed in its current scope, because the specification provides
inadequate guidance to do otherwise. The amount of direction or guidance presented in the
specification is very limited. As discussed in “[t]he Level of Predictability in the Art” section supra, the
specification teaches no working examples in the treatment of TBI and PTSD in a subject in need thereof. Also, as noted in the “Breadth of the Claims and Nature of Invention” section, the specification does not provide evidence that a subject , is administered a phophylactic amount to reduce onset of TBI and/or PTSD.
As such, the specification is not indicative broadly of a method of treatment with the desired result of amelioration of symptoms. It is further noted that Applicant provides no data, examples, figures, etc. demonstrating a subject in need thereof and the end points of the therapeutic purpose. In the absence of such information, a person of ordinary skill in the art would reasonably
require undue quantity of experimentation.
Conclusion of Enablement Analysis 35 USC § 112(a)
MPEP § 2164.01(a), 4th paragraph states that “A conclusion of lack of enablement means that,
based on the evidence regarding each of the above factors, the specification, at the time the application
was filed, would not have taught one skilled in the art how to make and/or use the full scope of the
claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d
1510,1513 (Fed. Cir. 1993).
After applying the Wands factors and analysis to claims 1-16, in view of the Applicant’s
entire disclosure, it is concluded that the practice of the invention as claimed in claims 1-16 would not
be enabled by the written disclosure for treatment of TBI and/or PTSD. Therefore claims 1-16 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to treat a subject as claimed.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 8, 9 and 12 are rejected under 35 U.S.C. 102 (a)(1) and 35 U.S.C. 102 (a)(2) as being anticipated by Hibbah O. Awwad et al., hereinafter Awwad (Hibbah O. Awwad et al., Post-blast treatment with Nociceptin/Orphanin FQ peptide (NOP) receptor antagonist reduces brain injury-induced hypoxia and signaling proteins in vestibulomotor-related brain regions, Behavioural Brain Research 340 (2018) 183–194)
Regarding claim 1, embodiments of the specification disclose “treating,” as administering the composition to a subject for therapeutic purposes and/or for prevention ([0029] lines 2-4). Awwad teaches administration of (5 mg/kg) of the NOP receptor antagonist, SB-612111 (SB), intraperitoneally, to rats, 30 min post-blast (i.e. traumatic brain injury model)(see section 2.5, page 3; see Fig 3).
Regarding claim 8, the claim limitation ‘selected from a group consisting of’ is interpreted as a Markush group presenting a closed set of alternatives. Awwad teaches SB612111 (section 2.5, page 3; see Fig 3).
Regarding claim 9, Awwad teaches that results from a recent clinical trial for treatment of major depressive disorder reveals improved emotional test scores after only one week of treatment with the NOP receptor antagonist, LY2940094, and improved GRID-Hamilton Depression Rating Scale-17 item total score after 8 weeks (see page 9, 1st paragraph).
Regarding claim 12, as noted in the rejection for claim 8, Awwad teaches SB612111.
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.
Claim(s) 1-3, 8-9, 12 are rejected under 35 U.S.C. 103 as being unpatentable over Hibbah O. Awwad et al., hereinafter Awwad (Hibbah O. Awwad et al., Post-blast treatment with Nociceptin/Orphanin FQ peptide (NOP) receptor antagonist reduces brain injury-induced hypoxia and signaling proteins in vestibulomotor-related brain regions, Behavioural Brain Research 340 (2018) 183–194) in view of Norikazu Kiguchi at al., hereinafter Kiguchi (Norikazu Kiguchi at al., BU10038 as a safe opioid analgesic with fewer side effects after systemic and intrathecal administration in primates, British Journal of Anaesthesia, 122 (6): e146-e156 (2019)).
Regarding claim 2, Examiner interprets “group consisting of..thereof” as a Markush group presenting a set of alternatives.
The teachings of Awwad have been set forth above. Notably, Awwad teaches that TBI-induced up-regulation of N/OFQ contributes to impaired cerebral reactivity and increased neuronal excitotoxicity (See introduction, 3rd paragraph). Awwad teaches that the N/OFQ-NOP receptor pathway is an excellent target for therapeutic development to reduce blast trauma effects (i.e. TBI) on the CNS (see concluding paragraph; page 11).
Awwad does not teach administering PPL-138 (BU10038).
Kiguchi teaches that systemic administration of BU10038 dose-dependently produces long-lasting antinociceptive and antihypersensitive effects. Unlike the MOP agonist oxycodone, BU10038 lacks reinforcing effects (i.e. little or no abuse liability), and BU10038 does not compromise the physiological functions of primates including respiration, cardiovascular activities, and body temperature at antinociceptive doses. After intrathecal administration, BU10038 (3 mg) exerts morphine-comparable antinociception and anti-hypersensitivity without itch scratching responses. BU10038 does not cause the development of physical dependence and tolerance after repeated and chronic administration in primates (see Abstract).
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to target the N/OFQ-NOP receptor pathway, as suggested in Awwad, using the antinociceptive BU10038 as suggested in Kiguchi. One motivated to do so would have a reasonable expectation of success, as BU10038 produces long-lasting antinociceptive effects. Thus, one would have recognized that applying the teaching of Awwad to the method of Kiguchi, would have yielded predictable results, by antinociceptive targeting by BU10038 to reduce blast trauma effects (i.e. TBI) on the CNS (See MPEP §2143).
Regarding claim 3, the obviousness rationale for claim 2 has been set forth above.
Claim(s) 1, 4-5, 8-9, 12 are rejected under 35 U.S.C. 103 as being unpatentable over Hibbah O. Awwad et al., hereinafter Awwad (Hibbah O. Awwad et al., Post-blast treatment with Nociceptin/Orphanin FQ peptide (NOP) receptor antagonist reduces brain injury-induced hypoxia and signaling proteins in vestibulomotor-related brain regions, Behavioural Brain Research 340 (2018) 183–194) in view of Federica Ferrari et al., hereinafter Ferrari (Federica Ferrari et al., In vitro functional characterization of novel nociceptin/orphanin FQ receptor agonists in recombinant and native preparations, Eur J Pharmacol. 2016 December 15; 793: 1–13).
Regarding claim 4, Awwad teaches N/OFQ is rapidly up-regulated in response to percussive or stab injury to the brain, and TBI-induced up-regulation of N/OFQ contributes to impaired cerebral reactivity and increased neuronal excitotoxicity (See 3rd paragraph, introduction). Behavioral deficits post blast TBI correlate with increases in N/OFQ and NOP in plasma and brain. Notably, a single treatment with SB-612111, delays behavior deficits and prevents cerebral hypoxia (see page 1, highlights).
Awwad does not teach AT-035.
Ferrari teaches that AT compounds display high NOP affinity and behave as NOP agonists in all functional assays consistently showing the following rank order of potency AT-127≥AT-090≥AT-035 > AT-004= AT-001. AT compounds behave as NOP full agonists in the calcium mobilization and mouse colon assays (see Abstract). Notably, Ferrari teaches that AT compounds bind the same NOP site recognized by N/OFQ and SB-612111, recently described at atomic level (see Discussion, 3rd paragraph, last 3 lines).
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to target the N/OFQ-NOP receptor pathway, as suggested in Awwad, using AT-035 (or the AT compounds in Ferrari) as suggested in Ferrari. One motivated to do so would have a reasonable expectation of success, as AT compounds bind the same NOP site recognized by N/OFQ and SB-612111, as suggested in Ferrari. Thus, one would have recognized that applying the method of Awwad to the teaching in Ferrari, would have yielded predictable results, as the N/OFQ-NOP receptor pathway is an excellent target for therapeutic development, to reduce blast trauma effects (i.e. TBI) on the CNS (see concluding paragraph in Awwad) (See MPEP §2143).
Regarding claim 5, the obviousness rationale has been set forth above in the rejection for claim 4.
Claim(s) 1, 7-12 are rejected under 35 U.S.C. 103 as being unpatentable over Hibbah O. Awwad et al., hereinafter Awwad (Hibbah O. Awwad et al., Post-blast treatment with Nociceptin/Orphanin FQ peptide (NOP) receptor antagonist reduces brain injury-induced hypoxia and signaling proteins in vestibulomotor-related brain regions, Behavioural Brain Research 340 (2018) 183–194) in view of Nurulain T. Zaveri hereinafter Zaveri (Nurulain Zaveri, The Nociceptin Opioid Receptor (NOP) as a Therapeutic Target: Progress in Translation from Preclinical Research to Clinical Utility, J Med Chem. 2016 August 11; 59(15): 7011–7028).
Regarding claim 7, the teachings of Awwad have been set forth above.
Awwad does not teach SER100 (ZP120).
Zaveri teaches NOP receptor-targeted compounds in the pipeline from research to the clinic. Among peptidic NOP agonists, Zaveri teaches compound 6 (ZP-120, Table 1), a dodecapeptide NOP partial agonist, also called SER100 (page 4, 1st paragraph).
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to target the N/OFQ-NOP receptor pathway, as suggested in Awwad, using SER100 (ZP120) as suggested in Zaveri. One motivated to do so would have a reasonable expectation of success, as SER100 is a NOP receptor-targeted compound in the pipeline from research to the clinic, as suggested in Zaveri. Thus, one would have recognized that applying the method of Awwad to the teaching in Zaveri, would have yielded predictable results, as the N/OFQ-NOP receptor pathway is an excellent target for therapeutic development, to reduce blast trauma effects (i.e. TBI) on the CNS (see concluding paragraph in Awwad) (See MPEP §2143).
Regarding claim 10, the teachings of Awwad have been set forth above.
Awwad does not teach MK-5757.
Zaveri teaches MK-5757 (compound 3, Table 1), a NOP antagonist identified as a clinical candidate after extensive optimization (see page 3, last three lines; page 32 Table 1).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to target the N/OFQ-NOP receptor pathway, as suggested in Awwad, using MK-5757 as suggested in Zaveri. One motivated to do so would have a reasonable expectation of success, as MK-5757 is a NOP receptor-targeted compound in the pipeline from research to the clinic, as suggested in Zaveri. Thus, one would have recognized that applying the method of Awwad to the teaching in Zaveri, would have yielded predictable results, as the N/OFQ-NOP receptor pathway is an excellent target for therapeutic development, to reduce blast trauma effects (i.e. TBI) on the CNS (see concluding paragraph in Awwad) (See MPEP §2143).
Regarding claim 11, the teachings of Awwad has been set forth above.
Awwad does not teach JTC-801.
Zaveri teaches NOP-targeted compounds that advanced into clinical development, specifically JTC-801, NOP antagonist (Table 1, compound 7; see page 4, 2nd paragraph; page 15, 2nd paragraph; page 32, Table 1).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to target the N/OFQ-NOP receptor pathway, as suggested in Awwad, using JTC-801 as suggested in Zaveri. One motivated to do so would have a reasonable expectation of success, as JTC-801 is a NOP receptor-targeted compound in the pipeline from research to the clinic, as suggested in Zaveri. Thus, one would have recognized that applying the method of Awwad to the teaching in Zaveri, would have yielded predictable results, as the N/OFQ-NOP receptor pathway is an excellent target for therapeutic development, to reduce blast trauma effects (i.e. TBI) on the CNS (see concluding paragraph in Awwad) (See MPEP §2143).
Claim(s) 1, 8-9, 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Hibbah O. Awwad et al., hereinafter Awwad (Hibbah O. Awwad et al., Post-blast treatment with Nociceptin/Orphanin FQ peptide (NOP) receptor antagonist reduces brain injury-induced hypoxia and signaling proteins in vestibulomotor-related brain regions, Behavioural Brain Research 340 (2018) 183–194) in view of Omar N. Al Yacoub et al., hereinafter Yacoub (Omar N. Al Yacoub et al., Therapeutic potential of nociceptin/orphanin FQ peptide (NOP) receptor modulators for treatment of traumatic brain injury, traumatic stress, and their co-morbidities, Pharmacology & Therapeutics 231 (2022) 107982).
Regarding claim 13, the teachings of Awwad have been set forth above.
Awwad does not teach treatment of post-traumatic stress disorder.
Yacoub teaches that PTSD is often a consequence of TBI. PTSD and TBI share common symptoms, and negatively influence outcomes as comorbidities of the other. Notably, Yacoub teaches that PTSD and TBI preclinical models elicit changes in the N/OFQ-NOP receptor system, and that administration of NOP receptor ligands alleviate some of the neurobiological and behavioral changes induced by brain injury and/or traumatic stress exposure (see Abstract). Specifically, (i) Yacoub teaches that daily systemic administration of the NOP receptor antagonist, JTC-801, from days 7-21 in male rats blocks the SPS-induced (i.e. PTSD rat model) increase in N/OFQ levels in serum, CSF, PAG and HIPPO at day 21 after SPS (see page 5, section 4.1); (ii) daily systemic administration of the NOP receptor antagonist, JTC-801, reverses SPS-induced hypocortisolism (see page 7, section 4.2); rats that received the NOP receptor antagonist, JTC-801 systemically during days 7–21 after exposure to SPS exhibit significantly fewer anxiety like behaviors (page 8, section 4.3, 4th paragraph); (iii) daily systemic administration of the NOP receptor antagonist JTC-801 on days 7-21 reverses SPS induced mechanical allodynia and thermal hyperalgesia (see page 9, 1st paragraph).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to target the N/OFQ-NOP receptor pathway, as Yacoub teaches, that PTSD and TBI preclinical models elicit changes in the N/OFQ-NOP receptor system, and that administration of NOP receptor ligands alleviate some of the neurobiological and behavioral changes induced by brain injury and/or traumatic stress exposure. One motivated to do so would have a reasonable expectation of success, as SB612111, suggested in Awwad is a NOP receptor antagonist for treatment of TBI and JTC-801, suggested in Yacoub, is a NOP receptor-targeted compound for treatment of PTSD. One would have recognized that applying the method of Awwad to the teaching in Yacoub, would have yielded predictable results, as the N/OFQ-NOP receptor pathway is altered in TBI and PTSD and that compounds that target the N/OFQ-NOP receptor pathway are used to alleviate symptoms associated with TBI/PTSD (See MPEP §2143).
Regarding claims 14 and 16, the obviousness rationale has been set forth above in the combined teachings of Yacoub and Awwad.
Claim(s) 1, 8-9, 12, 14-15 is rejected under 35 U.S.C. 103 as being unpatentable over Hibbah O. Awwad et al., hereinafter Awwad (Hibbah O. Awwad et al., Post-blast treatment with Nociceptin/Orphanin FQ peptide (NOP) receptor antagonist reduces brain injury-induced hypoxia and signaling proteins in vestibulomotor-related brain regions, Behavioural Brain Research 340 (2018) 183–194) in view of Omar N. Al Yacoub et al., hereinafter Yacoub (Omar N. Al Yacoub et al., Therapeutic potential of nociceptin/orphanin FQ peptide (NOP) receptor modulators for treatment of traumatic brain injury, traumatic stress, and their co-morbidities, Pharmacology & Therapeutics 231 (2022) 107982) further in view of Federica Ferrari et al., hereinafter Ferrari (Federica Ferrari et al., In vitro functional characterization of novel nociceptin/orphanin FQ receptor agonists in recombinant and native preparations, Eur J Pharmacol. 2016 December 15; 793: 1–13).
The teachings of Awwad, Yacoub and Ferrari have been set forth above.
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to target the N/OFQ-NOP receptor pathway, as Yacoub teaches that PTSD and TBI preclinical models elicit changes in the N/OFQ-NOP receptor system, and that administration of NOP receptor ligands alleviate some of the neurobiological and behavioral changes induced by brain injury and/or traumatic stress exposure. One motivated to do so would have a reasonable expectation of success, as SB612111, suggested in Awwad is a NOP receptor antagonist for treatment of TBI. Notably, Ferrari teaches that AT compounds bind the same NOP site recognized by N/OFQ and SB-612111, recently described at atomic level (see Discussion, 3rd paragraph, last 3 lines).
One would have recognized that applying the method of Awwad to the teaching in Yacoub, would have yielded predictable results, as the N/OFQ-NOP receptor pathway is altered in TBI and PTSD and that compounds that target the N/OFQ-NOP receptor pathway, such as AT compounds, in place of SB-612111, can be used to alleviate symptoms associated with TBI/PTSD (See MPEP §2143).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 19 of copending Application No. 19485481 (reference application) in view of Omar N. Al Yacoub et al., hereinafter Yacoub (Omar N. Al Yacoub et al., Therapeutic potential of nociceptin/orphanin FQ peptide (NOP) receptor modulators for treatment of traumatic brain injury, traumatic stress, and their co-morbidities, Pharmacology & Therapeutics 231 (2022) 107982) further in view of Norikazu Kiguchi at al., hereinafter Kiguchi (Norikazu Kiguchi at al., BU10038 as a safe opioid analgesic with fewer side effects after systemic and intrathecal administration in primates, British Journal of Anaesthesia, 122 (6): e146-e156 (2019)). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, reference application ‘481 teaches a method of treating a patient diagnosed with post-traumatic stress disorder and alcohol use disorder, comprising administering a compound (i.e. NOP receptor partial agonist PPL-138). See claims 1-3, 19.
Reference application does not teach TBI.
The teachings of Yacoub and Kiguchi have been set forth above.
Notably, Yacoub teaches that PTSD and TBI preclinical models elicit changes in the N/OFQ-NOP receptor system, and that administration of NOP receptor ligands alleviate some of the neurobiological and behavioral changes induced by brain injury and/or traumatic stress exposure (see Abstract).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to target the N/OFQ-NOP receptor pathway, as Yacoub teaches, using the antinociceptive BU10038 as suggested in Kiguchi for treatment. One motivated to do so would have a reasonable expectation of success, as BU10038 produces long-lasting antinociceptive effects. Thus, one would have recognized that applying the teaching of Yacoub to method of Kiguchi, would have yielded predictable results, by antinociceptive targeting by BU10038 for therapeutic benefit (See MPEP §2143).
Regarding claims 2 and 3, the rejection is set forth above.
Regarding claims 14 and 15, reference application ‘481 teaches a method of treating comprising administering a compound (i.e. NOP receptor partial agonist PPL-138). See claims 1-3, 19.
The obviousness rationale has been set forth above in the teachings of Yacoub and Kiguchi.
Conclusion
No claim is allowed.
Correspondence
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/ARCHANA VARADARAJ/ Examiner, Art Unit 1658
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
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