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 .
DETAILED ACTION
RCE – Final Rejection
Claim Status
Claims 14, 16, and 25-26 were pending as of the Office Action of 10/22/2024.
Upon amendment entrance, Claim 15 remains cancelled.
Upon amendment entrance, Claims 17-24 remain withdrawn.
Upon amendment entrance, Claims 14 and 25 were amended.
Claims 14, 16 and 25-26 are currently pending examination.
Priority Status
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Examiner acknowledges the effective filing date of the application is 09/21/2018.
Examiner Responses to Arguments/Amendments
The issues raised in the Office Action mailed 10/22/2024, are addressed below:
I. Response to Double Patenting Rejection -
Applicant has stated in regards to the Double Patenting Rejection that “Choi provides no indication that Choi's compound for treating CNS disorders, such as anxiety, can also treat PTSD.”
In view of the Applicant’s amendment, Applicant’s arguments have been fully considered and is the Double Patenting Rejection has been withdrawn.
II. Claim Rejections -
A. Claims 14, 16, and 25-26 under 35 U.S.C. 102(a)(1) and 102(a)(2)
Applicant's arguments filed 12/23/2025 have been fully considered but they are not persuasive for the following reasons:
Applicant states the following arguments:
(1) Choi describes anticonvulsant Compounds 20 and 21, which read on Formula I of claims 14 and 25, and describes Formula II of claim 16,
(2) Choi describes treatment of disorders of the central nervous system (CNS),
(3) CSAT describes symptoms of posttraumatic stress disorder (PTSD) and acute stress disorder (ASD),
(4) Choi describes symptoms such as irritability, anxiety, and sleep disorders, and
(5) the present application describes symptoms of PTSD.
Examiner disagrees. The art is good for the claims for the following reasons:
Post-traumatic stress disorder (PTSD) and its impact on the central nervous system (CNS) are deeply intertwined, as PTSD is characterized by significant, lasting changes to brain chemistry and structure. The similarities between PTSD and various CNS disorders (including traumatic brain injury and other stress-related conditions) lie in the underlying neurobiology, specifically affecting neurochemical regulation, structural integrity, and autonomic functioning
The evidentiary reference of CSAT (Diagnostic and Statistical Manual of Mental Disorders; Exhibit 1.3-3, pg. 78), teaches the DSM-5 Criteria for PTSD -which by definition is a reference book on mental health and brain-related conditions and disorders - (pg. 82-83). In its explanation, the prior art uses Treatment Improvement Protocols (TIPs) developed by the Substance Abuse and Mental Health Services Administration (SAMHSA) as criteria to determine ASD, PTSD and other mental disorders stemming from dysfunction of the central nervous system. PTSD is associated with changes in several brain regions and neurochemical systems, leading to dysregulation and dysfunction. Neurotransmitters like norepinephrine and cortisol are also impacted, contributing to the characteristic symptoms of PTSD.
CSAT states signs/symptoms of varied patient populations affected by trauma (which is the core of PTSD/ASD), which affects the central nervous system, in immediate and delayed emotional, physical and cognitive responses & reactions (pg. 62-63).
Again, all are linked to dysfunction of the central nervous system. By definition (according to the Merriam-Webster Dictionary) the CNS is the part of the nervous system which in vertebrates consists of the brain and spinal cord, to which sensory impulses are transmitted and from which motor impulses pass out, and which supervises and coordinates the activity of the entire nervous system compare autonomic nervous system, peripheral nervous system.
This links Choi to PTSD/ASD via symptoms such as irritability, anxiety, and sleep disorders. PTSD symptoms significantly affect brain regions involved in processing emotions, memory, and stress responses. These impacts manifest as intrusive thoughts, hyperarousal, avoidance behaviors, and negative alterations in cognition and mood. . While its primary indication is epilepsy, its unique mechanism of action—combining GABAergic enhancement with sodium channel inhibition—has led to research into its potential neuroprotective effects and its relationship to CNS-related side effects.
Further, the Instant Specification supports the interpretation. On para. [0005] it is disclosed “symptoms of post-traumatic stress disorder include full or partial amnesia of mental trauma or situation (traumatic events), flashback re-experiencing traumatic events by intrusive memories of that time even though the traumatic events had passed, avoidance of stimuli associated with traumatic events- e.g., activities or places associated with traumatic events, nightmares associated with traumatic events, irritability, hyperarousal (enhanced state of threat sensitivity with the potential for danger), hypervigilance, rage, poor concentration and emotional withdrawal…” These are symptoms that arise from trauma.
Finally, and with evidence by CSAT, Choi, Merriam Webster Dictionary and Applicant’s Specification, the functional language is met for the claims.
B. Claims 14, 16, and 25-26 under 35 U.S.C. 103
Applicant's arguments filed 03/24/2025 have been fully considered but they are not persuasive for the following reasons:
Applicant states the following arguments:
Applicant traverses this rejection on the grounds that:
(A) the cited references fail to disclose all elements; and
(B) there is no motivation combine.
Examiner disagrees. Based on Broadest Reasonable Interpretation, reading the claims in light of the specification, in view of the Choi reference, the CSAT reference linking these symptoms to PTSD, as well as the Choi reference teaching treating of the symptoms with the compounds of the Instant Claims indicates the claims are met. If the prior art structure is capable of performing the intended use, then it meets the claim.
Further, this argument is not found to be persuasive because the Examiner used the DSM-5 (DSM-V) updated version of current disorders of mental health, and it includes ASD and PTSD (CSAT cited reference above). Based on the teaching of Choi and the art, the compound the Applicant claims, Example 24 (Carbamic acid, 1-(2-chloro-phenyl)-2-tetrazol-2-yl-ethyl ester; Exact Structure; col. 34, lns. 39-67), is known with CAS registry number 913088-80-9 as cenobamate, an antiepileptic drug used to treat partial-onset seizures. While antiepileptic drugs (also known as antiseizure medications or anticonvulsants) are used to treat and prevent seizures, not all seizures involve convulsions.
As such, there are connections to PTSD as listed above but reiterated below:
First, the amygdala (part of the brain that processes fear and emotions) in people with PTSD, is overactive, which can disrupt the brain's electrical signals and lead to seizures. When faced with a perceived threat, the amygdala triggers the release of stress hormones, preparing the body for a fight-or-flight reaction. This process can lead to heightened alertness, increased heart rate, and other physiological changes associated with stress.
Second, neuroinflammation is an essential component of neurological disorders. This inflammatory response involves the activation of immune cells like microglia and astrocytes, and changes in inflammatory markers within the brain. Furthermore, neuroinflammation has been linked to cognitive and emotional disturbances often observed in PTSD. Stress can induce neuronal dysfunction, impacting both the structure and function of neurons, particularly in brain regions like the prefrontal cortex and hippocampus.
Finally, the prior art teaches on the relationship between inflammation and PTSD Neuroinflammation, unlike acute inflammation of the central nervous system, is considered a type of chronic inflammation. Acute inflammation of the central nervous system occurs immediately after damage, causing reactions such as activation of the inflammatory molecules, endothelial cells, and tissue edema. On the other hand, neuroinflammation is when nerve cells are continuously activated, and other immune cells are mobilized to the brain. It is closely related to neurodegenerative diseases. IL-1β, IL-6, and TNF-α are reported to affect the brain at its cognitive, functional, and morphological levels, as well as neurogenesis, synaptic plasticity, and memory learning.
The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art (See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
II. Maintained Rejections -
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.
A. 35 U.S.C. 102 Rejection 1 -
Claims 14 and 25 are rejected under 35 U.S.C. 102(a)(1) & 102(a)(2) as being anticipated by S.C. Lim, et. al in US 9,434,970 B2 (pub’d 04/21/2011; hereinafter “’970”)
With respect to claims 14 and 25, Patent ’970 teaches the carbamate compounds prepared useful in the treatment of CNS disorders such as convulsion azole compounds, which includes Applicant’s compound (col. 12, ln. 59 to col. 14, ln. 12 - Carbamic acid, 1-(2-chloro-phenyl)-2-tetrazol-2-yl-ethyl ester; Exact Structure; as evidenced by STN on Nov. 13, 2006; CAS RN: 913088-80-9 and CAS RN: 913087-59-9). It also teaches to the population of one taking the Applicant’s compound for the treatment of CNS disorders.
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B. 35 U.S.C. 102 Rejection 2 -
Claims 14, 16, 25, and 26 are rejected under 35 U.S.C. 102(a)(1) & 102(a)(2) as being anticipated by Yong Moon Choi, et. al in US 7,598,279 B2 (pub’d 10/06/2009; hereinafter “Choi”) as evidenced by (Center for Substance Abuse Treatment (US): DSM-5 Diagnostic Criteria for PTSD - Trauma- Informed Care in Behavioral Health Services - NCBI Bookshelf, published 2014; hereinafter “CSAT”).
With respect to Claims 14, 6, 25, and 26, Choi discloses neurotherapeutic azole compounds, which includes Applicant’s compound (Compounds 20 and 21; cols. 79-80; Example 24: Carbamic acid, 1-(2-chloro-phenyl)-2-tetrazol-2-yl-ethyl ester; Exact Structure; col. 34, lns. 39-67; as evidenced by STN on Nov. 13, 2006; CAS RN: 913088-80-9 and CAS RN: 913087-59-9).
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Choi also teaches Compounds 20 and 21, and Example 24 (Cpds. 20 and 21: cols. 79-80; Ex. 24, col. 34, lns. 39-67) as “azole compounds containing carbamoyl group and pharmaceutically salts as compounds used in the treatment of disorders of the central nervous system, demonstrating as anxiety, depression, convulsion, epilepsy, migraine, sleep disorder, neuropathic pain, stroke, cognitive impairment, neurodegeneration, stroke” (abstract; col. 4, lns. 21-27; col. 9, lns 21-28). This is linked to the CSAT through those symptoms.
As evidenced by CSAT (Diagnostic and Statistical Manual of Mental Disorders; Exhibit 1.3-3, pg. 78), the DSM-5 Criteria for PTSD states symptoms associated, pg. 82-83, as well as immediate and delayed emotional, physical and cognitive responses/reactions, pg. 62-63). This is disclosed in Patent ’279 via further symptoms such as irritability, anxiety, and sleep disorders (see above) which also read on the claims for stress disorders from dysfunction of the central nervous system.
The genus of the claims of Patent ’279, (Choi) teaches overlapping Formula (I) and Formula (II). Further Post-traumatic stress disorder (PTSD) is considered a neuropsychiatric disorder, meaning it involves both psychological and neurological components. While it's not strictly categorized as a central nervous system (CNS) disease in the same way as conditions like Alzheimer's or Parkinson's, PTSD does involve significant changes in the brain's structure and function.
This is further support by the Instant Specification. On para. [0005] of the Instant Specification states “symptoms of post-traumatic stress disorder include full or partial amnesia of mental trauma or situation (traumatic events), flashback re-experiencing traumatic events by intrusive memories of that time even though the traumatic events had passed, avoidance of stimuli associated with traumatic events- e.g., activities or places associated with traumatic events, nightmares associated with traumatic events, irritability, hyperarousal (enhanced state of threat sensitivity with the potential for danger), hypervigilance, rage, poor concentration and emotional withdrawal…”
As stated above, with evidence by Patent ’279, CSAT and Applicant’s Specification, the functional language is met for the claims.
Patent ’279 further teaches (col. 24, lns. 13-53) that the Cpds. 20 and 21, and Example 24 of the prior art, which are identical to Applicants are used in a similar method as the Instant Application “for the treatment of diseases of the central nervous system of anxiety, depression, convulsion, epilepsy, migraine, lar disorder, drug abuse, smoking, ADHD, obesity, sleep disorder, neuropathic pain, cognitive impairment, smoke and muscle spasm, it is preferred to administer the compounds orally. For oral administration, the compounds are preferably combined with a pharmaceutical carrier.”
Patent ’279 finally teaches the therapeutic use of the compounds and their pharmaceutically useful salts are established via tests (col. 24, ln. 50 to col. 29, ln. 40) looking at varied symptoms, such as anxiolytic (anxiety) and anticonvulsant activity (seizures, spasms) in the LDB test, MES test, PTZ test and TBPS assay with GABA-related activities used for treatment of sleep disorder or muscle spasms. This is better illustrated in Table 1 of test results obtained with the compounds 20 and 21 (lns. 7-8 of Table 1)and pharmaceutically useful salts.
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.
Joint Inventors
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.
Claims 14, 16, 25, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Choi and in view of CSAT.
With respect to claims 14, 16, 25, and 26, Choi teaches the Instant case specie election (Compounds 20 and 21, cols. 79-80; Example 24-Exact Structure; col. 34, lns. 39-67- col. 34, lns. 39-67). Choi continues teaching that this treatment can have oral dosage administration, in various formulations, to aid in the treatment of disorders to the central nervous system (which are known to occur in those suffering from PTSD; col. 24, lns. 13-53).
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Choi fails to teach symptoms of trauma explicitly stated to be PTSD, or to specifically state that anxiety is a symptom of PTSD. This is an alternative interpretation from above.
CSAT though, explicitly teaches mental disorders like PTSD (pg. 61-63; pgs. 80-83, Posttraumatic Stress Disorder). According to Exhibit 1.3-1: Immediate and Delayed Reactions to Trauma and Exhibit 1.3-4: DSM-5 Diagnostic Criteria for PTSD (pg. 77-84), “PTSD symptoms are represented in a number of other mental illnesses, including major depressive disorder, anxiety disorders, and psychiatric disorders” (pg. 81, col. 1, para. 1).
Therefore, it would have been prima facie obvious to use the teachings of Choi with the in-depth information from CSAT (Trauma-Informed Care in Behavioral Health Services) to comprehend the varying symptoms brought on by trauma and apply the appropriate treatment. The Examiner’s position is that treating symptoms known for anxiety/stress, or using compounds to treat anxiety/stress for use in PTSD have commonality. The prior art structure is capable of performing the intended use, and so it meets the claim.
Finally, one could substitute anxiety from PTSD for general anxiety disorder because one indices of trauma is anxiety. The combination of Choi and CSAT teaches that one would expect success treating or alleviating anxiety, with these compounds (referenced above).
It therefore would be prima facie obvious to arrive at the instantly claimed compounds because structurally similar compounds are expected to have similar properties. In the matter of the Instant Application and the referenced, the genus of the claims of Patent ’531 teaches overlapping Formula (I) and Formula (II). Further Post-traumatic stress disorder (PTSD) is considered a neuropsychiatric disorder, meaning it involves both psychological and neurological components. While it's not strictly categorized as a central nervous system (CNS) disease in the same way as conditions like Alzheimer's or Parkinson's, PTSD does involve significant changes in the brain's structure and function.
Conclusion
Claims 14, 16 and 25-26 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Josmalen M. Ramos-Lewis whose telephone number is (571)272-0084. The examiner can normally be reached M-F 9:30-5:30 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Josmalen M. Ramos-Lewis, Ph.D.
Patent Examiner
Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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