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
The instant application is a 35 USC 371 National Stage filing of international application PCT/JP2023/030980, which claims priority under 35 USC 119(a)-(d) from Japanese applications JP2022-135949 and JP2023-027426, filed August 29, 2022 and February 24, 2023, respectively. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statements (IDS) dated April 26, 2024; May 19, 2025; December 1, 2025; January 9, 2026; May 18, 2026 and July 24, 2026 were in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the IDS documents were considered and signed copies of the 1449 forms are attached.
Status of Claims
Currently, claims 1-14, 20-24 and 35-58 are pending in the instant application and under consideration herein.
Claim Objections
Claims 39-46 are objected to for depending on a rejected base claim but would be allowable if rewritten in independent form.
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)(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) 1-14, 20-24, 35-38 and 47-58 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2024/214046 (“the ‘046 publication”).
The instant claims are drawn to a compounds of Formula IA as well as methods of using them for inhibiting NLRP inflammasome or for treating or preventing a disease as claimed.
The ‘046 publication teaches the compound of formula
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95
177
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(see Abstract) for treatment of a disease, disorder or condition associated with NLRP3. The prior art teaches a number of anticipatory compounds, which are too numerous to describe how each reads on the claimed formula. As particular relevant examples, the prior art teaches
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68
135
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as Example 2;
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66
138
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as Example 23; and Example 297 which is identical to the first compound listed in claim 13, as well as specifically recited in claims 35-38. The reference goes on to disclose that the compounds disclosed therein are used to treat conditions associated with NLRP3 including Parkinson’s disease, AD, ALS, TBI and others. Since the prior art teaches all required limitations of the instant claims, the claims are rejected as anticipated.
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.
As stated in the MPEP 2164.01 (a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
Claims 21-24, 50-53 and 55-58 are rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, 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. The specification is not enabled for the treatment of the full scope of diseases nor for the prevention of any of the claimed conditions. The specification falls short because data essential for treating numerous diseases by administering a therapeutically effective amount of the claimed compounds to a person in need is not described in the specification, nor is there any description or examples of prevention of the onset of any of the claimed disorders.
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. § 112, first paragraph, have been described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
The Nature of the Invention
The claims recite that a method of treating various distinct classes of disease, such as a neurological or psychiatric disease comprising administering a compound of claim 1, where the diseases to be treated include, for example, multiple sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, ALS and traumatic brain injury.
The scope of the claimed method includes the prevention of all claimed diseases, which indicates that treating refers to any action that inhibits or at least delays the development of a disorder, condition, or symptoms associated therewith. Further, prevention includes primary, secondary and tertiary prevention (thus reading on administration to a healthy individual to prevent a would-be initial onset of disease).
The State of the Prior Art
The state of the prior art is as follows:
Parkinson's disease is a progressive neurodegenerative disorder (synucleopathy) diagnosed on the basis of characteristic motor disturbances, asymmetry of symptoms onset and response to levodopa (Litvan et al., 2003). Lewy bodies, neurofibrillary tangles and plaques are observed in nigral, limbic and neocortical regions. These degenerations are supposed to affect catecholaminergic (dopamine and norepinephrine) and cholinergic neurotransmission. In particular, an important part of cognitive deficits (executive function and working memory) have been related to a decreased prefrontal dopaminergic signaling in non demented patients (Nandakumar et al., 2013). The predictability or lack thereof in the art
The instant claimed invention is highly unpredictable as discussed below:
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instant claimed invention is highly unpredictable since one skilled in the art would recognize that the method of treatment requiring an enzymatic response in the patient using the claimed compound could result in the possibility of off target effects since only small groups of compounds are completely specific for one of several enzymes that degrade catecholamines (such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol structure; this kind of treatment can not be translated to all the possible treatment of all the well-known disorders related to nerve injury as wells their corresponding symptoms in regards to their therapeutic effects.
Hence, in the absence of a showing of correlation between all the claimed conditions, which include neurodegenerative and psychiatric disorders and conditions, one of skill in the art is unable to fully predict possible results from the administration of the claimed compounds of formula due to the unpredictability of the role of treating any nerve injury by the claimed enzyme in the patient with the claimed compounds, i.e. whether promotion or inhibition would be beneficial for the treatment of the above diseases. This is especially true given the broadly claimed methods which also include prevention of each of these conditions, many of which are known in the art to be unpreventable and uncurable.
The nature of pharmaceutical arts is that it involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities. There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
Neurological disorders are diseases of the central and peripheral nervous system. In other words, the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscles. There are more than 600 diseases of the nervous system. These disorders include epilepsy, Alzheimer disease and other dementias, cerebrovascular diseases including stroke, migraine and other headache disorders, multiple sclerosis, Parkinson's disease, neuroinfections, brain tumours, traumatic disorders of the nervous system due to head trauma, and neurological disorders as a result of malnutrition.
Regarding Alzheimer’s Disease (AD), many scientists and medical doctors are in search for finding the main causative factors in order to treat the Alzheimer’s Disease. For example, according to Meda et al (Nature 374,647 (1995) and Larner (Neurosci. Res. Commun. 20 , 147 (1997), -amyloid peptide was shown to exert direct toxic effects on neutrons and to inhibit neurite growth in vitro. Thus, therapeutic approaches that can modulate A peptide toxicity have been hypothesized to represent important methods for controlling the onset of AD. It is postulated that if neuronal cells can be protected from A peptide/senile plaque-induced toxicity, the onset of AD may be delayed; furthermore, St. George-Hyslop et al (Nature 400, 116 (1999) indicates that an anti-A protein antiboby was shown to clear senile plaques and protect mutant PDAPP mice from the onset of AD. From this, the generation of reactive oxygen intermediates through oxidative stress caused by A peptide has been suggested to be the major pathway of A peptide-induced cytotoxicity. Thus, there is no positive correlation between the peptide-induced toxicity against certain cells and the treatment as claimed.
From these findings, there is no single common cause for all these disorders; therefore, there is no clear assurance that only the interaction of the claimed compound with the recited enzymes would be resulted in the prevention or cure of the above diseases.
The amount of direction or guidance present
The direction present in the instant specification is that the compounds of formula I can be used to treat nerve injury related to physical trauma or a host of related conditions, as well as their corresponding symptoms of disorders, as well as prevention and cure of each of the claimed conditions. These disorders include multiple sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, ALS and traumatic brain injury.
However, the specification is silent and fails to provide guidance as to whether all those diseases require the same mechanistic nature of enzyme activity in the patient with the claimed Compound IA, i.e. the specification fails to provide a correlation between all those diseases and the inhibition of the same enzyme in a patient. Also, there is no direction and guidance for how all those diseases would be prevented by using the claimed compound.
The presence or absence of working examples
There is no working example for all those disorders-treatment by using the mechanistic nature of enzyme modulation in the patient with Compound IA. Also, the compounds which are disclosed in the specification have no pharmacological data regarding the treatment of the entirety of the scope of claimed diseases using the claimed compound. Also, the specification fails to provide sufficient working examples as to how those listed diseases can be prevented or treated in the patient with the compound of formula I, i.e. again, there is no direct correlation between the entirety of the listed diseases and the claimed compound. Rather, the specification provides in vitro and in vivo tests which pertain to nerve cell regeneration in cases of physic trauma and injury. There is no disclosure of a test or data which would correlate to the use of the claimed compounds for the inhibition or prevention of the onset of disease mechanism for the wide variety of diseases and conditions as claimed.
The breadth of the claims
The breadth of the claim is that the Compound IA can be used to treat and prevent all the known diseases mentioned in the above.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine which kinds of those disorders would be benefited by the effect of the claimed compounds and would furthermore then have to determine whether the claimed compounds would provide treatment of all the known diseases listed in the above.
The level of the skill in the art
The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
Thus, the specification fails to provide sufficient support of the broad use of the compounds of formula I for all kinds of diseases-treatment. As a result, necessitating one of skill to perform an exhaustive search for which all the known diseases can be treated by the compounds of formula I in order to practice the claimed invention.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001 (3/13/1997), states that “ a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated by the compound encompassed in the instant claims, with no assurance of success.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alicia L. Otton whose telephone number is (571)270-7683. The examiner can normally be reached on Monday – Thursday 8:00-6:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Fereydoun Sajjadi can be reached on (571)272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALICIA L OTTON/Primary Examiner, Art Unit 1699
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