DETAILED ACTION
This office action is in response to applicant’s filing dated October 27, 2025.
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 Claims
Claims 1-8, 10, 11, and 16-25 are pending in the instant application. Acknowledgement is made of Applicant's remarks filed October 27, 2025. Claims 9 and 12-15 were previously canceled.
Election/Restrictions
Applicant’s election of Group I, drawn to a compound of formula (Id) as the elected invention and Compound (II): (4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a- octahydrobenzo[g]quinolin-7-yl sulfamate, having the structure:
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as the elected species of Formula (Id) in the reply filed on October 27, 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)).
Compound II has been found free of prior art. Thus, examination has been expanded to encompass the full scope of formula (Id). Compounds of formula (Id) have been found to be free of prior art.
Claims 1-5, 7, 8, 10, and 20-25 are allowable. Claims 16-19, are previously withdrawn from consideration as a result of a restriction requirement, require all the limitations of an allowable claim. Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement between inventions Groups I and II, as set forth in the Office action mailed on August 27, 2025, is hereby withdrawn and claims 16-19 are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Priority
The present application is a 371 of PCT/EP2021/081678 filed on November 15, 2021, which claims benefit of foreign priority to EP 20207969.5 filed on November 17, 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on August 11, 2023; October 25, 2023; and October 27, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner, except where marked with a strikethrough.
Drawings
Acknowledgement is made of the drawings received on May 11, 2023. These drawings are accepted.
Claim Objections
Claim 6 is objected to because of the following informalities:
Claim 6 contains a grammatical error. Claim 6 recites “wherein said compound is on an isolated form substantially free of the compound of formula (I).” The phrase should be written “wherein said compound is an isolated form substantially free of the compound of formula (I).”
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
Indefinite
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11 and 16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 11 and 16, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112(a)
Enablement
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 16-19 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. This is an enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention relates to a method for the treatment of a neurodegenerative disease or disorder comprising administering a therapeutically effective amount of a compound of formula (Id) or pharmaceutically acceptable salt thereof to a patient in need thereof.
The relative skill of those in the art is high, generally that of a D.V.M. or Ph.D. The artisan using Applicant’s invention would generally be a veterinarian with a V.M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain). As illustrative of the state of the art, the examiner cites Akhtar et al (Journal of Controlled Release, 2021; 330:1152–1167) and Guha et al (Drug Delivery Strategies in Neurological Disorders: Challenges and Opportunities, (2023); Mishra, A., Kulhari, H. (eds), Springer, Singapore).
Akhtar, cited for evidentiary purposes only, teaches with the aging of the world population, neurological disorders are responsible for contributing 6.3% of the global burden of all diseases; as a consequence, these disorders causes major health issues of disability and are leading to additional medical treatment and prolonged care; the drug delivery through central nervous system is a major challenge although there is relatively a high flow of blood; the series of barriers to protect itself have been emerged by CNS including the blood brain barrier (BBB), blood–cerebrospinal fluid (CSF) barrier, the blood–retinal barrier, and the blood–spinal cord barrier (page 1152, right bridge paragraph). Akhtar teaches in the USA more than 5 million people have been affected by Alzheimer’s disorder (AD) and this is the leading cause of global memory disorder; accumulation of amyloid-beta peptide (Aβ) (senile plaques), memory loss brain atrophy presence of hyper phosphorylated tau filaments (neurofibrillary tangles), and cerebrovascular changes are the main characteristic of AD; abnormal proteins, oxidative stress, reduced acetylcholine (ACh) levels and excessive metal ion accumulation in brain, and are so supposed to take part an important role in its pathogenesis; AD is treated with two classes of drugs: cholinesterase inhibitors and glutamate regulators (page 1157, right, last paragraph). Akhtar teaches the only approved glutamate regulating medication is Namenda this is used to treat Alzheimer’s, which is connected to memory and learning; the effectiveness of Namenda is on par with the cholinesterase inhibitors, in that it works for approximately half of the individuals taking it, and then only for a short time (page 1158, left, 1st paragraph). Akhtar teaches Huntington’s disease and amyotrophic lateral sclerosis are two ND ailments of relatively less occurrence but are lethal and horrifying; HD, the most common monogenic neurological disease present in developed countries, is an autosomal dominant disease that occurs on account of genetic mutation (page 1158, right, last paragraph); up till now no treatment is available for this disease, the single option is the management of the symptoms (page 1158, left, 1st paragraph). Akhtar teaches Amyotrophic Lateral Sclerosis (ALS) or motor neuron disease is the one that is identified by the breakdown of lower and upper motor neurons that basically control actions of voluntary muscles; on account of its grave and lethal impacts many drugs have recently being experimentally analyzed for their utilization in ALS treatment like Masitinib, Ibudilast, Triumeq, Retigabine and Tamoxifen; however, only two drugs named riluzole and edaravone are currently available and being used; unfortunately, even these two drugs are only effective to slow down the progression of the disease but cannot help to get rid of the disease fully and are unable to revert manifested symptoms of ALS (page 1159, left, 2nd paragraph). Akhtar teaches ND diseases are the most devastating challenge all over the world, and in the future increased number of ND patients are expected due to worsening of the life style and burden; even though developed strategies effectively offer delivery of drugs into the brain of these patients; but none of these approaches provide satisfactory results in the cases of CNS diseases disorder; this remains a challenge due to the unique physiology of the brain, including tight regulation and limited distribution of substances along ECF flow routes; thus, immediate development of novel approaches for ND diseases are highly demanded that can impede the disease progression (page 1165, left, 2nd paragraph).
Guha, cited for evidentiary purposes, teaches the central nervous system (CNS) is an integral part comprising the brain and spinal cord; CNS serves as the processing center of our body, serving several functions, starting from receiving sensory signals from organs like eyes, ears, and skin through sensory neurons, processing of the sensory signals by the brain, and transmission of the motor signals to the motor organs by the spinal cord; it collects information from around the body and regulates activities throughout the whole system giving it the "central" terminology; being a key mediator of our normal bodily activities and owing to its organs' highly sensitive and complex architecture, CNS is prone to many disorders; neurological disorders are becoming more common over the globe as a result of variables such as the increased aging rate of the population due to poor diet and lifestyle and the increasing pollution rate in most nations (page 28, 1st paragraph). Guha teaches the nonregenerative property of CNS neurons makes any damage to them irreversible; so, it poses an unmet need to develop effective drugs for the treatment; drug discovery is the lengthy, costly, and complex process of discovering and developing new chemical entities (NCEs) for curative, symptomatic, or diagnostic therapeutic interventions for diseases; no drug has effectively treated the core symptoms of autism spectrum disorders; the last one being given the green light was chlorpromazine, which was first released to the market over 60 years ago (page 28, last paragraph). Guha teaches some pharmaceutical companies have even stopped or significantly reduced their efforts to develop treatments for mental health issues; popular names like Glaxo Smith Kline (GSK) and Pfizer Smith Kline are in this group, as are psychiatry-focused companies like Eli Lilly; GSK even pulled out of drug discovery of a large number of screening of compounds in some aspects of neuroscience, including pain and psychiatric disorders, leaving many researchers in the field of neurology concerned; CNS illnesses have bigger, more complicated clinical trials with tighter inclusion criteria, making drug research more expensive and time-consuming (page 28, last paragraph). Guha teaches CNS is a very complex system; so, the drug development process for neurological disorders has been a challenge that results in very few drugs reaching the market, leading investors and sponsors pulling out from their drug development process (page 29, last paragraph). Guha teaches CNS diseases include a number of them, such as stroke, Alzheimer's and Parkinson's disease, spinal muscular atrophy (SMA), multiple sclerosis, Huntington's disease, amyotrophic lateral sclerosis (ALS), and glioblastoma; several risk factors, including aging, genetic endocrine conditions, hypertension, inflammation, depression, infection, diabetes, polymorphism, vitamin deficiencies, metabolic conditions, dietary supplements, chemical exposure, and oxidative stress, have been identified as potential contributors to the pathogenesis of these disorders; due to our CNS's complexity, some versatile factors are involved in their pathology, like apoptosis, immunological factors, inflammation, and other spontaneous factors; due to the involvement and crosstalk of many pathways and their associated proteins, most of the cause for CNS pathology remains unclear; the other issue in exploring disease biology is the involvement of many orphan and even unexplored receptors that have a major role in their pathology and our limited efforts to explore them; primitive instruments to map the brain; despite advances in genetics and clinical biology, most nervous system illnesses lack established molecular targets; only a few novel targets have been properly researched in recent times, making it challenging to design cutting-edge medications; the scarcity of appealing biomarkers and creative disease models hinders researchers' capacity to examine the pharmacology of potential medicines in proof-of-concept studies (functional, behavioral, electrophysiological) (page 30, last paragraph).
Thus, Akhtar and Guha establish that the art of treating neurodegenerative diseases is extremely unpredictable.
The breadth of the claims
Claims 16-19 are directed to a method for the treatment of a neurodegenerative disease or disorder comprising administering a therapeutically effective amount of a compound of formula (Id) or pharmaceutically acceptable salt thereof to a patient in need thereof. Claim 16 is extremely broad with regards to the diseases to be treated as well as the compounds that can be used. Claim 17 narrows the scope of diseases but is broad in terms of the compound that can be used. Claim 18 narrows the scope of the compounds of formula (Id) that can be used, but is broad in terms of diseases to be treated, but is broad in terms of compounds that can be used. Claim 19, is narrow in terms of the scope of disease to be treated and the compounds to be used. However, in view of the predictability in the art and lack of working examples, the specification does not support enablement for the narrow scope encompassed by claim 19.
The amount of direction or guidance provided and the presence or absence of working examples
The specification provides no direction in the specification that the disclosed compounds can and do treat all the various disorders Parkinson's Disease, Huntington's disease, Restless leg syndrome, Alzheimer's disease, schizophrenia, attention deficit hyperactivity disorder, or drug addiction. The instant specification does not have any working examples in which the disclosed compounds are used for the claimed method.
The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that any compound of formula (Id) could be predictably used as treatment for any neurodegenerative disease.
Determining if a particular compound of formula (Id) will treat any neurodegenerative disease would require formulation into a dosage form, and subjecting into clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the inventions of claims 16-19 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Conclusion
Claims 16-19 are rejected.
Claim 6 is objected.
Claims 1-5, 7, 8, 10, and 20-15 are free of prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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/Rayna Rodriguez/Primary Examiner, Art Unit 1628