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 on 12/15/2023, is a national phase application under 35 U.S.C. § 371 of International Application No. PCT/EP2021/068532, filed on 07/05/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 04/02/2024, 05/08/2024, 06/04/2024, 07/31/2024, 12/23/2024, 03/07/2025, and 07/24/2025, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Status of claims
Claims 1-20 are pending.
Abstract
The Abstract of the disclosure is objected to because the Abstract recites “the present invention relates to”. Applicant is reminded of the proper language and format for an abstract of the disclosure. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 10-20 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only and cannot depend from any other multiple dependent claims. See MPEP § 608.01(n). Claims 1, 3, 5, and 6 are independent claims, however, claim 7 recites “… according to any one of the previous claims, …”. Similarly, claims 10-15, and 19 recite “… according to any one of the previous claims, …”, and claims 16-18 and 20 are dependents of claims 15, 16, 17 or 19.
"In view of compact prosecution, for the purpose of applying prior art, claims 10-20 are interpreted as depending on claim 1 (or whatever claim is a reasonable interpretation)."
Claim 1 is objected to for the following informalities:
Claim 1 recites “… at steady state at at least about 35 ng/mL at trough. The repeated recitation of the “at” appears to be a typo. The repeated “at” can be replaced with “of” and the claim reads “at steady state of at least about 35 ng/mL at trough.”
Appropriate correction is required.
Rejections 35 U.S.C. 112(b)
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.
Claims 1-20 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.
Pursuant to 35 U.S.C. 112, the claim must apprise one of ordinary skill in the art of its scope so as to provide clear warning to others as to what constitutes infringement. MPEP 2173.02(II); Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000). The meaning of every term used in a claim should be apparent from the prior art or from the specification and drawings at the time the application is filed. Claim language may not be ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention. MPEP § 2173.05(a).
Claim 1 is rejected pursuant to 35 U.S.C. 112, as indefinite because it is unclear whether this claim is directed to the statutory category of a method or a composition. Claim 1 is reproduced below.
Claim 1. A compound of formula (1) and/or its tautomers for use in a method of treating a human subject, the method comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (1) and/or its tautomers in a dose and at a daily dosing frequency sufficient to maintain the plasma concentration of the compound of formula (1) and/or its tautomers at steady state at at least about 35 ng/mL at trough.”
The claim 1 preamble recitation of “a compound of formula (I)” indicates the statutory category of a composition. However, the body of claim 1 further recites “… for use in a method of treating …”. Similarly claim 2-20 recites “for use”. A single claim which claims both an apparatus/product and the method steps of using the apparatus/product is indefinite under 35 U.S.C. 112(b). MPEP § 2173.05(p) (citing Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990); In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011)). Further, the claimed invention must be to one of the four statutory categories, processes, machines, manufactures and compositions of matter. MPEP § 2106(I). Here it is unclear whether claims 1-20 are directed to the statutory category of composition of matter or process or both.
Independent claims 1, 3, 5, and 6 are rejected for insufficient antecedent basis. The claims recite “… the method comprises the repeated administration of one or more dosage forms …”. The recitation “the repeated administration” lacks antecedent basis.
Dependent claims 2, 4, 7-20 are indefinite due to their dependence on a rejected claim and lacking any limitations that cure the ambiguities resulting from the parent claim(s).
Claim Rejections - 35 USC § 112 (a)
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 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating Progressive Supranuclear Palsy (PSP), does not reasonably provide enablement for the treatment of the claimed scope of:
neurological disorders or neurodegenerative diseases, sleep disorders, neuropsychiatric conditions, diabetes, cancer, cardiovascular diseases, stroke, selected from the group of one or more tauopathies, synucleinopathies and Alzheimer's disease, amyotrophic lateral sclerosis, amyotrophic lateral sclerosis with cognitive impairment, argyrophilic grain disease, behavioral variant frontotemporal dementia, non-fluent and semantic variant primary progressive aphasia, Bluit disease, corticobasal degeneration, Dementia pugilistica, Dementia with Lewy Bodies, diffuse neurofibrillary tangles with calcification, Down's syndrome, Familial British dementia, Familial Danish dementia, frontotemporal dementia with parkinsonism linked to chromosome 17, frontotemporal lobar degeneration, ganglioglioma, gangliocytoma, Gerstmann-Straussler- Scheinker disease, globular glial tauopathy, Guadeloupean parkinsonism, Hallevorden-Spatz disease, lead encephalopathy, lipofuscinosis, meningioangiomatosis, multiple system atrophy, myotonic dystrophy, Niemann-Pick disease, Pallido-ponto-nigral degeneration, Parkinson's disease, Parkinson's disease dementia, Parkinsonism-dementia complex of Guam, Pick's disease, postencephalitic parkinsonism, Prion diseases, fatal Familial Insomnia, Kuru, progressive supercortical gliosis, progressive supranuclear palsy, pure autonomic failure, Richardson's syndrome, subacute sclerosing panencephalitis, Tangle-only dementia, tuberous sclerosis, Huntington's disease or mild cognitive impairment, Chronic traumatic encephalopathy, Primary progressive aphasia, Progressive nonfluent aphasia, Semantic dementia, Steele- Richardson-Olszewski syndrome, epilepsy, chronic and acute inflammation, Crohn disease, neuroinflammation, subarachnoid hemorrhage, multiple sclerosis, Friedreich's Ataxia and Adrenoleukodystrophy.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Please note that the claims are not considered enabled for treating a subject “at increased risk of developing a disease or condition” of any of the foregoing diseases, including Progressive Supranuclear Palsy.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)”. The “use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Liebel-Flarsheim Co. v. Medrad, Inc. 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required:
(1) The breadth of the claims
(2) The nature of the invention
(3) The state of the prior art
(4) The level of one of ordinary skill
(5) The level of predictability in the art
(6) The amount of direction provided by the inventor
(7) The existence of working examples
(8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
(1) The breadth of the claims:
The presently claimed invention is directed to a compound of formula (1) and/or its tautomers for use in a method of treating a human subject, wherein the disease or condition is selected from neurological disorders or neurodegenerative diseases, sleep disorders, neuropsychiatric conditions, diabetes, cancer, cardiovascular diseases and stroke, wherein the disease or condition is selected from the group of one or more tauopathies, synucleinopathies and Alzheimer's disease, amyotrophic lateral sclerosis, amyotrophic lateral sclerosis with cognitive impairment, argyrophilic grain disease, behavioral variant frontotemporal dementia, non-fluent and semantic variant primary progressive aphasia, Bluit disease, corticobasal degeneration, Dementia pugilistica, Dementia with Lewy Bodies, diffuse neurofibrillary tangles with calcification, Down's syndrome, Familial British dementia, Familial Danish dementia, frontotemporal dementia with parkinsonism linked to chromosome 17, frontotemporal lobar degeneration, ganglioglioma, gangliocytoma, Gerstmann-Straussler-Scheinker disease, globular glial tauopathy, Guadeloupean parkinsonism, Hallevorden-Spatz disease, lead encephalopathy, lipofuscinosis, meningioangiomatosis, multiple system atrophy, myotonic dystrophy, Niemann-Pick disease, Pallido-ponto-nigral degeneration, Parkinson's disease, Parkinson's disease dementia, Parkinsonism-dementia complex of Guam, Pick's disease, postencephalitic parkinsonism, Prion diseases, fatal Familial Insomnia, Kuru, progressive supercortical gliosis, progressive supranuclear palsy, pure autonomic failure, Richardson's syndrome, subacute sclerosing panencephalitis, Tangle-only dementia, tuberous sclerosis, Huntington's disease or mild cognitive impairment, Chronic traumatic encephalopathy, Primary progressive aphasia, Progressive nonfluent aphasia, Semantic dementia, Steele- Richardson-Olszewski syndrome, epilepsy, chronic and acute inflammation, Crohn disease, neuroinflammation, subarachnoid hemorrhage, multiple sclerosis, Friedreich's Ataxia and Adrenoleukodystrophy.
The disease genera of claims 1-20 are broad. For example, the claim 17 recitation of “neuropsychiatric conditions” encompasses a number of mechanistically divergent conditions may stem from multiple genetic and environmental factors.
Neuropsychiatric conditions are disorders of cognition as taught by B. Sahakian (Sahakian BJ et al. 2015 Phil. Trans. R. Soc. B 370: 20140214, “Sahakian”) (see Sahakian at page 2, col. 1). Cognitive manifestations of neuropsychiatric disorders include disturbances in the regulation of attention (attentional biases), learning (aberrant learning), and in top– down regulation by the prefrontal cortex. Sahakian at page 2, col. 1. Furthermore, impairments of memory and executive function have been found in many neuropsychiatric disorders. Sahakian at page 2, col. 1. Many neuropsychiatric disorders have a neurodevelopmental origin and an onset or prodromal stage in childhood. Sahakian at page 2, col. 1.
Claim 18 is facially broad based on the fact that it lists mechanistically different diseases e.g., neuropsychiatric conditions, metabolic disorders, cancer, etc. these diseases are disease genera that are themselves broad. For example, Grassetto (G. Grassetto et al. Nuclear Medicine Communications 2014, Vol 35 No 11, 1085-1092 “Grassetto” cited in the PTO-892) teaches that Dementia is not a single nosological entity and many types of dementia exist and may be classified as follows: (a) reversible dementia, if resulting from another disease (generally infective, metabolic, or psychiatric conditions, tumoral lesions, normal pressure hydrocephalus); (b) vascular dementia; and (c) neurodegenerative primary dementia. (see Grassetto page 1085, col. 2). Cancer is not a single disease, or a cluster of closely related disorders. There are hundreds of proliferative diseases, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain, and salivary glands. They can occur in every part of the body. The specification and the art of record fail to disclose a validated marker or method for predicting a benefit from the instantly claimed compounds. Therefore, the scope of the diseases covered is deemed very broad, and cannot be considered enabled by the instant specification.
(2) The nature of the invention:
The present claims describe a compound of formula (1) and/or its tautomers for use in a method of treating a human subject, wherein the disease or condition is selected from neurological disorders or neurodegenerative diseases, sleep disorders, neuropsychiatric conditions, diabetes, cancer, cardiovascular diseases and stroke, wherein the disease or condition is selected from the group of one or more tauopathies, synucleinopathies and Alzheimer's disease, amyotrophic lateral sclerosis, amyotrophic lateral sclerosis with cognitive impairment, argyrophilic grain disease, behavioral variant frontotemporal dementia, non-fluent and semantic variant primary progressive aphasia, Bluit disease, corticobasal degeneration, Dementia pugilistica, Dementia with Lewy Bodies, diffuse neurofibrillary tangles with calcification, Down's syndrome, Familial British dementia, Familial Danish dementia, frontotemporal dementia with parkinsonism linked to chromosome 17, frontotemporal lobar degeneration, ganglioglioma, gangliocytoma, Gerstmann-Straussler- Scheinker disease, globular glial tauopathy, Guadeloupean parkinsonism, Hallevorden-Spatz disease, lead encephalopathy, lipofuscinosis, meningioangiomatosis, multiple system atrophy, myotonic dystrophy, Niemann-Pick disease, Pallido-ponto-nigral degeneration, Parkinson's disease, Parkinson's disease dementia, Parkinsonism-dementia complex of Guam, Pick's disease, postencephalitic parkinsonism, Prion diseases, fatal Familial Insomnia, Kuru, progressive supercortical gliosis, progressive supranuclear palsy, pure autonomic failure, Richardson's syndrome, subacute sclerosing panencephalitis, Tangle-only dementia, tuberous sclerosis, Huntington's disease or mild cognitive impairment, Chronic traumatic encephalopathy, Primary progressive aphasia, Progressive nonfluent aphasia, Semantic dementia, Steele- Richardson-Olszewski syndrome, epilepsy, chronic and acute inflammation, Crohn disease, neuroinflammation, subarachnoid hemorrhage, multiple sclerosis, Friedreich's Ataxia and Adrenoleukodystrophy. That is; in order to be enabled to practice the present invention, the skilled artisan would have to accept that by administering the compound of claim 1 to a patient that such therapeutic objectives could actually be achieved. However, in light of the fact that the specification fails to provide the skilled artisan with any direction or guidance as to how the treatment of claimed conditions in general could be achieved, or how the claimed dose or regimen will be selected for treating any particular condition, the present specification is viewed as lacking an enabling disclosure of the entire scope of the claimed invention.
(3) The state of the Prior Art:
The instant claims are directed to a compound of formula (1) and/or its tautomers for use in a method of treating a human subject, wherein the disease or condition is selected from neurological disorders or neurodegenerative diseases, sleep disorders, neuropsychiatric conditions, diabetes, cancer, cardiovascular diseases, stroke and the diseases listed in claim 18.
However, art respecting treatment of claimed conditions is unpredictable as evidenced by art as the relevant filing date. For example, Lee (H. Lee et al., Schizophr. Res. Treatment. 2016; 2016:6378137, “Lee” cited on the PTO-892) teaches that: there are four primary reasons why it is difficult to develop therapeutic agents against neuropsychiatric disorders: (1) CNS disorders have a complex etiology (heterogeneity; gene to environment), (2) limitations of understanding pathophysiology in neuropsychiatric disorders, (3) lack of appropriate biomarkers and/or molecular targets, and (4) lack of appropriate animal models. (see page 2, col. 1). Lee further teaches that: “[s]ince the etiological complexity restricts our understanding of pathophysiology of CNS disorders, it is difficult to identify and/or characterize appropriate biomarkers and/or molecular targets. As a result, it is difficult to evaluate the mechanism(s) of action of therapeutic agents”. Lee at page 2, col. 1. In another example, Gibbs (R. Gibbs et al., Cell Stem Forum (2018), 21-24, “Gibbs”, cited in the PTO-892) teaches that “The genetic complexity, clinical variability, and inaccessibility of affected tissue in neurodegenerative and neuropsychiatric disorders have largely prevented the development of effective disease-modifying therapeutics”. Gibbs further teaches that “CNS disorders result from a complex interplay between genetics and environment, and likely represent a broad categorization of many different molecular pathologies leading to uniform clinical presentations” [Gibbs at page 21, col. 2. At page 2, col. 3]. Gibbs further lists a number of significant challenges in developing therapeutics to treat neuropsychiatric disorders, for example, “the biological pathways driving key pathogenic processes remain largely unknown, making it difficult to identify discrete drug targets that modify disease progression”. In another example, Ritchie (Ritchie et al. Alzheimer's Research & Therapy (2015) 7:31, p. 1-11, “Ritchie”, cited in the PTO-892) teaches that Despite decades of research, a cure or effective preventative treatment for dementia remains elusive. (see Abstract). Ritchie provides and in-depth discussion of challenges regarding treatment of dementia, including difficulty in diagnosis and problems with translating animal models to humans. Ritchie concludes that dementia 'cure' remains elusive and that problems with trial design, endpoint definitions and analysis may be contributory. Ritchie at page 9, col. 1. In another example, Chakraborty (S. Chakraborty, et al. Ecancermedicalscience. 2012, 14;6:ed16, “Chakraborty” cited in the PTO-892), teaches that “the cure for cancer is like the Holy Grail since most of the existing treatments are not effective enough to provide full protection from this disease”. Chakraborty teaches that “in recent years the burgeoning of sophisticated genomic, proteomic and bioinformatics techniques has made it possible for us to get a glimpse of the intricate interplay of numerous cellular genes and regulatory genetic elements that are responsible for the manifestation of cancerous phenotypes. With the use of modern genomic technologies, we are now beginning to understand the enormous complexity of cancer, however, there are few success stories as far as the treatment of cancer is concerned, [Abstract]. Chakraborty teaches that the non-specific nature of cancer symptoms makes diagnosis difficult (let alone treatment and prevention). Chakraborty teaches examples of cancer with diagnosis difficulties include esophageal cancer, prostate cancer, and pancreatic cancer. [Page 3-4]. Numerous mechanisms have been proposed as methods of treating assorted cancers a selection of which follow. Cytotoxic agents could be applied directly to the tumor’s cells, directly killing them. Immunotherapy to stimulate the patient's immune system to attack cancer cells, either by immunization of the patient, in which case the patient's own immune system is trained to recognize tumor cells as targets, or by the administration of therapeutic antibodies as drugs, so the patient's immune system is recruited to destroy tumor cells by the therapeutic antibodies. Increasing the amount or activity of the body’s tumor suppressor genes, PTEN, APC and CD95, which can, for example, activate DNA repair proteins, suppress the Akt/PKB signaling pathway, or initiate apoptosis of cancer cells. Angiogenesis inhibitor strategies based on cutting off the blood supply that growing tumors need by shutting off the growth of new blood vessels by, for example, suppressing proliferation of endothelial cells or inducing apoptosis of endothelial cells. A number of these approaches – and others as well – have produced anti-cancer drugs. However, despite high hopes for success, and a plausible theory why these should work for cancers generally, these approaches have yet to produce a drug which can claim such a goal. Specifically, the prior art demonstrates that there never has been a compound capable of treating cancers generally. “The cancer therapy art remains highly unpredictable, and no example exists for efficacy of a single product against tumors generally.” A similar statement appears at In re Application of Hozumi et al., 226 USPQ 353: “In spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in treating all types of cancer. Cancer is not a simple disease, nor is it even a single disease, but a complex of a multitude of different entities, each behaving in a different way”. There are compounds that treat a modest range of cancers, but no one has ever been able to determine how to get a compound to be effective against cancer generally, or even a majority of cancers. Accordingly, there is substantive “reason for one skilled in the art to question the objective truth of the statement of utility or its scope” (In re Langer, 183 USPQ 288, 297), specifically, the scope of covering cancer generally. Similarly, In re Novak, 134 USPQ 335, 337-338, says “unless one with ordinary skill in the art would accept those allegations as obviously valid and correct, it is proper for the examiner to ask for evidence which substantiates them.” There is no such evidence in this case. Likewise, In re Cortright, 49 USPQ2d 1464, states: “Moreover, we have not been shown that one of ordinary skill would necessarily conclude from the information expressly disclosed by the written description that the active ingredient” does what the specification surmises that it does. That is exactly the case here. Moreover, even if applicants’ assertion that cancer in general could be treated with these compounds were plausible, which it is not, that “plausible” would not suffice, as was stated in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297, 1301: “If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success.”
(4) The skill of those in the art:
The skill of those in the art is expected to be high, requiring advanced training in chemistry, medicine, or pharmacology.
(5) The level of predictability in the art:
In view of Grassetto, Lee, Gibbs, Ritchie and Chakraborty, the art of record teaches that treatment of claimed diseases is unpredictable due to the range of underlying causes, complex etiologies, and different disease mechanisms. With specific reference to cancer, Ex parte Kranz, 19 USPQ2d 1216, 1219 notes the “general unpredictability of the field [of] …anti-cancer treatment.” In re Application of Hozumi et al., 226 USPQ 353 notes the “fact that the art of cancer chemotherapy is highly unpredictable”. More generally, the invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
With this in mind, the level of predictability in the art is low. The level of unpredictability in the art renders the scope of instant claim to be not enabled.
(6) The amount of direction provided/(7) Working examples:
The art of record does not disclose that the claimed compound is reported to have the claimed activity to treat the claimed diseases. Further, neither the art of record nor the specification provides any reasonable correlation between the claimed compound and treatment of the claimed diseases and conditions. Neither the art of record nor the specification provides any statistically relevant data documenting the activity of compound of claim 1 in the treatment of the diseases claimed. Moreover, while the treatment of claimed diseases and condition is discussed in broad terms, the necessary specifics, i.e. dosing, therapeutic index, contraindications, drug interaction, toxicity etc., are completely absent.
The exemplary embodiments of the specification in this case only sets forth a clinical trial for treating patients with Progressive Supranuclear Palsy, PSP. The limited study directed to a single condition, PSP do very little to provide the necessary information, and, in light of the immense diversity of the claimed diseases and conditions, the guidance provided is very limited.
Skilled artisan would not be able to draw correlation between treatment of PSP and for example, cancer, diabetes, cardiovascular disease, etc. Studies for treating PSP does not reasonably provide enablement for the claimed diseases and conditions. For example, the exceptional diversity of cancers, and the treatment of them, is not well represented by these studies. It is well known that there is no single treatment that works for all kinds of cancers, cardiovascular diseases, diabetes, etc., so the experimentation required to practice the instant invention would be egregious.
(8) The quantity of experimentation needed:
Upon balancing the unpredictability in the art, the lack of correlation in the prior art or specification between compound of claim 1 and the claimed treatment, and the lack of working examples, the quantity of experimentation is undue. The claims are broadly directed to treatment of “neurological disorders or neurodegenerative diseases, sleep disorders, neuropsychiatric conditions, diabetes, cancer, cardiovascular diseases, stroke, tauopathies, synucleinopathies and Alzheimer's disease, etc.” but neither the art of record nor the specification teach any working models, mechanisms of action, or other reasonable correlation linking the claimed compound to treatment of the full scope of diseases claimed. In this regard, as discussed above, the claimed breadth of diseases is large and the claimed diseases have different mechanisms, underlying causes and etiologies. The art of record teaches significant unpredictability in the treatment of neuropsychiatric disorders. For example, Gibbs lists a number of significant challenges in developing therapeutics to treat neuropsychiatric disorders: “the biological pathways driving key pathogenic processes remain largely unknown, making it difficult to identify discrete drug targets that modify disease progression”. Gibbs at page 3, col. 3. In another example, Ritchie teaches that despite decades of research, a cure or effective preventative treatment for dementia remains elusive. Ritchie at Abstract. The complex etiology and divergent mechanisms of claimed diseases and disorders and unpredictability taught by the art of record impose significant challenges in developing therapeutics to treat the claimed diseases. The specification does not supplement the art of record with the additional guidance needed to enable the full claim scope. Rather, the specification provides almost no guidance in this regard. In sum, the primary factors underling this 112 Rejection are lack of guidance in the specification and art of record; particularly a lack of a disclosed reasonable correlation between the claimed compound and treatment of the claimed diseases. Further, neither the art of record nor the specification discloses or propose a therapeutic mechanism by which the claimed compound could be predicted to treat the full scope of claimed diseases. These primary factors are balanced with the large number of mechanistically diverse diseases claimed and the unpredictability in treating these diseases to establish a prima facie case that the experimentation required by one of skill in the art to practice the full claim scope is undue.
MPEP 2164.01(a) states, “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).” That conclusion is clearly justified here.
Claim 15 recitation “increased risk of developing a disease or condition”
Claim 15 recites “… wherein the human subject suffers from a disease or condition, or is at increased risk of developing a disease or condition”.
The specification provides no guidance regarding “increased risk” of developing a disease or condition, how do identify subjects who are at increased risk, and there are no examples/studies/guidance on how administering an effective amount of the claimed compound would decrease the risk of developing the claimed diseases and conditions.
In view of the lack of guidance and unpredictability, the experimentation required to identify and treat a subject at “increased risk of developing a disease or condition” o comprising administering the claimed compound is undue. Rather, Lee teaches that the etiological complexity of CNS disorders stems from multiple genetic and environmental factors. Lee ta page 2, col. 1. Lee teaches that since the etiological complexity restricts our understanding of pathophysiology of CNS disorders, it is difficult to identify and/or characterize appropriate biomarkers and/or molecular targets. Lee ta page 2, col. 1. In another example, Grassetto teaches that “[t]he diagnosis of dementia is still essentially clinical and it is currently made in terms of probability as the certainty of diagnosis can be reached only on post-mortem tissue examination”. Grassetto at page 1086, col. 1.
Per the above discussion, neither the art of record nor the specification teaches one of skill how to predict whether one is at risk of developing, for example dementia. If one of skill cannot predict dementia, one of skill cannot practice claim 15; at least without developing appropriate prediction methods, which development the art teaches has not been attained as of the relevant filing date. The specification provides no guidance supplementing the deficiencies of the art of record. Accordingly, a prima facie case is made that the experimentation required by one of skill in the art to practice the full claim scope of “reducing the risk” is undue
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 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.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over A. Quattropani et al. (US Patent No. 10336775B2, 07/02/2019 (Priority date 08/27/2015), “Quattropani” cited in the IDS dated 04/02/2024).
Quattropani teaches human glycosidase inhibitors of formula (I) and salts thereof, wherein A, R, W, Q, m, and n are defined, [col. 5-8]:
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168
220
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Quattropani teaches compound N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide, as species of formula (I), [col. 39, Table 1, compound 69, col. 186, ln. 35, and claim 1]:
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200
514
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Quattropani teaches that the enantiomer 69 is more active than 68, with an IC50 of less than 0.05 µM (enantiomer 68 is 1-10 µM) [ending of Table 1, col. 91].
Quattropani teaches a pharmaceutical composition of the compound as medicament in human and veterinary medicine for treating neurodegenerative diseases, most preferably one or more tauopathies, highly preferably Alzheimer's disease and dementia. [col. 110, ln. 63- col. 111, 6].
With regard to the dosing amount and dosing frequency, Quattropani teaches that “it will be understood that the specific dose level, frequency and period of administration to any particular human will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general state of health, route of administration, etc., and the exact dose can be determined by one of skill in the art as a matter of routine experimentation using well-known means and methods,.” [col. 110, ln. 5-14]. Quattropani teaches that the compound is administered in a unit dosage form in doses of 0.5-1000 mg, more preferably 1-700 mg or 5-100 mg per dose unit. [col. 110, ln. 18-27]. Quattropani teaches that “although a therapeutically effective amount of a compound according to the invention has to be ultimately determined by the treating doctor or vet by considering a number of factors, an effective amount of the compound above for the treatment of neurodegenerative diseases, for example tauopathies and Alzheimer's disease, is usually between 70 mg and 700 mg, where this amount can be administered as a single dose per day or usually in a series of part-doses, i.e., two, three, four, five or six per day, so that the total daily dose is the same. Quattropani teaches that the compound administered orally. [col. 108, ln. 62-63].
With regard to human subject, Quattropani teaches that method can be performed either in-vitro or in-vivo, wherein host or patient can belong to any mammalian species, for example a primate species, particularly humans; rodents, including mice, rats and hamsters; rabbits; horses, cows, dogs, cats, etc. Animal models are of interest for experimental investigations, providing a model for treatment of human disease. [col. 106, ln. 40-55].
With regard to the pharmacokinetics, Quattropani teaches that in-vitro liver microsomal assays provide significant improvements in the pharmacokinetic profiles of compounds of the formula (I) in terms of increases in the in vivo half-life (t/2), concentration at maximum therapeutic effect (Cmax), area under the dose response curve (AUC), [col. 112, ln. 1-10].
In view of the foregoing, Quattropani teaches the claimed compound of formula (I) for use in a method of treating a human subject by repeating administration of compound of formula (I) two, three, four or five times. However, one of ordinary skill in the art need to specifically pick Quattropani’s compound 69 from the human glycosidase inhibitors taught by Quattropani.
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of instantly claimed invention to pick Quattropani’s compound 69 for the treating human subjects. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Quattropani teaches that compound 69 is very potent O-GlcNAcase inhibitor; [col. 91, ln. 29]; Quattropani teaches that compound 69 is one of the compound that demonstrate adequate properties for use as a drug by showing high solid state stability, high stability in the presence of liver microsome, high oxidation stability, suitable permeability and potent biological activity; and Quattropani’s patent is directed to compound 69, composition of compound 69, and salt of compound 69 which indicates that compound 69 is the most potent compound of Quattropani, and therefore, skilled artisan would have been motivated to also pick compound 69 for use in a method of treating a human subject.
The pharmacokinetics of the plasma concentration of the compound of formula (I) of at least about 35 ng/mL, 45-2000 ng/mL, at least about 155 ng/mL, 270-2000 ng/mL, 1650-7390 ng/mL, plasma AUC of about 13850-90500 ng*h/mL, plasma Cmax of about 3580-7390 ng/mL is met for the following reasons: Quattropani teaches the claimed compound for use in a method of treating a disease. Quattropani is silent on the pharmacokinetics of the compound but otherwise teaches a substantially identical method as claimed. As such, it is reasonable to presume that the resulting plasma concentration, plasma AUC, and plasma Cmax is inherently met. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112.
Therefore, claims 1-6, 8-9, 11-12, and 15-18 are prima facie obvious over Quattropani.
With regard to claims 19 and 20, Quattropani teaches that the salt is hydrochloric salt. [col. 103, ln. 36]
With regard to claim 7, 10, and 13-14, Quattropani teaches that the compound is administered in doses of 0.5-1000 mg, more preferably 1-700 mg. [col. 110, ln. 25-27]. Quattropani also teaches that the doses can be between 70 mg and 700 mg administered as a single dose per day or usually in a series of part-doses, e.g., two, three per day. [col. 110, ln. 40-60]. Quattropani teaches amounts that encompasses or overlapped with the claimed amounts. As provided in the MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005). Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Furthermore, the optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05. As such, an artisan having ordinary skill in the art would have been motivated to modify the amounts to achieve 150-500 mg, 300-500mg, 240-1500 mg, and therefore, meets claims 7, 10, and 13-14.
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.
Non-statutory Double Patenting over US Patent No. 10,336,775 B2
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of US Patent No. 10,336,775 B2 (cited in the IDS dated 04/02/2024) in view of a, Quattropani et al. (US PG-PUB 2019/0055233A1, 02/21/2019, “Quattropani II” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-20 recites “a compound of formula (1) for use in a method of treating a human subject comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I) at a daily dosing frequency sufficient to maintain the plasma concentration of the compound of formula (1) at steady state at at least about 35 ng/mL at trough in a range of about 45 -2000 ng/mL at trough, a plasma Cmax of the compound of formula (I) of about 1650-7390 ng/mL, a plasma AUC over 24 hours of the compound of formula (I) of about 13850-90500 ng*h/mL, wherein the dose of the compound of formula (I) is administered orally in the range of about 150 mg to about 500 mg twice a day or thrice a day, wherein the human subject suffers from a disease or condition, or is at increased risk of developing a disease or condition, wherein the disease or condition is selected from one or more proteinopathies, neurodegenerative diseases, sleep disorders, neuropsychiatric conditions, cancer, Alzheimer's disease, etc., wherein the compound is administered in form of a pharmaceutically usable solvate and/or salt thereof, wherein the compound is administered in form of its hydrochloride salt:
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US Patent No. 10,336,775 B2recites a compound, N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide, or enantiomers or mixtures thereof, or pharmaceutically acceptable salt, wherein the pharmaceutically acceptable salt is hydrochloric salt:
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US Patent No. 10,336,775 B2does not recites using the above compound for treating a human subject, the amount of the compound administered, or the claimed pharmacokinetics.
However, the specification of US Patent No. 10,336,775 B2recites a method for treating neurodegenerative diseases in human using compound N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide, most preferably one or more tauopathies, highly preferably Alzheimer's disease and dementia. [col. 110, ln. 63- col. 111, 6]. MPEP 804 states: The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) ("[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning."); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998) ("Where there are several common meanings for a claim term, the patent disclosure serves to point away from the improper meanings and toward the proper meanings."). "The Patent and Trademark Office (‘PTO’) determines the scope of the claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ " Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004); see also MPEP § 2111.01. Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized "that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim," but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first "determine how much of the patent disclosure pertains to the invention claimed in the patent" because only "[t]his portion of the specification supports the patent claims and may be considered." The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
Moreover, Quattropani II teaches compound of formula I, [0005], and compound N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide as species of formula I [0027], for treating tauopathies and Alzheimer's disease, Dementia, etc. [0048], wherein the compound administered in doses of approximately 0.5 to 1000 mg, more preferably between 1 and 700 mg, most preferably 5 and 100 mg per dose unit [0046].
One of ordinary skill in the art have access to Quattropani II would have been motivated with reasonable expectation of success to administered US Patent No. 10336775B2 compound in an amount of 0.5 to 1000 mg or between 1 and 700 because Quattropani II teaches the same compound for treating the same conditions. Quattropani II’s amounts encompasses or overlapped with the claimed amounts. As provided in the MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005). Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Furthermore, the optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05. As such, an artisan having ordinary skill in the art would have been motivated to modify the amounts to achieve 150-500 mg, 300-500mg, 240-1500 mg.
The pharmacokinetics of the plasma concentration of the compound of formula (I) of at least about 35 ng/mL, 45-2000 ng/mL, at least about 155 ng/mL, 270-2000 ng/mL, 1650-7390 ng/mL, plasma AUC of about 13850-90500 ng*h/mL, plasma Cmax of about 3580-7390 ng/mL is met for the following reasons: US Patent No. 10336775B2 recites the claimed compound for use in a method of treating a disease. US Patent No. 10336775B2 is silent on the pharmacokinetics of the compound but otherwise teaches a substantially identical method as claimed. As such, it is reasonable to presume that the resulting plasma concentration, plasma AUC, and plasma Cmax is inherently met. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112.
Therefore, claims 1-20 are met by the combination of US Patent No. 10336775B2 and Quattropani II.
Non-statutory Double Patenting over US Patent No. 10,696,668 B2
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of US Patent No. 10,696,668 B2 (cited in the IDS dated 04/02/2024) in view of a, Quattropani et al. (US PG-PUB , 10/19/2017, “Quattropani III” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-20 recites “a compound of formula (I) for use in a method of treating a human subject comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I) at a daily dosing frequency sufficient to maintain the plasma concentration of the compound of formula (1) at steady state at at least about 35 ng/mL at trough in a range of about 45 -2000 ng/mL at trough, a plasma Cmax of the compound of formula (I) of about 1650-7390 ng/mL, a plasma AUC over 24 hours of the compound of formula (I) of about 13850-90500 ng*h/mL, wherein the dose of the compound of formula (I) is administered orally in the range of about 150 mg to about 500 mg twice a day or thrice a day, wherein the human subject suffers from a disease or condition, or is at increased risk of developing a disease or condition, wherein the disease or condition is selected from one or more proteinopathies, neurodegenerative diseases, sleep disorders, neuropsychiatric conditions, cancer, Alzheimer's disease, etc., wherein the compound is administered in form of a pharmaceutically usable solvate and/or salt thereof, wherein the compound is administered in form of its hydrochloride salt:
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US Patent No. 10,696,668 B2recites compound N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide mono-hydrochloride, and solid oral dosage form comprising the compound:
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US Patent No. 10,696,668 B2does not recites using the above compound for treating a human subject, the amount of the compound administered, or the claimed pharmacokinetics.
However, US Patent No. 10,696,668 B2specification recites a method for treating tauopathies and Alzheimer's disease, Dementia, etc. using compound N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide, [col. 10, ln. 49]. MPEP 804 states: The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) ("[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning."); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998) ("Where there are several common meanings for a claim term, the patent disclosure serves to point away from the improper meanings and toward the proper meanings."). "The Patent and Trademark Office (‘PTO’) determines the scope of the claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ " Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004); see also MPEP § 2111.01. Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized "that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim," but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first "determine how much of the patent disclosure pertains to the invention claimed in the patent" because only "[t]his portion of the specification supports the patent claims and may be considered." The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
Moreover, Quattropani III teaches compound of formula I, [0001], and compound N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide as species of formula I [0083, Table 1, comp. 69], for treating tauopathies and Alzheimer's disease. [00164], wherein the compound administered in doses of approximately 0.5 to 1000 mg, more preferably between 1 and 700 mg, most preferably 5 and 100 mg per dose unit [0154].
One of ordinary skill in the art have access to Quattropani III would have been motivated with reasonable expectation of success to administered US Patent No. 10,696,668 B2compound in an amount of 0.5 to 1000 mg or between 1 and 700 because Quattropani III teaches the same compound for treating the same conditions. Quattropani III’s amounts encompasses or overlapped with the claimed amounts. As provided in the MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005). Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Furthermore, the optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05. As such, an artisan having ordinary skill in the art would have been motivated to modify the amounts to achieve 150-500 mg, 300-500mg, 240-1500 mg.
The pharmacokinetics of the plasma concentration of the compound of formula (I) of at least about 35 ng/mL, 45-2000 ng/mL, at least about 155 ng/mL, 270-2000 ng/mL, 1650-7390 ng/mL, plasma AUC of about 13850-90500 ng*h/mL, plasma Cmax of about 3580-7390 ng/mL is met for the following reasons: US Patent No. 10696668B2 recites the claimed compound for use in a method of treating a disease. US Patent No. 10696668B2 is silent on the pharmacokinetics of the compound but otherwise teaches a substantially identical method as claimed. As such, it is reasonable to presume that the resulting plasma concentration, plasma AUC, and plasma Cmax is inherently met. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112.
Therefore, claims 1-20 are met by the combination of US Patent No. 10,696,668 B2. and Quattropani III.
Non-statutory Double Patenting over US Patent No. 11,046,712 B2
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of US Patent No. 11,046,712 B2 cited in the IDS dated 04/02/2024, in view of a, Quattropani et al. (US PG-PUB , 10/19/2017, “Quattropani III” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-20 recites “a compound of formula (I) for use in a method of treating a human subject comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I) at a daily dosing frequency sufficient to maintain the plasma concentration of the compound of formula (1) at steady state at at least about 35 ng/mL at trough in a range of about 45 -2000 ng/mL at trough, a plasma Cmax of the compound of formula (I) of about 1650-7390 ng/mL, a plasma AUC over 24 hours of the compound of formula (I) of about 13850-90500 ng*h/mL, wherein the dose of the compound of formula (I) is administered orally in the range of about 150 mg to about 500 mg twice a day or thrice a day, wherein the human subject suffers from a disease or condition, or is at increased risk of developing a disease or condition, wherein the disease or condition is selected from one or more proteinopathies, neurodegenerative diseases, sleep disorders, neuropsychiatric conditions, cancer, Alzheimer's disease, etc., wherein the compound is administered in form of a pharmaceutically usable solvate and/or salt thereof, wherein the compound is administered in form of its hydrochloride salt:
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US Patent No. 11,046,712 B2recites in claim 1 a compound of formula (I), and recites in claim 8 compound 44, and recites in claims 9-12, a method of treating a disease by administering therapeutically effective amount of compound of formula (I), wherein the disease is tauopathies, Alzheimer's disease, Dementia, etc.:
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US Patent No. 11,046,712 B2does not recites the amount of the compound administered, or the claimed pharmacokinetics.
Quattropani III teaches compound of formula I, [0001], and compound N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide as species of formula I [0083, Table 1, comp. 69], for treating tauopathies and Alzheimer's disease. [00164], wherein the compound administered in doses of approximately 0.5 to 1000 mg, more preferably between 1 and 700 mg, most preferably 5 and 100 mg per dose unit [0154].
One of ordinary skill in the art have access to Quattropani III would have been motivated with reasonable expectation of success to administered US Patent No. 11,046,712 B2compound in an amount of 0.5 to 1000 mg or between 1 and 700 because Quattropani III teaches the same compound for treating the same conditions. Quattropani III’s amounts encompasses or overlapped with the claimed amounts. As provided in the MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005). Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Furthermore, the optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05. As such, an artisan having ordinary skill in the art would have been motivated to modify the amounts to achieve 150-500 mg, 300-500mg, 240-1500 mg.
The pharmacokinetics of the plasma concentration of the compound of formula (I) of at least about 35 ng/mL, 45-2000 ng/mL, at least about 155 ng/mL, 270-2000 ng/mL, 1650-7390 ng/mL, plasma AUC of about 13850-90500 ng*h/mL, plasma Cmax of about 3580-7390 ng/mL is met for the following reasons: US Patent No. 11,046,712 B2recites the claimed compound for use in a method of treating a disease. US Patent No. 11,046,712 B2is silent on the pharmacokinetics of the compound but otherwise teaches a substantially identical method as claimed. As such, it is reasonable to presume that the resulting plasma concentration, plasma AUC, and plasma Cmax is inherently met. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112.
Therefore, claims 1-20 are met by the combination of US Patent No. 11,046,712 B2 and Quattropani III.
Non-statutory Double Patenting over US Patent No. 11,591,327 B2
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of US Patent No. 11,591,327 B2 cited in the IDS dated 04/02/2024, in view of a, Quattropani et al. (US PG-PUB , 10/19/2017, “Quattropani III” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-20 recites “a compound of formula (I) for use in a method of treating a human subject comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I) at a daily dosing frequency sufficient to maintain the plasma concentration of the compound of formula (1) at steady state at at least about 35 ng/mL at trough in a range of about 45 -2000 ng/mL at trough, a plasma Cmax of the compound of formula (I) of about 1650-7390 ng/mL, a plasma AUC over 24 hours of the compound of formula (I) of about 13850-90500 ng*h/mL, wherein the dose of the compound of formula (I) is administered orally in the range of about 150 mg to about 500 mg twice a day or thrice a day, wherein the human subject suffers from a disease or condition, or is at increased risk of developing a disease or condition, wherein the disease or condition is selected from one or more proteinopathies, neurodegenerative diseases, sleep disorders, neuropsychiatric conditions, cancer, Alzheimer's disease, etc., wherein the compound is administered in form of a pharmaceutically usable solvate and/or salt thereof, wherein the compound is administered in form of its hydrochloride salt:
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US Patent No. 11,591,327 B2recites a hydrochloric acid salt of N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide mono-hydrochloride, and solid oral dosage form comprising the compound:
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US Patent No. 11,591,327 B2does not recites using the above compound for treating a human subject, the amount of the compound administered, or the claimed pharmacokinetics.
However, US Patent No. 11,591,327 B2specification recites a method for treating tauopathies and Alzheimer's disease, Dementia, etc. using compound N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide, [col. 10, ln. 47]. MPEP 804 states: The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) ("[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning."); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998) ("Where there are several common meanings for a claim term, the patent disclosure serves to point away from the improper meanings and toward the proper meanings."). "The Patent and Trademark Office (‘PTO’) determines the scope of the claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ " Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004); see also MPEP § 2111.01. Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized "that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim," but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first "determine how much of the patent disclosure pertains to the invention claimed in the patent" because only "[t]his portion of the specification supports the patent claims and may be considered." The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
Moreover, Quattropani III teaches compound of formula I, [0001], and compound N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide as species of formula I [0083, Table 1, comp. 69], for treating tauopathies and Alzheimer's disease. [00164], wherein the compound administered in doses of approximately 0.5 to 1000 mg, more preferably between 1 and 700 mg, most preferably 5 and 100 mg per dose unit [0154].
One of ordinary skill in the art have access to Quattropani III would have been motivated with reasonable expectation of success to administered US Patent No. 11,591,327 B2compound in an amount of 0.5 to 1000 mg or between 1 and 700 because Quattropani III teaches the same compound for treating the same conditions. Quattropani III’s amounts encompasses or overlapped with the claimed amounts. As provided in the MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005). Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Furthermore, the optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05. As such, an artisan having ordinary skill in the art would have been motivated to modify the amounts to achieve 150-500 mg, 300-500mg, 240-1500 mg.
The pharmacokinetics of the plasma concentration of the compound of formula (I) of at least about 35 ng/mL, 45-2000 ng/mL, at least about 155 ng/mL, 270-2000 ng/mL, 1650-7390 ng/mL, plasma AUC of about 13850-90500 ng*h/mL, plasma Cmax of about 3580-7390 ng/mL is met for the following reasons: US Patent No. 11,591,327 B2recites the claimed compound for use in a method of treating a disease. US Patent No. 11,591,327 B2is silent on the pharmacokinetics of the compound but otherwise teaches a substantially identical method as claimed. As such, it is reasonable to presume that the resulting plasma concentration, plasma AUC, and plasma Cmax is inherently met. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112.
Therefore, claims 1-20 are met by the combination of US Patent No. 11,591,327 B2 and Quattropani III.
Non-statutory Double Patenting over co-pending Application No 18/062,295
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-39 of co-pending Application No 18/062,295 (US PG-PUB 2023/0120169 A1 cited in the IDS dated 04/02/2024, now US Patent No 12,398,130 B2 (not published yet)) in view of Quattropani et al. (US PG-PUB , 10/19/2017, “Quattropani III” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-20 recites “a compound of formula (I) for use in a method of treating a human subject comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I) at a daily dosing frequency sufficient to maintain the plasma concentration of the compound of formula (1) at steady state at at least about 35 ng/mL at trough in a range of about 45 -2000 ng/mL at trough, a plasma Cmax of the compound of formula (I) of about 1650-7390 ng/mL, a plasma AUC over 24 hours of the compound of formula (I) of about 13850-90500 ng*h/mL, wherein the dose of the compound of formula (I) is administered orally in the range of about 150 mg to about 500 mg twice a day or thrice a day, wherein the human subject suffers from a disease or condition, or is at increased risk of developing a disease or condition, wherein the disease or condition is selected from one or more proteinopathies, neurodegenerative diseases, sleep disorders, neuropsychiatric conditions, cancer, Alzheimer's disease, etc., wherein the compound is administered in form of a pharmaceutically usable solvate and/or salt thereof, wherein the compound is administered in form of its hydrochloride salt:
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Co-pending Application No 18/062,295 recites in claim 15 a compound of formula (I), and recites in claim 25 compound N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide as species of formula (I), recites in claim 26 the hydrochloric acid salt of the compound, recites in claim 19 an oral solid dosage of the compound, and recites in claims 20-21, a method of treating a disease by administering the compound of formula (I), wherein the disease is tauopathies, Alzheimer's disease, Dementia, etc.:
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Co-pending Application No 18/062,295 does not recites the amount of the compound administered, or the claimed pharmacokinetics.
Quattropani teaches compound of formula I, [0001], and compound N-(5-(4-(1-(Benzo[d][1,3]dioxol-5-yl)ethyl)piperazin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide as species of formula I [0083, Table 1, comp. 69], for treating tauopathies and Alzheimer's disease. [00164], wherein the compound administered in doses of approximately 0.5 to 1000 mg, more preferably between 1 and 700 mg, most preferably 5 and 100 mg per dose unit [0154].
One of ordinary skill in the art have access to Quattropani would have been motivated with reasonable expectation of success to administered Co-pending Application No 18/062,295 compound in an amount of 0.5 to 1000 mg or between 1 and 700 because Quattropani teaches the same compound for treating the same conditions. Quattropani’s amounts encompasses or overlapped with the claimed amounts. As provided in the MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005). Moreover, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Furthermore, the optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05. As such, an artisan having ordinary skill in the art would have been motivated to modify the amounts to achieve 150-500 mg, 300-500mg, 240-1500 mg.
The pharmacokinetics of the plasma concentration of the compound of formula (I) of at least about 35 ng/mL, 45-2000 ng/mL, at least about 155 ng/mL, 270-2000 ng/mL, 1650-7390 ng/mL, plasma AUC of about 13850-90500 ng*h/mL, plasma Cmax of about 3580-7390 ng/mL is met for the following reasons: Co-pending Application No 18/062,295 recites the claimed compound for use in a method of treating a disease. Co-pending Application No 18/062,295 is silent on the pharmacokinetics of the compound but otherwise teaches a substantially identical method as claimed. As such, it is reasonable to presume that the resulting plasma concentration, plasma AUC, and plasma Cmax is inherently met. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112.
Therefore, claims 1-20 are met by the combination of Co-pending Application No 18/062,295. and Quattropani III.
Conclusion
Claims 1-20 are rejected. No claim is allowed.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622