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 .
Status of the Application
Claims 22-34, 36-41 are pending as of the response filed 08/19/2025. Claim 42 is cancelled in the response dated 08/19/2025. Claims 1-21 and 35 were previously cancelled. Claims 22-34, 36-41 are examined herein.
The claim objection of previous record is withdrawn in consideration of the claim amendment.
The 35 U.S.C. 112(b) rejection of previous record is withdrawn in consideration of the claim amendment.
In view of the pending claims, Applicants have properly invoked the 35 U.S.C. 102(b)(2)(C) exception over the Miller reference for the 35 U.S.C. 102(a)(2) portion of the rejection over the Miller reference, by providing a statement that “the disclosed subject matter and the claimed inventions were commonly owned or subject to an obligation of assignment to the same entity on or before the effective filing date of the claimed invention” on page 6 of the remarks dated 08/19/2025. Therefore, the 35 U.S.C. 102(a)(2) rejection over the Miller reference is withdrawn.
However, the 35 U.S.C. 102(a)(1) rejection of record over the Miller reference still applies and is maintained. All other rejections are maintained, as discussed below.
Applicant’s arguments have been fully considered and are addressed below.
Claim Rejections - 35 USC § 102 – Maintained and modified
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 22-26, 32-34 and 36-41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Miller et al. (WO 2019/206871 A1, publication date 31 October 2019, hereinafter Miller) as evidenced by Song et al. (NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies, 09 March 2017, hereinafter Song).
Regarding instant claims 22-26 and 41, Miller teaches a sodium salt of N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide, hydrates, solvates and polymorphic forms thereof (Abstract, Pg. 3, Lns. 28-30; Pg. 4, Lns. 1-10), with the free acid having the following formula (Pg. 5, Lns. 11-15).
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Miller teaches pharmaceutical compositions comprising the compound and the use of this compound in the treatment and prevention of medical disorders and diseases, most especially by NLRP3 inhibition (Abstract; Pg. 4, Lns. 20-27). Miller teaches a seventh aspect of invention provides a method of treatment or prevention of a disease, disorder or condition, the method comprising the step of administering an effective amount of a salt, hydrate or solvate of the first aspect of the invention, a polymorphic form of the second aspect of the invention, or a pharmaceutical composition of the fourth aspect, to thereby treat or prevent the disease, disorder or condition (Pg. 18, Lns. 10-15). Miller teaches the diseases, disorders or conditions which may be responsive to NLRP3 inhibition and which may be treated or prevented in accordance with various aspects of the present invention include central nervous system diseases such as Parkinson’s disease, Alzheimer’s disease, dementia, motor neuron disease, Huntington’s disease (Pg. 24, Lns. 29-30). Parkinson’s disease, Alzheimer’s disease, dementia, motor neuron disease, Huntington’s disease are examples of neurodegenerative disorders as evidenced by page 1, lines 7-10 of the instant specification. Miller teaches pharmaceutical compositions comprising a salt, hydrate or solvate of the first aspect of the invention or a polymorphic form of the second aspect of the invention, and a pharmaceutically acceptable excipient (Pg. 16, Lns. 5-8). Miller teaches the medicaments of the invention can be administered by the oral route (Pg. 37, Lns. 28-29). Miller teaches dosage forms for oral administration of the salt, hydrate, solvate, polymorphic form or pharmaceutical composition to include tablets, capsules, hard or soft gelatine capsules, caplets, troches or lozenges, as a powder or granules, or as an aqueous solution, suspension or dispersion (Pg. 38, Lns. 4-7). Based on the teachings of Miller, a person of ordinary skill in the art would have clearly envisaged the instant method claims drawn to a method for the treatment or prevention of a neurodegenerative disorder in a patient in need thereof, wherein the method comprises orally administering to the patient in need thereof a therapeutically or prophylactically effective amount of a compound as in instant claim 22.
Regarding instant claims 33-34, 36-40, Miller teaches the salt is a monosodium salt (Pg. 4, Lns. 1-4; Claim 2). Miller teaches the salt is a monosodium monohydrate salt (Pg. 4, Lns. 1-4; Claim 3). Miller teaches the sodium salt of N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide is a crystalline monosodium monohydrate salt (Pg. 6, Lns. 20-25; Claims 4-5). Miller teaches the XRPD spectrum of the polymorph comprising peaks at approximately 4.3 °2θ, 8.7 °2θ and 20.6 °2θ, ±0.2 °2θ (Pg. 7, Lns. 23-31; Claim 6). Miller teaches XRPD in which the 10 most intense peaks include 5 or more (e.g. 6 or more, 7 or more, 8 or more, 9 or more, or 10) peaks which have an approximate 2θ value selected from 4.3 °2θ, 6.2 °2θ, 6.7 °2θ, 7.3 °2θ, 8.7 °2θ, 9.0 °2θ, 12.1 °2θ, 15.8 °2θ, 16.5 °2θ, 18.0 °2θ, 18.1 °2θ, 20.6 °2θ, 21.6 °2θ, and 24.5 °2θ (Pg. 8, Lns. 1-5; Claim 7).
Regarding instant claim 32, Miller teaches the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activity is pathogenic in inherited disorders such as cryopyrin-associated periodic syndromes (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer’s disease and atherosclerosis (Pg. 1, Lns. 11-15). Miller is silent on wherein the treatment or prevention comprises the treatment or prevention of neuroinflammation.
Song teaches neuroinflammation as a fundamental innate immune response in the central nervous system (CNS) by which the brain and spinal cord react to cellular damage (Pg. 1, last paragraph). Song teaches the NLRP3 inflammasome as a key contributor of neuroinflammation in neurodegenerative diseases (Abstract; Pg. 2, first column, second full paragraph). Song teaches targeting NLRP3 inflammasome signaling as a promising approach to reduce neuroinflammation in neurological disorders (Abstract ; Figure 3). Thus, Song evidences the method of Miller would result in treating or preventing neuroinflammation.
As such, the limitations of the instant claims 22-26, 32-34 and 36-41 are anticipated by Miller and therefore deemed unpatentable over the cited prior art.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 22-26, 32-33, 37 and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by O’Neill et al. (US 2018/0044287 A1, publication date 15 February 2018, hereinafter O’Neill).
Regarding instant claims 22-26, 32-33, 37 and 41, O’Neill teaches sulfonylureas and related compounds which have advantageous properties and show useful activity in the inhibition of activation of the NLRP3 inflammasome (Abstract). O’Neill teaches compounds are useful in the treatment of a wide range of disorders in which the inflammation process, or more specifically the NLRP3 inflammasome, have been implicated as being a key factor (Abstract; Claim 40). O’Neill teaches compounds of formula (I) or a pharmaceutically acceptable salt, solvate or prodrug thereof (Paras. [0016]-[0021]; Claim 1). O’Neill teaches pharmaceutically acceptable salts to include a sodium salt (Para. [0045]; Para. [0310]). O’Neill teaches the compounds may exist in stable and metastable crystalline forms (Para. [0308]). O’Neill teaches the exemplary compound N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide (Para. [0237]; Para. [0777]; Claim 36), having an IC50 value of 13 nM (Para. [1019]).
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O’Neill teaches compound MCC7840 exhibited good pharmacokinetic parameters of bioavailability (Para. [1021]-[1023]; Para. [0035]; Fig. 2A-2C). O’Neill teaches a method of treatment or prevention of a disease, disorder or condition including the step of administering an effective amount of a compound of formula (I) to (VII), or a pharmaceutically effective salt, solvate or prodrug thereof, or the pharmaceutical composition of the second aspect to thereby treat or prevent the disease disorder or condition (Para. [0323]; Claim 39). O’Neill teaches embodiments in which the disease, disorder or condition is selected from the group consisting of central nervous system diseases (Para. [0346]; Claim 51) including Parkinson's disease, Alzheimer's disease, motor neuron disease, Huntington's disease (Para. [0354]; Paras. [0357]-[0358]; Claim 52). O’Neill teaches Parkinson’s disease is characterized by chronic microglial neuroinflammation that drives the pathology of the disease (Para. [0357]) (the method of O’Neill would result in treating neuroinflammation). O’Neill teaches a pharmaceutical composition comprising a compound of the first aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof, and a pharmaceutically acceptable carrier, diluent and/or excipient (Para. [0022]). O’Neill teaches routes of administration to include oral administration (Para. [0326]). O’Neill teaches the compounds exhibit improved oral bioavailability over the sulfonylureas of the prior art (Para. [0228]).
Based on the teachings of O’Neill, a person of ordinary skill in the art would have clearly envisaged the instant method claims drawn to a method for the treatment or prevention of a neurodegenerative disorder in a patient in need thereof, wherein the method comprises orally administering to the patient in need thereof a therapeutically or prophylactically effective amount of a compound as in instant claim 22.
As such, the limitations of the instant claims 22-26, 32-33, 37 and 41 are anticipated by O’Neill and therefore deemed unpatentable over the cited prior art.
Claim Rejections - 35 USC § 103 – Maintained and modified
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 27 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Miller et al. (WO 2019/206871 A1, publication date 31 October 2019, hereinafter Miller) as evidenced by Song et al. (NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies, 09 March 2017, hereinafter Song) as applied to claims 22-26, 32-34 and 36-41 above, in view of Li et al. (NLRP3 Inflammasome-Related Proteins Are Upregulated in the Putamen of Patients With Multiple System Atrophy, November 2018, hereinafter Li).
The teachings of Miller are set forth in the anticipation rejection above and incorporated herein by reference.
Regarding instant claims 27 and 30, the teachings of Miller anticipate the method of instant claim 22. Miller do not teach wherein the neurodegenerative disorder is multiple system atrophy or ataxia.
Li teaches multiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia, and autonomic dysfunction (Abstract). Li teaches NLRP3 inflammasome is implicated in MSA and that NLRP3 inflammasome is significantly upregulated and correlates with the neurodegenerative process in MSA (Abstract; Pg. 1064, first column, first paragraph; Figure 7). Li concludes that the NLRP3 inflammasome may be a therapeutic target for neurodegenerative diseases, including MSA (Pg. 1065, first column, first full paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Miller and Li to have extended the method of Miller, i.e., administering N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide or a salt thereof to a patient suffering from multiple system atrophy or ataxia, to arrive at the instant method claims with a reasonable expectation of success. Miller anticipates the method for the treatment or prevention of a neurodegenerative disorder in a patient in need thereof, as in instant claim 22. Miller teaches administering the compounds and pharmaceutical compositions comprising the compound result in NLRP3 inhibition. Li teaches multiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia, and autonomic dysfunction. Li teaches NLRP3 inflammasome is implicated in MSA and that NLRP3 inflammasome is significantly upregulated and correlates with the neurodegenerative process in MSA. Li concludes that the NLRP3 inflammasome may be a therapeutic target for neurodegenerative diseases, including MSA.
Therefore, one of ordinary skill in the art would have been motivated to apply the method of Miller that results in NLRP3 inhibition, in the treatment or prevention of multiple system atrophy or ataxia, with a reasonable expectation of success in treating such a condition.
Claims 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Miller et al. (WO 2019/206871 A1, publication date 31 October 2019, hereinafter Miller) as evidenced by Song et al. (NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies, 09 March 2017, hereinafter Song) as applied to claims 22-26, 32-34 and 36-41 above, in view of Stancu et al. Aggregated Tau activates NLRP3–ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded Tau pathology in vivo, 05 February 2019, hereinafter Stancu) as evidenced by Taylor et al. (Frontotemporal Dementias, Careful clinical, neuropsychologic, and imaging investigations make differential diagnosis of variants possible, June 2019, hereinafter Taylor).
The teachings of Miller are set forth in the anticipation rejection above and incorporated herein by reference.
Regarding instant claims 28-29, the teachings of Miller anticipate the method of instant claim 22. Miller do not teach wherein the neurodegenerative disorder is frontotemporal dementia or progressive supranuclear palsy.
Stancu teaches that aggregated tau activates the NLRP3-ASC inflammasome that exacerbates tau pathology in tau mice in vivo (Abstract; Pg. 601, first column, second full paragraph; Fig. 1). Stancu teaches pharmacological inhibition of NLRP3 with the inflammasome inhibitor MCC950 (a sulfonylurea similar to that of the instant claims) in tau-seeded transgenic tau mice resulted in significantly reduced tau pathology (Pg. 606, first column, last paragraph – Pg. 607, first column, continued paragraph; Fig. 3).
Taylor evidences that frontotemporal dementia or progressive supranuclear palsy are primary tau pathologies (Pg. 75, second column, second paragraph; Pg. 72, first column, first paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Miller and Stancu as evidenced by Taylor, to have extended the method of Miller, i.e., administering N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide or a salt thereof to a patient suffering from frontotemporal dementia or progressive supranuclear palsy, to arrive at the instant method claims with a reasonable expectation of success. Miller anticipates the method for the treatment or prevention of a neurodegenerative disorder in a patient in need thereof, as in instant claim 22. Miller teaches administering the compounds and pharmaceutical compositions comprising the compound result in NLRP3 inhibition. Stancu teaches that aggregated tau activates the NLRP3-ASC inflammasome that exacerbates tau pathology. Stancu teaches pharmacological inhibition of NLRP3 with the inflammasome inhibitor MCC950 (a sulfonylurea similar to that of the instant claims) in tau-seeded transgenic tau mice resulted in significantly reduced tau pathology. Taylor evidences that frontotemporal dementia or progressive supranuclear palsy are primary tau pathologies.
Therefore, one of ordinary skill in the art would have been motivated to apply the method of Miller that results in NLRP3 inhibition, in the treatment or prevention of frontotemporal dementia or progressive supranuclear palsy, with a reasonable expectation of success in treating such a condition.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Miller et al. (WO 2019/206871 A1, publication date 31 October 2019, hereinafter Miller) as evidenced by Song et al. (NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies, 09 March 2017, hereinafter Song) as applied to claims 22-26, 32-34 and 36-41 above, in view of Walsh et al. (Inflammasomes in the CNS, 08 February 2014, hereinafter Walsh).
The teachings of Miller are set forth in the anticipation rejection above and incorporated herein by reference.
Regarding instant claim 31, the teachings of Miller anticipate the method of instant claim 22. Miller do not teach wherein the neurodegenerative disorder is neurodegenerative prion disease.
Walsh teaches inflammasomes function as intracellular sensors for infectious agents as well as for host-derived danger signals that are associated with neurological diseases (Abstract). Walsh teaches the prion protein (PrP) fibrils or neurotoxic fragments activate the NLRP3 inflammasome in microglia of prion disease (Pg. 92, Table 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Miller and Walsh to have extended the method of Miller, i.e., administering N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide or a salt thereof to a patient suffering from neurodegenerative prion disease, to arrive at the instant method claims with a reasonable expectation of success. Miller anticipates the method for the treatment or prevention of a neurodegenerative disorder in a patient in need thereof, as in instant claim 22. Miller teaches administering the compounds and pharmaceutical compositions comprising the compound result in NLRP3 inhibition. Walsh teaches inflammasomes function as intracellular sensors for infectious agents as well as for host-derived danger signals that are associated with neurological diseases. Walsh teaches the prion protein (PrP) fibrils or neurotoxic fragments activate the NLRP3 inflammasome in microglia of prion disease.
Therefore, one of ordinary skill in the art would have been motivated to apply the method of Miller that results in NLRP3 inhibition, in the treatment or prevention of neurodegenerative prion disease, with a reasonable expectation of success in treating such a condition.
Claims 27 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over O’Neill et al. (US 2018/0044287 A1, publication date 15 February 2018, hereinafter O’Neill) as applied to claims 22-26, 32-33, 37 and 41 above, in view of Li et al. (NLRP3 Inflammasome-Related Proteins Are Upregulated in the Putamen of Patients With Multiple System Atrophy, November 2018, hereinafter Li).
The teachings of O’Neill are set forth in the anticipation rejection above and incorporated herein by reference.
Regarding instant claims 27 and 30, the teachings of O’Neill anticipate the method of instant claim 22. O’Neill do not teach wherein the neurodegenerative disorder is multiple system atrophy or ataxia.
Li teaches multiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia, and autonomic dysfunction (Abstract). Li teaches NLRP3 inflammasome is implicated in MSA and that NLRP3 inflammasome is significantly upregulated and correlates with the neurodegenerative process in MSA (Abstract; Pg. 1064, first column, first paragraph; Figure 7). Li concludes that the NLRP3 inflammasome may be a therapeutic target for neurodegenerative diseases, including MSA (Pg. 1065, first column, first full paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of O’Neill and Li to have extended the method of O’Neill, i.e., administering N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide or a salt thereof to a patient suffering from multiple system atrophy or ataxia, to arrive at the instant method claims with a reasonable expectation of success. O’Neill anticipates the method for the treatment or prevention of a neurodegenerative disorder in a patient in need thereof, as in instant claim 22. O’Neill teaches administering the compounds and pharmaceutical compositions comprising the compound result in NLRP3 inhibition. Li teaches multiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia, and autonomic dysfunction. Li teaches NLRP3 inflammasome is implicated in MSA and that NLRP3 inflammasome is significantly upregulated and correlates with the neurodegenerative process in MSA. Li concludes that the NLRP3 inflammasome may be a therapeutic target for neurodegenerative diseases, including MSA.
Therefore, one of ordinary skill in the art would have been motivated to apply the method of O’Neill that results in NLRP3 inhibition, in the treatment or prevention of multiple system atrophy or ataxia, with a reasonable expectation of success in treating such a condition.
Claims 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over O’Neill et al. (US 2018/0044287 A1, publication date 15 February 2018, hereinafter O’Neill) as applied to claims 22-26, 32-33, 37 and 41 above, in view of Stancu et al. Aggregated Tau activates NLRP3–ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded Tau pathology in vivo, 05 February 2019, hereinafter Stancu) as evidenced by Taylor et al. (Frontotemporal Dementias, Careful clinical, neuropsychologic, and imaging investigations make differential diagnosis of variants possible, June 2019, hereinafter Taylor).
The teachings of O’Neill are set forth in the anticipation rejection above and incorporated herein by reference.
Regarding instant claims 28-29, the teachings of O’Neill anticipate the method of instant claim 22. O’Neill do not teach wherein the neurodegenerative disorder is frontotemporal dementia or progressive supranuclear palsy.
Stancu teaches that aggregated tau activates the NLRP3-ASC inflammasome that exacerbates tau pathology in tau mice in vivo (Abstract; Pg. 601, first column, second full paragraph; Fig. 1). Stancu teaches pharmacological inhibition of NLRP3 with the inflammasome inhibitor MCC950 (a sulfonylurea similar to that of the instant claims) in tau-seeded transgenic tau mice resulted in significantly reduced tau pathology (Pg. 606, first column, last paragraph – Pg. 607, first column, continued paragraph; Fig. 3).
Taylor evidences that frontotemporal dementia or progressive supranuclear palsy are primary tau pathologies (Pg. 75, second column, second paragraph; Pg. 72, first column, first paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of O’Neill and Stancu to have extended the method of O’Neill, i.e., administering N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide or a salt thereof to a patient suffering from frontotemporal dementia or progressive supranuclear palsy, to arrive at the instant method claims with a reasonable expectation of success. O’Neill anticipates the method for the treatment or prevention of a neurodegenerative disorder in a patient in need thereof, as in instant claim 22. O’Neill teaches administering the compounds and pharmaceutical compositions comprising the compound result in NLRP3 inhibition. Stancu teaches that aggregated tau activates the NLRP3-ASC inflammasome that exacerbates tau pathology. Stancu teaches pharmacological inhibition of NLRP3 with the inflammasome inhibitor MCC950 (a sulfonylurea similar to that of the instant claims) in tau-seeded transgenic tau mice resulted in significantly reduced tau pathology. Taylor evidences that frontotemporal dementia or progressive supranuclear palsy are primary tau pathologies.
Therefore, one of ordinary skill in the art would have been motivated to apply the method of O’Neill that results in NLRP3 inhibition, in the treatment or prevention of frontotemporal dementia or progressive supranuclear palsy, with a reasonable expectation of success in treating such a condition.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over O’Neill et al. (US 2018/0044287 A1, publication date 15 February 2018, hereinafter O’Neill) as applied to claims 22-26, 32-33, 37 and 41 above, in view of Walsh et al. (Inflammasomes in the CNS, 08 February 2014, hereinafter Walsh).
The teachings of O’Neill are set forth in the anticipation rejection above and incorporated herein by reference.
Regarding instant claim 31, the teachings of O’Neill anticipate the method of instant claim 22. O’Neill do not teach wherein the neurodegenerative disorder is neurodegenerative prion disease.
Walsh teaches inflammasomes function as intracellular sensors for infectious agents as well as for host-derived danger signals that are associated with neurological diseases (Abstract). Walsh teaches the prion protein (PrP) fibrils or neurotoxic fragments activate the NLRP3 inflammasome in microglia of prion disease (Pg. 92, Table 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of O’Neill and Walsh to have extended the method of O’Neill, i.e., administering N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide or a salt thereof to a patient suffering from neurodegenerative prion disease, to arrive at the instant method claims with a reasonable expectation of success. O’Neill anticipates the method for the treatment or prevention of a neurodegenerative disorder in a patient in need thereof, as in instant claim 22. O’Neill teaches administering the compounds and pharmaceutical compositions comprising the compound result in NLRP3 inhibition. Walsh teaches inflammasomes function as intracellular sensors for infectious agents as well as for host-derived danger signals that are associated with neurological diseases. Walsh teaches the prion protein (PrP) fibrils or neurotoxic fragments activate the NLRP3 inflammasome in microglia of prion disease.
Therefore, one of ordinary skill in the art would have been motivated to apply the method of O’Neill that results in NLRP3 inhibition, in the treatment or prevention of neurodegenerative prion disease, with a reasonable expectation of success in treating such a condition.
Response to Arguments
Applicants argue on pages 6-8 of the response dated 08/19/2025, “Miller relates to salt forms of the compound of formula (I). However, Miller discloses a vast number of diseases (see page 78 line 4 to page 85 line 25) and many forms of administration (see the paragraph spanning pages 76-77). There is nothing within Miller to specifically link the compound of formula (I) with the selected treatment of neurodegenerative disorders, nor to specifically link the selected treatment of neurodegenerative disorders with oral as opposed to any other form of administration”. Applicants further cite to other case decisions and argue “… the prior art reference - in order to anticipate under 35 U.S.C. §102 - must not only disclose all elements of the claim within the four corners of the document, but must also disclose those elements ‘arranged as in the claim.’ The “arranged as in the claim” language requires that an anticipatory reference “show all of the limitations of the claims arranged or combined in the same way as recited in the claims, not merely a particular order”” and conclude “Likewise, here the large number of diseases and large number of routes of administration disclosed by Miller is insufficient to anticipate the specific combination of the disease and route of administration now claimed. Nor is Song able to overcome this deficiency”.
Applicant's arguments have been fully considered but they are not persuasive.
Applicants are reminded that instant claim 22 is drawn broadly to a method the treatment or prevention of a neurodegenerative disorder in a patient in need thereof, wherein the method comprises orally administering to the patient in need thereof a compound of formula (I) or a pharmaceutically acceptable salt thereof. As discussed in the 102 rejection over Miller, Miller explicitly teaches a sodium salt of N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide (i.e., a sodium salt of the exact compound of formula(I) of instant claim 22) for use in a method of treatment or prevention of central nervous system diseases, disorders or conditions such as Parkinson’s disease, Alzheimer’s disease, dementia, motor neuron disease, Huntington’s disease (the exact species of neurodegenerative diseases of instant claims 23-26). Miller teaches the medicaments of the invention can be administered by the oral route. Therefore, all the limitations of instant claim 22 are recited within the four corners of the Miller reference and anticipate the instant method claims.
Contrary to Applicant’s contention that all of the limitations of the claims must be arranged or combined in the same way as recited in the claims, MPEP 2131.02(III) states, “A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962)).
In the instant case, in view of the teachings of Miller, a person of ordinary skill in the art would have clearly envisaged a method of treating or preventing a neurodegenerative disorder in a patient in need thereof, wherein the method comprises orally administering to the patient in need thereof a compound of formula (I) or a pharmaceutically acceptable salt thereof. Song was simply used to evidence the limitations of instant claim 32 drawn to “treatment or prevention of neuroinflammation”. Therefore, instant method claims 22-26, 32-34 and 36-41 are anticipated by Miller and the 102(a)(1) rejection over Miller is maintained.
Applicants argue on pages 8-10 of the response dated 08/19/2025, “Thus, while the compound of formula (I) was known from the cited art and had been demonstrated to be an effective inhibitor of NLRP3 and hence inflammation, and while the inhibition of NLRP3 had been implicated in the treatment of numerous conditions including Parkinson’s and Alzheimer’s disease, it was not known whether the compound in question could be delivered to the brain from systemic circulation, and more particularly via oral administration, so as to achieve the treatment of neurological disorders via a highly convenient (oral) route of administration. The skilled person on reading Miller would therefore have no reason to select the compound of formula (I) for the particular treatment of neurodegenerative disorders via an oral route of administration, and even if they did they would have no reasonable expectation of achieving a successful treatment.” Applicants argue “Moreover, the present inventors have demonstrated not only that the compound can be delivered to the brain via oral administration, but that it is highly effective at inhibiting NLRP3 in primary microglia cells once it gets there, showing greater efficacy than the art standard MCC950 (see Studies E, F and G). Such efficacy could not have been predicted from the cited art, where only inhibition in human monocyte derived macrophages (HMD™M) is reported (see O’ Neill, US 2018/0044287, page 133)”.
Applicant's arguments have been fully considered but they are not persuasive. As admitted by Applicants, Miller teaches the compound of formula (I) to be an effective inhibitor of NLRP3. Miller teaches use of the compound of formula (I) in a method of treatment of numerous conditions including Parkinson’s and Alzheimer’s disease. The disclosure of Miller anticipates a method of treatment of neurodegenerative disorders in a patient, since a species will generally anticipate a claim to a genus. See MPEP 2131.02(I). The 103 rejections are made to teach a method of treating the additional species of neurodegenerative disorders as in claims 27-31, wherein NLRP3 inflammasome is implicated and are taught to respond to NLRP3 inflammasome inhibition.
While the examiner appreciates the Applicants discussion of unexpected results, they are not applicable to the instant situation, since Miller is an anticipatory reference with respect to treatment of Parkinson’s or Alzheimer’s. Applicants results of improved efficacy appear to indicate unexpected results in mouse models of Parkinson’s (studies C, D, and H). According to MPEP 2131.04 “Evidence of secondary considerations, such as unexpected results or commercial success, is irrelevant to 35 U.S.C. 102 rejections and thus cannot overcome a rejection so based. In re Wiggins, 488 F.2d 538, 543, 179 USPQ 421, 425 (CCPA 1973).” Additionally, Miller teaches administering the same compound (i.e., a compound of formula (I) to the same patient population (a subject afflicted with a neurodegenerative disorder) via the same route (oral).
According to MPEP 2112.01(II), “Products of identical chemical composition can not have mutually exclusive properties.” Any properties exhibited by or benefits from are not given any patentable weight over the prior art provided the composition is inherent. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the disclosed properties are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990). In the instant case, the method of Miller when practiced in treating a subject afflicted with Parkinson’s or Alzheimer’s, would have necessarily resulted in the same treatment effects.
Moreover, according to MPEP 2112.02 (II): “The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 154, 163 {(CCPA 1957}. However, when the claim recites using an old composition or structure and the “use’ is directed to a result or property of that composition or structure, then the claim is anticipated”. In re May, S74 F.2d 1082, 1090, 197 USPO 601, 607 (CCPA 1978). In the instant case, the results alluded by Applicants is an inherent property of compound of formula (I) when utilized in a method of treatment of neurodegenerative conditions, such as, Parkinson’s and Alzheimer’s disease. Thus, the results referred to by Applicants - that it is highly effective at inhibiting NLRP3 in primary microglia cells once it gets there, showing greater efficacy than the art standard MCC950 – are necessarily anticipated by the Miller reference (which teaches administering the same compound to the same patient population via the same route). Therefore, the rejections of record are maintained.
Applicants argue on pages 10-11 of the response dated 08/19/2025, “O’Neill is further removed from claim 22 than Miller. O’Neill discloses a vast number of different compounds, only one of which corresponds to the compound of formula (I) of claim 22, a vast number of diseases (see paragraphs [0331]- [0364]) and many forms of administration (see paragraph [0326]). There is nothing within O’Neill specifically to link the compound of formula (I) with the selected treatment of a neurodegenerative disorder, let alone by oral administration.”
Applicant's arguments have been fully considered but they are not persuasive. As discussed in the 102 rejection, O’Neill teaches sulfonylureas and related compounds which have advantageous properties and show useful activity in the inhibition of activation of the NLRP3 inflammasome. O’Neill teaches the compounds exhibit improved oral bioavailability over the sulfonylureas of the prior art. O’Neill teaches the exemplary compound N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide (or MC7840) (i.e., the compound of instant formula (I)). O’Neill teaches MCC7840 exhibited good pharmacokinetic parameters of oral bioavailability versus MCC950 (Paras. [1024]-[1025], Tables 6 and 8), having an IC50 value of 13 nM. O’Neill teaches embodiments in which the disease, disorder or condition being treated is a central nervous system disease including Parkinson's disease, Alzheimer's disease, motor neuron disease, Huntington's disease (i.e., the neurodegenerative disorders of the instant claims).
According to MPEP 2143(I)(B), Example 9, “The Federal Circuit in Eisai makes it clear that from the perspective of the law of obviousness, any known compound might possibly serve as a lead compound …Office personnel might also base an obviousness rejection on a known compound that pharmaceutical chemists would not select as a lead compound due to expense, handling issues, or other business considerations. However, there must be some reason for starting with that particular lead compound other than the mere fact that the "lead compound" exists”. In the instant case, the MCC7840 compound of O’Neill is taught to exhibit a good potency of 13 nM towards NLRP3 inflammasome inhibitory activity and anticipates the instant compound of claim 22. Thus, there is enough motivation/incentive for a person of ordinary skill in the art at the time the application was effectively filed, to further explore MCC7840 of O’Neill as promising therapeutic candidate as a NLRP3 inflammasome inhibitory agent, for use in a method of treating a neurodegenerative disease or disorder.
According to MPEP 2123 (I), A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). In the instant case, O’Neill teach all the limitations of instant claim 22 within the four corners of the document and provides motivation for a person of ordinary skill in the art to choose the instant compound of formula (I) due to its improved pharmacokinetic parameters.
In view of the foregoing discussion, all rejections over O’Neill are maintained.
Double Patenting – Maintained and modified
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 22-26, 32-34, 36-41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims 18, 24 and 26-33 of co-pending Application No 17/775,260 in view of O’Neill et al. (US 2018/0044287 A1, publication date 15 February 2018, hereinafter O’Neill).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a method for the treatment or prevention of a disorder in a patient in need thereof, wherein the method comprises administering to the patient in need thereof a therapeutically or prophylactically effective amount of a compound of formula (I).
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The instant claims are drawn to a method for the treatment or prevention of a neurodegenerative disorder in a patient in need thereof, wherein the method comprises orally administering a compound of formula (I) or a pharmaceutically acceptable salt thereof.
The claims of co-pending ‘260 application are drawn to a method for the treatment or inhibition of neuroinflammation or an inflammatory brain disorder in a patient in need thereof wherein the method comprises orally administering a compound of formula (I) or a pharmaceutically acceptable salt thereof. The reference application anticipates a monosodium monohydrate salt, or crystalline forms thereof characterized by the XRPD patterns of compound of formula (I) as in instant claim 22 and oral formulations thereof.
The reference application does not teach treatment or prevention of a neurodegenerative disorder in a patient in need thereof.
O’Neill teaches sulfonylureas and related compounds which have advantageous properties and show useful activity in the inhibition of activation of the NLRP3 inflammasome (Abstract). O’Neill teaches compounds are useful in the treatment of a wide range of disorders in which the inflammation process, or more specifically the NLRP3 inflammasome, have been implicated as being a key factor (Abstract; Claim 40). O’Neill teaches the exemplary compound N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide (Para. [0237]; Para. [0777]; Claim 36) having the following structure (i.e., the compound of instant formula (I)).
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O’Neill teaches embodiments wherein the sulfonylurea compounds are used in the treatment of conditions such as multiple sclerosis (a neuroinflammatory condition) (Para. [0354]; Para. [0003]) and diseases of the central nervous system (CNS) (Para. [0346]; Claim 51). O’Neill teaches the CNS diseases treated by the sulfonylurea compounds include Parkinson's disease, Alzheimer's disease, motor neuron disease, Huntington's disease (Para. [0354]; Paras. [0357]-[0358]; Claim 52). O’Neill teaches Parkinson’s disease is characterized by chronic microglial neuroinflammation that drives the pathology of the disease (Para. [0357]). O’Neill indicates NLRP3 inflammasome being implicated in neuroinflammatory conditions, such as, multiple sclerosis as well as CNS conditions, such as, Parkinson's disease, Alzheimer's disease, motor neuron disease, Huntington's disease. Therefore, the administration of the same NLRP3 inflammasome inhibitory agent, the compound of formula (I) as in the reference application, to a patient afflicted with CNS diseases would result in the treatment of the CNS diseases of the instant invention.
Thus, the methods of the reference ‘260 application render the instant method claims prima facie obvious in view of O’Neill.
The instant claims 22-26, 32-34, 36-41 and claims 18, 24 and 26-33 of co-pending Application No 17/775,260 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 22-26, 32-34, 36-41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims 19, 21-23 and 28-35 of co-pending Application No 17/775,230 in view of O’Neill et al. (US 2018/0044287 A1, publication date 15 February 2018, hereinafter O’Neill).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a method for the treatment or prevention of a disorder in a patient in need thereof, wherein the method comprises administering to the patient in need thereof a therapeutically or prophylactically effective amount of a compound of formula (I).
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The instant claims are drawn to a method for the treatment or prevention of a neurodegenerative disorder in a patient in need thereof, wherein the method comprises orally administering a compound of formula (I) or a pharmaceutically acceptable salt thereof.
The claims of co-pending ‘230 application are drawn to a method for the treatment of an autoinflammatory disorder in a patient in need thereof, wherein the method comprises orally administering a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the autoinflammatory disorder is cryopyrin-associated periodic syndrome (CAPS), Schnitzler syndrome, tumor necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD), familial mediterranean fever (FMF), Behcet Disease, Pyoderma Gangraenosum, systemic onset of juvenile idiopathic arthritis (sJIA), or Hidradenitis Suppurativa. The reference application anticipates a monosodium