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 Claims
This Office Action is in response to Applicant's arguments filed on July 25, 2025. Claim(s) 18-24 and 26-33 are pending and examined herein.
Response to Arguments
Applicant’s amendments and arguments with respect to the nonstatutory double patenting as being unpatentable over claims 1-10 and 22-32 of US Patent 10,973,803 have been fully considered. Applicant argues:
US’803 relates to salt forms of the compound of formula (1). However, US’803 claims a vast number of diseases (see claims 26 and 27) without specifying a specific route of administration. There is nothing within the claims of US’803 to specifically link treatment of neuroinflammation or an inflammatory brain disorder by oral administration.
Examiner respectfully notes that while the patented claims teach administration of formula I, the claims do not specifically teach oral administration. Nonetheless, administration as defined in the body of the patent embraces oral administration, among other routes. Therefore, applicant’s argument is not persuasive.
In view of applicant’s amendments, the 112(a) rejection over claims 18-34 while being enabling for treatment of neuroinflammation or an inflammatory brain disorder, does not reasonably provide enablement for the prevention or prophylaxis of neuroinflammation or an inflammatory brain disorder is hereby withdrawn.
In view of applicant’s statement that the disclosed subject matter in Miller (WO 2019/206871) was commonly owned to the same entity on or before the effective filing date of the claimed invention, the 102(a)(2) rejection of claims 18-34 as being anticipated by Miller (WO 2019/206871) is hereby withdrawn.
Applicant’s amendments and arguments with respect to the 103 rejection of claims 18-34 as being unpatentable over O’Neill (WO 2016/131098) has been fully considered, but not persuasive.
Applicant argues:
In contrast, the present inventors have found and demonstrated with data in the application as filed, that the compound of formula (1) is successfully absorbed and crosses the blood-brain barrier following oral administration (Study A of the specification). Such a result could not have been predicted from the prior art. This discovery opens up the possibility of treating neuroinflammation via the oral administration of the compound of formula (1). 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 prior art standard MCC950 (see Studies B and C of the specification). Such efficacy could not have been predicted from the prior art, where only inhibition in human monocyte derived macrophages (HMDM) is reported (see O’Neill, WO 2016/131098, page 293). By demonstrating (i) the ability of the compound of formula (I) to reach microglia cells in the brain following oral administration, and (11) the ability of the compound of formula (I) to inhibit NLRP3 and hence inflammation in such cells, the inventors of the application have demonstrated for the first time that the compound of formula (I) will be effective in treating neuroinflammation and hence inflammatory brain disorders following oral administration.
Examiner notes that O’Neill teaches particularly those of formulae (II) to (VI), provide a range of unexpected benefits over those sulfonylureas of the prior art, which benefits may be selected from: improved microsomal stability; improved permeability; reduced Pgp liability; reduced plasma protein binding; increased half-life; improved oral bioavailability; improved AUC; Improved Cmax; Reduced Cyp inhibition; improved inhibition of activation of the NLRP3 inflammasome; and improved solubility. The solubility, and certain other, improvements may be seen particularly in an aqueous environment [00114]. Moreover, compound MCC-7480 (formula I of the instant claims) is disclosed among other compounds. However, this compound is clearly the preferred compound as it has been singled out in a number of comparative examples against the reference compound of the prior art MCC-950 (figures 2A-2C).
The reason or motivation to modify a reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. While there must be motivation to make the claimed invention, there is no requirement that the prior art provide the same reason as the applicant to make the claimed invention. MPEP 2144 Sources of Rationale Supporting a Rejection Under 35 U.S.C. 103. /www.uspto..qov/web/offices/pac/mpep/documents/2100 2144.htm>.
Any rejection from the previous Office action not set forth on record below is hereby withdrawn.
The maintained/modified rejections are made in the Final Office action below as necessitated by amendment.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 18-24 and 26-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 22-32 of US Patent 10,973,803. Although the claims at issue are not identical, they are not patentably distinct from each other. The instant claims are drawn to method for the treatment or prevention of neuroinflammation or an inflammatory brain 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). The patented claims are drawn to the sodium salt of N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide (claims 1-10) and a method of ameliorating, palliating, delaying onset of, or reducing risk of the disease, disorder or condition, wherein the disease, disorder or condition is responsive to NLRP3 inhibition employing the same compound.
The patented claims teach administration of formula I, the claims do not specifically teach oral administration. Nonetheless, administration as defined in the body of the patent embraces oral administration, among other routes. The two inventions as a whole are prima facie obvious over one another.
Based on the foregoing reasons, the instant claims are unpatentable over the cited patent.
Claim Rejections - 35 USC § 103
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 of this title, 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.
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 18-24 and 26-33 are rejected under 35 U.S.C. 103 as being unpatentable over O’Neill (WO 2016/131098).
O’Neill teaches sulfonyl ureas and related compounds which have advantageous properties and show useful activity in the inhibition of activation of the NLRP3 inflammasome (abstract).
O’Neill teaches formula I (page 350, column 1, 2nd compound) and pharmaceutically acceptable salts.
O’Neill specifically exemplifies compound MCC-7840 (formula I of instant claims) directed to NLRP3 inflammasome inhibitors for the treatment of a number of diseases, including multiple sclerosis. Compound MCC-7480 is disclosed among other compounds, however, is clearly the preferred compound as it has been singled out in a number of comparative examples against the reference compound of the prior art MCC-950 ([0030]; figures 2A-2C).
O’Neill teaches the term "pharmaceutically acceptable salt", as used herein, refers to salts which are toxicologically safe for systemic or localized administration such as salts prepared from pharmaceutically acceptable non-toxic bases or acids including inorganic or organic bases and inorganic or organic acids. The pharmaceutically acceptable salts may be selected from the group including alkali and alkali earth, ammonium, aluminium, iron, amine, glucosamine, chloride, sulphate, sulphonate, bisulphate, nitrate, citrate, tartrate, bitarate, phosphate, carbonate, bicarbonate, malate, maleate, napsylate, fumarate, succinate, acetate, benzoate, terephthalate, palmoate, piperazine, pectinate and S-methyl methionine salts and the like [0040].
O’Neill teaches if a compound described herein as an active agent is an acid, the desired salt may be prepared by any suitable method known in the art, including treatment of the free acid with an inorganic or organic base, such as an amine (primary, secondary or tertiary), an alkali metal or alkaline earth metal hydroxide or the like. Illustrative examples of suitable salts include organic salts derived from amino acids such as glycine and arginine, ammonia, primary, secondary and tertiary amines, and cyclic amines such as piperidine, morpholine and piperazine, and inorganic salts derived from sodium, calcium, potassium, magnesium, manganese, iron, copper, zinc, aluminum and lithium [00157].
O’Neill teaches the compound may be crystallized in order to resolve optical isomers [0148].
O’Neill teaches in the case of solid compositions, the compounds used in the methods of the invention may exist in different forms. For example, the compounds may exist in stable and metastable crystalline forms and isotropic and amorphous forms [00155].
O’Neill teaches the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation 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 [0003].
O’Neill teaches [00200] the disease, disorder or condition is selected from the group consisting of constitutive inflammation including the cryopyrin-associated periodic syndromes (CAPS): Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS) and neonatal-onset multisystem inflammatory disease (NOMID); including autoinflammatory diseases: familial Mediterranean fever (FMF), TNF receptor associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), hyperimmunoglobulinemia D and periodic fever syndrome (H IDS), deficiency of interleukin 1 receptor (DIRA) antagonist, Majeed syndrome, pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), haploinsufficiency of A20 (HA20), pediatric granulomatous arthritis (PGA), PLCG2 -associated antibody deficiency and immune dysregulation (PLAID), PLCG2-associated autoinflammation, antibody deficiency and immune dysregulation (APLAID), sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD); Sweet s syndrome, chronic nonbacterial osteomyelitis (CNO), chronic recurrent multifocal osteomyelitis (CRMO) and synovitis, acne, pustulosis, hyperostosis, osteitis syndrome (SAPHO); autoimmune diseases including multiple sclerosis (MS), type-1 diabetes, psoriasis, rheumatoid arthritis, Behcet's disease, Sjogren's syndrome and Schnitzler syndrome; respiratory diseases including chronic obstructive pulmonary disorder (COPD), steroid-resistant asthma, asbestosis, silicosis and cystic fibrosis; central nervous system diseases including Parkinson's disease, Alzheimer's disease, motor neuron disease, Huntington's disease, cerebral malaria and brain injury from pneumococcal meningitis; metabolic diseases including Type 2 diabetes, atherosclerosis, obesity, gout, pseudo-gout; ocular diseases including those of the ocular epithelium, age-related macular degeneration (AMD), corneal infection, uveitis and dry eye; kidney disease including chronic kidney disease, oxalate nephropathy and diabetic nephropathy; liver disease including non-alcoholic steatohepatitis and alcoholic liver disease; inflammatory reactions in skin including contact hypersensitivity and sunburn; inflammatory reactions in the joints including osteoarthritis, systemic juvenile idiopathic arthritis, adult-onset Still's disease, relapsing polychondritis; viral infections including alpha virus (Chikungunya, Ross River) and flavivirus (Dengue and Zika Virus), flu, HIV; hidradenitis suppurativa (HS) and other cyst-causing skin diseases; cancers including lung cancer metastasis, pancreatic cancers, gastric cancers, myelodysplastic syndrome, leukemia; polymyositis; stroke; myocardial infarction; Graft versus Host Disease; hypertension; colitis; helminth infection; bacterial infection; abdominal aortic aneurism; wound healing; depression, psychological stress; pericarditis including Dressler's syndrome, ischaemia reperfusion injury and any disease where an individual has been determined to carry a germline or somatic non-silent mutation in NLRP3 ([00200] and claim 52).
O’Neill teaches the disease, disorder or condition being treated is Parkinson's disease. Parkinson's is the most common neurodegenerative movement disorder and is characterized by a selective loss of dopaminergic neurons, accompanied by the accumulation of mis-folded a-synuclein (Syn) into Lewy bodies that are pathological hallmarks of the disease. Chronic microglial neuroinflammation is evident early in the disease, and has been proposed to drive pathology. [00204] A central role for microglial NLRP3 is postulated in Parkinson's progression. The NLRP3 inflammasome is activated by fibrillar Syn via a Syk kinase dependent mechanism, and also occurs in the absence of Syn pathology at the early stages of dopaminergic degeneration, and drives neuronal loss. The compounds of the first aspect may block NLRP3 inflammasome activation by fibrillar Syn or mitochondrial dysfunction and thereby confer effective neuroprotection of the nigrostriatal dopaminergic system and assist with treatment of Parkinson's [00203].
O’Neill teaches the routes of administration may include topical, parenteral and enteral which include oral, buccal, sub-lingual, nasal, anal, gastrointestinal, subcutaneous, intramuscular and intradermal routes of administration, although without limitation thereto [00173].
O’Neill teaches particularly those of formulae (II) to (VI), provide a range of unexpected benefits over those sulfonylureas of the prior art, which benefits may be selected from: Improved microsomal stability; Improved permeability; reduced Pgp liability; reduced plasma protein binding; increased half-life; Improved oral bioavailability; improved AUC; Improved Cmax; Reduced Cyp inhibition; improved inhibition of activation of the NLRP3 inflammasome; and improved solubility. The solubility, and certain other, improvements may be seen particularly in an aqueous environment [00114].
O’Neill teaches a pharmaceutically acceptable carrier, diluent and/or excipient may be or include one or more of diluents, solvents, pH buffers, binders, fillers, emulsifiers, disintegrants, polymers, lubricants, oils, fats, waxes, coatings, viscosity-modifying agents, glidants and the like [00159].
The reference teaches a generic group of compounds which embraces applicants’ claimed compounds (as discussed above). The claims differ from the reference by reciting specific species and a more limited genus than the reference. However, it would have been obvious to one having ordinary skill in the art at the time of the invention to select any of the species of the genus taught by the reference, including those instantly claimed, because the skilled chemist would have the reasonable expectation that any of the species of the genus would have similar properties and, thus, the same use as taught for the genus as a whole. One of ordinary skill in the art would have been motivated to select the claimed compounds from the genus in the reference since such compounds would have been suggested by the reference as a whole. It has been held that a prior art disclosed genus of useful compounds is sufficient to render prima facie obvious a species falling within a genus. In re Susi, 440 F.2d 442, 169 USPQ 423, 425 (CCPA 1971), followed by the Federal Circuit in Merck & Co. v. Biocraft Laboratories, 847 F.2d 804, 10 USPQ 2d 1843, 1846 (Fed. Cir. 1989).
Regarding claims 31 and 32, O’Neill does not specifically teach a crystalline salt with an XRPD spectrum with peaks as required by the limitations of claims 31 and 32.
The MPEP 2112 states:
“SOMETHING WHICH IS OLD DOES NOT BECOME PATENTABLE UPON THE DISCOVERY OF A NEW PROPERTY.
The claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).”
In this case, the “unknown property” is the particular crystalline form. This is unknown because the reference is silent on this property. MPEP 2112 goes on to state:
“A REJECTION UNDER 35 U.S.C. 102/103 CAN BE MADE WHEN THE PRIOR ART PRODUCT SEEMS TO BE IDENTICAL EXCEPT THAT THE PRIOR ART IS SILENT AS TO AN INHERENT CHARACTERISTIC.
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103, expressed as a 102/103 rejection.”
Again, the “CHARACTERISTIC” which the prior art is silent on is the crystalline form (crystalline form is considered to be in the category of chemical properties; see Zenith Laboratories Inc. v. Bristol-Myers Squibb Co. 30 USPQ2d 1285, 1288); In re Grose and Flanigen, 201 USPQ 57 (CCPA 1979).
This is not an ordinary inherency situation where it is not explicitly stated what the product actually is. In every reference applied, the reference explicitly teaches exactly what the compound is. In fact, it is the opposite. In a normal inherency situation, the claim is of known structure, and the reference is of unknown structure. Here, the latter is not true, and hence the legal circumstances of inherency-in-the-prior-art do not apply. The only difference is the property about which the reference happens to be silent. Recitation of a property, inherently possessed by the prior art thing, does not distinguish a claim drawn to those things from the prior art, In re Swinehart, 169 USPQ 226, 229.
See for example Ex parte Anderson, 21 USPQ 2d 1241 at 1251, discussion of Rejection E. The claims had “numerical or functional values for certain properties which [the authors of the references] did not measure”. The PTO presented no reasoning as to why the prior art material would have been expected to have those properties. Instead, the decision states, “There is ample precedent for shifting the burden to an applicant to reproduce a prior art product whose final structure or properties are, at least, in part determined by the precise process used in its manufacture.” (page 1253).
In another example, certain claims of Ex parte Raychem Corp. 25 USPQ2d 1265 required a linearity ratio of less than 1.2. The decision notes that neither reference discloses any values of the linearity ratio. The PTO presented no reasoning as to what the ratio would be expected to be in the references. The Decision states: “However, this does not end the inquiry since, where the Patent and Trademark Office is not equipped to perform the needed testing, it is reasonable to shift the burden of proof to Raychem to establish that (1) the argued difference exists….”
And indeed, there have been a number of cases in which applicants have pointed to silence of the prior art with regard to this or that property: In re Pearson, 181 USPQ 641; In re Zierden 162 USPQ 102; In re Lemin, 140 USPQ 273; Titanium Metals Corporation of America v. Banner, 227 USPQ 773; In re Benner, 82 USPQ 49; In re Wilder, 166 USPQ 545; Ex parte Kucera, 165 USPQ 332; General Electric Co. v. Jewel Incandescent Lamp Co., 67 USPQ 155; In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607; In re Parker, 43 USPQ 457. Such efforts to avoid anticipation on that basis invariably failed. Going further, if silence about properties of prior art compounds could be relied on, then one could not reject over references with no utility (see In re Schoenwald, 22 USPQ2d 1671), since applicants could always insert the utility into the claim as a property.
It is well settled that the PTO can require an applicant to establish that a prior art product does not necessarily possess the characteristics of the claimed product when the prior art and claimed products are identical or substantially identical. An applicant's burden under these circumstances was described in In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-434 (CCPA 1977) as follows:
Where, as here, the claimed and prior art products are identical or
substantially identical, or are produced by identical or substantially
identical processes, the PTO can require an applicant to prove that the
prior art products do not necessarily or inherently possess the
characteristics of his claimed product. . . . Whether the rejection is based
on ‘inherency' under 35 U.S.C. § 102, or ‘prima facie obviousness’ under
35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same,
and its fairness is evidenced by the PTO's inability to manufacture
products or to obtain and compare prior art products (footnote omitted).
Overcoming the rejection is very straightforward. One simply replicates the prior art procedure. If the claimed characteristic does not appear at all in the product, or if on repetition, it sometimes does not appear in the product, then the rejection is overcome. Applicant may also overcome the rejection by submitting a declaration as noted above.
Thus, based on the foregoing reasons, the instant claims are deemed unpatentable over the cited reference.
Conclusion
Claims 18-24 and 26-33 are not allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not
mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sahar Javanmard whose telephone number is (571)270-3280. The examiner can normally be reached on Monday-Friday, 9:00-5:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/SAHAR JAVANMARD/Primary Examiner, Art Unit 1627