DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application is a 371 National Stage Entry of PCT/EP2022/057628 filed on March 23, 2022 which claims priority to foreign application No. EP21305384.6 filed on March 26, 2021.
Status of Claims
Acknowledgement is made of previously presented (1-5, 7-10, 13, 15-16, 18-26, 29, 32) and cancelled (6, 11-12, 14, 17, 27-28, 30-31, 33) claims filed on October 12, 2023. Claims 1-5, 7-10, 13, 15-16, 18-26, 29, 32 are pending in instant application.
Information Disclosure Statement
The information disclosure statements filed on September 26, 2023; October 12, 2023; November 14, 2025 and February 18, 2026 have been considered.
Claim Rejections - 35 USC § 112
Claim 22 is 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.
Claim 22 recites “…Table 1”. There is insufficient antecedent basis for this limitation in the claim. For purposes of applying prior art, claim 22 is presumed to be an attempt to incorporate by reference Table 1 (instant spec. at pp. 27-28); however, this is improper (see MPEP § 2173.05(s), which states that where possible, claims are to be complete in themselves). The Examiner recommends amending to incorporate the list of peaks from Table 1 into the claim.
Claim 22 recites “substantially the same as Fig 1” which renders the claim indefinite because “substantially” is not defined in the specification (is it 4 peaks? 5? 20?). The Examiner recommends amending to “(c) an XRPD spectrum
Claim 22 recites the phrases “(±2°C)” and "(each time ± 0.2)" which renders the claim indefinite because it is unclear whether the limitation(s) in the parentheses are part of the claimed invention. See MPEP § 2173.05(d). The Examiner recommends amending to remove the parentheses and clearly indicating which peaks may be ±0.2
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, 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, 10, 15 are rejected under 35 U.S.C. 103 as being unpatentable over Friedlander1 as evidenced by Google Translate2 in view of Mohrig et. al.3
Friedlander teaches the synthesis of phenyldinolinamine (see Friedlander at p. 1533), which corresponds to instant Formula I if R, R’, and R’’’ were H.
Instant Claim 1
PNG
media_image1.png
133
395
media_image1.png
Greyscale
Freiderlander
PNG
media_image2.png
140
392
media_image2.png
Greyscale
Freidlander teaches heating chloroquinoline and aniline (see instant claim 1 step i) at 200 °C, cooled, then boiled with dilute sodium hydroxide solution (reading on a base, see instant claim 1 step ii), cooled, then recrystallized with alcohol (reading on purification or crystalizing with a solvent, see instant claim 15) to give shiny white flakes (see Google Translate at p. 1, corresponding to Friederlander p. 1532). Freidlander does not mention the presence of a metal catalyst.
The prior art differs from the claims as follows: while Friedlander teaches forming phenylquinolineamine, Friedlander does not teach wherein R or R’ are not hydrogen, or specify a molar ratio of chloroquinoline to aniline.
However,
Regarding non-H substituents, instant R or R’ may be methyl.
Regarding ratios, Mohrig teaches it is common practice to modify known reactions (see Mohrig at p. 85 “Technique 9 Designing a Chemical Reaction). Mohrig teaches that when adjusting scale of a known reaction, proportionality may need to be adjusted (see Mohrig at p. 87 ¶2), and that optimum product yields are achieved after multiple iterations (see Mohrig at p. 87 ¶3).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding H for Methyl, per MPEP § 2144.08(II)(A)(4)(c), the closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. In instant case, a change of H for Me is a small structure change, and a methyl analog of chloroquinoline and aniline would be expected to yield a methyl analog of phenylquinolinamine with a reasonable expectation of success because the reactants are still suitable for undergoing the Friederlander reaction because of the same structure core (aniline, chloroquinoline) and reaction sites (Cl, NH2).
Regarding ratios, per MPEP § 2144.05(II), generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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). It would have been obvious to one skilled in the art to vary molar ratios of known reactants in a known reaction (as taught by Friedlander) because it is common practice in order to optimize yield (as taught by Mohrig) (see also MPEP § 2143(I)(C)).
Furthermore, it is well-within the ordinary skill in art to use methyl analogs of known reactants for use in a known coupling reaction. Furthermore, it is well-within the ordinary skill in art to vary proportions of known reaction components in a known reaction.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 1, 7-10, 13, 15, 20, 22 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/158201 A1 to Rabe et. al.4 in view of Bunnett5 as exemplified by Mettler Toledo6.
Instant Claim 1
PNG
media_image1.png
133
395
media_image1.png
Greyscale
Rabe
PNG
media_image3.png
166
1036
media_image3.png
Greyscale
Regarding claim 1, 20, Rabe teaches compounds of Formula I for treating HIV (see Rabe at p. 1). Rabe teaches the synthesis of “(8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine (free base) without a palladium catalyst” from 2,8-dichloroquinoline (reading on compound 3, see instant claim 20) and 4-(trifluoromethoxyaniline) (see instant claim 20) (see Rabe at p. 14) via a nucleophilic aromatic substation reaction (see Rabe at p. 5 ¶2). (8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine reads on instant Formula I when R’ is a halogen atom specifically chlorine, R’’’ is H, and R is (C1-C3)fluoroalkoxy group specifically OCF3 (see also instant claim 20). The synthesis of Rabe is for (8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine (free base) (reading on recovering the compound of Formula I in the form of a free base, instant claim 1 step ii).
Further regarding claim 1 and addition of a base, Rabe teaches embodiments where a base such as K2CO3 is used (see Rabe at p. 16). Rabe also teaches excess 4-(trifluoromethoxy)aniline is used as a base in lieu of a heterogenous inorganic base to yield the free base product of Formula I because it is sufficiently basic (see Rabe at p. 5 ¶3).
Further regarding claims 1, 10 and ratios, Rabe teaches an embodiment of 0.63 mol of 2,8-dichloroquinoline and 1.58 mol of 4-(trifluoromethoxy)aniline which amounts to 1.00 : 2.50 ratio of a compound of Formula II to a compound of Formula III (see Rabe at p. 14). Rabe also teaches multiple embodiments where the ratio is 1:1.5 at 140 and 70 °C (see Rabe at p. 16).
Regarding claim 8 and HCl salt of Formula I, Rabe teaches the synthesis of (8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine HCl addition salt (see Rabe at p. 17) (reading on “hydrochloride salt of the compound of Formula I” at instant claim 8).
Regarding claim 13 and solvent or temperature, Rabe teaches the reaction is carried out in isopropanol (reading on an organic solvent) (see Rabe at p. 14). Rabe also teaches the reaction is at a temperature of 90 °C (see Rabe at p. 14).
Regarding claim 15 and recrystallizing or purifying, Rabe teaches recrystallizing the product with cyclohexane (see Rabe at p. 14) (reading on a purification step or recrystallizing in at least one solvent).
Regarding claim 22, Rabe teaches 8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine has a DSC thermogram onset temperature of 120 ± 2 °C (see Rabe at Figure 4 and at p. 14 lines 24-25). Mettler Toledo explains the DSC onset temperature corresponds to the melting point of a pure substance (see Mettler Toledo at p. 3 right col. “Melting, crystallization and mesophase transitions”).
The claims differ from the prior art as follows:
a) While Rabe teaches the synthesis of Formula I from compounds of Formula II and III, Rabe does not specify the addition of acid or seeding the reaction with a hydrochloride salt or the compound of Formula I.
b) While Rabe teaches ratios of compounds Formula II:Formula III of 1:1.5 and 1:2.5, Rabe does not specify an embodiment within the instantly claimed 1.00:0.80 to 1.00:1.20.
However,
Regarding a) and acid and claims 7-9, Rabe notes the synthesis is a nucleophilic aromatic substitution reaction, wherein the aniline reactant is serving as the nucleophile and the pyridine moiety in the quinoline reactant has a limited electron withdrawing power (see Rabe at p. 5 ¶2).
Bunnett states,
"The hetero-nitrogen atom in bases such as pyridine, quinoline, and thiazole is an activating structure… The amount of activation provided at various positions in numerous heterocyclic systems has been studied. Positions α and γ to the nitrogen atom are most strongly activated… Conversion of the hetero-nitrogen atom into the 'onium condition amplifies its activating power. Quaternisation of 3-halogenopyridines greatly increases the mobility of the halogen. Protonation also has this effect, and thus nucleophilic substitution in heterocyclic halides is subject to acid catalysis, sometimes of much use in synthesis." (see Bunnett at pp. 10-11 “Heterocyclic Bases”).
Applied to instant case, the α position of the 2,8-dichloroquinoline is the chlorine substituent at the 2 position of the quinoline structure (the chlorine that gets replaced by the incoming 4-(trifluoromethoxy)aniline). There is a partial positive charge at this carbon due to resonance that encourages this chlorine to be replaced in lieu of the chlorine at the 8 position. This activation (or increased halogen mobility as taught by Bunnett) is amplified when the nitrogen of the quinoline core (a heterocyclic halide, as taught by Bunnett) is protonated by the addition of an acid, thus speeding up the reaction (subject to acid catalysis, as taught by Bunnett).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding a) and acid and claims 7-9, a person of ordinary skill in the art would have a reasonable expectation of success in modifying the nucleophilic aromatic substitution synthesis taught by Rabe to incorporate an early acid addition step because it known in the art that acid catalysis enhances nucleophilic substitution at pyridinyl ring systems, per the teaching of Bunnett. An artisan would thus want to add acid near the beginning of the reaction, in order to expedite reaction progress. Rabe teaches the HCl salt form of a compound of Formula I, so an artisan is also guided by the prior art to select HCl or the HCl salt form of a compound of Formula I when choosing an acid to incorporate in step i.
Regarding b) and ratios and claims 1, 10, per MPEP § 2144.05(I), 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). Rabe teaches an embodiment of 1:1.5 which is close to the instantly claimed 1.00:1.20. Moreover, Rabe teaches attempting different ratios of reactants resulting in different product conversions, indicating the reactant ratio is an optimizable variable. Moreover, after modifying the Rabe reaction to include an acid catalyst, it would have been obvious to a person of skill in the art to optimize the reactant ratios since Rabe teaches the ratios are an optimizable variable. In addition, an artisan would be motivated to alter the ratios in an attempt to reduce the amount of reactants needed for cost or efficiency purposes (i.e. reduce the amount of a compound of Formula III, which would no longer be needed in excess).
Furthermore, it is well-within the ordinary skill in art to incorporate a method step known to improve a reaction class in a known method of that same reaction class (e.g. acid catalyst for nucleophilic aromatic substitution). Furthermore, it is well-within the ordinary skill in the art to optimize a variable known to be optimizable (e.g. reactant ratios).
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 23, 25-26, 29 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/158201 A1 to Rabe in view of Bunnett and exemplified by Mettler Toledo as applied to claims 1, 7-10, 13, 15, 20, 22, and in further view of Olunsami et. al.7
Regarding claims 23, 25-26, 29 Rabe teaches 8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine is an off-white solid (see Rabe at p. 14).
The instant claims differ from the prior art as follows: While Rabe and Bunnett teach the synthesis of crystalline (8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine, they do not teach the milling of the obtained solid product to obtain a powder.
However,
Olunsami discusses varying micronization techniques and teaches micronization is a type of milling (see Olunsanmi at p. 223 left col. ¶3 and at Abstract). Olusanmi teaches size reduction via micronization is important for obtaining consistent in vivo exposure (see Olunsanmi at Abstract). Olusanmi teaches micronization is an optimizable variable stating,
"In cases where bioavailability of drug entities can be improved by size and shape modification the ideal scenario would be to "dial a particle size and shape distribution" using robust bottom-up approaches from crystallization that can be scaled up to commercial scale while maintaining required polymorphic form, crystallinity, and stability.” (see Olusanmi at p. 222 right col ¶2)
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2143(I)(D), a prima facie case of obviousness exists for applying a known technique to a known method or product ready for improvement to yield predictable results. It would have been obvious to one skilled in the art to improve upon crystalline (8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine (as taught by Rabe and Bunnett) by milling the solid product in order to achieve optimal and reproduceable bioavailability (as taught by Olunsami). In addition, an artisan would be motivated to optimize the particle size and size distribution (e.g. D50, D10, and D90) because the prior art teaches these parameters influence bioavailability and processing (as taught by Olunsami).
Furthermore, it is well-within the ordinary skill in art to incorporate a method step known to improve a process (e.g. milling a product) in a known synthesis. Furthermore, it is well-within the ordinary skill in the art to optimize a variable known to be optimizable (e.g. size distribution).
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 24, 32 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/158201 A1 to Rabe in view of Bunnett and Olunsanmi and exemplified by Mettler Toledo as applied to claims 1, 7-10, 13, 15, 20, 22, 23, 25-26, 29 and in further view of Remington8.
Regarding claims 24, 32 and a pharmaceutical composition, Rabe teaches 8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine is also known as ABX-464 which is an oral HIV treatment (see Rabe at p. 1).
The instant claims differ from the prior art as follows: While Rabe teaches ABX-464 is an orally taken HIV treatment, Rabe does not specify a composition with an excipient.
However,
An artisan would readily appreciate that an oral treatment comprising ABX-464 taught by Rabe indicates the presence of a composition.
Remington teaches oral solid dosaging forms such as tablets (see Remington at p. 889). Remington teaches tablets, in addition to the active ingredient, comprise excipients (see Remington at p. 891 left col. ¶3 “Tablet Ingredients”) which can improve stability, bioavailability, and/or manufacturing (see Remington at p. 891 left col. ¶4).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2143(I)(D), a prima facie case of obviousness exists for applying a known technique to a known method or product ready for improvement to yield predictable results. It would have been obvious to one skilled in the art that a known treatment suitable for oral dosaging (as taught by Rabe and Bunnett) could be formulated as a composition with an excipient such as a tablet with a reasonable expectation of success because the prior art teaches such modification improves stability, bioavailability, and/or manufacturing (as taught by Remington).
Furthermore, it is well-within the ordinary skill in the art to formulate a known active substance for oral dosaging as a composition with excipients for the same purposes as taught by the prior art (e.g. oral administration to treat a patient).
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 2-5, 16, 18, 19, 21 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/158201 A1 to Rabe in view of Bunnett and exemplified by Mettler Toledo as applied to claims 1, 7-10, 13, 15, 20, 22, and in further view of EP 2465502 A1 to Tazi et. al.9 and Angapelly et. al.10
Recall Rabe teaches compounds of Formula I for treating HIV (see Rabe at p. 1), including (8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine and in view of Bunnett, teach the final step of the instantly claimed synthesis (see Rabe at p. 14).
The prior art differs from the claims as follows: While Rabe and Bunnett teach the synthesis of reactants Formula II and Formula III to yield Formula I, they do not specify the other prior synthetic steps.
However,
The prior synthetic steps are known in the prior art. Tazi teaches the synthesis of compounds corresponding with instant Formulas for treating AIDS (see Tazi at p. 4 ¶[0017]), a condition found in patients infected with HIV (see Tazi at p. 3 ¶[0003]). Angapelli teaches the chlorination step of claims 5, 16.
The following text analysis is given in synthetic order starting with the first claimed step (instant claim 5, defined species synthesis in claim 21). For the benefit of Applicant, a Table summary follows.
PNG
media_image4.png
142
1234
media_image4.png
Greyscale
Regarding claims 5, 16, 21 and VII to VI, Angapelly teaches the conversion of (2E)-3-(4-chlorophenyl)prop-2-enoic acid (Angapelly Compound 2e, reads on instant claim 21) to (2E)-3-(4-chlorophenyl)prop-2-enoyl chloride (Angapelly Compound 3e, reads on instant claim 21) in SOCl2 and dichloromethane (see Angapelly at p. 5728 Table 1, p. 5727 right col. ¶3, and at p. 5728 Scheme 1).
Regarding claim 4, 21 and VI to V, Tazi teaches the synthesis of a compound of Formula XI (corresponding with instant Formula V) from compounds of Formula IX (corresponding with instant Formula VI’) and Formula X (corresponding with instant Formula VI) (see Tazi at p. 23 Scheme 3).
PNG
media_image4.png
142
1234
media_image4.png
Greyscale
Regarding claims 3, 18 and V to IV, Tazi teaches the synthesis of a compound of Formula XII (corresponding with instant Formula IV) from a compound of Formula XI (corresponding with instant Formula V) (see Tazi at p. 23 Scheme 3) in chlorobenzene in the presence of aluminum trichloride (see Tazi at p. 23 ¶[0055]).
Regarding claims 2, 19 and IV to II, Tazi teaches the synthesis of a compound of Formula IV (corresponding with instant Formula II) from a compound of Formula XII (corresponding with instant Formula IV) (see Tazi Scheme 3 at p. 23) in an aprotic solvent such as acetonitrile in presence of POCl3 (see Tazi p. 23 ¶[0056]).
Instant Claim
Synthetic Scheme
Prior Art
2
PNG
media_image5.png
134
316
media_image5.png
Greyscale
PNG
media_image6.png
320
168
media_image6.png
Greyscale
Tazi Scheme 3 at p. 23
19
wherein the chlorination step (claim 2) is carried out using SOCl2, PCl3, POCl3, or PCl5 and optionally a solvent
Compound of Formula XII can be placed in an aprotic solvent such as acetonitrile in presence of POCl3
Tazi p. 23 ¶[0056]
3
PNG
media_image7.png
142
426
media_image7.png
Greyscale
PNG
media_image8.png
300
220
media_image8.png
Greyscale
Tazi Scheme 3 at p. 23
18
wherein cyclization (of claim 5) is carried out using:
-chlorobenzene, trifluorotoluene, fluorobenzene, toluene, dichloroethane, or a mix
-lewis acid AlCl3, BF3, trifluoromethanesulfonic acid, titanium chloride, methanesulfonic acid
Compound XI can be placed in an aprotic solvent such as chlorobenzene in the presence of aluminum trichloride
Tazi at p. 23 ¶[0055]
4
PNG
media_image9.png
176
528
media_image9.png
Greyscale
PNG
media_image10.png
158
538
media_image10.png
Greyscale
Tazi Scheme 3 at p. 23
5
PNG
media_image11.png
128
444
media_image11.png
Greyscale
PNG
media_image12.png
76
306
media_image12.png
Greyscale
Angapelly at p. 5728 Scheme 1
16
wherein the chlorination step (claim 2) is carried out using SOCl2, PCl3, POCl3, or PCl5 and optionally solvent
cinnamic acids 2a-p were converted to the corresponding
cinnamoyl chlorides 3a-p by using SOCl2
reaction scheme shows carried out in dichloromethane as solvent
Angapelly at
p. 5727 right col. ¶3 and at p. 5728 Scheme 1
21
PNG
media_image4.png
142
1234
media_image4.png
Greyscale
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2143(I)(A), a prima facie case of obviousness exists for combining prior art elements according to known methods to yield predictable results. It would have been obvious to form the starting materials required by the Rabe/Bunnett synthesis of 8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine by the methods taught by Tazi with an expectation of success because Tazi teaches the necessary synthetic steps to arrive at structurally similar compounds for the same purpose as Rabe (e.g. treating HIV with substituted phenylquinolinamines). Likewise, it would have been obvious to form the starting materials of Tazi with the synthetic method of Angapelly with an expectation of success because Angapelly teaches the synthetic step to arrive at the starting material (2E)-3-(4-chlorophenyl)prop-2-enoyl chloride necessary for the total synthesis of 8-chloro-quinolin-2-yl)-(4-trifluoromethoxyphenyl)-amine as taught by Tazi, Rabe, and Bunnett.
Furthermore, it is well-within the ordinary skill in art to retrosynthetically identify necessary reactants required to achieve a known product according to known reaction steps.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Conclusion
Claims 1-5, 7-10, 13, 15-16, 18-26, 29, 32 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, KORTNEY KLINKEL can be reached at 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Friedlander et. al. "310. Paul Friedlander und Arthur Weinberg: Zur Kenntnies dee Carbostyrile." Chem Bar. 1885, 18, 1528-1533. Hereinafter Friedlander.
2 Machine Translation of select pages of Friedlander et. al. Chem Bar. 1885, 18, 1528-1533, Translated by Google Translate Images on 2/26/26, 2 pages. Hereinafter Google Translate.
3 Mohrig et. al. "Techniques in Organic Chemistry" 3rd Ed; W. H. Freeman and Company: New York, NY. 2010. Select Pages. Hereinafter Mohrig.
4 Published September 21, 2017. Cite No. 2 in the IDS filed 9/26/23.
5 Bunnett, J. "Mechanism and reactivity in aromatic nucleophilic substitution reactions." Quarterly Reviews, 1958, 12, 1-16. DOI: 10.1039/QR9581200001. Hereinafter Bunnett.
6 Mettler Toledo "Interpreting DSC curves". UserCom Manual. January 2000 pp 1-28.
7 Olusanmi et. al. "A control strategy for bioavailability enhancement by size reduction: Effect of micronization conditions on the bulk, surface and blending characteristics of an active pharmaceutical ingredient" Powder Technology, 2014, 258, 222-233. DOI: 10.1016/j.powtec.2014.03.032. Hereinafter Olunsami.
8 Remington's Pharmaceutical Sciences (21st Ed) New York, NY: Lippincott Williams and Wilkins 2005. Select pages. Hereinafter Remington.
9 Published June 20, 2012. Hereinafter Tazi.
10 Angapelly et. al. "Development of sulfonamides incorporating phenylacrylamido functionalities as carbonic anhydrase isoforms" Bioorganic and Medicinal Chemistry 2017, 25, 20, 5726-5732. DOI: 10.1016/j.bmc.2017.08.047. NPL Cite No. 2 in the IDS filed 9/26/23. Hereinafter Angapelly.