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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/27/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
Claims 1-16 are pending in this application.
Claim Objections
Claim 15 is objected to because the acronym “TNBC” is not defined in the claims.
Appropriate correction is required.
Claims 7 and 9-10 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Examiner Notes
Claim 8 is also free of the prior art, but stands rejected over formal matters herein.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-4, 8, and 11-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 states:
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It is unclear how R2 can be absent in the groups where it appears. Does applicant intend R2 is absent in embodiments where it is supposed to be H? – if so, this is redundant and should be deleted, since R2 is already defined as being H. Or does applicant intend when R2 is absent it can be any other group not listed in the definition of R2? – for the purposes of applying art, it will be assumed Applicant intended when R2 is absent R2 is to be understood as being H.
Claims 3-4 and 11-16 are rejected for depending upon the limitations of claim 1 without remedying its deficiencies.
Claim 8 is indefinite because, as stated in MPEP 2173.05(s), claims should be complete to themselves and the reference to figures or tables renders the claims incomplete. Claims which recite figures or tables are only permitted in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into a claim.
Claim 14 recites the limitation "the cancer". There is insufficient antecedent basis for this limitation in the claim, or in claim 12 (which refers to “a disease”) from which it depends.
Claim 16 recites the limitation "the cancer". There is insufficient antecedent basis for this limitation in the claim, or in claim 15 (which refers to “TNBC breast cancer”) from which it depends.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2-6, 8, and 16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 is rejected for failing to further limit claim 1, from which it depends. Claim 1 is drawn to the compounds of Formula I, wherein Ar can be
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(2-substituted pyridine). However, claim 2 expands this limitation to encompass compounds wherein substitution with R2 can occur in other positions.
Claims 3-6 are rejected for depending upon the limitations of claim 2.
Claim 8 is rejected for failing to further limit claim 2, from which it depends. Claim 2 is drawn to the compounds of Formula II; however, claim 8 expands this limitation to encompass the compounds below, for example, which are not embraced by general formula II:
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Regarding compounds 13 and 20 above, Formula II is limited to only 1 R1 group, while these have 2 or 3 R1 groups. Thus, these compounds are not encompassed by Formula II.
Claim 16 is rejected for failing to further limit claim 15, from which it depends. Claim 15 is drawn to a method of treating TNBC breast cancer, however, claim 16 is drawn to a method of treating prostate cancer, which is not a TNBC breast cancer.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS 756436-14-3 CAS Registry File Accessed 07/13/2026 from STN, entered into STN 10/03/2004.
Regarding instant claim 1, the compound below anticipates the instant claims when Ar is
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; R2 is H; and R1 is -CF3.
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Claims 1 and 11-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Elkhalifa et al. (Eur. J. Med. Chem., 2020, 187, 111954 – cited in the IDS) (“Elkhalifa”).
Regarding claim 1, Elkhalifa discloses the compounds 12 and 14 below, which anticipate the instant claims when instant Ar is
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and R1 is 2/ 3-OMe.
Regarding claim 11, Elkhalifa discloses administration of compound 14 intraperitoneally in vehicle (DMSO) – thus anticipating a pharmaceutical composition comprising the instant compounds and a carrier.
Regarding claims 12-15, Elkhalifa discloses intraperitoneal administration of compound 14 to mice for the treatment of TNBC (page 9, col. 1).
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Claims 2-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lounsbury et al. (Bioorganic & Medicinal Chemistry 23 (2015) 5352–5359) (“Lounsbury”).
Claim 2 is broader than claim 1 – see 112(d). Thus, as it pertains to the scope of claim 2 not encompassed by claim 1, specifically regarding the position of group R2 on the pyridine ring, these rejections apply.
Regarding claims 2-4, Lounsbury discloses the compounds 8d-e below, which anticipate the instant compounds of Formula II when: R2 is -CF3 or -OMe and R1 is -CF3 (anticipating claim 4) or -OMe (anticipating claim 3).
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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.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Elkhalifa et al. (Eur. J. Med. Chem., 2020, 187, 111954 – cited in the IDS) (“Elkhalifa”); as applied to claims 1 and 11-15; in view of Szliszka et al. (Molecules 2010, 15, 5336-5353) (“Szliszka”).
The teachings of Elkhalifa are disclosed in the 102-section above and incorporated herein.
While Elkhalifa does not teach treatment of prostate cancer, the teachings of Szliszka are relied upon for these teachings.
Szliszka teaches that chalcone C1 (Fig. 1, page 5338) markedly augmented TRAIL-induced apoptosis and cytotoxicity in LNCaP (pancreatic cancer) cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer (abstract).
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Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Elkhalifa’s chalcone derivative 14 for the treatment of prostate cancer, in view of Szliszka. One of ordinary skill would have been motivated to do so because Elkhalifa teaches chalcone derivative 14 and pharmaceutical compositions thereof being administered for the treatment of breast cancer; further because Szliszka discloses chalcone C1 markedly augmented TRAIL-induced apoptosis and cytotoxicity in LNCaP (pancreatic cancer) cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer. A person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2143(E) KSR,550 U.S. at 421, 82 USPQ2d at 1397.
Applicant is advised, similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP 2144.08(d)).
Claims 1-4 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Lounsbury et al. (Bioorganic & Medicinal Chemistry 23 (2015) 5352–5359) (“Lounsbury”).
Regarding claims 1-4, Lounsbury discloses the compounds 8d-e below as Nrf2 activators for the treatment of inflammatory conditions, such as cancer (abstract; and page 5352, col. 1, para. 1) – which is the same intended use as the instant application. Lounsbury’s compounds render the instant compounds of Formula I obvious when: Ar is
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; R2 is -CF3 or -OMe; and R1 is -CF3 or -OMe.
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While Lounsbury’s compounds 8d-e have the group corresponding to instant R2 on a different position of the pyridine ring; Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1950). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950). The requisite motivation for arriving at the claimed compounds stems from the fact that they are positional isomers of the generic class of Nrf2 activator compounds disclosed by Lounsbury as useful for the treatment of inflammatory conditions, such as cancer. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Regarding claim 11, Lounsbury discloses their compounds in a phosphate buffer (see Table 2, page 5354).
Regarding claim 12, Lounsbury discloses administration of their compound 8d to mice (page 5356, col. 1, last para.). Therefore, it would have been prima facie obvious to one of ordinary skill to administer the instant compounds, which are isomeric with Lounsbury’s compounds and therefore obvious, for the treatment of inflammatory diseases with a reasonable expectation of success, as described by Lounsbury.
Claims 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Lounsbury et al. (Bioorganic & Medicinal Chemistry 23 (2015) 5352–5359) (“Lounsbury”); as applied to claims 1-4 and 11-12; in view of Stern et al. (JCI Insight. 2022; 7(12):e153868) (“Stern”).
The teachings of Lounsbury are disclosed above and incorporated herein.
Lounsbury discloses the compounds 8d-e below as Nrf2 activators for the treatment of inflammatory conditions, such as cancer (abstract; and page 5352, col. 1, para. 1).
While Lounsbury does not specifically teach treatment of TNBC, the teachings of Stern are relied upon for these disclosures.
Stern teaches Cyclophosphamide (CPA) and doxorubicin (DOX) are key components of chemotherapy for triple negative breast cancer (TNBC), although suboptimal outcomes are commonly associated with drug resistance and/or intolerable side effects (abstract). Stern teaches Nrf2-antioxidant signaling represses DOX-induced cytotoxicity in cardiomyocytes. Stern teaches CAR and Nrf2 as potentially novel combined therapeutic targets to improve the efficacy/toxicity ratio of CPA/DOX-containing chemotherapy in TNBC (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Lounsbury Nrf2 activators for the treatment of TNBC in view of Stern. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Lounsbury discloses their Nrf2 activators 8d-e as effective for the treatment of inflammatory conditions, such as cancer; further because Stern teaches DOX as a key component of TNBC treatment, which shows serious side effects including cytotoxicity in cardiomyocytes, and teaches that Nrf2-antioxidant signaling represses DOX-induced cytotoxicity. Thus, one of ordinary skill would have been motivated to, with a reasonable expectation of success, administer Lounsbury’s Nrf2 activators in a combination therapy comprising DOX for the treatment of TNBC.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Lounsbury et al. (Bioorganic & Medicinal Chemistry 23 (2015) 5352–5359) (“Lounsbury”); as applied to claims 1-4 and 11-12; in view of Khurana et al. (Obtained from urotoday.com [retrieved on 08/07/2026] <URL:https://www.urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/109460-targeting-crosstalk-between-nrf-2-nf-b-and-androgen-receptor-signaling-in-prostate-cancer-beyond-the-abstract.html> - Pub Date: Jan. 23, 2019) (“Khurana”).
The teachings of Lounsbury are disclosed above and incorporated herein.
Lounsbury discloses the compounds 8d-e below as Nrf2 activators for the treatment of inflammatory conditions, such as cancer (abstract; and page 5352, col. 1, para. 1).
While Lounsbury does not specifically teach treatment of prostate cancer, the teachings of Khurana are relied upon for these disclosures.
Khurana teaches Nrf2 is a nuclear transcription factor which gets activated in response to oxidative stress and controls the basal as well as inducible expression of several antioxidant and detoxification enzymes and is indeed the most critical defense pathway used by cells against oxidative stress. Nrf2 has been shown to inhibit the growth as well as the migration of prostate cancer (PCa) cells by upregulating ferroportin (para. 3). Khurana teaches the anti-cancer efficacy of phytochemicals like sulforaphane and curcumin in PCa is majorly attributed to the activation of Nrf-2, thus highlighting the importance of Nrf2 activation for the treatment of Pca (conclusion).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Lounsbury Nrf2 activators for the treatment of PCa in view of Khurana. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Lounsbury discloses their Nrf2 activators 8d-e as effective for the treatment of inflammatory conditions, such as cancer; further because Khurana teaches the anti-cancer efficacy of phytochemicals like sulforaphane and curcumin in PCa is majorly attributed to the activation of Nrf-2, and that Nrf2 has been shown to inhibit the growth as well as the migration of PCa cells by upregulating ferroportin.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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