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 .
DETAILED ACTION
Claims 1-25 are pending in the instant application.
Claims 4-17, 19-21, and 23-25 are amended.
Claims 1-25 are examined herein.
Priority
The instant application claims benefit of priority to U.S. Provisional Application No. 63/231,061, filed on 09 August 2021 and PCT/US2022/174621, filed on 05 August 2022. The claims to the benefit of priority are acknowledged. As such, the effective filing date of the claims is 09 August 2021.
Information Disclosure Statement
The information disclosure statements (IDS), submitted on 29 October 2024, 11 June 2025, and 15 June 2026, are acknowledged and considered. The submissions are in compliance with the provisions of 37 CFR 1.97.
Response to Arguments
The amendment filed on 15 June 2026 has been entered.
In view of applicant amendment to claims 4-17, 19-21, and 23-25, the objection of record is withdrawn.
In view of applicant amendment to claims 24 and 25, the 112(a)-enablement rejection of record is withdrawn.
In view of applicant amendment to claim 25, the 112(b) rejection of record is withdrawn.
In view of applicant arguments, the 102 rejection of record is withdrawn, as Van Leyen does not present a preferred embodiment.
With respect to the 103 rejections, Applicant amendment has been considered but is not found persuasive for at least the following reasons. Applicant argues that Patani does not guide the skilled artisan to the exact substitution pattern of the trisubstituted phenyl of the instant application. Van Leyen supports the substitution of R1 and R2, leaving 3 carbons for an additional chlorine substituent. It would be routine optimization to place an additional chloro group on one of the three remaining carbons from Van Leyen’s compound 7. Creating three different iterations would not be unexpected, especially in lead optimization. Compound 7 of Van Leyen, provides the second highest IC50 value of the 18 compounds tested (Table 1). The skilled artisan would be guided to this compound and motivated to substitute one of the unsubstituted hydrogens with chlorine, based on the teachings of Patani to inhibit metabolism of the compound as Van Leyen reports moderate and low metabolic stability of compound 7. Additionally, from the teachings of Patani, not only is chlorine shown to improve metabolic stability, it can also improve IC50 values as seen in Table 12. So the greater inhibitory effect of the reference compound is not unexpected. Additionally, structurally similar compounds are expected to have similar properties. The only difference between compound 7 of Van Leyen and the first instant compound of claim 22 is a hydrogen versus a chlorine in the ortho position. Van Leyen presents preferred embodiments of R11 in paragraph [00151] including 2,3-dichloro phenyl and 3-chloro phenyl, this would guide the skilled artisan to choosing the ortho position relative to the ring position for a chlorine substituent. For these reasons the rejection is maintained. The rejection has been modified to incorporate the 102 rejection that was referenced.
Regarding the double patenting rejections, these rejections are maintained for the reasons outlined above,
All rejections and objections not found below have been withdrawn.
MAINTAINED REJECTIONS
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claim(s) 1-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Van Leyen et al (WO2015027146A1; cited by applicant on 1449 IDS) in view of Patani et al. (Chemical Reviews. 1996;96(8):3147-3176; cited by Applicant on 1449 IDS).
Regarding claims 1-3 and 22, Van Leyen discloses compounds of Formula (I) (paragraph [0010]). This formula overlaps with the instant Formula (I) when:
X is O or S
R11 is optionally substituted aryl
R12 is hydrogen, C1-3- alkyl, or acyl
R13 is C1-6 alkyl, C1-6 alkenyl, C1-6 alkynyl, or acyl
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Van Leyen does not teach one of the preferred embodiments of the instant claims. Van Leyen teaches compound 7 (pictured below) (paragraph [0059]), which is the first recited compound of claim 22 without the third chloro substituent at carbon 5.
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Patani discloses substitution of hydrogen for chlorine to inhibit metabolic oxidation (page 3145, paragraph 3).
It would be prima facie obvious to one of ordinary skill in the art to substitute a hydrogen atom for a chlorine atom to prevent metabolism of the compound. Van Leyen discloses moderate stability to rat liver microsomes and lower stability to mouse live microsomes (paragraph 00203]). One skilled in the art would be motivated to inhibiting metabolism of the reference compounds and would be guided by the work of Patani to substitute a hydrogen atom with a chlorine atom.
Regarding claim 4, Van Leyen discloses R11 can be aryl, optionally substituted. This is defined in paragraph [00152], “Aryl and heteroaryls can be optionally substituted with one or more substituents at one or more positions, for example, halogen, alkyl…” This encompasses the instant limitation of R1, R2, and R3 being halo.
Regarding claim 5, Van Leyen discloses R11 can be aryl, optionally substituted. This is defined in paragraph [00152], “Aryl and heteroaryls can be optionally substituted with one or more substituents at one or more positions, for example, halogen, alkyl…” This encompasses the instant limitation of R2 and R3 being halo, and R1 being C1-3- alkyl.
Regarding claim 6, Van Leyen discloses R11 can be aryl, optionally substituted. This is defined in paragraph [00152], “Aryl and heteroaryls can be optionally substituted with one or more substituents at one or more positions, for example, halogen, alkyl…” This encompasses the instant limitation of R1 and R3 being halo, and R2 being C1-3- alkyl.
Regarding claim 7, Van Leyen discloses R11 can be aryl, optionally substituted. This is defined in paragraph [00152], “Aryl and heteroaryls can be optionally substituted with one or more substituents at one or more positions, for example, halogen, alkyl…” This encompasses the instant limitation of R1 and R2 being halo, and R3 being C1-3- alkyl.
Regarding claim 8, the reference Formula (I) teaches the instant formula (pictured below) when the reference X is O; R11 is phenyl substituted with 3 chloro groups; R12 is hydrogen, C1-3- alkyl, or acyl; and R13 is C1-6 alkyl, C1-6 alkenyl, C1-6 alkynyl, or acyl.
Regarding claim 9, Van Leyen discloses R13, which corresponds to the instant R5, can be alkyl (paragraph [0010]).
Regarding claim 10, Van Leyen discloses R13, which corresponds to the instant R5, can be alkenyl (paragraph [0010]).
Regarding claim 11, Van Leyen discloses R13, which corresponds to the instant R5, can be alkynyl (paragraph [0010]).
Regarding claim 12, Van Leyen discloses R13, which corresponds to the instant R5, can be alkyl, optionally substituted (paragraph [0010]). Paragraph [00144] defines substituents of a substituted alkyl which includes ethers.
Regarding claim 13, Van Leyen discloses R13, which corresponds to the instant R5, can be alkyl, optionally substituted (paragraph [0010]). Paragraph [00144] defines substituents of a substituted alkyl which includes phosphoryl groups.
Regarding claims 14 and 15, Ra1 corresponds to the substitution of the instant R5. R5 can be substituted with “halogen, hydroxy, nitro, thiols, amino, azido, imino, amido, phosphoryl (including phosphonate and phosphinate), sulfonyl (including sulfate, sulfonamide, sulfamoyl and sulfonate), and silyl groups, as well as ethers, alkylthios, carbonyls (including ketones, aldehydes, carboxylases, and esters),-CF3, -CN and the like” (paragraph [00144]), which encompasses Ra1 being H or C1-6 alkyl.
Regarding claim 16, Van Leyen discloses R12, which corresponds to the instant R4, can be H (paragraph [0010]).
Regarding claims 17-19, Van Leyen discloses R13, which corresponds to the instant R5, can be acyl (paragraph [0010]). This encompasses the instant C(O)ORa1 wherein Ra1 is C1-6 alkyl and C(O)Rb1.
Regarding claim 20, Van Leyen discloses R12, which corresponds to the instant R4, can be H or alkyl, and R13, which corresponds to the instant R5, can be alkyl, alkenyl, or alkynyl, optionally substituted with ether or phosphoryl.
Regarding claim 21, Van Leyen discloses R12, which corresponds to the instant R4, can be acyl, and R13, which corresponds to the instant R5, can be alkyl.
Regarding claim 23, Van Leyen discloses pharmaceutical compositions of Formula (I) comprising a pharmaceutically acceptable carrier (paragraph [0062]).
Regarding claim 24, Van Leyen discloses a method of treating a condition involving 12/15-LOX comprising administering a compound of Formula (I) (clam 1).
Regarding claim 25, Van Leyen discloses the conditions to be stroke, periventricular leukomalacia, cardiac arrest with resuscitation, atherosclerosis, Parkinson's disease, Alzheimer's disease, or breast cancer (claim 15) as well as diseases involving apoptosis in cancer cells such as prostatic cancer, gastric cancer, breast cancer, pancreatic cancer, colorectal or esophageal cancer and airways carcinoma; diseases involving hypoxia, or anoxia such as atherosclerosis, myocardial infarction, cardiovascular disease, heart failure (including chronic and congestive heart failure), cerebral ischemia, retinal ischemia, myocardial ischemia, post-surgical cognitive dysfunction and other ischemias; diseases involving inflammation, including diabetes, arterial inflammation, inflammatory bowel disease, Crohn's disease, renal disease, pre-menstrual syndrome, asthma, allergic rhinitis, gout; cardiopulmonary inflammation, rheumatoid arthritis, osteoarthritis, muscle fatigue and inflammatory disorders of the skin including acne, dermatitis and psoriasis; disorders of the airways such as asthma, chronic bronchitis, human airway carcinomas, mucus hypersecretion, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis caused by chemotherapy or other drugs, idiopathic pulmonary fibrosis, cystic fibrosis, and adult respiratory distress syndrome; diseases involving central nervous system (CNS) disorders including psychiatric disorders including anxiety and depression; neurodegeneration and neuro inflammation including Alzheimer's, dementia, and Parkinson's disease; peripheral neuropathy including spinal cord injury, head injury and surgical trauma, and allograft tissue and organ transplant rejection; diseases involving the autoimmune system such as psoriasis, eczema, rheumatoid arthritis, and diabetes; and disorders involving bone loss or bone formation (paragraph [00108]).
Claim(s) 1-4, 8-9, 16, 22, and 24-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rai et al. (J Med Chem. 2014;57(10):4035–4048; cited by applicant on 1449 IDS) in view of Patani et al. (Chemical Reviews. 1996;96(8):3147-3176).
Regarding claims 1, 2, 8 and 22, Rai discloses compound 7 (Table 1) (pictured below), an inhibitor of 12/15-LOX. This is a species of the instant compound when X1 is O; R1 is chloro; R2 is chloro; R4 is H; and R5 is methyl.
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Rai does not teach R3 to be chlorine, but hydrogen.
Patani discloses substitution of hydrogen for chlorine to inhibit metabolic oxidation (page 3145, paragraph 3).
It would be prima facie obvious to one of ordinary skill in the art to substitute a hydrogen atom for a chlorine atom to prevent metabolism of the compound. Rai discloses moderate stability to rat liver microsomes and lower stability to mouse live microsomes (paragraph 00203]). One skilled in the art would be motivated to inhibiting metabolism of the reference compounds and would be guided by the work of Patani to substitute a hydrogen atom with a chlorine atom.
Regarding claim 3, Rai does not teach a thiazole, but an oxazole.
Patani teaches that oxazole and thiazole are bioisosteres (page 3159, paragraph 3).
It would be prima facie obvious to one of ordinary skill in the art to substitute a thiazole ring for an oxazole knowing they are bioisosteres and would be expected to exhibit the same properties. The skilled artisan would be motivated to make the substitution as a thiazole ring would lower basicity and potentially increase permeability.
Regarding claim 4, Rai teaches R1 and R2 to be chlorine. The teachings of Patani would lead the skilled artisan to substituting carbon 5 with chlorine corresponding to the instant R3 being chlorine.
Regarding claim 9, Rai teaches the substituent corresponding to the instant R5 is C1 alkyl.
Regarding claim 16, Rai teaches the substituent corresponding to the instant R4 is H.
Regarding claims 24 and 25, Rai teaches the method of treating stroke by administering a 12/15-LOX inhibitor.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 24 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 15 of U.S. Patent No. 10287279B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 24, the patent discloses a method of treating a condition involving 12/15-LOX comprising administering an effective amount of a compound of Formula (I) (pictured below) where X is O or S; R11 is optionally substituted aryl; R12 is H or alky; and R13 is alkyl, alkenyl, alkynyl, or acyl (claim 1).
Regarding claim 25, the patent discloses a method of treating stroke, periventricular leukomalacia, cardiac arrest with resuscitation, atherosclerosis, Parkinson's disease, Alzheimer's disease, or breast cancer (claim 15).
Claims 1-4, 8-9, 16, and 22 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 18 of U.S. Patent No. 10287279B2 in view of Patani et al (cited above). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1, 2, 8 and 22, the patent discloses compound 7 (claim 18) (pictured below), a species of the instant compound when X1 is O; R1 is chloro; R2 is chloro; R4 is H; and R5 is methyl.
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The patent does not teach R3 to be chlorine, but hydrogen.
Patani discloses substitution of hydrogen for chlorine to inhibit metabolic oxidation (page 3145, paragraph 3).
It would be prima facie obvious to one of ordinary skill in the art to substitute a hydrogen atom for a chlorine atom to prevent metabolism of the compound. One skilled in the art would be motivated to inhibiting metabolism of the reference compounds and would be guided by the work of Patani to substitute a hydrogen atom with a chlorine atom.
Regarding claim 3, the patent does not teach a thiazole moiety in compound 7, but an oxazole.
Patani teaches that oxazole and thiazole are bioisosteres (page 3159, paragraph 3).
It would be prima facie obvious to one of ordinary skill in the art to substitute a thiazole ring for an oxazole knowing they are bioisosteres and would be expected to exhibit the same properties. The skilled artisan would be motivated to make the substitution as a thiazole ring would lower basicity and potentially increase permeability.
Regarding claim 4, the patent teaches R1 and R2 of compound 7 to be chlorine. The teachings of Patani would lead the skilled artisan to substituting carbon 5 with chlorine corresponding to the instant R3 being chlorine.
Regarding claim 9, the patent teaches the substituent of compound 7 corresponding to the instant R5 is C1 alkyl.
Regarding claim 16, the patent teaches the substituent of compound 7 corresponding to the instant R4 is H.
Conclusion
Claims 1-25 are rejected.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jerica K Wilson whose telephone number is (703)756-4690. The examiner can normally be reached Monday-Friday 9:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.K.W./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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