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 1-16, 19, 21-27 are pending in the instant application.
Claims 14 and 25 are amended.
Claims 2, 4, 7, 11, 12, 21, and 22 are withdrawn from consideration.
Claims 1, 3, 5, 6, 8-10, 13-16, 19, 20, and 23-27 are examined herein.
Priority
The instant application claims no benefit of priority. As such, the effective filing date of the claims is 31 December 2021.
Information Disclosure Statement
The information disclosure statements (IDS), submitted on 13 October 2023, 13 October 2023, 13 October 2023, 13 November 2023, 22 July 2024, 30 August 2024, 03 October 2024, 17 January 2024, 20 February 2025, 27 March 2025, 17 April 2025, 06 June 2025, 18 July 2025, 22 August 2025, 17 October 2025, and 28 November 2025 are acknowledged and considered. The submissions are in compliance with the provisions of 37 CFR 1.97.
Response to Arguments
The amendment filed on 23 December 2025 has been entered.
Examiner notes the Applicant is aware the Office will remove the word “novel” from the title should the claims be allowed and does not object to the removal. Therefore the formal objection is withdrawn.
In view of applicant amendment to claim 25, the objection of record is withdrawn as dependency has been amended to claim 6.
In view of applicant amendment to claim 14, the 112(b) rejection of record is withdrawn.
With respect to the 112(a)-written description rejection, Applicant amendment has been considered but is not found persuasive for at least the following reasons. Applicant argues selective quotes were pulled from The Regents of the University of California v. Eli Lilly and Company, 119 F.3d 1559 (Fed. Cir. 1997) (i.e., Lilly) and without context the Examiner’s position of a lack of written description is inadequate. As Lilly pertains to genetic material where no structural formula was presented, and the instant invention does not contain genetic material with a structural formula Applicant argues the generic formula is likely to possess adequate description. The Examiner is not arguing that the bounds of the structural formula are not defined, but due to the lack of a representative number of species tested for their utility of treating a viral disease, the bounds of the structural formula that can be used in the method as claimed is unknown. The Applicant is not claiming a genus of FAB4 inhibitors but a method of treating a viral disease with a genus of FAB4 inhibitors. The skilled artisan can clearly see the bounds of the chemical formula, but that is not what is being claimed. The claims are directed to treating a viral disease, and this method is not adequately described as only a small subset of the genus has been tested. The Applicant presents a long list of possible substituents and only demonstrates a select few across all the tested compounds. This is not a representative number of species. And making 110 compounds is not reduction to practice. The claims are not for the method of making the compounds of Formula (I). Applicant notes that the 18 compounds tested showed superior efficacy relative to the control, the Examiner is not arguing against this, but when the tested compounds only reflect a small subset of the genus the skilled artisan cannot determine the scope of the structure-function relationship. For example. Every tested compound recites R1 as aryl, yet R1 could be one of eighteen different categories of substituents. Without evidence to the contrary, this would imply that the aryl group, and more specifically a six-membered aryl group, is crucial to the structure-function relationship and the skilled artisan would be hesitant to believe substitution of that R1 group with hydrogen would meet the limitation of the claims. Therefore the rejection is maintained.
With respect to the 103 rejection, Applicant amendment has been considered but is not found persuasive for at least the following reasons. The Applicant argues stating that Hertzel teaches leukotriene A4 (LTA4) binds to FAB4 is an oversimplification of the teaching. That Hertzel teaches a complicated biological pathway. The Examiner agrees, Hertzel does teach more than the fact that LTA4 binds to FAB4, but this is taught. The Applicant additionally argues that Hertzel does not actually teach the binding of LTA4, but the stabilization of the ligand by FAB4 and that this does not necessarily mean binding. The Examiner respectfully disagrees, the stabilization of a ligand by a protein requires binding and Hertzel states on page 1355, paragraph 3, that FAB4 binds the unstable epoxide forming LTA4. The Applicant further argues that even if Hertzel teaches the binding of LTA4 by FAB4 that Hertzel does not teach where the ligand binds, and that allosteric binding could be taking place. As the Examiner has set forth a prima facie case, it is the Applicant’s burden to prove that Hertzel does not teach binding at the same site as the instant invention. See MPEP 2184. Therefore the rejection is maintained.
All rejections and objections not found below have been withdrawn.
Response to Election/Restrictions
Regarding the election/restriction, Applicant argues that the art is not relevant and the restriction requirement should be lifted. For the reasons stated above the art is relevant and the requirement is still deemed proper and is therefore made FINAL.
MAINTAINED REJECTIONS
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3, 5, 6, 8-10, 13, 14, 16, 19, 20, and 23-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is directed to a method of treating a viral disease in a subject comprising administering a compound of Formula (I), wherein the viral disease is coronavirus or severe acute respiratory syndrome (SARS). See MPEP 2163 II. A. 3. (a) (ii) with regards to the requirements for descriptive support and for functional limitations of generically described entities:
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”
“A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.”
The Applicant provides 110 preferred embodiments with spectral data, but only discloses the antiviral activity of 18 compounds. Of these 18 compounds (pictured above), Q is a bond in 17 compounds; R1 is phenyl in 17 compounds; A is always aryl; R2 is always H; R3 is C3-C8 alkyl in 17 compounds; R4 is H in 17 compounds; R5 is always H; R6 is C1 alkyl in 15 compounds; R7 is H in 13 compounds; R8 is H in 16 compounds; R9 is always COOH. This is a not a representative number of examples based on the genus claimed. The Applicant has described large classes of substituents for R1-9, the acid isosteres alone comprise 21 substituents, but a vast majority are not represented. He et al. (European Journal of Medicinal Chemistry. 2021;224:113720) demonstrate the change in FABP4 inhibitory activity when the substituents are not as varied as the instant invention. One skilled in the art would be hesitant to expect such a large genus would share the same utility.
Failure to depict the antiviral activity of a representative number of species, through relationship of structure and function, which would provide an overall depiction of the claimed subject matter, suggests the applicant is not in possession of the claimed invention. While the applicant provides spectral data for 110 compounds demonstrating possession of a larger number of compounds, the invention is the method of treating comprising administering the compounds, and the Applicant has not demonstrated the shared utility of the genus with a representative number of species.
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.
Claims 1, 3, 5, 6, 8-10, 13, 14, 15, 20, and 23-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Koyuncu et al (WO2021150645A1) in view of Hertzel et al. (Journal of Lipid Research. 2017;58:1354-1361) and Funk et al. (Front. Pharamcol. 2020:11:1-8).
Regarding claim 1, 6 and 8, Koyuncu discloses a method of treating a disease by inhibiting fatty acid binding protein 4 (FABP4) comprising administering a compound of Formula I, II, or III (pictured below, top row) (claim 22). Reference Formulas I and II are the same as the instant Formulas I and II (pictured below, bottom row). The reference Formula III encompasses the instant Formula IIIA (pictured below, bottom row) when the instant R1 is aryl or heteroaryl.
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Koyuncu fails to teach the FABP4 inhibitors as antiviral agents.
Hertzel teaches that FABP4 binds to leukotriene A4 (LTA4), which stabilizes it from degradation and stimulates the synthesis of other leukotrienes (LTs). Hertzel also demonstrates a reduction in leukotriene B4 (LTB4) in FABP4 knockout mice (Discussion, pages 1357-1369)).
Hertzel fails to teach leukotriene inhibition as a therapeutic target for viral infections.
Funk teaches the role of leukotrienes in COVID-19 pathogenesis and the elevated levels of LTs in those infected. Funk explains that production of all LTs need to be blocked to effectively reduce the fatal inflammatory response (page 5).
In KSR International Vo. V. Teleflex Inc., 82 USPQ2d (U.S. 2007), the Supreme Court particularly emphasized “the need for caution in granting a patent based on a combination of elements found in the prior art,” (Id. At 1395) and discussed circumstances in which a patent might be determined to be obvious.
In this case at least prong B of KSR applies – substitution of one known element for another. Koyuncu teaches FABP4 inhibitors, Hertzel teaches the role of FABP4 in the stabilization of the precursor, LTA4, of all other LTs and Funk teaches the method of blocking production of all LTs to treat COVID-19. It would be obvious to one of ordinary skill in the art, based on the teachings of Hertzel and Funk, that inhibiting FABP4 to inhibit production of all leukotrienes would be a therapeutic strategy for COVID-19. And in the efforts to repurpose developed inhibitors to hasten the search for an effective treatment strategy, the skilled artisan would be guided to the FABP4 inhibitors taught by Koyuncu.
Thus, all of the elements of claims were known to one of ordinary skill in the art at the time the invention was made and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art at the time of invention. Therefore, the claimed invention, as a whole, would have been obvious to one of ordinary skill in that art at the time the invention was made.
Regarding claim 3, Koyuncu discloses R3 is a Cn alkyl, wherein n is between 3-8 (claim 3).
Regarding claim 5, Koyuncu discloses the method where Q is a bond or O; X is C, N, or O; R1 is an optionally substituted phenyl; R2 and R5 are H; R4 is H, halo, or hexyl; and R3 is an optionally substituted C1-10 alkyl, hexene, halo, H, or phenylethylene (claim 1).
Regarding claim 9, Koyuncu discloses the method wherein X is N (claim 9).
Regarding claim 10, Koyuncu discloses the method wherein R6 is H and X is N (claim 10).
Regarding claim 13, Koyuncu discloses the method wherein X in N and n=1 (claim 13).
Regarding claim 14, Koyuncu discloses the method wherein X is N and Z1 and W1 are C (claim 14).
Regarding claim 15, Koyuncu discloses all the preferred embodiments recited by the instant application, including the elected species 2-[(6-hexyl-4-phenylquinolin-2-yl)(methyl)amino]acetic acid (claim 15).
Regarding claim 23, Funk teaches the treatment strategy for a coronavirus.
Regarding claim 24, Koyuncu discloses the subject is human (claim 23).
Regarding claim 25, Koyuncu discloses the method wherein X is N (claim 9).
Regarding claim 26, Koyuncu discloses the method wherein R3 is C1-10 alkyl (claim 8).
Regarding claim 27, Funk teaches the treatment strategy for SARS-CoV-2.
Conclusion
Claims 1, 3, 5, 6, 8-10, 13-16, 19, 20, and 23-27 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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