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 CON of Application No. 17/439,085 (now U.S. Patent No. 12,415,788) a 371 National Stage Entry of PCT/US2020/023654 filed on March 19, 2020 which claims benefit to domestic provisional application No. 62/821,853 filed on March 21, 2019.
Claims Status
Acknowledgement is made of original (1-3, 6, 9-11, 14, 17), amended (4-5, 7-8, 12-13, 15-16, 18-20), claims filed July 1, 2025. Claims 1-20 are pending in instant application.
Information Disclosure Statement
The information disclosure statements filed on July 1, 2025 and August 4, 2025 have been considered.
Claim Interpretation
At claim 20, the phrase “instructions for use in treating cancer” is understood to relate to printed matter that is not functionally related to the product. Per MPEP § 2112.01(III), non-functional printed matter does not distinguish the claimed product(s) from the prior art.
At claim 20, the term “anti-cancer agent” is not defined in the claims or specification. Rather, the specification broadly identifies such compounds by stating “[a]ny convenient anti-cancer agents can be utilized in the subject methods in conjunction with the subject compounds” (see instant spec at 108 lines 35-36).
For the purposes of applying art, the limitations of claim 20 are satisfied by a kit comprising an effective dose of a compound of claim 1 and an effective dose of any additional, art-recognized anti-cancer agent.
Claim Objections
Claims 1, 5 and 11 are objected to because of the following informalities:
Claim 1 states “provided that the compound is not
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” but the first and third compounds appear to be duplicates.
Claim 5 is objected to because the claim and claims it depends from (claims 1 and 2) fail to define the limitations of all the R groups shown in the listed formulae, specially R10-R18.
Claim 11 is objected because it currently recites “wherein the compound is selected from any one of the compounds of Table 1, Table 2, or Table 3”. Although it is presumed Applicant meant to incorporate by reference Tables 1-3, MPEP § 2173.05(s) states that where possible, claims are to be complete in themselves, and that incorporation by reference is a necessity doctrine. Here, no necessity has been established on record.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 16-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for lung cancer, glioblastoma, or melanoma, does not reasonably provide enablement for treating all cancer or inhibiting proliferation of all cancer cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the nature of the invention,
2- the breadth of the claims,
3- the state of the prior art,
4- the predictability of the art,
5- the amount of direction or guidance provided
6- the presence or absence of working examples,
7- the quantity of experimentation necessary, and
8- the relative skill of those in the art.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Undue experimentation is required by one skilled in the art to determine enablement of the instant disclosure as claimed due to the following:
The nature of the invention (1) and the breadth of the claims (2)
The nature of the invention and breadth of the claims is the treatment, prevention, and prophylaxis of cancer (claims 16-18) or inhibition of a cancer cell proliferation (claim 19).
The instant specification defines “treatment” as preventative, prophylactic, or a therapeutic partial or complete cure for disease or adverse effect (see instant spec. at p. 114 lines 19-22).
Since subjects include cells and individuals and treatment includes prophylaxis and “not worsening”, the broadest reasonable interpretation of claims 16-18 includes a patient population of anyone.
The state (3) and predictability (4) of the art
In regards to unpredictability of treating cancer with a PI4K kinase inhibitor, Waugh et. al.1 teaches that targeting PI4K kinases for cancer treatment is uncertain and under-developed; PI4kIIIα might be involved in pancreatic cancer (see Waugh at p. 127 left col. ¶2), targeting PI4K IIIβ has limited studies and might suggest utility in breast cancer (see Waugh at p. 127 right col. ¶1), PI4kIIα has been studied in melanoma, fibrosarcoma, breast cancer, bladder transitional carcinoma, and thyroid papillary carcinoma but signaling mechanisms are still not fully understood (see Waught at p. 128 left col. ¶2).
The prior art provides enablement for treating pancreatic cancer, melanoma, fibrosarcoma, breast cancer, bladder transitional carcinoma, and thyroid papillary carcinoma.
The amount of direction or guidance provided (5) and the presence or absence of working examples (6)
The specification provides the following embodiments regarding cancer and cancer cells:
Inhibition assays, inhibition of PI4k and PI3kIII kinases with six species (see instant spec. at p. 151 Example 2), inhibition of PI3K kinases with two species of Formula I (see instant spec. at p. 156 Example 7).
Anti-cancer cell lines, inhibition of lung cancer cells and lung cancer tumors in mice for one species of Formula I (see instant spec. at pp. 157-158), inhibition of glioblastoma or melanoma with two species of instant Formula I (see instants pec. At pp. 158-159 Table 12).
The specification provides enablement for treating lung cancer, glioblastoma, or melanoma.
Nowhere in the specification is it explained how any cancer is to be prevented through the administration of the claimed compounds. Also, it is not explained in the art or applicant’s disclosure how any other cancer is treated or any cancer cell proliferation inhibited by administering or contacting a compound of Formula I.
Therefore, the full scope of treatment in the methods of claim(s) 16-19 are not enabled.
The quantity of experimentation necessary (7) and the relative skill of those in the art (8)
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. Because of the unknown predictability in the art (as discussed above) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that compounds of Formula I could be used for treating all cancer or inhibiting the proliferation of all cancer cells.
Brenner v. Manson states "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent protection' is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" (Brenner v. Manson 383 U.S. 519, 536, 148 USPQ 689, 696 (1966), cited in Genentech Inc. vs. Nova Nordisk 42 USPQ 2d 1001, Fed. Circuit 1997).
As noted above, little experimentation provided is drawn to treatment, prevention, and prophylaxis of all cancer. A review of the state of the art fails to reveal that PI4k inhibitors are useful as therapeutic treatment as claimed (treating any and all cancer, or inhibiting any or all cancer cells). Determining if compounds of Formula I would be therapeutic for any particular cancer would require careful analysis and replicability of a composition comprising a compound of Formula I, formulation into a suitable dosage form, assay testing to correlate clinical efficacy, identifying off-targets, subjecting to animal trials, and subjecting to clinical trials.
All this is undue experimentation given the limited guidance and direction provided by Applicants.
Conclusion
Accordingly, the inventions of claims 16-19 do not comply with the enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Suggested Amendment
Examiner suggests amending to add a limitation wherein the cancer or the cancer cell is selected from lung cancer, glioblastoma, or melanoma (the cancers in which the specification provides enablement for).
Claim Rejections - 35 USC § 112(b)
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 5-6 and 11 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 5 recites the structural limitations of R10-R18 which are not defined in the claim, or the claims from which it depends. It is unclear what R10-R18 can and cannot be. Claim 6 defines R11, but no other variables.
Claim 11 recites “wherein the compound is selected from any one of the compounds of Table 1, Table 2, or Table 3”. There is insufficient antecedent basis for this limitation in the claim. For purposes of applying prior art, claim 11 is presumed to be an attempt to incorporate by reference Tables 1-3; however, this is improper (see MPEP § 2173.05(s), which states that where possible, claims are to be complete in themselves).
Claim 11 recites “or a prodrug thereof”, which renders the claim scope indefinite. The compounds disclosed in Tables 1-3 are structurally defined with no free valences for extra moieties (see, e.g., MPEP 2172.01, regarding omission of structural relationship). Furthermore, the genus of “a prodrug thereof” is not fully structurally defined; therefore it is unclear what is encompassed by the term “prodrug” (see, instant spec. at p. 81 lines 13-16, noting that no unambiguous structures are identified). Accordingly, the term “prodrug” appears to be utilized as a functional description corresponding to unknown structures conjugated at unknown points within the instant claim scope (see, e.g., MPEP 2173.05(g), noting that the use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite). Accordingly, the claim is considered indefinite because it is not clear what chemical derivatives are encompassed by Applicant’s definition of a prodrug, or what in vivo reactions would convert these derivatives to a defined, disclosed compound of Tables 1-3.
Accordingly, claims 5-6, 11 are rejected.
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(s) 1-5, 7-9, 12-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2017/147526 A12.
Claim interpretation: See above 112(b) Rejection. Formula IIA2g’s R12 is understood to be alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, trifluoromethyl, or halogen (see instant spec. at p. 22 lines 1-2), and n is understood to be 0-5 (see instant claim 3).
Regarding claim 1, 7-8 and Formula I, WO’526 teaches compound which reads on Formula I when Y1 is N, R1 is substituted aryl specifically chlorophenyl, R2 is alkoxy specifically methoxy, and R3-R6 are alkyl specifically methyl.
WO’526 S366 at p. 87
Instant Formula I
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Regarding claim 2-5 and Formula IIA2g, WO’526 teaches compound S371 which reads on instant Formula II and more specifically Formula IIA2g when Y1 is CH, R3 is alkyl specifically methyl, R4 and R5 are both alkyl specifically methyl, R2 is alkoxy specifically methoxy, R12 is alkyl specifically methyl, n is 0.
WO’526 S371 at p. 88
Instant Formula IIA2g
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Regarding claim 9 and Formula III, WO’526 teaches compound S365 which reads on instant Formula III when -- is absent, Y1 is N, Y2 is S, R1 is substituted aryl specifically chlorophenyl, R2 is alkoxy specifically methoxy, R3 is alkyl specifically methyl, one of R7 and R8 is alkyl specifically methyl and the other is hydrogen, R9 is alkyl specifically methyl.
WO’526 S365 at p. 87
Instant Formula III
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Regarding claim 12 and a pharmaceutical composition, WO’526 teaches a pharmaceutical composition comprising a compound of WO’526 claim 1 and a pharmaceutically acceptable excipient.
Regarding claim 13-14 and inhibiting a PI4 kinase, WO’526 teaches the disclosed compounds have inhibitory activity for PI4K, including PI4KIII, and PI3K kinases (see WO’526 at p. 112-114 Table 3). An artisan would readily appreciate that in order to run an inhibitory assay, the compound would need to be in contact with the respective kinase tested.
Regarding claim 15 and treating an infective disease, WO’526 teaches methods of treating infective diseases such as EV71, EV68, HCV (see WO’526 claims 14-17).
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.
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 10-11 are rejected under 35 U.S.C. 103 as being obvious over WO 2017/147526 A13 as applied to claims 1-5, 7-9, 12-15 above.
Regarding claims 10-11 and a compound of Formula I, II, or IIA1g, WO’526 teaches compound S323 (see WO’526 at 84 at Table 2) which renders obvious instantly disclosed and claimed compound S-1 (compare instant S-1 at 71, claims 1-5, and 8 with WO’526 S323 at 84 at Table 2). S323 reads on instant Formula I (claim 1), instant Formula II (claim 2), and instant Formula IIAIg (claim 5) as follows: wherein R1 a B ring system, specifically 1-fluoro-3-methylbenzene (claims 2-3, 10), R2 is methoxy, R3/R4 is methyl, R6 is an A ring system, specifically oxane (claims 2, 4), Y1 is CH and Y2 is S (claim 8). WO’526 also teaches S323 has PI4K inhibitory activity towards EV71 and HRV (compare WO’526 Table 5 entry S323 at pp. 116-117 with instant spec. Table 5 entry S-1 at p. 151).
WO’526
Instant Application
S323 at p. 84
Formula I
Claim 1
Formula II
Claim 2
Formula IIAIg
Claim 5
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S338 at p. 85
S-1 at 71
S-8 at 72
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The prior art of WO’526 differs from the pending claims as follows: WO’526 compound species differ from the pending claim scope at positions R4 and/or R5 (H vs Me substituents); similarly, the positional isomers of WO’526 S338 and instantly disclosed S-8 differ the same way.
However, such differences would have been obvious in view of the further teachings of the primary reference.
Regarding a gem-dimethyl, WO’526 also teaches variation in methyl versus gem-dimethyl substitution at the bridging carbon adjacent to the secondary amine, (compare WO’526 at S316 at p. 83 with S367 at 87; compare WO’526 at S315 at 83 with S371 at 88).
WO’526 S367 at p. 87
WO’526 S316 at p. 83
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WO’526 S371 at p. 88
WO’526 S315 at p. 83
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Accordingly, WO’526 reasonably informs artisans that gem-dimethyl substitutions at the bridging carbon adjacent to the secondary amine were contemplated in the prior art, and would have been understood to be a functionally equivalent substitution at the corresponding R4 and R5 positions.
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 change of methyl or isomerism, per MPEP 2144.09, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. Here, the prior art teaches highly similar compounds differing by a single methyl moiety which were taught for the same utility (i.e., inhibiting PI4K). Accordingly, such compounds are obvious. In addition, or alternatively, it would have been prima facie obvious to one skilled in the art to simply substitute a methyl for a hydrogen at the R4/R5 positions to form gem-dimethyl variants because WO’526 is reasonably understood to inform artisans such structural variation was acceptable at that position, and that such variation would have yielded functionally equivalent obvious variants of the disclosed structures predicted and expected to be suitable for the same purpose of inhibiting PI4K (see, e.g., MPEP 2144.09; 2144.06(II)).
Furthermore, it is well-within the ordinary skill in the art to incorporate the gem-dimethyl in lieu of a methyl. Therefore, an artisan would arrive at the same gem-dimethyl variants as presently claimed for reasons taught in the prior art.
Accordingly, claims 1-5, 7-12 are rejected.
Claims 20 is rejected under 35 U.S.C. 103 as being obvious over WO 2017/147526 A14 as applied to claims 1-5, 7-12 above, and in further view of Borden et al.5 and FDA6.
Claim interpretation: The claim interpretations set forth in the “claim interpretation” are hereby incorporated, including the discussion of the limitations of claim 20 regarding the preamble and written materials are incorporated herein.
The teachings of WO’526 as applied to claims 1-5, 7-8, and 10-12 have been set forth above, and those teachings are incorporated into the instant rejection.
The prior art of WO’526 differs from instant claim 20 as follows: WO’526 does not disclose a kit comprising a compound of instant claim 1 and an effective dose of an additional anticancer agent.
Regarding claim 20, WO’526 directs artisans to utilize “unit dosage forms” of the disclosed compounds and informs artisans to utilize effective amounts of compounds that are administered at different frequencies (see, e.g., WO’526 at 6 at lines 24-30, 94 at lines 5-25, 95 at lines 4-21). Accordingly, an artisan would readily appreciate and infer that such “unit dosage forms” could be packaged for use in individual administrations (e.g., a kit). Furthermore, WO’526 discloses “in some embodiments, the subject compound and an antiviral, e.g. interferon, ribavirin, … are administered to individuals in a formulation (e.g., in the same or separate formulations) with a pharmaceutically acceptable excipient(s)” (US’526 at 98 line 21 - 99 line 15).
Borden teaches the antiviral ribavirin is an effective cancer therapy for leukemia (see Borden abs).
FDA teaches the inclusion of instructions for use in drug products is known, including indicating diseases or conditions the drug is to be used for, dosing, administration, and warnings or precautions (see FDA at p. 2 “II General Principles”).
An artisan following the guidance of WO’526 would readily appreciate that that such unit dosage formulations and individual administrations (see, e.g., WO’526 at 6 at lines 24-30, 94 at lines 5-25, 95 at lines 4-21) could be packaged with the anti-cancer drug of ribavirin and instructions as taught and suggested by WO’526 in view of Borden and FDA.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention or otherwise at the time the invention was made, to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention would have been obvious because the primary reference teaches that such compounds may be co-administered with the anti-cancer agent of ribavirin, and an artisan would readily appreciate that such compositions could be manufactured and separated in a unit dosage form for individual administrations (e.g., kits) (see, e.g., MPEP 2143(I)(A), (G)). Furthermore, each component would merely perform its art-recognized function in combination as it does separately. An artisan would see benefit in the inclusion of instructions in a kit in order to inform an artisan or subject how to properly use the kit (see MPEP § 2143(I)(D)).
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see MPEP § 2121(I)) for all that it discloses (see, MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to formulate unit dosage formulations of known compounds for use in individualized administrations of such compounds for the same purpose as taught by the prior art.
Accordingly, claim 20 is rejected.
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 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,415,788 B27. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 1-4, 7-10, US’788 claims compounds of Formula I overlaps with instant Formula I as shown below (see US’788 claims 1-3, 5, 6).
US’788 Formula I
Instant Formula I
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Y1 is CH or N
Y1 is CH or N
Y2 is S, O, or NR19
Y2 is S, O, or NR19
R1 is aryl, substituted aryl, heteroaryl, or substituted heteroaryl
R1 may be aryl, substituted aryl, heteroaryl, or substituted heteroaryl
R2 is alkoxy or substituted alkoxy
R2 is alkoxy or substituted alkoxy
R3 is H, lower alkyl, or substituted lower alkyl
R3 is H, lower alkyl, or substituted lower alkyl
R4 and R5 are methyl
R4 and R5 may be methyl
R6 is aryl, substituted aryl, heteroaryl, or substituted heteraryl
R6 may be aryl, substituted aryl, heteroaryl, or substituted heteraryl
Regarding instant claims 5-6, US’788 also claims compounds of Formula IIA1a, IIA1b, IIA1c, IIA1d, IIA1e, IIA1f, IIA2a, IIA2b, IIA2c, IIA2d, IIA2e, IIA2f, IIC1a, IIC1b, IIC1c, IIC1d, IIC1e, IIC1f, IID1a, IID1b, IID1c, IID1d, IID1e, IID1f (see US’788 claim 4).
Regarding instant claim 11, US’788 claims species that read on the instantly claimed genus and species such as instant S-32 (see instant spec. at p. 75 Table 1 and above 112(b) Rejection) (US’788 claims 7, 17-21).
US’788 Claim 7 Exemplary Species
Instant S-32
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Regarding instant claim 12, US’788 claims compositions comprising compounds of Formula I and excipients (US’788 claim 8).
Regarding instant claims 13-14, US’788 claims methods of inhibiting PI4-kinase or PI4-III kinase by contacting with a compound of Formula I (US’788 claims 9-10).
Regarding instant claim 15, US’788 claims a method of treating a subject with an infective disease with a compound of Formula I (US’788 claim 11).
Regarding instant claim 16-18, US’788 claims a method of treating a cancer susceptible to PI4-kinase inhibition with a compound of Formula I (US’788 claims 12-14).
Regarding instant claim 19, US’788 claims a method of inhibiting proliferation of a cancer cell susceptible to PI4-kinase inhibition comprising contacting with a compound of FormulaI (US’788 claim 15),
Regarding instant claim 20, US’788 claims a kit comprising a compound of Formula I and an additional anticancer agent (US’788 claim 16).
Accordingly the claims are not patentably distinct from each other.
Allowable Subject Matter
Claim 6 is presently rejected, but would be allowable if a terminal disclaimer is filed, the indefinite issues fixed, and rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 6 depends from claim 5 and refers to R11 limited to acyl, a structural limitation of Formulas IIG1a-IIK1i. When R11 is acyl in Formulas IIG1a-IIK1i, the genae appear to be free of the prior art, the closest prior art being WO’526.
Regarding claim 6 and a compound of Formula IIG1i and R11 is acyl, WO’526 teaches Compound S123 (see WO’526 at p. 62) which corresponds with instant Formula IIG1i when R3 is alkyl specifically methyl, n is 0, R15-R18 are alkyl specifically methyl, R2 is alkoxy specifically methoxy.
WO’526 S-123 at p. 62
Instant Fomrula IIG1i
PNG
media_image23.png
82
158
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Greyscale
PNG
media_image24.png
240
248
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Greyscale
WO’526 differs from instant Formula IIG1i in i) a gem-dimethyl at R4/R5 and R11 as acyl. While the gem dimethyl is obvious in view of the prior art teachings (see above prior art rejections), no reasonable suggestion or motivation was found to modify the NH of S123 to N-acyl.
Conclusion
Claims 1, 5, 11 are objected to.
Claims 1-20 are rejected.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Waugh et. al. "Phosphatidylinositol 4-kinases, phosphatidylinositol 4-phosphate and cancer" Cancer Letters 2012, 325, 2, 125-131. DOI: 10.1016/j.canlet.2012.06.009
2 Cite No. 18 in the IDS filed 7/1/25. Published August 21, 2017, corresponding to application PCT/US17/19509. Hereinafter WO’526.
3 Cite No. 18 in the IDS filed 7/1/25. Published August 21, 2017, corresponding to application PCT/US17/19509. Hereinafter WO’526.
4 (published August 21, 2017, corresponding to application PCT/US17/19509, cited in the IDS filed January 5, 2022 Cite No. 18 hereinafter WO’526).
5 Borden et al “Ribavirin as an anti-cancer therapy: Acute Myeloid Leukemia and beyond?” Leuk Lymphoma, 2010, 51, 10, 1805-1815 (not provided in the IDS, hereinafter Borden).
6 FDA. "Indications and Usage Section of Labeling for Human Prescription Drug and Biological Products - Content and Format" July 3, 2018. Hereinafter FDA.
7 Patented September 16, 2025.
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