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
Three information disclosure statements (IDS) submitted: one on March 25th, 2025; one on April 3rd, 2025; and one on December 11th, 2025. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Claims
Claims 2, 4-8, 11-12, 14, 17, 23-29, and 36-38 are pending in this application. Claims 1, 3, 9-10, 13, 15-16, 18-22, 30-35, and 39-45 have been cancelled by applicant.
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 2, 4-8, 11-12, 14, 17, 23-29, and 36-38 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 2 uses the language: “may be optionally substituted” or “may optionally” on several occasions after defining a variable. The language of the claim raises a question as to whether or not the groups are optionally substituted, thus rendering the claim indefinite. Examiner suggests replacing “may be” with “are” or “is” as appropriate.
Claims 23-25 have the same issue described above for claim 2.
Claims 4-8, 11-12, 14, 17, 26-29, and 36-38 are rejected for depending upon the limitations of claim 2.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 2, 4-8, 11-12, 14, 17, 23-29, and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Keenan et al. (WO 2020/176761 A1) (“Keenan”).
Regarding instant claims 2 and 36, Keenan discloses the compounds of Formula I below (pages 12-22) in methods of treating cancer (abstract) – which is the same intended use as the instant invention. Keenan’s compounds render the instant compounds obvious when: Z is CH; m is 0; n is 2; X (corresponding to instant is R4 and R5) is halogen, alkyl, or alkoxide; q is 2; R5 (corresponding to instant R6 and R7) is halide; R4 can be amine or alkylamine; R2 can be H, alkyl, etc.; L can be a bond; and R3 can be cycloalkyl, heterocycloalkyl, aryl, or heteroaryl etc.
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, wherein R1 can be
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or
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Keenan specifically discloses preferred embodiments wherein their R1 group can be as shown below, corresponding to instant X being CH; R5 being Cl or F (halogen); R4 being F, methoxy, and methyl, respectively (page 83, lines 5-6).
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Furthermore, Keenan discloses their core of Formula I can have the following preferred structures Ib and Ic, corresponding to instant R6 and R7 being fluoro or chloro (page 81, lines 15-16). While Keenan shows these halo substituents para and ortho to each other, the instant claims require R6 and R7 to be meta to each other, Keenan’s general structure of Formula I shows that the R5 group can be in any position of the phenyl ring, thus, there are a limited number of options for substitution, and one of ordinary skill would have had a reasonable expectation of success in preparing any of the compounds encompassed by Kennan’s general structure. Applicant is advised that one of 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.
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While the cores of Keenan’s structure show R1 para to the 9-membered bicyclic heteroaryl group (corresponding to instant ring C), and the instant claims require meta-arrangement of the sulfonamide relative to ring C, 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 1970). 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).
Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Keenan’s disclosed formulae and preferred embodiments; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Keenan. 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.
Further regarding claim 36, the compounds below, in particular, are obvious in view of Keenan’s disclosure (instant spec., page 293, compound 78)
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Regarding claims 4-5, Keenan discloses their preferred embodiments above, wherein the group corresponding to instant R4 can be F, methoxy, and methyl
Regarding claims 6-7, Keenan discloses their preferred embodiments above, wherein the group corresponding to instant R4 can be Cl or F. Further regarding claim 7, Keenan teaches their X group can be alkyl, or alkoxide (reading on -CH3 and -OCH3).
Regarding claim 8, Keenan discloses their preferred embodiments above, wherein their R1 group can be
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, reading on instant X being N.
Regarding claims 11-12, 14, and 17, Keenan discloses their preferred embodiments above, wherein the group corresponding to instant R6 and R7 are F and/or Cl.
Regarding claims 23-25, Keenan discloses their preferred embodiments above, wherein the group corresponding to instant ring C is
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. Further regarding claims 24-25, Keenan discloses their ring can be substituted with -L-R3, wherein L can be a bond; and R3 can be alkyl cycloalkyl, heterocycloalkyl, aryl, or heteroaryl etc.
While Keenan’s compounds don’t show the connectivity claimed, Applicant is reminded 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. 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.
Regarding claims 26-27, Keenan discloses their preferred embodiments above, wherein R4 (corresponding to instant R3) can be amine or alkylamine, reading on instant RA and RB being H or alkyl (methyl).
Regarding claims 28-29, Keenan discloses their -L-R3 (corresponding to instant R3), wherein L can be -C(O)NH-; and R3 can be alkyl; thus, reading on
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. Further regarding the substitution pattern claimed in instant claim 29, Applicant is reminded 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. 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. Thus, Keenan’s disclosure renders
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obvious.
Regarding claim 37, Keenan discloses a pharmaceutical composition comprising their compounds and an acceptable carrier (Keenan’s claim 11).
Regarding claim 38, Keenan discloses a method of treating cancer comprising administration of therapeutically effective amounts of their compounds to a subject in need thereof (Keenan’s claims 13 and 25).
Claims 2, 4-8, 11-12, 14, 17, 23-24, and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Fujimoto et al. (US 10,696,651 B2) (“Fujimoto”); in view of Eno et al. (Current Medicinal Chemistry, 2015, 22, 465-489) (“Eno”).
Regarding claims 2 and 36, Fujimoto discloses the compounds of Formula I below as GCN2 inhibitors for treating cancer – which is the same intended use as the instant compounds – (abstract), wherein ring A is
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, wherein X1, X2, X3 can correspond to C, C, N, respectively, or C, C, C; R1 (corresponding to R5) can be methyl or -O-methyl (C1 alkyl/ alkoxy); R2 is (corresponding to instant R4) can be halogen, CN, etc.; X6 (corresponding to instant R7) is halogen; X7 (corresponding to instant R6) is halogen; X8 is C or N; X9 is N or C; X10 is H or amino (col. 2-3).
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Fujimoto’s specifically discloses the compounds 5 and 133 below (Table 1-1, col. 158 and 213), which read on the instant compounds when instant X is N or CR8, wherein R8 is alkoxy (-OMe); R6 and R7 are F; ring C is a 9-membered heterocycle (in 133); R4 is halo (Cl); and R5 is alkyl or alkoxy.
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(5)
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(133)
Regarding the 9-membered bicyclic heteroaryl of compound 5 above, while
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is not recited in the claim limitations, 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 1970). 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). Therefore, Fujimoto’s
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reads on the instant
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.
While Fujimoto’s compounds are limited to the alkyne functional group in the position corresponding to the bond between instant ring C and the rest of the molecule in the instant claims, the teachings of Eno are relied upon to leverage these differences.
Eno teaches that to decrease the probability of late clinical failures or market withdrawal of drugs, there have been an increased prioritization on understanding key metabolic processes that might cause drug toxicities. Eno states that it is widely accepted in the art that compounds with certain functional groups, such as alkynes, have a much greater associated risk towards formation of reactive metabolites than compounds lacking these “structural alerts” (abstract).
Therefore, regarding claims 2, it would have been prima faice obvious to one of ordinary skill prior to the effective filing of the claimed invention to prepare any of Fujimoto’s compounds without the alkyne linker between ring C and the rest of the molecule, in view of Eno. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Fujimoto discloses their compounds as GCN2 inhibitors for the treatment of cancer – which is the same intended use of the instant claims; further because Eno teaches that the presence of alkynes in drug candidates have been associated with increased risk towards formation of reactive metabolites, potentially resulting in late clinical failures or market withdrawal of drugs.
Applicant is advised that 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. Therefore, it would have been obvious to try the preparation of derivatives of Fujimoto’s compounds without the “structural alert” functionality of the alkyne in order to assess activity and reduce the risk of late clinical failures or market withdrawal of drugs.
Per MPEP § 2144.08(II)(A)(4)(c), the closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus.
Regarding claims 4-5, Fujimoto discloses their compounds 3 and 133 above wherein the group corresponding to instant R4 is Cl.
Regarding claims 6-7, Fujimoto discloses their compounds 3 and 133 above wherein the group corresponding to instant R5 is -OMe.
Regarding claim 8, Fujimoto discloses their compound 3 above wherein the group corresponding to instant X is N.
Regarding claims 11-12, 14, and 17, Fujimoto discloses their compounds 3 and 133 above wherein the group corresponding to instant R6-7 is F.
Regarding claims 23-24, Fujimoto discloses their compound 3 above wherein the group corresponding to instant ring C is
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, reading on at least
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. Applicant is reminded 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. 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.
Regarding claim 37, Fujimoto discloses a pharmaceutical composition (medicament) comprising their compounds and an acceptable carrier (Fujimoto’s claim 6).
Regarding claim 38, Fujimoto discloses a method of treating cancer in a subject comprising administration of their compounds in effective amounts (Fujimoto’s claim 7).
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 2, 4-8, 11-12, 14, 17, 23-29, and 36-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-29, 31-32, and 44-47 of copending Application No. 18/262,489 (Copending ‘489). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 2, 4-8, 11-12, 14, 17, 23-29, and 36-38, Copending ‘489 claims the compounds of Formula Ib below, which render the instant compounds obvious when instant: ring C is a 9-membered bicyclic heterocycle; X2 is CH; X1 is CR6, wherein R6 (corresponding to instant R6) can be halogen; X2 is CR7, wherein R7 (corresponding to instant R7) can be halogen; R5 is alkyl or alkoxy; R4 is halogen or cyano; and when instant X is N.
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While Copending ‘489’s has an L linker connecting ring C to the rest of the molecule, wherein L can be C1-6 alkelene, Applicant is advised that compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Copending ‘489’s disclosed formula; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Copending ‘489 when L can be an alkyl chain (-CH2)-. 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.
Further regarding instant claim 37, Copending ‘489 claims a pharmaceutical composition comprising their compounds and a carrier (Copending ‘489’s claim 46).
Further regarding instant claim 38, Copending ‘489’s claims a method of treating cancer comprising administration of their compounds (Copending ‘489’s claim 47).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 2, 4-8, 11-12, 14, 17, 23-29, and 36-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-46 of copending Application No. 18/869,103 (Copending ‘103). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 2, 4-8, 11-12, 14, 17, 23-29, and 36-38, Copending ‘103 claims a method of treating a solid tumor comprising administration of the compound of Formula I below in effective amounts, which anticipates the instant compounds when instant: ring C is a 9-membered bicyclic heterocycle substituted with -C(O)NHMe; R6 is F; R7 is F; R5 is -OMe; R4 is F; and X is N.
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Relevant Art of Record:
The prior art made of record and not relied upon is considered pertinent to Applicant’s disclosure:
Hagiwara et al. (US 2020/0188382 A1) discloses their compounds Va and VIa below [0112], wherein R6 can be alkyl, halogen, alkoxy, etc.; R1 and R2 can be halogen or alkyl (page 5). Hagiwara discloses their compounds in methods of inducing programmed cell death in cancer cells (abstract). Hagiwara, however, differs from the instant invention at least in the following ways: (i) Hagiwara’s ring substituted with R6 does not show the instant substitution pattern corresponding to instant R4 and R5; (ii) Hagiwara’s bicyclic heterocycle corresponding to instant ring C is a 10-membered ring (instant claims require 9-membered bicyclic heterocycles); (iii) and the ring corresponding to instant ring C is in the ortho-position relative to the sulfonamide, when instant claims require meta-substitution.
Therefore, Hagiwara doesn’t teach the instant compounds, or provide motivation to modify their invention to arrive at the instant claims.
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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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613