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 .
Status of the Claims
Claims 16-29, 31-32, and 44-47 are pending in this application. Claims 1-15, 30, 33-43, and 48-54 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 16-29, 31-32, and 44-47 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 16 reads: “may be optionally substituted” (lines 5 and 18) and “may each individually be optionally” (line 14). 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 31-32 have the same issue described above for claim 16.
Claims 17-29 and 44-47 have been rejected for depending upon the limitations of claim 16.
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 16-21, 29, 31-32, and 44-47 are rejected under 35 U.S.C. 103 as being unpatentable over Fujimoto et al. (US 10,696,651 B2 – Pub. Date: June 30th, 2020) (“Fujimoto”); in view of Eno et al. (Current Medicinal Chemistry, 2015, 22, 465-489) (“Eno”).
Regarding claims 16, 29, and 45, 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; 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 is H or halo; X7 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 below 3 and 5 below (Table 1-1, col. 158), which read on the instant compounds when instant X2 is C-H; X1, 3 are C-F; ring C is a 6 or 9-membered heterocycle; R4 is halo (Cl); and R5 is alkyl or alkoxy. Thus, Fujimoto discloses a small genus of compounds which renders the instant compounds obvious.
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(3)
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(5)
While Fujimoto’s compounds are limited to the alkyne functional group in the position corresponding to instant L, 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 16, 29, and 45, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to prepare any of the instant compounds wherein L is -CH2-CH2- in view of Fujimoto and Eno. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Fujimoto discloses their compounds, which are nearly identical to the instantly claimed structures, except for the fact that they have an acetylene (2 carbons, triple bonded) in the position corresponding to instant group L. Further because Fujimoto discloses their compounds as GCN2 inhibitors – which is the same intended use of the instant claims; and 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 alkelene derivatives of Fujimoto’s alkynes to assess activity and reduce the risk of late clinical failures or market withdrawal of drugs.
Further regarding claim 45, the compound below, for example, (compound 7, page 112 of the spec.) is particularly obvious:
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Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP 2144.08(d)).
Regarding claim 17, Fujimoto discloses their compounds 3 and 5 above wherein the group corresponding to instant R4 is Cl.
Regarding claim 18, Fujimoto discloses their compounds 3 and 5 above wherein the group corresponding to instant R5 is Me or -OMe.
Regarding claims 19-21, Fujimoto discloses their compounds 3 and 5 above wherein the group corresponding to instant X2 is C-H and X1, 3 are C-F.
Regarding claims 31-32, 44, Fujimoto discloses their compounds 3 and 5 above wherein the group corresponding to instant ring C is
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.
Regarding claim 46, Fujimoto discloses a pharmaceutical composition (medicament) comprising their compounds and an acceptable carrier (Fujimoto’s claim 6).
Regarding claim 47, Fujimoto discloses a method of treating cancer in a subject comprising administration of their compounds (Fujimoto’s claim 7).
Claims 22-28 are rejected under 35 U.S.C. 103 as being unpatentable over Fujimoto et al. (US 10,696,651 B2 – Pub. Date: June 30th, 2020) (“Fujimoto”); in view of Eno et al. (Current Medicinal Chemistry, 2015, 22, 465-489) (“Eno”); as applied to claims 16-21, 29, 31-32, and 44-47; further in view of Morita et al. (Obtained From gousei.f.u-tokyo.ac.jp [Retrieved on September 11th, 2025] <URL: https://gousei.f.u-tokyo.ac.jp/seminar/index.html#2012> - Published May 2012) (“Morita”).
The teachings of Fujimoto and Eno are disclosed above and incorporated herein.
While Fujimoto in view of Eno does not specifically teach the instant compounds wherein the groups corresponding to instant X2, X3, or X1 are N; the teachings of Morita are relied upon for these disclosures.
Morita teaches the design of bioisosteres introduces structural changes that can be beneficial to optimize shape, size, lipophilicity, polarity, etc., thus improving potency, enhancing selectivity, and metabolism etc. (page 3, bottom). Morita further teaches that phenyl and pyridine are ring equivalents and common bioisosteres in drug design (page 4, top).
Therefore, regarding claims 22, 25, and 27, wherein X2, X3, or X1 are N, respectively, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to prepare any of the claimed compounds in view of Fujimoto and Eno, further in view of Morita. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Fujimoto in view of Eno disclose the instant compounds wherein the groups corresponding to X2, X3, and X1 are always carbon, with the group corresponding to X2 always limited to C-H as in the instant claims (corresponding to having a phenyl in the position corresponding to instant ring B); further because Morita teaches that phenyl and pyridine are ring equivalents and common bioisosteres in drug design, and that the design of bioisosteres can lead to improved potency, selectivity, and metabolism etc. Therefore, a person of ordinary skill would have been motivated to replace any one of the carbons corresponding to instant X2, X3, or X1 with nitrogen to arrive at a pyridine heterocycle, as in the instant claims.
Regarding claims 23-24, 26, and 28, Fujimoto discloses their compounds 3 and 5 above wherein the groups corresponding to instant R6 and R7 are F.
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 16-29, 31-32, and 44-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4, 5-8, 11-12, 14, 17, 23-29, 37-38 of copending Application No. 18/626,493 (Copending ‘493). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 16-29, 31-32, and 44-47, Copending ‘493 claims the compounds of Formula Ia 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 can be halogen; X2 is CR7, wherein R7 can be halogen; R5 is alkyl or alkoxy; R4 is halogen or cyano; and Copending ‘493’s X is N.
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While Copending ‘493’s compounds lack the L linker present in the instant compounds, 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 ‘493’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 ‘493. 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 46, Copending ‘493 claims a pharmaceutical composition comprising their compounds and a carrier (Copending ‘493’s claim 37).
Further regarding instant claim 47, Copending ‘493 claims a method of treating cancer comprising administration of their compounds (Copending ‘493’s claim 38).
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:
Burns et al. (WO 2008/058341 A1) discloses their compounds of Formula I (page 12-13) wherein: Q is -O- or -NR3-, wherein R3 (corresponding to instant RA) can be H or C1-4 alkyl (all corresponding to instant L being C1-6 alkelene-O- or C1-6 alkelene-NRA-); R2 and R17 can be H or alkyl; A and Y can be N or CH (on the ring corresponding to instant ring C); R4 and R5 can be H, C1-4 alkyl, CF3, etc.; X can be -NHSO2-; W can be 6-membered heteroaryl with 1-3 substituents, like C1-4 alkyl/ alkoxy or halogen; and Z1-4 can be N or CR1, wherein R1 (corresponding to instant R6-7 and H) can be H or halogen.
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Burns specifically discloses their preferred embodiment 67 below (page 39), which reads on the instant compounds when ring C is a chloro-pyrazine (6-membered heteroaryl); X1-3 are all CH. While there’s overlap between Burns general formula, their closest preferred embodiment below differs in at least the following: group corresponding to instant R6 is H, when instant claims require halogen or CN; group corresponding to instant R7 is H, when instant claims require halogen; group corresponding to instant R4 is H, when instant claims require halogen or CN; and group corresponding to instant R5 is H, when instant claims require alkyl or alkoxy. In addition, Burns preferred embodiment shows halo-substitution of the ring corresponding to instant C, while instant claims exclude halide substitution.
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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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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627