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
Election/Restriction
Applicant elected, without traverse, Group I invention, and the species, Compound No. 14, having following structure, in the reply filed on 05/21/2026.
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The elected Compound 14 is a compound of Formula I’
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It is noted there is error in Applicant’s identification of the claims encompassing the elected species. R1 is CH3 without R1a in the elected species, thus claim 7 reciting R1a is cyano does not read on instant elected species. RX1 is H and there is no RX1a in the elected species, thus claim 12 reciting definition of RX1a does not read on instant elected species. RA is alkyl substituted with cyano as RA1 and there is no RA2 in the elected species, thus claim 16 reciting definition of RA2 does not read on instant elected species.
Claims 1, 3, 5-6, 8-11, 13-15, 17-21, and 32-36 read on the elected species. Claims 7, 12, 16 and 37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
The elected species (CAS# 2919555-85-2) entered STN on April 07, 2023.
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To practice compact prosecution, the search/examination has expanded to non-elected species wherein W1 is CRw1; Rw1 is H or C1-C6 alkyl; W2 is CRW2; Rw2 is H or C1-C6 alkyl; W3 is CRw3; Rw3 is H or C1-C6 alkyl; W4 is CRW4; Rw4 is H or C1-C6 alkyl; R1 is H or C1-C6 alkyl; R2 is H; X1 is -NRX1 C(=O)-* ; Rx1 is H; A is 5- to 10-membered heteroaryl substituted with RA. The elected species and expanded non-elected species are rejected as obvious over Kaldor in the following 35 USC103 section. Other non-elected species are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species. The absence of other citations of prior art should not be interpreted as an indication that other subgenera within Formula I’ are free of prior art. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reconsidered. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reconsideration that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
Status of Claims
Claims 1, 3, 5-21, and 32-37 are pending in the instant application.
Claims 7, 12, 16 and 37 are withdrawn, .
Claims 1, 3, 5-6, 8-11, 13-15, 17-21, and 32-36 are currently under examination.
Priority
This instant application 18/689,967 filed on 03/07/2024 is a 371 of PCT/US2022/076164, filed September 9, 2022, which claims priority to U.S. provisional Application Nos. 63/351,158, filed June 10, 2022, and 63/242,845, filed September 10, 2021. Instant elected species is disclosed in US provisional 63/242,845, filed September 10, 2021.
Information Disclosure Statement
The information disclosure statement dated 12/17/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the reference listed in IDS are being considered by the Examiner.
Claim Objections
Claims 1, 3 and 21 are objected to because of the following informalities:
Claim 1 recites R2 is oxo and R3 is oxo. However, R2 and R3 are substitute on heteroaryl ring which is not compatible with the valence of oxo.
Claim 3 is objected to because the figure of compound of Formula I is blurry. Claim 3 recites R2 is oxo which valence is not compatible with heteroaryl ring. Claim 3 recites “compound, stereoisomer or pharmaceutically acceptable salt” multiple times that are repetitive.
Claim 21 recites pharmaceutical composition comprising the compound, stereoisomer, or pharmaceutically acceptable salt of claim 1 and one or more pharmaceutically acceptable carriers, diluents, adjuvants, or excipients. Carriers and excipients are interchangeable terms for pharmaceutically acceptable ingredients where diluents and adjuvants are narrow scope of pharmaceutically acceptable carriers/excipients.
Specification
Instant specification discloses vast variety of compound of Formula I, I’, II’ etc. with similar detonation, such as RX1 , R1a, RX1a, RA1 , RA2 , etc. The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 112
Claims 1, 3, 5-6, 8-11, 13-15, 17-19, 21 and 32-34 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 full-scope of compound genus of Formula I’. This is a written description rejection, rather than an enablement rejection under 35 U.S.C. 112, first paragraph. Applicant is directed to the MPEP 2163 and Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1st "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
MPEP 2163.02 states “ Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, the inventor was in possession of the invention, and that the invention, in that context, is whatever is now claimed.”
MPEP 2163 II states; “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 inventor was in possession of the claimed genus (see i)(C) above)”. While applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. “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” MPEP 2163 II.
Instant claims are drawn to compound of Formula I’ comprising vast variety of variables/moieties, e.g. A moiety, R groups, in combination with different X1 linking different aryl/heteroaryl ring, Dependent claims are drawn to variety of subgenus comprising narrow scope of A moiety, R groups, in combination with different X1 linking moiety.
Instant specification discloses about 326 compounds comprising X1 is -NR X1 C(=O)-* or -C(O)NRx1-*. There are no disclosure of compound of Formula I’ wherein X1 is NRX1 C(O)O-*, -NR X1 N=C-*, -NR X1CC=NR X1)-*, -NR X1C (=NH)NR X1 -*, -S(O)2NR X1-*, etc. There are no disclosure of compound of Formula I’, wherein R1 is C3-C12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl, or R1 and R3, together with the intervening atoms form a 4- to 12-membered heterocycloalkyl optionally substituted with one or more oxo. In addition to the species reduced to practice, instant specification only discloses general formula with lists of possible groups. This kind of disclosure is not representation of any species. A "laundry list" disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species. MPEP 2163.1.A. and Fujikawa v. Wattanasin, 93 ”.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996).
In conclusion, substantial structural variation exists in the genus/subgenus embraced by instant claims . The disclosed compound species are not sufficient for representing the variance encompassed by the general formula herein. The specification fails to provide adequate written description for the genus/subgenus of compounds claimed and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
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.
Claims 1, 3, 5-6, 8-11, 13-15, 17-19, 21 and 32-34 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor regards as the invention.
Claims 1, 3 and 5 recite RA is ORA1, NHRA1, N(RA1)2, wherein
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It’s not clear how RA1 is attached to O, wherein RA1 is halogen, cyano, OH, NH2, ORA2, etc. It’s not clear how RA2 is attached to O, wherein RA2 is halogen, cyano, OH, NH2, N(RA3)2. The lack of clarity renders claim 1 indefinite since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired.
Claims 3, 5-6, 8-11, 13-14, 17-19, 21 and 32-34 are also rejected due to dependency on claim 1.
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, 8-11, 13-15, 17-21 and 32-36 are rejected under 35 U.S.C. 103 as being unpatentable over Kaldor et al. (US 20200347052A2, corresponding to US 10927111 B2, Applicant’s IDS dated 12/17/2024), in view of Patani et al. (Chemical Reviews, 1996. Vol. 96, 8: p 3147-3176).
Regarding instant compound of formula I’, Kaldor et al. disclosed heteroaryl compound of Formula I, as inhibitors of the receptor tyrosine kinase effector Raf (RAF), pharmaceutical compositions comprising aforementioned compounds, and methods for using said compounds for the treatment of diseases( e.g. cancer) ( See abstract, [0003]- [0023], [0094]-[0111],[0143], [0161]-[0167], Examples 1-78, Tables 1-12 , claims 105-134).
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read on instant compounds wherein X1 is -NR X1 C(=O)-* , and Z read on instant A moiety wherein A is heteroaryl or heterocycloalkyl group. U read on instant R1, V read on instant R2.
Kaldor teaches variety of Z moiety with substitutes (e.g. pyridine, etc.) (See [0143]) (which read on instant A moiety optionally substituted with RA in claims 13-15). Kaldor teaches alkyl group (e.g. methyl, isopropyl, butyl, etc.) is optionally substituted by one or more of halo, cyano, etc. ( See [0036]) (which reads on RA1 of instant elected species) . Kaldor teaches compound species that are very similar to instant claimed compounds (See Table 1-11), e.g. compound 6, 7, 32-50, 52-53, 64-77 , etc.
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Kaldor compounds read on instant compound of Formula I’ wherein R1 is C1-C6 alkyl; R2 is H; X1 is -NR X1 C(=O)-* , wherein * denotes attachment to A; Rx1 is H; A is 5- to 10-membered heteroaryl substituted with RA; RA is C1-C6 alkyl substituted with RA1; and RA1 is F.
Regarding claim 21, Kaldor teaches pharmaceutical composition comprising the RAF inhibitors with one or more pharmaceutically acceptable carriers/excipient (See [0151]-[0153]).
Kaldor collectively teaches heteroaryl RAF inhibitors that are very similar to instant compounds.
The difference between Kaldor compounds and instant claimed compounds is N vs CH on the bicyclic heteroaryl ring:
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vs
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Patani teaches bioisosterism approach for the rational modification of lead compounds wherein classical or nonclassical bioisosteres exhibit similar biological activity. Patani teaches classical bioisosteres are a series of replacements defined by Grimm’s Hydride Displacement Law and Erlenmeyer’s definition of isosteres (See p. 3148-3149) and ring equivalents thereof (See page 3158-3160).
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Kaldor teaches embodiments wherein X is N or CH, which demonstrates CH and N as classical bioisosteres for SAR study as taught by Patani. Instant compounds reciting W1-4 is N or CH also demonstrate CH and N as commonly used bioisosteres.
According to MPEP § 2144.09, A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
It would have been obvious to one of ordinary skill in the art to further explore more RAF inhibitors based on the collective teachings of Kaldor, and general knowledge of structure similarity/ bioisosteric modification as taught by Patani, and arrive at instantly claimed invention with reasonable expected success. For example, compound 53 taught by Kaldor could have been modified by bioisosteric replacement of N with CH, and arrived at instant non-elected species of claim 20 (first compound on page 15). The non-elected species could have been further modified to instant elected species since Kaldor teaches alkyl group could be further substituted by cyano.
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One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
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.
Claim 1 and 3 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/120,169 (reference application). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claim 1 is drawn to method of treating or preventing cancer in a subject, comprising administering a compound of Formula (0), with substitutes/moieties A, X1, W and R that are similarly defined as instant claimed formula I’.
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The scope of reference compounds overlapped with instant claimed compounds. Based on the continuing data on the record, instant application is not related to the reference application, thus no 35 USC 121 shield exists.
Conclusion
No Claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Cho et al. ( US 20190300531 A1, Applicant’s IDS dated 12/17/2024). Cho teaches pyridine derivatives compound of Formula 1- 5 as RAF inhibitors and method of treating cell growth disease caused by RAS mutation (e.g. cancer, etc. ) (See abstract, Table 1, claims 10-19). Cho teaches compound species which is similar to instant elected species,
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30.
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/L.M./ Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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