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
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election of Group I without traverse in the reply filed on 08/21/2026 is acknowledged. Claims 1-7 and 11-15 read on the elected invention. Accordingly, claims 8-10 and 16-20 are withdrawn further consideration pursuant to 37 CFR 1.142(b).
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 5-6 and 14-15 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 that the polymorph is “crystalline form 1 of compound 1 hydrochloride”, “crystalline form 2 of compound 1 phosphate” and so on through “crystalline form 13 of compound 1”, and for each crystalline form recites a “characteristic X-ray powder diffraction peak at a 2θ value selected from” a listed group of values. However, it is unclear whether each crystalline form is defined by all of the recited X-ray powder diffraction peaks, one of the recited peaks, or some subset of the recited peaks. In particular, the phrase “selected from…and…” does not clearly establish whether a single peak is sufficient to characterize the polymorph or whether the entire set of listed peaks is required. Accordingly, the metes and bounds of claim 5 are unclear. Therefore, claim 5 is indefinite under 112(b).
Claim 6 recites DSC characteristics for “crystalline form 1,” “crystalline form 2,” and so forth, but as discussed above, claim 5 does not clearly establish the specific crystal form to which each recited DSC limitation corresponds. As a result, it is unclear whether the DSC limitations are intended to define the same polymorphs recited in claim 5 or to further limit them. Moreover, the use of “and/or” renders the claim scope ambiguous because it is unclear whether one, more than one, or all of the recited DSC peak sets are required. Accordingly, claim 6 is indefinite under 35 U.S.C. 112(b).
For the examination purpose, claims are construed that each crystalline form is defined by any one of the recited peaks or some subset of the recited peaks.
Claims 14 and 15 are included in this rejection because they include the limitations recited in claims 5 and 6, for the reasons above, do not the indefiniteness issues under 112(b).
Claim Rejections - 35 USC § 102
(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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-7 and 11-15 is/are rejected under 35 U.S.C. 102(1) as being anticipated by Guo et al. (WO2021083167A1, hereinafter “Guo”-CA3156777A1 is provided as English translation of WO’167, cited in the PTO-1449).
Guo discloses substituted heterocyclic fused cyclic compounds having selective inhibitory activity against KRAS gene mutation, pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising the compounds or salts. Guo specifically discloses compound
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(Z25-2), including a method for obtaining a single crystal thereof by dissolving the compound in isopropanol and allowing volatilization (see, e.g., abstract; description at pages 88 and 188; pages 108-112; page 225; claim 25). Guo further discloses that the compounds may be present as pharmaceutically acceptable salts, including inorganic acid salts such as phosphoric acid (see description at page 36).
Regarding claims 1-4, 7 and 11-15, claim 1 is anticipated by Guo to the extent it recites the disclosed compound or salt. Claim 2 is anticipated to the extent it recites a pharmaceutically acceptable salt expressly disclosed by Guo, including phosphoric acid salt. Claims 3 and 4 are anticipated because Guo discloses a single crystal form of compound Z25-2 obtained from isopropanol volatilization. Claims 7 and 11-15 are also anticipated since Guo discloses a pharmaceutical composition comprising said compounds in a pharmaceutically acceptable carrier (pages 60-61; claim 25).
Regarding claims 5-6 and 14-15, it is determined that claims 5-6 and 14-15 are likewise anticipated because the claimed crystalline forms are not clearly distinguished from the crystal form disclosed in Guo on the present record, particularly because the claims recite characteristic X-ray powder diffraction peaks in a manner that does not clearly require a full, unique diffraction pattern for each form. In the alternative, claims 5-6 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Guo as followings:
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 5-6 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO2021083167A1, hereinafter “Guo,” with CA3156777A1 provided as the English translation cited in PTO-1449) in view of Vippagunta et al. (“Crystalline Solids,” Advanced Drug Delivery Reviews 48 (2001), 3-26, hereinafter “Vippagunta”).
The teaching of Guo has been discussed in 102 rejection above. Guo is the closest prior art because it is directed to the same technical field and purpose as the claimed invention, namely KRAS inhibitory compounds and related pharmaceutical compositions. Guo discloses the parent compound, pharmaceutically acceptable salts thereof, and preparation of crystalline forms by routine crystallization techniques. The primary distinction between the claimed subject matter and Guo appears to reside in the recitation of particular crystalline forms of the salt and/or free base, as defined by characteristic X-ray powder diffraction peaks in claims 5-6 and 14-15.
Vippagunta teaches that polymorphs, solvates, and crystalline forms of active pharmaceutical ingredients are well known in the art, and that routine screening and characterization techniques are commonly used to identify crystalline forms having desirable properties, such as improved stability, handling, formulation, and bioavailability. See Vippagunta, abstract; pages 5-6, 11-13. Thus, one of ordinary skill in the art would have been motivated to prepare and screen the salts and crystalline forms disclosed by Guo in order to obtain alternative solid-state forms of the known active compound.
It would therefore have been obvious to a person having ordinary skill in the art at the time the invention was made to select the claimed salt forms and crystalline forms because salt screening and polymorph screening are routine in pharmaceutical development and would have been expected to yield predictable results. The claimed crystalline forms are merely expected variants of the known active ingredient, and the possibility that an active pharmaceutical ingredient may exist in different polymorphic forms with differing physical properties would have been well within the ordinary skill of the artisan, in absent evidence to the contrary.
With respect to any asserted improved properties, the present record does not provide persuasive evidence that such properties are commensurate in scope with the full breadth of the claimed subject matter. In particular, no comparative data have been provided for many of the recited forms, including forms 4, 5, 7, and 10-13. To the extent form 3 is alleged to exhibit improved hygroscopicity, solid-state stability, or formulation stability, the evidence of record does not establish that such properties are attributable to all of the claimed forms, nor that any such properties would have been unexpected over Guo in view of Vippagunta.
Accordingly, claims 5-6 and 14-15 would have been obvious over Guo in view of Vippagunta.
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 1-7 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-2 and 18 of U.S. Patent No. 12,054,497 B2 in view of Guo et al. (WO2021083167A1), and further in view of Vippagunta et al. (“Crystalline Solids,” *Advanced Drug Delivery Reviews* 48 (2001), 3-26).
Although the claims at issue are not identical, they are not patentably distinct from the claims of U.S. Patent No. 12,054,497 B2 because the claims of the ’497 patent either anticipate or render obvious the present claims. Specifically, claims 1-2 and 18 of the ’497 patent recite the same compound as that recited in present claim 1. Claim 2 of the ’497 patent also recites a pharmaceutical composition, which corresponds to the pharmaceutical composition recited in present claim 7.
As discussed above in the 35 U.S.C. 102 and 103 rejections over Guo, Guo discloses the parent compound, its salts, and crystalline forms prepared by routine crystallization methods. Vippagunta further teaches that polymorph screening, salt screening, and solid-state characterization are routine in pharmaceutical development, and that crystalline forms may be identified and distinguished by analytical techniques including X-ray powder diffraction. Accordingly, even though the copending application is silent as to the phosphate salt form and the particular crystalline form, it would have been obvious to a person having ordinary skill in the art, absent evidence to the contrary, to prepare and screen pharmaceutically acceptable salts and polymorphs of the disclosed compound in order to obtain crystalline forms having particular X-ray powder diffraction peak patterns.
In particular, the selection of a polymorph characterized by a specific XRPD peak or combination of peaks would have been an expected result of routine crystallization and screening efforts. Once the compound itself was known, one of ordinary skill in the art would have had a reasonable expectation of success in obtaining a crystalline form exhibiting a desired diffraction pattern through conventional polymorph screening, crystallization solvent selection, temperature variation, evaporation conditions, seeding, and other routine solid-state development techniques. Therefore, the claimed polymorph defined by a particular X-ray powder diffraction peak pattern would have been obvious to prepare and isolate.
Accordingly, claims 1-7 are not patentably distinct from claims 1-2 and 18 of U.S. Patent No. 12,054,497 B2 in view of Guo and Vippagunta.
Claims 1-7 are also rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 3, 24, and 31 of copending Application No. 18/381,121 in view of Guo et al. (WO2021083167A1), and further in view of Vippagunta et al. (“Crystalline Solids,” *Advanced Drug Delivery Reviews* 48 (2001), 3-26).
Although the claims at issue are not identical, they are not patentably distinct from the claims of the ’121 application because the claims of the copending application either anticipate or render obvious the present claims. Specifically, claim 24 of the ’121 application recites the same compound, e.g., Z25-2, as that recited in present claim 1. Claim 31 of the ’121 application recites a pharmaceutical composition, which corresponds to the composition recited in present claim 7. Claims 1-3 of the ’121 application recite a pharmaceutical composition comprising a compound of Formula (I), a pharmaceutically acceptable salt, a stereoisomer, a solvate, or a prodrug thereof, which overlaps with the structure recited in present claim 1 where R is CH3. Claims 4-5 of the ’121 application further disclose the same compound recited in present claim 1.
As discussed above, Guo teaches the parent compound, its salts, and crystalline forms, and Vippagunta teaches that routine salt and polymorph screening would have been obvious to one of ordinary skill in the art. Therefore, the claimed phosphate salt form and the polymorph defined by a particular X-ray powder diffraction peak pattern would have been obvious to prepare and screen, absent evidence to the contrary, with a reasonable expectation of success.
This is a provisional double patenting rejection because the claims directed to the same invention have not in fact yet been patented.
Claims 1-7 are also rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-5 of copending Application No. 18/853,078 in view of Guo et al. (WO2021083167A1), and further in view of Vippagunta et al. (“Crystalline Solids,” *Advanced Drug Delivery Reviews* 48 (2001), 3-26).
Although the claims at issue are not identical, they are not patentably distinct from the claims of the ’078 application because the claims of the copending application either anticipate or render obvious the present claims. Specifically, claims 1-3 of the ’078 application recite a pharmaceutical composition comprising a compound of Formula (I), a pharmaceutically acceptable salt, a stereoisomer, a solvate, or a prodrug thereof, which overlaps with the structure recited in present claim 1 where R is CH3. Claims 4-5 of the ’078 application further disclose the same compound recited in present claim 1.
As discussed above, Guo discloses the parent compound, its salts, and crystalline forms, and Vippagunta teaches that routine salt and polymorph screening would have been obvious to one of ordinary skill in the art. Accordingly, it would have been obvious to prepare and screen polymorphs having particular X-ray powder diffraction peak patterns, absent evidence to the contrary, using conventional crystallization and solid-state characterization techniques.
This is a provisional double patenting rejection because the claims directed to the same invention have not in fact yet been patented.
Conclusion
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/BRIAN-YONG S KWON/Supervisory Patent Examiner, Art Unit 1613
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