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, filed 04/13/2023, is a 371 filing of PCT/US2021/054662, filed 10/13/2021, which claims domestic priority to U.S. Application no. 63/091,703, filed 10/14/2020.
Preliminary Amendments and Claim Status
The preliminary amendment filed on 10/27/2023 is acknowledged and entered.
Claims 5, 7, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 29 are amended;
Claims 6, 9, 11, 13, 15, 17, 19, 21, 22, 25, 27, are cancelled;
Claims 1-5, 7, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 29-31 are pending and are under current prosecution.
Information Disclosure Statement
The Information Disclosure Statement filed on 01/02/2024 is acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statement is considered.
Claim Interpretation
The claims are subject to the following interpretation
As there are no specific embodiments of a compound of Formula (I) named, or drawn in two-dimensions within the instant claims, the preferred embodiments as detailed within the instant specification (page 12-22 and page 27-30), are interpreted to be intended and possessed exemplifications of the instantly claimed compounds.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of pre-AIA 35 U.S.C. § 103 which forms the basis for all obviousness rejections set forth in this Office action:
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 1-5, 7, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 29-31 are rejected under 35 U.S.C. § 103 as being unpatentable over Zhang et al. (WO 2015057873 A1, published April 23, 2015, cited on applicant IDS dated January 2, 2024), hereinafter Zhang, in view of Patani et al., (Chem Rev, Volume 96, Issue 8, pg. 3147-3176, published December 19, 1996), hereinafter Patani.
The instant claims are drawn to a compound of Formula (I), and a pharmaceutical composition thereof. The claims are further drawn to a method of treating a disease or condition (systemic mastocytosis and gastrointestinal stromal tumors comprising the administration of a compound of Formula (I).
Zhang discloses compounds and compositions useful for treating disorders related to mutant KIT (Abstract). Zhang teaches compound 63 (page 32) also known as CAS Registry Number: RN 1703793-67-2. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 1703793-67-2, Entered STN: 13 May 2015] which is directly compared to a compound of formula 1, as well as embodiment D56 found on page 17 of the instant specification in Figure 1, below. Zhang teaches wherein the compounds described may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compound, such as deuterium (2H) (page 9, lines 18-20). Zhang teaches wherein the compounds claimed are useful for treating conditions associated with aberrant KIT activity, in humans or non-humans, including systemic mastocytosis, GIST (gastrointestinal stromal tumors) (page 45, lines 1-4). The disclosure further details both indolent and smoldering systemic mastocytosis as explicit disorders of systemic mastocytosis (page 45, lines 7-13).
Figure 1. Structural comparison of prior art compound, instantly claimed Formula (I), and a specific embodiment of the instant specification
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Figure 1. a) Zhang CAS Registry Number: RN 1703793-67-2; b) instantly claimed formula (I); c) Embodiment D56 on page 17 of the instant specification
The teachings by Zhang render obvious the instant claims, wherein
A is CH2CH3
Ra-Rs are H
R1 is C(R2)3 and R2 is H
Although Zhang teaches compounds of similar structure and provides several embodiments, the compounds taught do not appear to anticipate the instant claims.
The deficiencies of Zhang in teaching the exact compounds claimed, specifically the ethyl alcohol substituent at position A, and embodiments that feature the substitution of deuterium for hydrogen in the instant claims is remedied by Patani, who teaches rational approaches in drug design, which encompass substitutions used by those skilled in the art to develop novel and more-potent therapeutics.
Wherein A is CH2CH3 in the prior art compound, and A is CH2CH2OH in the instantly claimed: this substitution of H for OH is considered to be a classical bioisosteres, well-known to the ordinary artisan in skilled in rational drug design. With respect to classical Bioisosteres, Patani teaches that the substitution of Hydrogen by Hydroxide is one of the more commonly employed isosteric replacements (page 3152, section II, segment A, item 4 of Patani). This teaching is based on Grimm’s Hydride displacement law which describes how chemical groups can mimic each other, and is one of the most crucial lead modification tools in rational drug design. Therefore, it would’ve been obvious for a person having ordinary skill in the art prior to the effective filing date to modify the compounds described by Zhang to include Hydroxide in the place of Hydrogen, as taught by Patani on the A substituent, in order to chemically modify the original compounds.
Although not explicitly exemplified within a specific embodiment from the disclosure, Zhang teaches compounds of Formula (I)
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, and specifically discloses wherein Z is a C1-C6 alkyl, independently substituted with RC (page 2, lines 12-17), wherein RC (is OR2) (page 3, line 10), and R2 is H (page 3, line 18) , effectively yielding CH2CH2OH at the instantly claimed position A. This teaching is in the prior art by Zhang, would specifically motivate a person of ordinary skill in the art to modify CH2CH3 in the prior art compound, to CH2CH2OH, following the teachings of Patani, to arrive at the substituent as instantly claimed (see claims 2-4 and 7).
In addition to the explicit teaching of isotopic substitution (Hydrogen for Deuterium) within the disclosure by Zhang (page 9, lines 18-20), the courts also have determined that such a substitution will yield compounds which are obvious variants of each other. The courts have stated:
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)).
Thus, substitutions for Hydrogen found in the prior art embodiments by Deuterium in the instant claims produce compounds which are considered to be obvious variants.
Therefore, all the limitations of the instant claims are rendered obvious in view of the prior art teachings. The prior art is not anticipatory insofar as these combinations must be selected from various lists/locations in the reference, and there is no specific embodiment of a compound of Formula (I) as detailed by Zhang which anticipates the instantly claimed. It would have been obvious, however, to make the combination since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art (see MPEP § 2143 (I)(A)).
In the interest of compact prosecution and brevity, the aforementioned teachings are individually applied to all claims, and the claims thus, stand 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 1-5, 7, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 29-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of U.S. Patent No. U.S. 10,829,493 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent document would lead to the creation of compounds as well as methods that directly overlap with the instantly claimed compounds.
The patent teaches a long list of compounds which overlap with the instantly claimed. In the interest of brevity, only one will be addressed. Claim 8 and 9 within the patent document teach CAS Registry Number: RN 2505078-08-8. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 2505078-08-8, Entered STN: 05 Nov 2020]. This compound is compared to the instantly claimed compound of Formula (I). This is compared to the embodiment D56 found on page 17 of the instant specification, in Figure 2 below. The patent document also claims a method of treating systemic mastocytosis and gastrointestinal stromal tumors (claim 36) as well as indolent systemic mastocytosis (claim 39), overlapping in scope with claims 29-31 of the instant application.
Figure 2. Structural comparison of prior art compound, instantly claimed Formula (I), and a specific embodiment of the instant specification
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Figure 2. a) Zhang CAS Registry Number: RN 2505078-08-8; b) instantly claimed formula (I); c) Embodiment D56 on page 17 of the instant specification
Wherein the compounds found within the patent document feature Hydrogen in the place of Deuterium within the instantly claimed compounds, the courts also have determined that such a substitution will yield compounds which are obvious variants of each other. The courts have stated:
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)).
Thus, substitutions for Hydrogen found in the prior art embodiments by Deuterium in the instant claims produce compounds which are considered to be obvious variants.
Claims 1-5, 7, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 29-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 58 and 62 of copending Application No. 18/549,769, (reference application, US 20240254130 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the co-pending application document detail a compound as well as a method that directly overlap with the instantly claimed compounds.
Claim 58 within the co-pending application teaches CAS Registry Number: RN 2505078-08-8. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 2505078-08-8, Entered STN: 05 Nov 2020], as shown in Figure 2, above. The method of claim 62, drawn to the treatment off indolent systemic mastocytosis comprising the administration of RN 2505078-08-8 to a patient within the co-pending application overlaps in scope with claims 29-31 of the instant application.
The exemplary compound RN 2505078-08-8 which overlaps in scope with the instant claims as rejected in the previous nonstatutory double patenting rejection over US 10829493 B2 is herein incorporated, in the interest of brevity.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. If a notice of allowance is issued in the co-pending application 18/549,769, upon issue of the patent, the provisionary NSDP rejection over the co-pending application will convert to a NSDP rejection over the published patent.
Conclusion
No claim is allowed.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623