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 1-20 are pending. Claims 8-20 are withdrawn. Claims 1-7 are rejected.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-10) and the species of formula (V) (per claim 7) in the reply filed on October 17, 2025 is acknowledged. The traversal is on the ground(s) that “restriction requirements are optional in all cases.” Remarks 14. This is not found persuasive because the traversal does not address the basis of the restriction requirement, which is the lack of unity of invention. Since PCT Rule 13.1 permits restriction based on lack of unity, and the claims were found to be lacking unity, the restriction is maintained and made final.
Claims 1-7 read on Applicant’s species election of
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. Examination of the elected invention was conducted in accordance with the MPEP 803.02.
The elected species was found allowable in view of the prior art; therefore, examination of the Markush-type claim has been extended to the scope of Formula (I)
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, wherein, X1 is O, X2 is N, R1 is H or CF3, and R2 is H, methyl substituted with 4-methoxyphenyl or ethyl substituted with NMe2 and 4-methoxyphenyl
Since art was found on a nonelected species, subject matter not embraced by the elected species or the rejected non-elected species is withdrawn from further consideration. Claims 8-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be amended in compliance with 37 CFR 1.48(b) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. Any amendment of inventorship must be accompanied by a request under 37 CFR 1.48(b) and by the fee required under 37 CFR 1.17(i).
Priority
This application is a 371 of PCT/US2021/056595, filed 10/26/2021 which claims benefit of PRO 63/198,532, filed 10/26/2020.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed provisional application, Application No. 63/198,532, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) for one or more claims of this application.
The ‘532 provisional application discloses three examples embraced by instant Formula (I),
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(claim 1). There is no disclosure of the elected species of instant claim 7. See, e.g., Fig. 2 and Table 1, shown in-part below:
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According to MPEP 2163(II)(A)(3)(ii), sufficiently describing a genus requires a description of a claimed genus disclosing either (1) “a representative number of species falling within the scope of the genus” or (2) “structural features common to the members of the genus,” either of which must enable “one of skill in the art [to] ‘visualize or recognize' the members of the genus.” The ‘532 application discloses a narrow subset of the Markush groups instantly claimed. The three examples in the ‘532 application correspond to instant Formula (I), (II), (III), (IV), wherein X1 is O, X2 is N, R1 is H or CF3, R2 is H or dimethylamino- and/or 4-methoxy-substituted benzyl or phenethyl. The ‘532 application provides no disclosure of a generic Markush group encompassing the above species, nor is there any disclosure of species or subgenus of instant Formula (I) wherein X1 is C or N, X2 is C, and R1 and R2 is F, OH or generic C1-20 hydrocarbyl groups. Since the limited disclosure does not provide a representative number of species and no Markush genus is disclosed, the ‘532 application does not provide adequate written description of the claims. Claims 1-7 are accorded an effective filing date of 10/26/2021
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/25/2023 and 8/18/2025 is in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. Accordingly, the IDS has been considered by the examiner and a signed copy is enclosed herewith.
Claim Objections
Claims 1, 3, 6 and 7 are objected to because of the following informalities:
Claims 1 and 3 recite “R1 and R2 are independently” instead of “R1 and R2 are each independently”.
Claims 3, 6 and 7 depict a “HCL” salt, wherein the “L” in “HCL” is improperly capitalized.
Claims 6 recites “Wherein” which is improperly capitalized.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-7 are rejected under 35 U.S.C. 112(b) being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(1 of 3) Claim 1 is a product claim that recites the intended-use limitation “used to treat an epithelial disease,” which is an indefinite intended use. According to MPEP 2173.05(q):
Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986).
In addition, “statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim.” MPEP 2111.02(II).
Since the intended use must be analyzed to determine the scope claimed, a “use” that is unclear renders the claim indefinite. The claimed “use” fails to set forth any steps involved in the process of use, which renders the “use” unclear. Therefore, claims 1-7 are indefinite for requiring an unclear intended use.
(2 of 3) Claim 1 defines R1 and R2 as “independently selected from the group consisting of -H, -OH, and substituted or unsubstituted (C1-C20) hydrocarbyl, and combinations thereof.” However, claims 2 and 4 recite an embodiment “wherein the (C1-C20) hydrocarbyl is selected from the group consisting of []…(C1-C20)alkoxy,… and combinations thereof.”
The specification defines “hydrocarbyl” as “a functional group derived from a straight chain, branched, or cyclic hydrocarbon, and can be alkyl, alkenyl, alkynyl, aryl, cycloalkyl, acyl, or any combination thereof” (p. 19 ll. 6-8). There is no definition of “combination thereof”; however, there is guidance in the definition of “cycloalkenyl”: “The term ‘cycloalkenyl’ alone or in combination denotes a cyclic alkenyl group.” Therefore, a “hydrocarbyl” of R1 and R2 in combination with another group (listed in R1 and R2) should still be a hydrocarbyl group.
In light of the specification, (C1-C20) hydrocarbyl and combinations thereof do not encompass (C1-C20)alkoxy. Since it is unclear and chemically untenable for a hydrocarbyl group to be an alkoxy group, claims 2 and 4 are indefinite.
(3 of 3) Claims 5 and 6 recite “Y1, Y2, and Y3 are independently selected from the group consisting of -C-, -N-, -O-, and combinations thereof”, referring to the ring atoms of Formula (III) and (IV),
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. Combining two or three elements (C, N and/or O) would appear to change the ring size if, for example, Y1 were -C-N=. Furthermore, the carbon atom would not have a satisfied valence, which would be chemically impossible. In light of the specification, no ring sizes other than 6-membered were contemplated for the “Y” ring. Additionally, when Y1, Y2 or Y3 are -C-, the carbon would have an unsatisfied valence, which would be chemically impossible. Since it is unclear and chemically untenable for Y1 or Y2 or Y3 to be -C- or a “combination” of -C-, -N- and -O- claims 5 and 6 are indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3 and 5 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 3 and 5 recite fluoro as an alternative for R1 and R2; however, claim 1 (from which claims 3 and 5 depend) does not permit R1 or R2 to be halogen. Therefore, claims 3 and 5 fail to further limit claim 1.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-7 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for treating gastrointestinal mucosal wounds, does not reasonably provide enablement for treating all epithelial diseases. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As stated in the MPEP 2164.01(a) and In re Wands, 8 USPQ2d 1400 (1988), in determining whether a disclosure meets the enablement requirement, factors to be considered are:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The Breadth of the Claims/Nature of the Invention
The claims are drawn to substituted-urea chemical compounds “used to treat an epithelial disease,” which encompasses a massive physiological genus of diseases. The invention seeks to treat epithelial disease by activating Focal Adhesion Kinase (FAK) with compounds of Formula (I),
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, which mimic a specific subdomain of the N-terminal FERM domain to block FAK-AKT binding and promote wound closure. See, e.g., Specification p. 22 ll. 14-24.
The State of the Prior Art and the Predictability or Lack Thereof in the Art
Both the chemical and physiological aspects of treating epithelial disease are highly unpredictable. Designing small molecule activators of allosteric interfaces (like the FERM-kinase interface) is unpredictable because protein conformational shifts are highly sensitive to steric interactions from bound molecules. Physiologically, the predictability of a uniform therapeutic response across the entire genus of “epithelial tissue” is scientifically unsupported.
Different epithelial tissues operate differently. For example, EGFR inhibitors can induce inflammation and cause a papulopustular rash (Lacouture, M. E., Nat. Rev. Cancer 2006, 6, 803-812, esp. p. 803 left column, p. 804 right column and Fig. 1). In the gastrointestinal tract, the EGFR inhibition does not cause a rash, but instead leads to an “endoplasmic reticulum (ER) stress response” that causes epithelial injury (Hong et al. Life Sci. 2014, 119, 28-33, esp. p. 28 abstract and p. 32 right column).
Regarding FAK, the prior art teaches that FAK activation does not always promote tissue repair. In some instances, FAK activation worsens epithelial disease, such as lung fibrosis. “FAK activation [] is a hallmark of fibrotic cells” and “we found a highly significant
association between the thickening of the media layer and the extent of FAK activation.” Lagares et al., Arthritis Rheum. 2012, 64, 1653-1664, at 1662.
FAK activation “increases with tumour progression” and “promotes cell motility, survival and proliferation” of tumours. Increased levels of FAK mRNA “are correlated with poor overall patient survival.” Sulzmaier et al., Nature Rev. Cancer 14.9, 2014, pp. 598-610, esp. p. 598 left column. See also Fig. 1a, showing a variety of epithelial carcinomas associated with increased FAK mRNA levels.
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Therefore, by claiming the treatment of all epithelial diseases with a FAK activator, the claim encompasses the treatment of conditions where the proposed mechanism of action is scientifically proven to exacerbate the disease.
The Amount of Direction Present and Presence or Absence of Working Examples
The specification limits its guidance and working examples to variations of the 1-(2-morpholino-5-(trifluoromethyl)phenyl)urea pharmacophore for treating gastrointestinal mucosal ulcers. There are no examples of compounds featuring fully aliphatic rings or larger hydrocarbyl substitutions. Also, there are no examples demonstrating the treatment of skin, lung, or corneal epithelial diseases, nor any examples treating epithelial carcinomas.
Level of Skill in the Art
A person having ordinary skill in the art would be a medicinal chemist with an advanced degree and experience in kinase drug discovery and molecular biology.
The Quantity of Experimentation Needed
Because the chemical and physiological art is highly unpredictable, the claims are structurally broad, and the specification provides guidance on treating a narrow subset of epithelial diseases, a PHOSITA would be required to engage in an undue amount of experimentation to treat all epithelial diseases with the claimed compounds. A PHOSITA would need to synthesize millions of compounds encompassed by Formulas I-IV and test them across different organ systems to identify operable FAK activators that ameliorate rather than exacerbate an epithelial disease. Since the results of FAK activation is unpredictable in different tissues, practicing the claimed invention requires an undue amount of experimentation.
This rejection may be overcome by replacing the limitation “used to treat an epithelial disease” with “for treating gastrointestinal mucosal wounds.”
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(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.
(1 of 2) Claims 1, 2 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al. ACS Med. Chem. Lett. 2021, 12, 356-364 (pub. Feb. 16, 2021).
Wang teaches FAK-activating compounds 5 and 6,
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. See, e.g., Fig. 2. These compounds anticipate the molecule of Formula I,
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, wherein X1 is O, X2 is N, R1 is H or CF3 (i.e., substituted C1-alkyl) and R2 is H, methyl substituted with 4-methoxyphenyl (i.e., substituted C1-alkyl) or ethyl substituted with NMe2 and 4-methoxyphenyl (i.e., substituted C2-alkyl), encompassed by claims 1, 2 and 5.
(2 of 2) Claims 1, 2 and 5 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Basson et al. WO 2019/199353 A1 (pub. Oct. 17, 2019).
Basson teaches “FAK-activating agents/compounds that can specifically promote epithelial restitution and mucosal healing” (p. 6 ll. 10-11). Compound M6 is representative:
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(p. 8 ll. 1), also labeled Formula VII
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(p. 11 ll.4-
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, wherein
X1 is O, X2 is N, R1 is H or CF3 (i.e., substituted C1-alkyl) and R2 is H or ethyl substituted with NMe2 and 4-methoxyphenyl (i.e., substituted C2-alkyl), encompassed by claims 1, 2 and 5.
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.
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.
(1 of 2) Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. ACS Med. Chem. Lett. 2021, 12, 356-364 (pub. Feb. 16, 2021).
Wang prepares FAK-activating compounds of instant claim 1 (namely, compounds 5 and
6), but not the HCl salts thereof, required by instant claims 3-4 and 6. See, e.g., Fig. 2.
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Wang teaches preparing HCl salts of the FAK activators and provides a few examples. “When required, the hydrochloride salts of these analogues were pursued following standard experimental procedures” (Wang 359 right column). “In order to enhance the solubility of 3 and at the same time facilitate treatment of cells or potentially intact organisms to induce FAK activation, we synthesized its hydrochloride salt 14 (Table S2). [] Similarly, to reduce the lipophilicity, we also pursued the removal of the CF3 moiety to obtain 15 and synthesized its corresponding hydrochloride salt 16” (Wang 360 right column).
Since compound 6 is a lead compound, a PHOSITA would have been motivated to optimize the compound’s pharmaceutical properties. Wang’s teachings about making HCl salts of the compounds would have guided the PHOSITA towards making the HCl salt of compound 6. Since Wang teaches how to make the salts and a PHOSITA would have expected that compound 6 could successfully be converted to its HCl salt using Wang’s process, the HCl salt of compound 6 would have been obvious. This HCl salt is embraced by the claims as follows:
Claim 1, Formula (I), wherein X1 is O, X2 is N, R1 is H or CF3 (i.e., substituted C1-alkyl) and R2 is H or ethyl (C2-alkyl) substituted with NMe2 and 4-methoxyphenyl, as the HCl salt.
Claim 2, wherein the hydrocarbyl is C1-alkyl or C2-alkyl, as the HCl salt.
Claim 3, Formula (II), wherein X1 is O, X2 is N, R1 is H or substituted C1-alkyl and R2 is H or substituted C2-alkyl.
Claim 4, wherein the hydrocarbyl is C1-alkyl or C2-alkyl.
+Claim 5, Formula (III),
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wherein R1 is H or -CF3 and Y1, Y2 and Y3 are -C-, in the HCl salt form.
Claim 6, Formula (IV), wherein R1 is H or -CF3 and Y1, Y2 and Y3 are -C-.
(2 of 2) Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over by Basson et al. WO 2019/199353 A1 in view of Stahl, P. H. Handbook of Pharmaceutical Salts: Properties, Selection, and Use. P. H. Stahl and C. G. Wermuth (Eds.), Verlag Helvetica Chimica Acta, Zürich, Switzerland, and Wiley-VCH, Weinheim, Germany. 2002.
Basson teaches “FAK-activating agents/compounds that can specifically promote epithelial restitution and mucosal healing” (p. 6 ll. 10-11). Compound M6 is representative:
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(p. 8 ll. 1), also labeled Formula VII
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(p. 11 ll.4-
5).
Basson also teaches that “[p]harmaceutically acceptable salts can be synthesized from the parent compound which contains a basic or acidic moiety by convention methods” (p. 20 ll. 27-28). However, Basson does not actually prepare any salts of the exemplified compounds, which salts are required by instant claims 3, 4 and 6.
Stahl categorized pharmaceutical salts based on their usefulness “into classes of first, second, and third choice” (p. 331). The “First Class” is reserved for “hydrochlorides/chlorides and sodium salts,” which “form physiologically ubiquitous ions or occur as intermediate metabolites in biochemical pathways” (p. 331). Figure 1 confirms that hydrochloride salts are the most frequently used pharmaceutical acid salts in drug formation.
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Since compound M6 is one of Basson’s lead compounds (see, e.g., p. 27), a PHOSITA would have been motivated to optimize the compound’s pharmaceutical properties. Since Basson teaches about making pharmaceutical salts of the parent compounds and since Stahl teaches that HCl are among the first salts a PHOSITA would choose to make, the PHOSITA would have been guided towards making the HCl salt of compound M6 in attempting to improve the compound’s properties. The PHOSITA would have expected that compound M6 could successfully be converted to its HCl salt using standard acid-base chemistry. The M6-HCl salt is embraced by the claims as follows:
Claim 1, Formula (I), wherein X1 is O, X2 is N, R1 is H or CF3 (i.e., substituted C1-alkyl) and R2 is H or ethyl (C2-alkyl) substituted with NMe2 and 4-methoxyphenyl, as the HCl salt.
Claim 2, wherein the hydrocarbyl is C1-alkyl or C2-alkyl, as the HCl salt.
Claim 3, Formula (II), wherein X1 is O, X2 is N, R1 is H or substituted C1-alkyl and R2 is H or substituted C2-alkyl.
Claim 4, wherein the hydrocarbyl is C1-alkyl or C2-alkyl.
+Claim 5, Formula (III),
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wherein R1 is H or -CF3 and Y1, Y2 and Y3 are -C-, in the HCl salt form.
Claim 6, Formula (IV), wherein R1 is H or -CF3 and Y1, Y2 and Y3 are -C-.
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.
(1 of 2) Claims 1, 2 and 5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of copending Application No. 18/412,006 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 8 of ‘006 teaches a compound of Formula VII
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,
which anticipates the molecule of instant Formula I,
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, wherein
X1 is O, X2 is N, R1 is H or CF3 (i.e., substituted C1-alkyl) and R2 is H or ethyl substituted with NMe2 and 4-methoxyphenyl (i.e., substituted C2-alkyl), encompassed by claims 1, 2 and 5.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(2 of 2) Claims 1-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of copending Application No. 18/412,006 in view of Basson et al. WO 2019/199353 A1 and Stahl, P. H. Handbook of Pharmaceutical Salts: Properties, Selection, and Use. P. H. Stahl and C. G. Wermuth (Eds.), Verlag Helvetica Chimica Acta, Zürich, Switzerland, and Wiley-VCH, Weinheim, Germany. 2002.
Claim 8 of ‘006 teaches a compound of Formula VII
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, but does not teach salts (e.g., HCl salt) thereof.
Basson teaches “FAK-activating agents/compounds that can specifically promote epithelial restitution and mucosal healing” (p. 6 ll. 10-11). Compound M6 is representative:
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(p. 8 ll. 1), which is identical to the compound of claim 8 of ‘006.
Basson also teaches that “[p]harmaceutically acceptable salts can be synthesized from the parent compound which contains a basic or acidic moiety by convention methods” (p. 20 ll. 27-28). However, Basson does not actually prepare any salts of the exemplified compounds, which salts are required by instant claims 3, 4 and 6 (and encompassed by instant claims 1, 2 and 5).
Stahl categorized pharmaceutical salts based on their usefulness “into classes of first, second, and third choice” (p. 331). The “First Class” is reserved for “hydrochlorides/chlorides and sodium salts,” which “form physiologically ubiquitous ions or occur as intermediate metabolites in biochemical pathways” (p. 331). Figure 1 confirms that hydrochloride salts are the most frequently used pharmaceutical acid salts in drug formation.
Compound M6 is one of Basson’s lead compounds (see, e.g., p. 27); therefore, a PHOSITA would have been motivated to optimize the compound’s pharmaceutical properties. Since Basson teaches making pharmaceutical salts of the parent compounds and since Stahl teaches that HCl salts are among the first salts a PHOSITA would choose to make, the PHOSITA would have been guided towards making the HCl salt of the claim 8 compound in attempting to improve the compound’s properties. The PHOSITA would have expected that the HCl salt could be formed using standard acid-base chemistry. The HCl salt of the claim 8 compound is embraced by the claims as follows:
Claim 1, Formula (I), wherein X1 is O, X2 is N, R1 is H or CF3 (i.e., substituted C1-alkyl) and R2 is H or ethyl (C2-alkyl) substituted with NMe2 and 4-methoxyphenyl, as the HCl salt.
Claim 2, wherein the hydrocarbyl is C1-alkyl or C2-alkyl, as the HCl salt.
Claim 3, Formula (II), wherein X1 is O, X2 is N, R1 is H or substituted C1-alkyl and R2 is H or substituted C2-alkyl.
Claim 4, wherein the hydrocarbyl is C1-alkyl or C2-alkyl.
+Claim 5, Formula (III),
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wherein R1 is H or -CF3 and Y1, Y2 and Y3 are -C-, in the HCl salt form.
Claim 6, Formula (IV), wherein R1 is H or -CF3 and Y1, Y2 and Y3 are -C-.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
Claim 7 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(a) and U.S.C. 112(b) set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
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/AMANDA L. AGUIRRE/ Primary Examiner, Art Unit 1626
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