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 .
Election/Restrictions
Applicant's election with traverse of Group I (Claims 1, 2, 5, 19, 26, 27, 41, 42, 45, 48, 58, 98, 103, 106, 121, 130, 132, and 141) and the species Example 16
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, which reads on Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 in the reply filed on 17 March 2026 is acknowledged. The traversal is on the ground(s) that it has not been shown that examining all claimed subject matter would impose a serious search burden. This is not found persuasive because the restriction was not due to the imposition of a serious search burden, but rather due to the lack of unity of species due to the presence of compounds which render the compounds of Group I obvious, as explained in the restriction requirement. Thus, there is no unity of invention.
The requirement is still deemed proper and is therefore made FINAL.
Claims 19, 41, 42, 45, 48, 58, 103, 121, 130, 136, and 138 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species and group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 17 March 2026.
Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141, submitted on 15 May 2024, represent all claims currently under consideration.
Priority
This application is a 371 of PCT/CA2022/050678, filed 2 May 2022, which claims priority to provisional US 63/182,203, filed 30 April 2021. The effective filing date is 30 April 2021.
Information Disclosure Statement
One Information Disclosure Statement (IDS), submitted on 15 May 2024, is acknowledged and has been considered.
Claim Objections
Claim 1 is objected to because of the following informalities: The definition for variable R6a and R6b is missing “member” or “carbon” in the limitation of “3- to 6- saturated or unsaturated ring”. Appropriate correction is required.
Claim 5 is objected to because of the following informalities: There appears to be a superfluous comma after R6C in the definition for Q. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 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 the claimed invention. Factors to be considered in making the determination as to whether one skilled in the art would recognize that applicant was in possession of the claimed invention as a whole at the time of filing include : (a) Actual reduction to practice; (b) Disclosure of drawings of structural chemical formulas; (c) Sufficient identifying characteristics such as: (i) Complete structure, (ii) Partial structure, (iii) Physical and/or chemical properties or (iv) Functional characteristics when coupled with a known or disclosed correlation between function and structure; (d) Method of making the claimed invention; (e) Level of skill and knowledge in the art and (f) Predictability in the art. While all of these factors are considered, a sufficient number for a prima facie case are discussed below:
The claims are directed to compounds of Formula (I), as well as their prodrugs. The specification states that “the term “prodrug” as used herein means a compound, or salt and/or solvate of a compound, that, after administration, is converted into an active drug (Paragraph 056)”. The specification does not provide any examples of moieties which can function as prodrugs within the compound, nor does it demonstrate that compounds of the invention are capable of undergoing metabolic transformation into biologically active forms due to the cleavage of a prodrug functional group. Pro-drugs can be structurally distinct from the parent compound, but from the claim language and specification, it is unclear if Applicant is in possession of the other types of pro-drugs. For example, glucose and hypoxanthine are pro-drugs which do not contain a carbonyl group. The specification provides no indication of what can be considered a “pro-drug” outside of the definition in paragraph 056. Table 2 (Page 741) contains all compounds which are fully defined for this application, and does not contain compounds with moieties that function as prodrugs. The artisan would recognize what a prodrug is, and how these function, as well as which moieties are commonly employed in the use of prodrugs. However, without guidance from the specification as to what moieties can function as prodrug, as well as where within the compound these moieties can be placed and allow the compound to retain biological activity, the artisan would have no predictability in practicing this invention as claimed. Thus, there is no support in the specification that Applicant was in possession of the invention as a whole at the time of filing.
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.
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 1, 2, 5, 26, 27, 98, 106, and 141 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 1 has the limitation of “wherein all available hydrogen atoms are optionally substituted with a fluorine atom”. This statement is indefinite because it is unclear if the hydrogen atoms form a cation by binding to a fluorine atom (forming a -H+-F moiety), or if the limitation should be interpreted as the hydrogens can be replaced by fluorine. Claims 2, 5, 26, 27, 98, 106, and 141 are rejected as indefinite for depending upon an indefinite claim without resolving the underlying issues of indefiniteness.
Claims 1, 2, 5, 26, 27, 98, 106, and 141 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 1 has the limitation of “Q is C1-C4 alkylene optionally interrupted by a heteromoiety selected from O, S, S(O), S(O)2, and NR5 and/or optionally substituted with one or more R6 and/or optionally disubstituted on one carbon with R6a and R6b” (emphasis added). It is unclear how the limitation “and/or” modifies the claim, leading to indefiniteness. Claims 2, 5, 26, 27, 98, 106, and 141 are rejected as indefinite for depending upon an indefinite claim without resolving the underlying issues of indefiniteness.
Claim 132 is 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. There is a lack of antecedent basis for the compound I-424
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as the heteromoiety is not separated from the ring amide by other than methylene, which is required in Claim 1.
Claim 132 is 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. There is a lack of antecedent basis for the compound I-465
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as the nitrogen in the ring amide is substituted with NH-2, which has no antecedent basis in Claim 1 as this moiety is only noted as being NH.
Claim 132 is 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 132 is indefinite due to the reference to table. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (See MPEP § 2173.05 (s)).
Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 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. The claims are indefinite because the claims have the limitation of “and/or prodrug”. It is unclear if the claim is directed to both a parent compound (the prodrug) along with the active/metabolite form of the drug. The claim should be directed to one singular compound. The Examiner suggests amending the claim to read “or prodrug” to overcome this rejection.
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claim 132 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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. The compound I-424
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of Table 2 is broader than, and thus does not further limit, Claim 1 as the heteromoiety (SO2) is not separated from the ring amide by other than methylene. Claim 1 requires that this moiety is separated from the amide by other than methylene. The compound I-465
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has the nitrogen in the ring amide is substituted with NH-2, which is not found in Claim 1, causing Claim 132 to be broader than claim 1, and thus does not further limit claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 are rejected under 35 U.S.C. 103 as being unpatentable over Augeri (US 2012/0225857; Publication Date: 6 September 2012) in view of Meanwell (Journal of Medicinal Chemistry, 2018, 61, 5822-5880).
Augeri (See IDS, 15 May 2024) discloses compounds which inhibit mammalian Ste20-like kinase 1 (MST1), along with their compositions and methods of use in the treatment of diseases (Abstract). The invention is directed to compounds useful for the inhibition of MST1. One embodiment of the invention encompasses compounds of the formula
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(Paragraph 0004). Another embodiment encompasses a formulation comprising a compound of the invention and a pharmaceuticalyl acceptable excipient (Paragraph 0005). Particular compounds of the invention are of the formulae
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wherein Y1 and Y2 are independently N or CH, r is 1 or 2, and R4 is hydrogen or alkyl (Paragraph 0047). Other compounds are of the formula
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(Paragraph 0056). Compounds of the invention include
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(Paragraph 0103),
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(Paragraph 0110),
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(Paragraph 0116),
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(Paragraph 0165), and
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(Paragraph 0191). These compounds, along with many others, are shown in Table 1 to have the ability to inhibit MST1 in vitro (Paragraphs 0236, 0237). The compound
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was tested in vivo and was shown to significantly reduce clinical manifestations of EAE in a disease model (Paragraph 0243, Figure 2A). The compound
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in a rat EAE model, hepatitis model, mouse EAE model, and collagen-induced arthritis model, and showed significant clinical responses (Paragraphs 0249-0252, Figures 7A, 7B, 8, 9A, 9B, 10A, 10B, 10C, and 10D). These compounds each have X1, X2, and X3 as CH, Q as C2 alkylene, Cy1 as phenyl or heteroaromatic, with different R9 substituents.
Augeri does not teach halogenation, in particular, fluorination, at the analogous R1 or R2 location.
Meanwell teaches the use of fluorine and fluorinated motifs in drug development and their use as bioisosteres. The electronic properties and relatively small size of fluorine endow it with considerable versatility as a bioisostere and it has found application as a substitute for lone pairs of electrons, the hydrogen atom, and the methyl group while also acting as a functional mimetic of the carbonyl, carbinol, and nitrile moieties. Fluorine substitution can influence the potency, conformation, metabolism, membrane permeability, and P-gp recognition of a molecule (Abstract). The use of bioisosteres is a common principle in drug design. Introduction of fluorine can increase the overall lipophilicity of a molecule (Page 5823). The replacement of hydrogen with fluorine can lead to resistance towards oxidative metabolism, and fluorination has developed into a popular approach to address the poor pharmacokinetic performance of drug-like compounds in vitro and in vivo (Page 5824). The judicious replacement of a hydrogen atom in aromatic and heteroaromatic rings by a fluorine atom can exert a significant impact on the properties of a molecule that are beneficial to both drug design and development. An early focus of the introduction of fluorine to aromatic rings was as a tactic to slow metabolism. Fluorine is also introduced in order to improve the membrane permeability of compounds, improving bioavailability. Introduction of fluorine ortho- to an NH influences conformation, which resulted in both improved binding to the protein target, as well as improved pharmacokinetics and solubility (Replacing Hydrogen by Fluorine in Aromatic Rings).
Augeri and Meanwell are considered analogous to the claimed invention as all are involved in drug development and design. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the cited compounds of Augeri by fluorination of the central pyridine ring as Meanwell teaches that fluorination, in particular, the fluorination of aromatic and heteroaromatic moieties, is commonly employed in drug development to improve the metabolic properties of compounds, enhance permeability, and has been shown to result in improved binding efficacy when placed proximal to an NH group, as is seen in the compounds of the examined application. The fluorination of the kinase inhibitors of Augeri in view of the teachings of Meanwell is prima facie obvious application of a known technique to a known product ready for improvement to yield predictable results (See MPEP § 2143 I (D)); the compounds of Augeri are shown to be effective both in vitro and in vivo, and fluorination is a known method to improve pharmacokinetic and pharmacodynamic properties. The artisan would recognize this, and would be motivated to select one of the cited compounds for improvement as they are shown to have inhibitory activity, predictably resulting in a compound which inhibits MST1. The fluorination of these compounds is also prima facie obvious as the only difference is the presence of a fluorine atom, and the artisan would not expect these compounds to have significantly different properties due to the close chemical structure (See MPEP § 2144.09 I).
Regarding Claim 132, Compound I-65
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differs from
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by the placement of fluorine. As described previously, the artisan would not expect this modification to significantly alter the properties of the resulting compound due to the close chemical structure (See MPEP § 2144.09 I).
Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 are rejected under 35 U.S.C. 103 as being unpatentable over Gray (WO 2016/161145; Publication Date: 6 October 2016) in view of Meanwell (Journal of Medicinal Chemistry, 2018, 61, 5822-5880).
Gray (See IDS, 15 May 2024) discloses compounds of Formula (I’) which modulate the activity of a kinase (e.g., STK4), a pharmaceutical composition comprising the compound, and a method of treating a disease or disorder associated with the modulation of a kinase such as STK4 (Abstract). The compounds of the invention are of Formula (I’) or (I):
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(Paragraph 0006). In another embodiment, the compounds of Formula (I) have the structure of Formula (Ic) or (Id)
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wherein
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(Paragraph 00396). Paragraph 00462 contains a table which lists several compounds which render those of the examined application obvious, such as I-3
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, I-2
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, I-6
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, I-12
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, I-20
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, I-21
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, I-27
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, I-28
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, I-38
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, I-40
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, I-41
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, I-49
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, I-51
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, I-59
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, I-63
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, and I-71
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, among others found within the table. These compounds each have X1, X2, and X3 as CH, Q as C2 alkylene, Cy1 as phenyl with different R9 substituents. Table 1 (Beginning on Page 202) lists the activity of the claimed compounds against various kinases, and shows that these compounds have low nanomolar inhibitory capacity against STK4, with several being highly specific for SKT4 alone. Another aspect of the invention relates to a pharmaceutical composition comprising a compound of any of the formulae described herein and a pharmaceutically acceptable carrier (Paragraph 0007).
Gray does not teach fluorination or halogenation at the analogous variable R1 or R2 positions.
The teachings of Meanwell are previously described and are fully incorporated into this rejection.
Gray and Meanwell are considered analogous to the claimed invention as in drug development and design. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the cited compounds of Gray by fluorination of the central pyridine ring as Meanwell teaches that fluorination, in particular, the fluorination of aromatic and heteroaromatic moieties, is commonly employed in drug development to improve the metabolic properties of compounds, enhance permeability, and has been shown to result in improved binding efficacy when placed proximal to an NH group, as is seen in the compounds of the examined application. The fluorination of the kinase inhibitors of Gray in view of the teachings of Meanwell is prima facie obvious application of a known technique to a known product ready for improvement to yield predictable results (See MPEP § 2143 I (D)); the compounds of Gray are shown to be effective both in vitro and in vivo, and fluorination is a known method to improve pharmacokinetic and pharmacodynamic properties. The artisan would recognize this, and would be motivated to select one of the cited compounds for improvement as they are shown to have inhibitory activity, predictably resulting in a compound which inhibits STK4. The fluorination of these compounds is also prima facie obvious as the only difference is the presence of a fluorine atom, and the artisan would not expect these compounds to have significantly different properties due to the close chemical structure (See MPEP § 2144.09 I). Several of the cited compounds such as
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are isomers of compounds of the examined application, having the fluorine in a different location than what is claimed. As these are structural isomers which merely differ by the placement of the fluorine atom, the artisan would not expect these compounds to have significantly different properties from the parent compound.
Regarding Claim 132, Compound I-16
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and I-19
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differ from
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by the presence of fluorine on the central ring, as well as the presence of an NO2 group. The artisan would not expect moving the fluorine to the pyridine ring, and the removal of the NO2 group to significantly alter the properties of the parent compound due to the close chemical structure (See MPEP § 2144.09 I).
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, 2, 5, 26, 27, 98, 106, 132, and 141 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 25, 27, 132 and 141 of copending Application No. 18/288,222 (Amended Claims of 14 May 2024) (‘222) in view of Thornber (Chemical Society Reviews, Issue 4, 1979).
Claim 1 of ‘222 is directed to a compound of Formula (I)
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which has identical limitations to the compounds of the examined application, save for requiring that one of variable X4 or X5 is N with the other being CR3. Claim 25 is directed to the compound of Claim 1 wherein X4 is N and X5 is CR3. Claim 27 is directed to the compound of claim 1 wherein Cy1 is phenyl and is unsubstituted or is substituted with one or more R9, or is substituted with Z-Cy2 or is substituted with Z-Cy2 and one or more of R11. Claim 132 is directed to a compound of Claim 1 found in Table 1, such as I-1
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. This table contains dozens of compounds which only differ from those claimed in the examined application by the central ring being pyrazine rather than pyridine. Claim 141 is directed to a pharmaceutical composition comprising a compound of Claim 1 and a pharmaceutically acceptable excipient.
‘222 does not teach that the central ring is pyridine.
Thornber teaches the concept of bioisosterism, which is the concept wherein groups or molecules which have chemical and physical similarities produce broadly similar biological properties (Page 563). Table 1 (Page 564) lists the classical isosteres, and includes ring equivalents. Such ring equivalents include -CH=CH-, =CH-, =N-, and S. These atoms have similar electronic properties and as such, their replacement within a ring system is not expected to significantly alter the properties of that ring.
‘222 and Thornber are considered analogous to the claimed invention as all are involved in drug development and design. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the compounds of ‘222 by replacing the central pyrazine ring with pyridine as Thornber teaches that =N- and =CH- function as ring equivalents, and thus the artisan would not expect the properties of these compounds to be significantly altered by performing this substitution as due to the close chemical structure (See MPEP § 2144.09 I). The artisan would expect these compounds to have similar properties, and would not expect there to be significant differences in activity by performing this substitution.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 72, 129, and 130 of copending Application No. 18/288,219 (Amended Claims of 14 May 2024) (‘219) in view of Thornber (Chemical Society Reviews, Issue 4, 1979). and Meanwell (Journal of Medicinal Chemistry, 2018, 61, 5822-5880).
Claim 1 of ‘219 is directed towards a compound of Formula (I)
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246
291
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which has identical limitations to the compounds of the examined application, save for requiring that at least one of X4 and X5 is N. Claim 72 of ‘219 is directed towards a compound of Formula (II)
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271
277
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which has identical limitations to the compounds of the examined application, save for requiring that at least one of X9 and X10 is N. Claim 129 of ‘219 is directed towards a compound of Claim 72 selected from Table 1-A, such as II-1
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131
263
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. Claim 130 of ‘219 is directed to a pharmaceutical composition comprising a compound of Claim 1 and a pharmaceutically acceptable carrier or diluent.
‘219 does not teach that the central ring is pyridine, or the fluorination of the pyridine ring.
The teachings of Thornber and Meanwell are previously described and are fully incorporated into this rejection.
‘219, Thornber, and Meanwell are considered analogous to the claimed invention as all are involved in drug design and development. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the compounds of ‘219 in view of the teachings of Thornber and Meanwell by replacing the central pyrazine ring with a pyridine ring which is fluorinated. Thornber teaches that =N- and =CH- function as ring equivalents, while Meanwell teaches that fluorination is commonly employed to enhance pharmacokinetic and pharmacodynamics. Fluorination as taught by Meanwell is prima facie obvious application of a known technique to a known product ready for improvement to yield predictable results (See MPEP § 2143 I (D)); the compounds of ‘219 are shown to be effective both in vitro and in vivo, and fluorination is a known method to improve pharmacokinetic and pharmacodynamic properties. Moreover, the artisan would not expect the properties of these compounds to be significantly altered by performing these modifications due to the close chemical structure (See MPEP § 2144.09 I). The artisan would expect these compounds to have similar properties, and would not expect there to be significant differences in activity by performing these changes.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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/P.M.R./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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