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, 3, 5, 25, 26, 28-37 are pending. Acknowledgment is made of the amendment to claims 28, 30, 31, and 34-36, and the cancellation of claim 27, in the reply filed 02/24/2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/24/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restriction Requirement
Claims 25, 26, and 28-37 are allowable. Claims 1, 3, and 5, previously withdrawn from consideration as a result of a restriction requirement, require all the limitations of an allowable claim. Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement among inventions Groups I-III, as set forth in the Office action mailed on 10/22/2024, is hereby withdrawn and claims 1, 3, and 5 are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Withdrawn Rejections
Applicant’s amendment to the claims, filed 02/24/2026, overcomes the rejection of claims 27 and 30-36 under 35 U.S.C. 112(a) for scope of enablement. The rejection of claims 27 and 30-36 has been withdrawn.
New Rejections
Necessitated by Claim Amendment, Over Previously Withdrawn Claims
Improper Markush Grouping
Claims 1 and 3 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of Formulas (I) and (II) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the various permutations of variables Ar1, Ar2, B, L, R1, R2, R3, n and m in Formula (I) results in compounds that do not require a structural similarity. The various permutations of variable Ar, D, E, L AA, R1, R2, R3, and m in Formula (II) results in compounds that only require a structure of an amine in common, which is not a significant structural similarity. The varying permutations in Formulas (I) and (II) are not recognized to belong to the same physical or chemical class or to be the same art-recognized class.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. There would appear to be several different ways in which a proper Markush grouping could be derived from the scope instantly claimed. However, defining the Ar1 or Ar2 variables of Formula (I), and the D and E variables of Formula (II), to constitute a common core structure would appear to be a minimum requirement.
Claim Rejections - 35 USC § 112
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, 3, and 5 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for compounds of Formula (I) where B is NR4 or (CH2)1-3, Ar1 is thiazole, pyrazole, or
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, and Ar2 is pyridine, pyrimidine, or pyrrole; compounds of Formula (II) where D is N and Ar is thiazole or pyrazole; and compounds of Formula (III) where E is N and B is NR7, does not reasonably provide enablement for compounds of Formulas (I), (II), and (III). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention
The nature of the invention relates to compounds of Formulas (I), (II), and (III) in claims 1, 3, and 5. Such compounds are useful for the inhibition of tyrosine kinases FMS, KIT, FLT-3, FGR, and RON. This invention is also directed to compositions comprising said compounds.
Predictability of the art
The compounds synthesized in the instant specification appear novel. However, the hypothetical compounds in claims 1, 3, and 5 would be unpredictable in terms of one skilled in the art being able to synthesize every possible compound claimed in instant claims 1, 3, and 5. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of skill in the art
An ordinary artisan in the area of drug development would have experience in synthesizing and screening chemical compounds for particular activities, such as a medical doctor or chemist. Screening of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target, (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems.
4. The breadth of the claims
The scope of the claims involves compounds of Formulas (I), (II), and (III), shown below.
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Claims 1, 3, and 5 are very broad in the number of variables and the options of substituents for each variable. There is an extremely large amount of hypothetical compounds included in claims 1, 3, and 5.
5. The amount of direction provided, the presence or absence of working examples, and the quantity of experimentation necessary
The specification only provides the synthesis of 30 compounds. In all of the compounds of Formula (I) synthesized, B is NR4 or (CH2)1-3, Ar1 is thiazole, pyrazole, or
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, and Ar2 is pyridine, pyrimidine, or pyrrole. In the compounds of Formula (II) synthesized, D is N and Ar is thiazole or pyrazole. In the compounds of Formula (III) synthesized, E is N and B is NR7.
Synthesis methods are not taught in the specification to provide for the aforementioned variables to include all of the possible substituents listed in the claims. It would be expected that the varying ring sizes (e.g., Ar1, Ar2, Ar) and heteroatoms in the rings (e.g., variables Ar1, Ar2, Ar, D, E) would change the reactivity of the compounds, and therefore would require alternate synthesis methods. It could also be possible that some combinations of compounds may not be able to be synthesized due to their instability. It would require one skilled in the art, such as a chemist, to perform thousands of reactions to determine which compounds of Formulas (I), (II), and (III) can be prepared and would require synthesis methods other than those provided in the specification. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Takasaki et al. (WO 2013157540 A1).
Takasaki et al. teaches, in paragraph [0002], compounds that inhibit type III tyrosine kinases, specifically FLT3, c-KIT, and FMS. One specific compound taught, in Table 166, is compound 10-40, shown below.
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In this compound, with respect to Formula (I) of instant claim 1, R2 is OMe, Ar2 is pyridinyl, B is NH, Ar1 is pyrimidinyl, n is 1, m is 1, AA is
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, R4 is methyl, R5 is methyl, R3 is COCH=CHCH3 substituted by R6, wherein R6 is NMe2, R1 is D-Ar3, D is NH, Ar3 is phenyl substituted with F.
In this compound, with respect to Formula (II) of instant claim 3, R2 is H, Ar is pyridinyl, D is N, E is N, m is 1, AA is
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, R4 is methyl, R6 is methyl, R5 is OMe, R3 is COCH=CHCH3 substituted by R6, wherein R6 is NMe2, R1 is B-Ar1, B is NH, Ar1 is phenyl substituted with F.
This compound differs from instant claims 1 and 3 in that L is C≡C-(CH2)3-NH-, rather than (CH2)5-NH-. The L group of this compound contains an alkyne rather than an alkane. The compound differs from instant claim 3 in that the L group is a positional isomer, attached to a different point of the pyrimidinyl ring than in instant Formula (II).
However, -----regarding close structural similarity, MPEP 2144.09 I states: “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).”
Regarding positional isomers, MPEP 2144.09 II states: “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).”.
Therefore, instant Formulas (I) and (II) are rendered prima facie obvious in view of the close structural similarity of the compounds of the prior art, since the compounds of the instant invention are taught to be used for the same purpose as the compounds of the prior art, and only differ in structure with the alteration of an alkyne to an alkene, which would be expected to have the same physical properties.
Conclusion
Claims 25, 26, and 28-37 are allowed.
Claims 1, 3, and 5 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RILLA M SAMSELL whose telephone number is (703)756-5841. The examiner can normally be reached Monday-Friday, 7-3.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624