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 .
Current Status of 18/266,793
This Office Action is responsive to the amended claims and Applicant remarks of 04/17/2026. Claims 1, 20, 25, 27, 30, 38-40, 43-44, 46, 49-52, and 54-58 are pending and have been examined on the merits.
Priority
The instant application is a national stage entry of PCT/US2021/063724, filed 12/16/2021, which claims priority to U.S. Provisional Patent Application No. 63/126,364, filed 12/16/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/17/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments and Amendments
In response to the rejections under 35 U.S.C. §112(b), Applicants have amended the claims language of claims 1, 25, and 30 to remove the phrase "optionally substituted." This amendment clearly establishes the metes and bounds of the allowed substitutions of R1-R4. This renders the previous rejections moot and the rejection is withdrawn.
Regarding the rejection of claim 25. Applicants have amended the claim to recite that m is 2. This amendment renders the previous rejection moot. The rejection is withdrawn.
The amendments discussed above render the objections to claims 54-58 moot. The objections are withdrawn.
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 43-44 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 a method for treating a proliferation disorder, does not reasonably provide enablement for a method of preventing a proliferation disorder. 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.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to a method of treating and/or preventing a proliferation disorder comprising administering to a subject a therapeutically effective amount of a compound of claim 1. Thus, the claims taken together with the specification imply that the administration of any compound of claim 1 is capable of treating any proliferative disease. Thus, the scope of the claims is extremely broad.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
The prior art teaches that the MEK pathway is one of the best-characterized kinase cascades in cancer biology and that MEK inhibition is a promising target in the treatment of cancer (Neuzillet et al., pg. 160, Abstract). The prior art teaches that MEK inhibition may be useful in the control and survival of cancer patients though predictive biomarkers and evaluation of combination therapies for the treatment of cancer require further evaluation (Neuzillet et al., Conclusion, pg. 169). The prior art does not teach that MEK inhibitors are capable of preventing cancer.
The state of the art is that no general procedure is art-recognized for determining which patients generally will suffer from the claimed diseases before the fact. The state of the art is that cancer is not preventable (see American Cancer Society https://www.cancer.org/cancer/risk-prevention.html). 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). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed diseases.
The use of the term “prevention” is, unless otherwise defined, interpreted to mean inhibition of proliferative disease once the active agent has been administered. Applicant must show that the Claimed method “prevents” proliferative disease in a broad range of conditions. The specification fails to enable the claimed compounds for the prevention of proliferative diseases.
The specification does not provide sufficient data or provide substantive evidence that the claimed compounds are capable of inducing protective immunity against proliferative disorders broadly. Without this demonstration, the skilled artisan would not be able to reasonably predict the outcome of the administration of the claimed compound, i.e. would not be able to accurately predict if a proliferative disorder had been prophlaxed.
(5) The relative skill of those in the art:
The artisan would have experience developing and evaluating small molecule inhibitors of MAP kinases, including MEK inhibitors. The artisan would be familiar with the role of MAP kinase signaling in cancer growth and development. The artisan would have understood how to assess whether MEK inhibitors were reasonably useful in the treatment of cancers mediated by dysregulation of the MAPK/ERK signaling pathway.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The specification has provided guidance for inhibition assays using the claimed compounds and measuring their inhibitory properties against MEK1/2 (Example B1, [0220-0222]); assays measuring the growth inhibition of compounds 1-20 against A375 melanoma cells and HT-29 colon cancer cells (Example B1, [0223-0228]); permeability assays for compounds 5-7, 11, and 13 in MDCK-MDR1 cells (Example B2, [0229-0232]); permeability assays for compounds 6 and 11 in Caco-2 cells (Example B3, [0233-0236]); and murine pharmacokinetic and pharmacokinetic studies for compounds 6 and 11 (Examples B4 and B5, [0237-0242])..
However, the specification does not provide evidence that the claimed compounds are capable of preventing proliferative disorders as claimed.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to the lack of evidence demonstrating that the claimed compounds are capable of preventing proliferative disorders and the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
Close Art
The closest prior art is Abel (WO 2006/045514, found in IDS filed 02/06/2024) which discloses 3-arylamino pyridine compounds that are MAP kinase inhibitors useful in the treatment of hyperproliferative diseases (Abstract). The reference discloses 129 species of the claimed compound. Example 19 of the disclosure is the closest compound to the instantly claimed compounds and has the following structure
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. This compound corresponds to the instantly claimed compound of formula (I) when m is 2; one R1 is F, the other R1 is I; G1, G3, and G4 are CH; G2 is N, q is 3; and p is 0. Example 19 differs from the instantly claimed compounds in its connectivity of the piperidine ring at the nitrogen atom, compared to the same moiety of the instant compounds that connect at a carbon. While structure activity relationship studies, including modification of heterocycle attachment connectivity, are commonly employed in medicinal chemistry, the reference does not provide any teaching that would have led the artisan to select this particular compound from among the disclosed species as a starting point for modifications.
Conclusion
Claims 1, 20, 25, 27, 30, 38-40, 46, 49-52, and 54-58 are allowed.
Claims 43-44 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONNOR KENNEDY ENGLISH whose telephone number is (571)270-0813. The examiner can normally be reached Monday Friday, 8 a.m. 5 p.m. ET..
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/C.K.E./ Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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