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 .
Applicant’s amendments and remarks filed January 29, 2026 have been received and reviewed. Claims 1, 2, 5, 7-10 and 12-21 are now pending in this application.
Election/Restrictions
The search and examination is limited to compounds of formula (III) wherein, X1 is C(Ra); X2 is N; X3 is C(Ra); X4 is N; X 5 is C(Ra); X6 is N; along with the full scope of the remaining variables.
The rings embraced at “A” are so diverse in scope that a serious burden exists to search the application as a whole. Therefore, restriction to a specific core is required. Each ring formed by X1, X2, X3, X4, X5 and X6 supports a different patent.
The search required is too burdensome for the office. The compounds of formula (III) embrace rings with multiple heteroatoms and additional ring fusions that a reasonable search of the entire genus could not be conducted without undue burden.
If, say a compound wherein X1 as CH were anticipated, applicants would not acquiesce in the rejection of, say, a compound wherein X1 is N (wherein every one of the remaining variable has the same value) thereover or vice-versa.
The search required for any one of the rings at X1-X6 is not required for another.
Subject matter not included by this subgenus is withdrawn from consideration.
Improper Markush Rejection
Claims 1, 2, 5, 7-10, 12-21 are again rejected under a judicially created doctrine as being drawn to an improper Markush group, that is, the claims lack unity of invention. The variables X1, X2, X3, X4, X5, X6, B, C and D are still defined in such a way that they keep changing the core of the compound that determines the classification. The basis of this rejection is the same as given in the previous office action and is incorporated herein fully by reference.
Applicants argue that compounds of claim 1 have common core structure and that the Markush group is proper. However, there is no common significant structural feature that is shared by all of its alternatives which is inventive. The structural formula (III) does not have a common structural feature, it only has a N-C(O)- fragment as common. The common structural feature is not a patentable advance over the prior art. The special technical feature is defined as meaning those technical features that define the contribution which each claimed invention, considered as a whole, makes over the prior art. The feature is, thus, not special if it is known. That what is common here is known. The claims are drawn to structurally dissimilar compounds which are classified separately, require separate literature searches and are not art recognized equivalents.
Limiting the claims to compounds of formula (III) wherein X1, X3 and X5 represent C(Ra) and X2, X4 and X6 represent N would overcome this rejection.
Claim Rejections - 35 USC § 112
Claims 1, 5 and 8 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 nature of the “additional heteroatoms as ring atoms” in the heterocyclyl has still not been given in the rings formed at Rb and R3, as well as, the heteroaryl at “D.” Which atoms are present?
Claim 10 is again rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention.
The claim has been amended to a “method for treating or preventing diseases or disorders related to programmed cell necrosis and/or human receptor-interacting protein - 1 kinase (RIPK1), comprising administering to a subject in need thereof a therapeutically effective amount of the compound according to claim 1 or the pharmaceutically acceptable salt, the hydrate or the solvate thereof, or the pharmaceutical composition comprising the same, wherein the disease or condition is selected from the group consisting of: multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), ischemia-reperfusion injury, inflammation, pathogen infection, age-related macular degeneration, retinal detachment-induced photoreceptor cell necrosis, glaucoma, cisplatin- induced renal injury and traumatic brain injury, and atherosclerosis caused by hyperlipidemia.”
The basis of this rejection is the same as given in the previous office action and is incorporated herein fully by reference. The treatment, much less, prevention of multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), ischemia-reperfusion injury, inflammation, pathogen infection, age-related macular degeneration, retinal detachment-induced photoreceptor cell necrosis, glaucoma, cisplatin- induced renal injury and traumatic brain injury, and atherosclerosis caused by hyperlipidemia cannot possibly be considered enabled.
Applicants argue that the compounds of claim 1 have RIPH1 inhibitory activity, and, therefore, can treat or prevent the disease recited. Applicants also provide references.
First, there is no teaching on prevention. One skilled in the art cannot say for sure who is going to come down with any of the diseases. The skilled artisan cannot say whether prevention has been achieved or the subject would not come down with the disease in the first place. When it comes to prevention, this is generally not enabled outside of the infectious diseases.
The scope of uses embraced by these claims are not remotely enabled based solely on instant compounds ability to inhibit RIPH1. The references do not go as far as Applicants claims and mostly state that further research is required.
Determining if any particular claimed compound would treat or prevent multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), ischemia-reperfusion injury, inflammation, pathogen infection, age-related macular degeneration, retinal detachment-induced photoreceptor cell necrosis, glaucoma, cisplatin- induced renal injury and traumatic brain injury, and atherosclerosis caused by hyperlipidemia would require synthesis of the compound, formulation into a suitable dosage form, and subjecting it to clinical trials with a number of fundamentally different diseases, or to testing them in an assay known to be correlated to clinical efficacy of such treatment. This is a large degree of experimentation. The direction in the references concerning treating these diseases merely states intentions to do so and speculative. No RIPH1 inhibitor has ever been used to treat or prevent the diseases embraced by the instant claims.
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 BRUCK KIFLE whose telephone number is (571)272-0668. The examiner can normally be reached 8 AM - 6 PM, M-F.
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March 13, 2026
/BRUCK KIFLE/Primary Examiner, Art Unit 1624