Detailed Action
The present office action is in response to the amendments filed 25 Nov 2022.
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
Claims 1, 3-7, and 14 of the pending application have been examined on the merits. Claims 2, 8-13, and 15 stand withdrawn (see “Response to Applicant Election” below). Acknowledgement is made of the amendments filed 25 Nov 2022.
Priority
Applicants identify the instant application, Serial #: 17/999,749 filed 23 Nov 2022, as a National Stage Entry of International Patent Application #: PCT/EP2021/063890, filed 25 May 2021, which claims foreign priority from Foreign Application #: EP20305546.2, filed 26 May 2020.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 23 Nov 2022, 05 Nov 2024, and 06 Nov 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Applicant Election
Applicant's election with traverse of Group I, claims 1-14, with an additional election of species of Compound 15 (below) in the reply filed on 10 Sep 2025 is acknowledged. Prior art was returned after a search for the elected species.
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The traversal is for the following reasons: Applicant argues that claim 15 in Group II depends on claim 1 and thus contains all the requirements of claim 1 and there is no undue burden on examination and claim 15 should be considered with the elected Group I, claims 1-14. Applicant further argues that the requirement for election of species should be withdrawn because the art relied on by the examiner to make the restriction requirement does not teach the technical features of the claimed invention. Applicant argues that the variable bonds of the instant formula I are not found in the art, and thus the instant claims are special over the technical feature taught in the art.
Regarding the argument that there is no undue burden on examination for claim 15, this is not found persuasive because the instant application is subject to the “Unity of Invention” restriction standard and not the “Independent and Distinct/Undue Search Burden” restriction standard. Examiner respectfully reminds applicant that, as set forth in Rule 13.1 of the Patent Cooperation Treaty (PCT), "the international application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept.” Moreover, as stated in PCT Rule 13.2, "where a group of inventions is claimed in one and the same international application, the requirement of unity of invention referred to in Rule 13.1 shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features." Furthermore, Rule 13.2 defines "special technical features" as "those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art."
Regarding the argument that the prior art does not teach the special technical feature, the prior art includes the core compound of the claim. The bonds taught by instant formula (I) are variable, and thus may be different between compounds represented by instant formula (I). The prior art teaches all the technical features shared by all compounds of the instant formula (I) and thus breaks Unity of Invention for Groups I and II.
Claim 15 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group, there being no allowable generic or linking claim. Claims 2 and 8-13 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10 Sep 2025.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
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 and 6 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 contains the following limitations, “aryl, said aryl being optionally substituted with at least one substituent; or heteroaryl said heteroaryl being optionally substituted with at least one substituent…aryloxy, said aryloxy being optionally substituted with at least one substituent; heteroaryloxy said heteroaryloxy being optionally substituted with at least one substituent.” The limitation of “at least one substituent” is very broad and would leave a person having ordinary skill in the art to question which substituents are included in the claim. There are no definitions in the claim itself and so the artisan would go to the specification to find what “substituent” has been defined as in the disclosure. However, there is no definition of substituent found in the specification. It is unclear what the limits of the term substituent are, and so the claim is indefinite.
Claim 6 contains the following limitations, “aryloxy, said aryloxy being optionally substituted with at least one substituent.” The limitation of “at least one substituent” is very broad and would leave a person having ordinary skill in the art to question which substituents are included in the claim. There are no definitions in the claim itself and so the artisan would go to the specification to find what “substituent” has been defined as in the disclosure. However, there is no definition of substituent found in the specification. It is unclear what the limits of the term substituent are, and so the claim is indefinite.
Regarding claim 6, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 6, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1, 3-7, and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Champiré et al. (Actes du 29eme Coll. Biotechnocentre, 2016, PC29), hereinafter Champiré, further in view of Harrison et al. (J Med Chem, 2009, 52:6515-6518), hereinafter Harrison.
Applicant elected group I, claims 1-14, drawn to compounds of Formula I:
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Applicants further Compound 15 as a species of Group I:
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Compound 15 is a species of Formula I when R is aryl substituted by aryloxy; a is a single bond; b is a double bond; R1 is methyl; R2 is H; and n is 0.
Champiré teaches that LIM-Kinase has been shown to be involved in the signaling pathway of neurofibromatosis which effects 1 in 3500 people worldwide (pg. 66). Champiré further teaches that reference structure I (below) is one of the most efficient inhibitors of LIM-Kinase which Champiré references as found in Harrison (pg. 66).
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Champiré teaches synthesizing several pyrrolopyrimidine and azaindole libraries including reference structures III and IV which replace the central piperazine of structure I with a piperidine or a 1,2,3,6-tetrahydropiperadine to test on a kinase panel to determine the central piperazines influence on inhibitor activity (pg. 66).
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When the core is 1,2,3,6-tetrahydropiperidine, structure III overlaps with the core structure of the instantly elected compound. However, Champiré does not define R2 as -O-Ph as in the instantly elected invention.
Harrison teaches a variety of LIM-Kinase 2 inhibitors with several core structures including analogues of reference Compound 1 (pg. 6515, column 2):
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Where R may be H, 2-Me, 3-Me, 4-Me, 3-OMe, 4-OMe, 3-OPh, and 3-Br. Harrison teaches that the 3-OPh group, which aligns with the 3-OPh group of the instantly claimed invention, has the lowest IC50 of the reference R groups at 64 nM.
By following the teachings of Champiré and Harrison, a person of ordinary skill in the art would synthesize a library of LIM-Kinase pyrrolopyrimidine inhibitors with a 1,2,3,6-tetrahydropiperidine core and various R groups off the phenyl substituent to test the effect a change from the piperazine core would have on LIM-Kinase inhibition, as taught by Champiré, and include in the R groups 3-OPh, as taught by Harrison. The artisan would be motivated to include 3-OPh as one of the R groups because it had a low IC50 against LIM-Kinase 2.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Moltzen et al. (J Med Chem, 1994, 37:4085-4099) is pertinent for teaching substitution of piperidine with tetrahydropyridine to modulate drug affinity for a target receptor. WO 2009/021169 is considered pertinent for teaching LIM-Kinase 2 inhibitors with piperidine cores, pyrrolopyrimidine moieties, and the same substituents as the instant compounds.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625