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 without traverse of Group I, drawn to a method of promoting oligodendrocyte precursor cell differentiation, comprising administering to one or more oligodendrocyte precursor cells an effective amount of a compound of formula (IV) or a pharmaceutically acceptable salt thereof; and compound number CN045 having the structure of:
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as the elected compound species of formula (IV) in the reply filed on January 7, 2026 is acknowledged.
Claims 4-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 7, 2026.
Expansion of Election of Species Requirement
A reasonable and comprehensive search of the elected species conducted by the Examiner determined that the prior art at the time of the present invention was such that it did not anticipate or render obvious the elected compound species of formula (IV).
In light of this discovery, the search is expanded to the subject matter of the subgenus of the elected species, i.e., the compound of formula (IV) having the structure of:
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and
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, such that it does not encompass the full scope of the claims.
Status of the Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on January 7, 2026, wherein claims 1-18 are unchanged; and claims 19-23 are cancelled.
Claims 1-18 are pending. Claims 4-18 are withdrawn.
Claims 1-3 are under examination in accordance with the elected species.
Priority
The instant application 18/003,807 filed on December 29, 2022 is a 371 of PCT/US2021/040294 filed on July 2, 2021, which claims priority to, and the benefits of U.S. Provisional Application No.
63/047,364 filed on July 2, 2020.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/047,364, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, the disclosure of the prior-filed application fails to disclose the following compound species of formula (IV):
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,
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and a pharmaceutically acceptable salts thereof; Therefore, to the extent that claims 1-3 are drawn to the compound species of formula (IV) noted above, the claims are not entitled to the benefit of prior-filed application and will receive an effective filing date of December 29, 2022, which is the filing date of 371 of PCT/US2021/040294.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 25, 2024 is in compliance with the provisions of 37 CFR 1.97 unless otherwise noted. Accordingly, the information disclosure statement is being considered by the examiner.
Cahn et al. (cited under “Nonpatent literature documents”, no. 5” in the IDS filed on June 25, 2024) fail to comply with 37 CFR 1.98(a)(3)(i), because it is written in foreign language and no English translation is provided. The information disclosure statement does not include a concise explanation
of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most
knowledgeable about the content of the information, of the reference listed that is not in the English
language. The cited references have been placed in the application file, but they have not been
considered by the Examiner.
Claim Rejections - 35 USC § 112
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.
Claim 1 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.
Regarding claim 1, the recitation of “X” in the phrase of “X is selected from N and CH” renders the claim indefinite, because there is insufficient antecedent basis for this limitation in the claim. Specifically, there is no “X” in the compound of formula (IV), it is not clear what “X” is being referred to by the Applicant. Therefore, claims 2-3 are rejected based on their dependency on the rejected base claim.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rapacz et al. (MedChemComm vol. 8, 1 220-238; cited in the IDS filed on June 25, 2024).
Rapacz et al. teaches a compound 19, 1-{2-[2-(2,3-dimethylphenoxy)ethoxy]ethyl}piperidin-3-ol hydrochloride, having the structure of:
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is the most promising compound (see e.g., Fig. 10; Table 1, Compd. 19; abstract). Rapacz et al. further teaches in the maximal electroshock seizure threshold (MEST) test, two compounds, 19 and 27, caused a significantly elevated electroconvulsive threshold (ECT) in comparison to vehicle-treated mice shown below:
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, specifically, compound 19 at a dose of 30 mg kg−1 increased the ECT by 75% (p < 0.001) (see e.g., p. 226, left column, line 17-20; Table 3).
Please note the compound 19 of Rapacz et al. is a compound of instant formula (IV):
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or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each CH3; R3, R4 and R5 are each hydrogen; Ra and Rb are taken together with the nitrogen atom to which they are attached to form
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(an substituted heterocyclyl).
Rapacz et al. is silent regarding “promoting oligodendrocyte precursor cell differentiation”; However, “promoting oligodendrocyte precursor cell differentiation” will necessarily present by practicing the method of Rapacz et al. Since the same compound (compound 19 of Rapacz et al.) at an effective amount (30 mg/kg) is being administered to a subject (mice), it will necessarily deliver said compound at a cellular level, in this case, to one or more oligodendrocyte precursor cells in the subject even though the prior art was not aware of it.
MPEP 2112 I states: “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).”
Therefore, the claimed invention is being anticipated by Rapacz et al.
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.
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 are rejected under 35 U.S.C. 103 as being unpatentable over Ghamari et al. (Chem Biol Drug Des, 2019. Vol. 93(5): 832-843).
Ghamari et al. teaches Compound 5 having the structure of:
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appears as a pitolisant counterpart and has affinity at human histamine H3 receptor (H3R) (see e.g., Table 1; Table 3; p. 840, right column, line 10-11). Please note the pitolisant taught by Ghamari et al. has the structure of
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(see e.g., Figure 1 (c)). Ghamari et al. further teaches said compound is one of the lead candidates that may serve as starting point for further medicinal chemistry optimization for development of novel CNS selective H3R antagonist to be used in neurodegenerative disease (see e.g., p. 840, right column, “5 | conclusion” section). Ghamari et al. further teaches candidate molecules have lead-likeness properties, and are predicted to be of desirable blood–brain barrier (BBB) permeability and of oral bioavailability, inferred from Abbott bioavailability score with potential synthetic accessibilities (see e.g., p. 837, right column, 2nd paragraph). Ghamari et al. further teaches on the basis of several recent investigations, H3R antagonists and inverse agonists would be effective in CNS-related diseases and neuronal abnormalities such as attention deficit hyperactivity disorder (ADHD), Alzheimer’s disease, schizophrenia, learning and memory disorders, sleep disorders epilepsy, and obesity (see e.g., p. 833, left column, line 20-25).
Please note the compound 5 of Ghamari et al. is a compound of formula (IV)
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, wherein R4 is Cl [a halo]; R1, R2, R3 and R5 are each hydrogen; Ra and Rb are taken together with the nitrogen atom to which they are attached to form
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.
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to administer the compound 5 of Ghamari et al. at an effective amount to a subject for treating CNS-related diseases and neuronal abnormalities to arrive at the claimed invention. One would have been motivated to do so, because Ghamari et al. teaches compound 5 is an anti-H3R agent predicted to have desirable blood–brain barrier permeability and oral bioavailability that can be used in the treatment of neurogenerative disease. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the administration of compound 5 of Ghamari et al. at an effective amount to a subject would have successfully treat neurodegenerative disease by binding to the histamine H3 receptor.
In the present case, Ghamari et al. is silent about “promoting oligodendrocyte precursor cell differentiation”; However, by practicing the method of Ghamari et al. sets forth above, one will also be “promoting oligodendrocyte precursor cell differentiation” by delivering the compound 5 at a cellular level in the subject, and that renders obvious the limitation instantly claimed.
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Ghamari et al. (Chem Biol Drug Des, 2019. Vol. 93(5): 832-843) as applied to claims 1-2 above, and further in view of Schwartz et al. (WO 00/06254).
The teachings of Ghamari et al. are set forth above and applied as before.
Ghamari et al. does not teach the compound of formula (IV) in claim 3.
Schwartz et al. teaches compound no. 117, 3-(4-chlorophenyl)propyl 3-piperidinopropyl ether, 7 mmol, having the structure of:
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(see e.g., p. 96, no. 117) is an exemplary compound having the following formula (IIa) and (IIb):
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(see e.g., claims 29 and 38; p. 19, line 7). Schwartz et al. further teaches a method comprising administering a therapeutically effective dose of the compound of formula (I) to (XVIII) (see e.g., p. 73, line 21-22). Schwartz et al. further teaches a medicament acting as an antagonist and/or agonist of the histamine H3-receptors, characterized in that it comprises as active ingredients, an effective amount of the compound no. 117 (see e.g., claim 80); and for the treatment of central nervous system disorders, in particular, inter alia, Alzheimer disease and mood and attention alterations (see e.g., claim 81). Schwartz et al. further teaches formula (IIa) and (IIb), characterized in that XII is preferably an oxygen atom (see e.g., claim 31); AII is a chain –(CH2)nII- with nII preferably from 1 to 4 (see e.g., claim 35; p. 15, line 22-24); chain BII represents –(CH2)nII(hetero atom)-, where the hetero atom is preferably a sulphur or oxygen atom, nii is preferably an integer between 1 and 4 (see e.g., p. 15, line 31 to p. 16, line 3); YII represents a phenyl group, unsubstituted or mono- or polysubstituted with one or more identical or different substituents selected from, inter alia, halogen atoms (see e.g., p. 16, line 4-6). Schwartz et al. further teaches the term “halogen, as used herein refers to any of fluorine, chlorine, bromine and iodine (see e.g., p. 35, line 4-5). Schwartz et al. further teaches said compound is useful derivatives in human or veterinary medicine (see e.g., p. 66, line 6-7). In the present case, the difference between the compound 5 of Ghamari et al. and the claimed compound is that the prior art contains a chloro at the meta position on the phenyl group rather than the para position, and does not contain a bromine at the ortho position on the phenyl group shown below (see shaded):
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. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the compound 5 of Ghamari et al. in the method sets forth above by modifying the position of chlorine atom in the phenyl ring to the para position, and further substituted said phenyl ring with a bromine as the halogen at the ortho position as taught by Schwartz et al. One would have been motivated to do so, because Ghamari et al. teaches Compound 5 is a pitolisant counterpart and an anti-H3R agent; and Schwartz et al. teaches compound no. 117, which is the pitolisant taught by Ghamari et al., is an exemplary compound of formula (IIa) and (IIb) with a chlorine at the para position acting as an antagonist and/or agonist of the histamine H3-receptors, and said formulae can contains a phenyl group at YII which can be unsubstituted or mono- or polysubstituted with one or more identical or different substituents selected from halogen atoms, such as chlorine and bromine. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the compound 5 of Ghamari et al. and the compound no. 117 of Schwartz et al. are structurally similar with similar utilities (anti-H3R agent); and said compound 5 modified in view of the formula (IIa) and (IIb) of Schwartz et al. by substituting the phenyl with bromine at the ortho position, and changing the position of chlorine atom to the para position just like the compound no. 117 of Schwartz et al. would have successfully arrive at the compound that is similarly useful; and therefore, by administering the modified compound 5 of Ghamari et al. in view of Schwartz et al. at an effective amount to a subject would have successfully treat neurodegenerative disease by binding to the histamine H3-receptors. It is noted that Ghamari et al. and Schwartz et al. is silent about “promoting oligodendrocyte precursor cell differentiation”; However, by practicing the method of Ghamari et al. and Schwartz et al. sets forth above, one will also be “promoting oligodendrocyte precursor cell differentiation” by delivering the modified compound 5 of Ghamari et al. and Schwartz et al. at a cellular level in the subject, and that renders obvious the limitation instantly claimed.
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628