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 .
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.
Current Status of 18/710,091
This Office Action is responsive to the amended claims received 14 May 2024.
Claims 1-2, 4-13, 15-16, 19, 22, 24, 26, 28, and 33 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed patent applications PCT/US2022/049748 (filed 14 November 2022) and 63/279,488 (filed 15 November 2021) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) received on 30 April 2026, 6 March 2025, 6 February 2025, and 14 May 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, these information disclosure statements are being considered by the examiner.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application for the following reasons: Figures 7A-7F contain data that is intended to be differentiated by shades of grey that cannot be distinguished. The Examiner suggests that changing the shapes of some of the datapoints in this figure may prove useful (circles, triangles, squares, etc.).
Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: Fig. 2 is described in the specification as a “bar graph”, but appears to be a box and whisker plot in the drawings. Appropriate correction is required.
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 22, 24, 26, and 28 are 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 claims contain 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 make and/or use the invention.
Factors to be considered in making this determination include: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number for a prima facie case are discussed below.
Claims 22, 24, and 26 recite methods of preventing traumatic brain injury. BRAIN (American Brain Foundation “Common Causes of Brain Injury” 19 September 2023) teaches that “Firearms are a major cause of traumatic head injuries, as in the case of a gunshot wound to the head”. It is not clear how the instantly claimed compounds could, in any way, prevent gunshot wounds to the head. The instant application does not provide sufficient direction to allow one of ordinary skill in the art to administer the instant compounds to prevent traumatic brain injury due to firearms.
Claim 28 recites a method of preventing brain damage arising from cerebral ischemia. COLUMBIA (Columbia Neurosurgery in New York City “Cerebral Ischemia Diagnosis & Treatment” Last Updated 3 January 2024) teaches that a heart attack can lead to cerebral ischemia. It is not clear how the instantly claimed compounds, described in the instant application as interacting with GABAA receptors, can act to prevent heart attacks. The instant application does not provide sufficient direction to allow one of ordinary skill in the art to administer the instant compounds to prevent heart attacks.
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 16, 19, 22, 26, 28, and 33 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 16 recites “a cell” twice. This causes it to be unclear whether the claim is referring to the same cell, or two distinct cells. This renders claim 16 indefinite. Applicant may choose to replace the second use of the quoted phrase with “the cell”.
Claims 16, 19, 22, and 33 each refer to “a compound of claim 1”. This renders claims 16, 19, 22, 26, 28, and 33 indefinite, because it is not clear whether these claims are referring to the same compound chosen in claim 1. Applicant may amend the quoted claim above as follows “the compound of claim 1”.
Claim 28 contains a series of limitations within parentheses preceded by “e.g.”, and another series of limitations within parentheses preceded by “such as”. Each of these quoted phrases and the parentheses separately render claim 28 indefinite, because it is not clear if the limitations are exemplary or required limitations within the claim. Applicant may choose to: remove all parentheses, remove the quoted phrases above, and incorporate the limitations that were previously in parentheses as alternatives within the Markush group of claim 28.
Claim Interpretation
The Examiner would like to note that the first and fifth compounds disclaimed in claim 1 does not appear to fall within the scope of Formula (I), even if the disclaimer was not present.
Claim Rejections - 35 USC § 102
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, 5-7, and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
MOLLER (Cited by Applicant in IDS of 14 May 2024; Moller, H.A.; Sander, T.; Kristensen, J.L.; et al. “Novel 4-(Piperidin-4-yl)-1-hydroxypyrazoles as γ-Aminobutyric Acid A Receptor Ligands: Synthesis, Pharmacology, and Structure-Activity Relationships” J. Med. Chem. 2010, 53, 3417–3421).
MOLLER teaches compound 2e in the excerpt from Scheme 1 below. This compound is identical to the first compound in instant claim 13.
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MOLLER teaches compound 6e in Scheme 1 therein. The 6e compound drawn from the teachings of MOLLER is shown below. The instant specification states, on page 30, “For purposes of this invention, the heteroatoms such as nitrogen may have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms”. Therefore, the 6e compound of MOLLER falls within the scope of instant claims 1 and 5-7.
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Claims 1, 4, 7, 15-16, 19, and 33 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
TUK (Cited by Applicant in IDS of 14 May 2024; WO 2017/065602 A1; International Publication Date 20 April 2017).
TUK teaches the compound drawn below as 5-(2-Phenyl-1H-imidazol-4-yl)-4-(piperidin-4-yl)-1H-pyrazol-1-ol dihydrobromide on page 56 therein, within the GABAA antagonist category of Table 5. This hydrobromide salt is not disclaimed by instant claim 1 and falls within the scope of instant claim 1. Claim 24 of TUK teaches pharmaceutical compositions of the compounds of Table 5. TUK teaches that pharmaceutical compositions may contain a pharmaceutically acceptable carrier (Pg. 30, Ln. 4-9).
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Regarding claims 16 and 19: The outcomes within instant claims 16 and 19 are solely the result of administering the compound therein to a patient. There are no positive steps recited therein that would alter these outcomes unrelated to administering the compound of instant claim 1 to a patient. Therefore, because the method of administering the compound of instant claim 1 to a patient has been found to be obvious, these direct outcomes are also rendered obvious.
Regarding claim 33: Claim 28 of TUK teaches that the pharmaceutical compositions therein may be used to treat a loss or muscle function or a loss of muscle coordination. TUK lists stoke-related ataxia as a disease within Table 1, which refers to the conditions therein as “Progressive neuromuscular disorders” in the table title (Pg. 47 and 48). The teachings of TUK read on the method of improving functional recovery after stroke of instant claim 33.
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 1-2, 4, 7, 9-10, 15-16, 19, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over:
TUK (Cited by Applicant in IDS of 14 May 2024; WO 2017/065602 A1; International Publication Date 20 April 2017)
in view of:
PATANI (Patani, G. A.; LaVoie, E. J. “Bioisosterism: A Rational Approach in Drug Design” Chem. Rev. 1996, 96, 3147-3176.).
TUK teaches the compound drawn below as 5-(2-Phenyl-1H-imidazol-4-yl)-4-(piperidin-4-yl)-1H-pyrazol-1-ol dihydrobromide on page 56 therein, within the GABAA antagonist category of Table 5. This hydrobromide salt is not disclaimed by instant claim 1 and falls within the scope of instant claim 1. Claim 24 of TUK teaches pharmaceutical compositions of the compounds of Table 5. TUK teaches that pharmaceutical compositions may contain a pharmaceutically acceptable carrier (Pg. 30, Ln. 4-9).
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PATANI teaches that benzene, thiophene, and pyridine are “classical bioisosteres” within the Ring Equivalents section of page 3158. PATANI provides examples of phenyl-pyridine replacements in Figures 31 and 32.
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to immediately envisage the replacement of the phenyl ring of the compound of TUK above with a pyridinyl ring, as is taught to be a “classical” replacement in the art by PATANI, for the purpose of tuning the GABAA antagonist activity of the compound taught by TUK.
Regarding claims 8 and 11-12: PATANI teaches that the substitution of hydrogen for fluorine is “one of the more commonly employed monovalent isosteric replacements. PATANI provides a specific example in Figure 2 and Table 4 therein of replacing the hydrogen atom on a phenyl substituent of a benzodiazepine, allowing for the affinity of the compound for its biological receptor to be increased by a great deal.
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to exchange the hydrogen atom at the 2-position of the phenyl ring for a fluorine atom (as taught by PATANI) within the compound taught by TUK, for the purpose of increasing the affinity of the compound for its biological receptor. The artisan would have expected success in such a replacement, because PATANI teaches this type of replacement to be commonly employed within the art.
Regarding claims 16 and 19: The outcomes within instant claims 16 and 19 are solely the result of administering the compound therein to a patient. There are no positive steps recited therein that would alter these outcomes unrelated to administering the compound of instant claim 1 to a patient. Therefore, because the method of administering the compound of instant claim 1 to a patient has been found to be obvious, these direct outcomes are also rendered obvious.
Regarding claim 33: Claim 28 of TUK teaches that the pharmaceutical compositions therein may be used to treat a loss or muscle function or a loss of muscle coordination. TUK lists stoke-related ataxia as a disease within Table 1, which refers to the conditions therein as “Progressive neuromuscular disorders” in the table title (Pg. 47 and 48). The teachings of TUK read on the method of improving functional recovery after stroke of instant claim 33.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 16, 19, 22, 24, 26, 28 and 33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 22-23 of copending Application No. 18/287,586 (referred to below as the ‘586 application).
Although the claims at issue are not identical, they are not patentably distinct from each other because: Claim 22 of the ‘586 application teaches the administration of the compound copied below for the treatment of a neurodegenerative disease. Claim 23 of the ‘586 application states that the disease of claim 22 therein may be Alzheimer’s disease, trauma-induced brain damage, or stroke.
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Regarding claims 16 and 19: The outcomes within instant claims 16 and 19 are solely the result of administering the compound therein to a patient. There are no positive steps recited therein that would alter these outcomes unrelated to administering the compound of instant claim 1 to a patient. Therefore, because the method of administering the compound of instant claim 1 to a patient has been found to be obvious, these direct outcomes are also rendered obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN D MCANANY whose telephone number is (571)270-0850. The examiner can normally be reached 8:30 AM - 5:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, ANDREW D 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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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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