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 .
Benefit of Earlier Filing Date
The instant application, filed 13 January 2025, is a continuation of 18/571,177, filed 15 December 2023, which is national stage application of PCT/US2022/034012, filed 17 June 2022, which claims the benefit of an earlier filing date to U.S. Provisional Patent Application Serial No. 63/300,551, filed 18 January 2022, and U.S. Provisional Patent Application Serial No. 63/211,636, filed 17 June 2021. Acknowledgment is made of Applicant’s claim.
Status of the Claims
The listing of claims filed 03 June 2025 has been examined.
Claims 1-16 and 20-36 are pending.
Claims 6, 12, 21, 26-28, and 33-36 are amended.
Claims 17-19 and 37-42 are cancelled.
Claims 1-16 and 20-36 are examined on the merits.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 02 July 2026 is acknowledged and has been considered. Note several listed IDS references (i.e., WO 2021/262617 A1 and all NPL (Non-Patent Literature) documents listed in the IDS filed on 02 July 2026) were provided in priority application 18/517,177. Any lined-through references have not been considered and must be submitted or resubmitted in proper format for consideration. Regarding, “WO 2017/106050 A1” (Cite. No. 4), it appears to possibly contain a typo as the submitted document is “WO 2017/016050 A1”. However, Examiner assumes Applicant meant to cite WO 2017/106050 A1 and has provided a copy of WO 2017/106050 A1 since it is cited in the prior art rejections below.
Claim Objections
Claims 2-5, 12, and 32 are objected to because of the following informalities:
Claim 1, upon which claims 2-5 and 12 depend, recites “Cmax”. However, claims 2-5 and 12 all recite “Cmax”. For clarity, Examiner requests subscript usage be made consistent throughout the claims.
Claim 32 recites, “…wherein TQS-168 of salt thereof…” [Emphasis added.] Examiner recommends changing “of” to “or”.
Appropriate correction is requested.
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 1-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nguyen (WO 2017/106050 A1).
Regarding claims 1-15, Nguyen teaches 2-(4-tert-butylphenyl)-1H-benzimidazole is a Ppargc1a activator and methods by which aging-associated cognitive impairments, such as Alzheimer’s disease, as well as neuroinflammation can be treated using 2-(4-tert-butylphenyl)-1H-benzimidazole (p. 1, Lines 6-8; p. 2, Line 4), shown below (p. 3, Line 12). Note 2-(4-tert-butylphenyl)-1H-benzimidazole (CAS RN: 49671-76-3), which is also called ZLN005, is the instantly recited compound of Formula (I).
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Nguyen suggests including ZLN005 in pharmaceutical compositions, “…in an amount of… about 1-90% for a tablet formulation, and 1-100% for a capsule formulation.” (p. 4, Lines 6-10). Furthermore, Nguyen states, “Dosing of the composition can vary based on the extent of the injury and each patient’s individual response… In one embodiment, the pharmaceutical composition is administered orally to the subject. The dosage for oral administration is generally 1-100, and preferably 1-50, or 1-25 mg/kg/day. For example, the active compound can be applied orally to an adult human at 50-1000 mg/dosage, or 100-600 mg/dosage, 1-4 times a day, depends on the patient’s condition and weight.” (p. 6, Lines 25-33). Thus, assuming the average human weight is approximately 60 kg, Nguyen recommends administering 60-6,000 mg/day. Additionally, Nguyen discloses various pharmaceutically acceptable carriers including non-aqueous based solutions and suspensions (p. 4, Lines 23-24).
Nguyen is silent on Cmax, Tmax, and AUC0-t values. However, Nguyen and the instant claims recommend administering the compound of Formula (I) to identical patient populations and disclose identical method steps. Consequently, administering the compound of Formula (I) as described by Nguyen, would inherently result in at least some patients having a Cmax of at least 750-1750 ng/mL, a Tmax of no more than 2 hours - 60 minutes, and/or a AUC0-t of at least 3000-7000 ng·hr/ml. Phrased differently, achieving the instantly recited Cmax, Tmax, or AUC0-t values would naturally flow from administering Nguyen’s composition as taught by Nguyen.
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 1-15, 21-28, and 33-36 are rejected under 35 U.S.C. 103 as being unpatentable over Nguyen (WO 2017/106050 A1).
Regarding claims 21-28 and 33-36, Nguyen teaches all of the claimed elements as stated above.
While Nguyen does suggest various dosage forms such as tablets and capsules, Nguyen does not explicitly teach a specific, exemplary solid dosage form which is administered to a human subject.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Nguyen would have found it prima facie obvious to reduce neuroinflammation and/or treat a neurodegenerative disease using the compound of Formula (I) because Nguyen discloses the compound of Formula (I) (i.e., ZLN005) is useful for reducing neuroinflammation and/or treating a neurodegenerative disease and recommends administering up to 100 mg/kg/day. Additionally, Nguyen recommends unit dosage forms including tablets and capsules and states, “A preferred route of administration is oral administration.” (Abstract). Thus, a PHOSITA would have had a reasonable expectation of success in using an orally administered solid unit dosage form, such as a sachet, capsule, or tablet, containing an amount of the compound of Formula (I) as suggested by Nguyen (i.e., 1-100 mg/kg/day).
Claims 16 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Nguyen (WO 2017/106050 A1) as evidenced by Banister (WO 2020/033359 A1).
Regarding claims 16 and 20, Nguyen teaches all of the claimed elements as stated above.
Nguyen does not explicitly teach the compound of Formula (II).
Banister teaches 2-arylbenzimidazole derivatives, which are Ppargc1a activators, as being useful in treating neurodegenerative diseases (p. 1, ¶ [01]). Two such 2-arylbenzimidazole derivatives are 2-(4-tert-Butylphenyl)-1H-benzo[d]imidazole (p. 23, Example 1; CAS RN: 49671-76-3) and 2-(4-tert-Butylphenyl)-1H-benzo[d]imidazole-5-ol (p. 31-32, Compound 32; CAS RN: 1513993-57-1), shown below. Note 2-(4-tert-Butylphenyl)-1H-benzo[d]imidazole and 2-(4-tert-Butylphenyl)-1H-benzo[d]imidazole-5-ol are the instantly claimed compounds of Formula (I) and Formula (II), respectively.
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Banister indicates neurodegenerative diseases wherein 2-arylbenzimidazole derivatives can be applied are amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, frontotemporal degeneration, dementia with Lewy bodies, Parkinson’s disease, Huntington’s disease, and demyelinating disease (p. 5, ¶ [17]). Banister discloses pharmaceutical formulations comprising the compounds shown above can be administered orally in discrete units such as capsules, cachets, or tablets (p. 17, ¶ [60]).
Banister does not explicitly teach exemplary daily dosages.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Nguyen would have found it prima facie obvious to administer the compound of Formula (I) in an amount sufficient to provide the instantly recited Cmax and Tmax values and compound of Formula (II) amounts based on the teachings of Banister because, in addition to disclosing the compound of Formula (I), Banister also teaches the compound of Formula (II) is useful for treating neurodegenerative diseases. Thus, a skilled artisan would have been motivated to apply the dosages recommended by Nguyen to Banister’s disclosure.
Furthermore, “Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical compound or chemical composition and its properties are inseparable. Therefore, if the prior art teaches the claimed chemical structure, the properties Applicant discloses and/or claims are necessarily present. See MPEP § 2112.01. Accordingly, ZLN005 being metabolized to another useful compound (i.e., Formula (II)), is an inherent property, regardless of whether or not said property was explicitly recognized by Nguyen.
Claims 29-32 are rejected under 35 U.S.C. 103 as being unpatentable over Nguyen (WO 2017/106050 A1) in view of Banister (WO 2020/033359 A1) as evidenced by Drakulich (Drakulich, A. (2012, August 1). Bioavailability Enhancement: When to Use Hot-Melt Extrusion versus Spray Drying. Pharmaceutical Technology Europe. Vol. 24, Issue 8).
Regarding claims 29-32, Nguyen in view of Banister teaches all of the claimed elements as stated above. Furthermore, Banister states, “As used herein, and as would be understood by the person of skill in the art, the recitation of ‘a compound’ – unless expressly further limited – is intended to include salts of that compound. In a particular embodiment, the term ‘compound of formula’ refers to the compound or a pharmaceutically acceptable salt thereof.” (p. 16, ¶ [56]). Likewise, Nguyen suggests “pharmaceutically acceptable salts thereof” are permissible (p. 10, Claim 1). Banister provides further guidance on how a “pharmaceutically acceptable salt” may be prepared, indicating such salts can be, “…prepared from pharmaceutically acceptable non-toxic acids or bases including inorganic acids and bases and organic acids and bases.” (p. 16, ¶ [57]). Additionally, Banister discloses several structurally similar compounds which are crystalline (p. 33, Compound 42; p. 34, Compound 44; p. 36, Compound 57; p. 37, Compound 58).
The combination of Nguyen and Banister does not explicitly teach an amorphous form, a spray-dried dispersion form, or a hot melt extrusion form.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Nguyen would have found it prima facie obvious to prepare various salt forms of the compound of Formula (I), such as crystalline, amorphous, spray-dried dispersion, and hot melt extrusion forms based on the teachings of Banister because both Nguyen and Banister suggest pharmaceutically acceptable salts of the compound of Formula (I) remain useful in reducing neuroinflammation and/or treating a neurodegenerative disease. Accordingly, a skilled artisan would have had a reasonable expectation of success in using salts of the compound of Formula (I) to reduce neuroinflammation and/or treat a neurodegenerative disease.
Furthermore, as evidenced by Drakulich, hot-melt extrusion and spray drying had been known in the art as processes by which amorphous solid dispersions having improved bioavailability can be prepared (p. 2, ¶ 1). Drakulich indicates hot-melt extrusion and spray drying each have certain advantages and disadvantages. For example, hot-melt extrusion uses no solvents, but may be less applicable for compounds having high melting points (p. 3). In contrast, spray drying does not require exposing compounds to high temperatures, but uses solvents which need to be recovered (p. 4). Accordingly, a skilled artisan would have been motivated to prepare an amorphous form via hot-melt extrusion and/or spray drying because these processes had been known in the pharmaceutical industry to produce products having better pharmaceutical properties.
Non-Statutory 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 1-16 and 20-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 16-17, 24, 28, 32, 54-59 of copending Application No. 18/707,062, claims 1, 3, 16, 27-28, 32, and 34 of copending Application No. 18/003,153, and claims 1, 3, 4, 32-36, 67-69, 79, 85, 87-90 of copending Application No. 19/813,981 each in view of Nguyen (WO 2017/106050 A1).
Application ‘062 claims a method of treating a subject (Claim 1), wherein the compound is Compound I or Compound II. Note Compounds I and II are identical to the instantly recited compounds of Formulas (I) and (II), respectively. Application ‘062 claims the subject receiving treatment, “…has not previously been diagnosed with, but is at risk for developing, neuroinflammation and/or a neurodegenerative disease…” (Claim 24).
Application ‘062 does not explicitly and specifically claim administering the compound of Formula (I) or Formula (II) to reduce neuroinflammation and/or treat a neurodegenerative disease.
Application ‘153 claims a method of treating a patient who has, or who is at risk for developing, systemic immune activation (Claim 1), by administering Compound 1 or Compound 4. Note Compounds 1 and 4 are identical to the instantly recited compounds of Formulas (I) and (II), respectively.
Application ‘153 does not explicitly claim the “systemic immune activation” is neuroinflammation.
Application ‘981 claims a method of treating a patient who has, or who is at risk for developing, systemic immune activation (Claim 1), by administering Compound 1 or Compound 4. Note Compounds 1 and 4 are identical to the instantly recited compounds of Formulas (I) and (II), respectively
Application ‘981 does not explicitly claim the “systemic immune activation” is neuroinflammation.
Nguyen teaches 2-(4-tert-butylphenyl)-1H-benzimidazole is a Ppargc1a activator and methods by which aging-associated cognitive impairments, such as Alzheimer’s disease, as well as neuroinflammation can be treated using 2-(4-tert-butylphenyl)-1H-benzimidazole (p. 1, Lines 6-8; p. 2, Line 4), shown below (p. 3, Line 12). Note 2-(4-tert-butylphenyl)-1H-benzimidazole (CAS RN: 49671-76-3), which is also called ZLN005, is the instantly recited compound of Formula (I).
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Nguyen suggests including ZLN005 in pharmaceutical compositions, “…in an amount of… about 1-90% for a tablet formulation, and 1-100% for a capsule formulation.” (p. 4, Lines 6-10). Furthermore, Nguyen states, “Dosing of the composition can vary based on the extent of the injury and each patient’s individual response… In one embodiment, the pharmaceutical composition is administered orally to the subject. The dosage for oral administration is generally 1-100, and preferably 1-50, or 1-25 mg/kg/day. For example, the active compound can be applied orally to an adult human at 50-1000 mg/dosage, or 100-600 mg/dosage, 1-4 times a day, depends on the patient’s condition and weight.” (p. 6, Lines 25-33). Thus, assuming the average human weight is approximately 60 kg, Nguyen recommends administering 60-6,000 mg/day. Additionally, Nguyen discloses various pharmaceutically acceptable carriers including non-aqueous based solutions and suspensions (p. 4, Lines 23-24).
A PHOSITA would have been motivated to use the compounds of Formulas (I) and (II) for reducing neuroinflammation and/or treating a neurodegenerative disease because Nguyen discloses the compound of Formula (I), which differs from the compound of Formula (II) by only an additional -OH group, is useful for reducing neuroinflammation and treating a neurodegenerative disease.
Because claims 1-16 and 20-36 in the instant application would have been obvious over claims 1-9, 16-17, 24, 28, 32, 54-59 of copending Application No. 18/707,062, claims 1, 3, 16, 27-28, 32, and 34 of copending Application No. 18/003,153, and claims 1, 3, 4, 32-36, 67-69, 79, 85, 87-90 of copending Application No. 19/813,981 each in view of Nguyen, claims 1-16 and 20-36 in the instant application are not patentably distinct from claims 1-9, 16-17, 24, 28, 32, 54-59 of copending Application No. 18/707,062, claims 1, 3, 16, 27-28, 32, and 34 of copending Application No. 18/003,153, and claims 1, 3, 4, 32-36, 67-69, 79, 85, 87-90 of copending Application No. 19/813,981.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-16 and 20-36 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANNA L BAUER whose telephone number is (571)272-5752. The examiner can normally be reached 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, ADAM C MILLIGAN can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/B.L.B./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
