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 .
Status of the Claims
The listing of claims filed 01 December 2023 has been examined.
Claims 1-9 and 11-21 are pending.
Claims 3-9 and 11-21 are amended.
Claims 10 and 22-24 are cancelled.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 29 February 2024 is acknowledged and has been considered. Any lined-through references have not been considered and must be submitted in a proper format for consideration. Specifically, a foreign patent document (EA200802223A1) lacks an English translation or concise explanation of its relevance (see CFR 1.56(c)).
Benefit of Earlier Filing Date
The instant application, filed 01 December 2023, is a national stage application of PCT/US2022/031977, filed 02 June 2022, which claims the benefit of an earlier filing date to U.S. Provisional Patent Application Serial No. 63/196,826, filed 04 June 2021, and U.S. Provisional Patent Application Serial No. 63/196,013, filed 02 June 2021. Acknowledgment is made of Applicant’s claim.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it uses a phrase which can be implied, specifically, “The present disclosure relates to…,” as well as legal phraseology, specifically the term “comprising.” A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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.
Claim 12 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention. Specifically, Applicants have not defined the recited genus “other mitochondrial disease focused vitamin or supplemental therapy” or provided a representative number of species these genre to demonstrate that Applicants were in possession. See MPEP 2163.
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.
Claims 1-9 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Lagu (WO 2018/067860 A1) in view of O’Carroll (WO 2020/172421 A1; IDS dated 29 February 2024, Cite No. 45).
Regarding Claims 1-9 and 11, Lagu teaches (R)-3-methyl-6-(2-((5-methyl-2-(4-(trifluoromethyl)phenyl)-1H-imidazol-1-yl)methyl)phenoxyl)hexanoic acid, which Lagu calls Compound A of the Formula (I) (p. 2, Lines 1-5; p. 15, Lines 11-15). Lagu’s Compound A is structurally identical to the instant application’s Compound (I). Additionally, Lagu describes a method by which a crystalline hemisulfate salt of Compound A can be prepared (p. 4, Lines 1-16).
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Fig 1. (R)-3-methyl-6-(2-((5-methyl-2-(4-(trifluoromethyl)phenyl)-1H-imidazol-1-yl)methyl)phenoxy)hexanoic acid as drawn by JChem.
Lagu indicates Compound A is a peroxisome proliferator-activated receptor δ (PPARδ) agonist (p. 1, Line 21) and has utility in treating diseases, developmental delays, and symptoms related to mitochondrial dysfunction such as Alpers Disease, myoclonic epilepsy and ragged-red fiber disease, Pearson syndrome (p. 3, Lines 17-22), chronic progressive external ophthalmoplegia, Kearns-Sayre Syndrome, Leber Hereditary Optic Neuropathy, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), myoclonic epilepsy and ragged-red fiber disease (MERRF), and neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) (p. 8, Lines 8-13; p. 35, Claim 16, Lines 5-9). Lagu states the “therapeutically effective amount” of Compound A which should be administered to a patient depends on the administration route, the disease, and the individual patient’s characteristics such as their age, sex, and body weight (p. 10, Line 32 – p. 11, Line 2). Furthermore, Lagu suggests a skilled artisan could determine the appropriate dosage (p. 11, Lines 2-3) and indicates a therapeutically effective amount could be 0.1-50,000 mg per day (p. 11, Lines 3-7).
Lagu does not explicitly teach 30-125mg or compound (I) per day or that the patient received a mitochondrial disease-focused vitamin or supplemental therapy prior to the administration of Compound A.
O’Carroll teaches the compound (R)-3-methyl-6-(2-((5-methyl-2-(4-(trifluoromethyl)phenyl)-1H-imidazol-1-yl)methyl)phenoxyl)hexanoic acid (p. 73, Lines 10-11) is a PPARδ agonist (p. 72, Claim 26) and discloses the use of such PPARδ agonists in treating primary mitochondrial myopathies (p. 1, Paragraph [0004-0005]) such as Kearns Sayre syndrome, Leigh syndrome, mitochondrial DNA depletion syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), mitochondrial neurogastrointestinal encephalomyopathy, myoclonus epilepsy with ragged red fibers (MERRF), neuropathy ataxia and retinitis pigmentosa (NARP), Pearson syndrome, and progressive external ophthalmoplegia (p. 4, Paragraph [0014]). O’Carroll describes administering 10-500 mg (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid, which is also a PPARδ agonist, to mammals (p. 7, Paragraph [0023]). Furthermore, O’Carroll indicates the PPARδ agonist can be administered once daily (p. 9, Lines 5-7) and at least one additional agent may be administered in addition to the PPARδ agonist (p. 10, Paragraph [0034]; p. 75, Claim 38). This additional agent may be creatine, L-carnitine, acetyl-L-carnitine, or coenzyme Q10 (CoQ10).
O’Carroll does not explicitly teach a specific Compound (I) dose or when the additional agent such as creatine should be administered in relation to Compound (I).
Prior to the filing of the instant application, a PHOSITA following the teachings of Lagu would have found it prima facie obvious administer a mitochondrial disease-focused vitamin or supplemental therapy prior to administering Compound (I) based on the teachings of O’Carroll because O’Carroll indicates such a combination therapy is advantageous when the drugs’ efficacy is greater in combination than either drug’s efficacy is alone or when decreasing each drug’s dosage helps minimize any undesirable side effects (p.61, Paragraphs [00250-00251]). Thus, a PHOSITA would have known to optimize the combination therapy administration schedule to achieve the desired reduction in symptoms or disease improvement while also minimizing unwanted side effects (MPEP 2144.05(II)).
Claims 13-21 are rejected under 35 U.S.C. 103 as being unpatentable over Lagu (WO 2018/067860 A1) in view of Nutalapati (US 2012/0258173 A1).
Regarding claims 13-21, Lagu teaches all of the claimed elements as stated above. Furthermore, Lagu indicates pharmaceutical compositions comprising Compound A and one or more additional components, such as excipients, can be prepared (p. 2, Lines 13-17; p. 11, Lines 18-20).
Lagu does not explicitly name specific excipients which may be included in the composition.
Nutalapati teaches multilayer functionally coated tablets formulated for oral administration (p. 1, Paragraph [0002]) containing a “quick release drug containing layer” comprising 30.00 mg Pioglitazone HCl [PPARᵞ agonist], as well as 50.00 mg microcrystalline cellulose, 78.00 mg lactose monohydrate, 30.00 mg hydroxypropyl cellulose, 10.00 mg Croscarmellose sodium, and 2.00 mg magnesium stearate (p. 5, Paragraph [0068]). In total, Nutalapati’s 200 mg quick release drug containing layer comprises 15% Pioglitazone HCl, 25% microcrystalline cellulose, 39% lactose monohydrate, 15% hydroxypropyl cellulose, 5% Croscarmellose sodium, and 1% magnesium stearate. In addition to the quick release layer, there is a modified release layer and, together, the quick and modified release layers form a core tablet which may receive a functional coating or film (p. 1-2, Paragraph [0013]). Nutalapati indicates the functional coating or film may be a hydrophilic or hydrophobic polymer and possible polymers include hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, acrylic acid, polyacrylic acid, and polyvinylalcohol (p. 4, Paragraphs [0056-0057]).
Nutalapati does not explicitly teach Compound (I) or a hemisulfate salt of Compound (I).
Prior to the filing of the instant application, a PHOSITA following the teachings of Lagu would have found it prima facie obvious to prepare a pharmaceutical composition comprising a hemisulfate salt of Compound (I), lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and a film-coating agent based on the teachings of Nutalapati because Lagu teaches a hemisulfate salt of Compound (I) and Nutalapati teaches compositions containing the other named components. Furthermore, a skilled artisan could have predicted success in substituting Compound (I), a PPARδ agonist, for Pioglitazone HCl, a PPARᵞ agonist, in the composition described by Nutalapati (p. 5, Paragraphs [0068-0080]). The instant specification states, “A film coating agent is a thin-polymer based coat optionally applied to a solid pharmaceutical dosage form such as a tablet… A film-coating agent typically contains a polymer, a plasticizer, a colorant, a glidant, a flavor, and/or a viscosity modifier…” (p. 14, Lines 25-29). Furthermore, the instant specification lists hydroxypropyl methyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, and polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer as potential polymers which may be used in the film-coating agent (p. 14, Line 30 – p. 15, Line 1). A PHOSITA would have had a reasonable expectation of success in combining the teachings of Lagu and Nutalapati to optimize the pharmaceutical compositions described by Nutalapati in order to produce a Compound (I)-containing composition which exhibits the desired pharmaceutical properties (MPEP 2144.05(II)).
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 1-9 and 11-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 4-7 and 10 of U.S. Patent No. 11,530,192 B2 and Claims 12-17 of U.S. Patent No. 10,399,958 in view of Nutalapati (US 2012/0258173 A1) and O’Carroll (WO 2020/172421 A1; IDS dated 29 February 2024, Cite No. 45).
Patents ‘192 and ‘958 claim a pharmaceutical composition containing Compound (I) and a pharmaceutically acceptable excipient as well as a method of treating a PPARδ-related disease, including mitochondrial diseases, using Compound (I).
Patents ‘192 and ‘958 do not claim a specific Compound (I) dosage amount or specific excipients to be included in the composition.
Nutalapati teaches multilayer functionally coated tablets formulated for oral administration (p. 1, Paragraph [0002]) containing a “quick release drug containing layer” comprising 30.00 mg Pioglitazone HCl, which is a PPARᵞ agonist, as well as 50.00 mg microcrystalline cellulose, 78.00 mg lactose monohydrate, 30.00 mg hydroxypropyl cellulose, 10.00 mg Croscarmellose sodium, and 2.00 mg magnesium stearate (p. 5, Paragraph [0068]). In total, Nutalapati’s 200 mg quick release drug containing layer comprises 15% Pioglitazone HCl, 25% microcrystalline cellulose, 39% lactose monohydrate, 15% hydroxypropyl cellulose, 5% Croscarmellose sodium, and 1% magnesium stearate. In addition to the quick release layer, there is a modified release and, together, the quick and modified release layers form a core tablet which may receive a functional coating or film (p. 1-2, Paragraph [0013]). Nutalapati indicates the functional coating or film may be a hydrophilic or hydrophobic polymer and possible polymers include hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, acrylic acid, polyacrylic acid, and polyvinylalcohol (p. 4, Paragraphs [0056-0057]).
Nutalapati does not explicitly teach Compound (I) or a hemisulfate salt of Compound (I).
O’Carroll teaches the compound (R)-3-methyl-6-(2-((5-methyl-2-(4-(trifluoromethyl)phenyl)-1H-imidazol-1-yl)methyl)phenoxyl)hexanoic acid (p. 73, Lines 10-11) is a PPARδ agonist (p. 72, Claim 26) and discloses the use of such PPARδ agonists in treating primary mitochondrial myopathies (p. 1, Paragraph [0004-0005]) such as Kearns Sayre syndrome, Leigh syndrome, mitochondrial DNA depletion syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), mitochondrial neurogastrointestinal encephalomyopathy, myoclonus epilepsy with ragged red fibers (MERRF), neuropathy ataxia and retinitis pigmentosa (NARP), Pearson syndrome, and progressive external ophthalmoplegia (p. 4, Paragraph [0014]). O’Carroll describes administering 10-500 mg (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid, which is also a PPARδ agonist, to mammals (p. 7, Paragraph [0023]). Furthermore, O’Carroll indicates the PPARδ agonist can be administered once daily (p. 9, Lines 5-7) and at least one additional agent may be administered in addition to the PPARδ agonist (p. 10, Paragraph [0034]; p. 75, Claim 38). This additional agent may be creatine, L-carnitine, acetyl-L-carnitine, or coenzyme Q10 (CoQ10).
O’Carroll does not explicitly teach a specific Compound (I) dose or when the additional agent such as creatine should be administered in relation to Compound (I).
A PHOSITA would have been motivated to prepare a pharmaceutical composition containing Compound (I) and other excipients, such as croscarmellose sodium and magnesium stearate, as disclosed by Nutalapati. Administering pharmaceutical compositions containing an active ingredient as well as one or more excipients had been known to potentially result in more favorable pharmaceutical properties compared to administering the active ingredient alone. Therefore, a PHOSITA would have had a reasonable expectation of success in arriving at the claimed compositions because the compositions are prepared from known components being used for their prior art-recognized utility. Regarding claim 12, the claims in Patents ‘192 and ‘958 are not limited to a specific patient population (e.g., patients who have previously received a mitochondrial disease-focused vitamin or supplemental therapy) and, consequently, the claims in Patents ‘192 and ‘958 are broad enough to encompass the patients in instant claim 12. Furthermore, prior to the filing of the instant application, a PHOSITA following the teachings of Lagu would have found it prima facie obvious administer a mitochondrial disease-focused vitamin or supplemental therapy prior to administering Compound (I) based on the teachings of O’Carroll because O’Carroll indicates such a combination therapy is advantageous when the drugs’ efficacy is greater in combination than either drug’s efficacy is alone or when decreasing each drug’s dosage helps minimize any undesirable side effects (p.61, Paragraphs [00250-00251]).
Because Claims 1-9 and 11-21 in the instant application would have been obvious over Claims 4-7 and 10 of U.S. Patent No. 11,530,192 B2 and Claims 12-17 of U.S. Patent No. 10,399,958 in view of Nutalapati and O’Carroll, Claims 1-9 and 11-21 in the instant application are not patentably distinct from Claims 4-7 and 10 of U.S. Patent No. 11,530,192 B2 and Claims 12-17 of U.S. Patent No. 10,399,958.
Conclusion
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/B.L.B./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
Prosecution Insights