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 .
DETAILED ACTION
Election of Species and Status of the Claims
Applicant’s election without traverse of the compound,
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as the single compound, encompassing claims 1-2, 6, 10-11, 17-18, 23-27, 29, 33, 39, and 42, as well as ‘Age-related Macular Degeneration’ as the single condition, encompassing claims 25-27, 29, and 33 in the reply filed on November 20th 2025 is acknowledged. Applicant’s elected species is not found in the art. As recognized by MEPEP § 803.02(III)(C)(2):
If the elected species or group of patentably indistinct species is not anticipated by or obvious over the prior art, the examiner should extend the search and examination to a non-elected species or group of species that falls within the scope of a proper Markush grouping that includes the elected species. The search and examination should be continued until either (1) prior art is found that anticipates or renders obvious a species that falls within the scope of a proper Markush grouping that includes the elected species, or (2) it is determined that no prior art rejection of any species that falls within the scope of a proper Markush grouping that includes the elected species can be made. The examiner need not extend the search beyond a proper Markush grouping. In other words, the examiner need not extend the search to any additional species that do not share a single structural similarity and a common use with the elected species (i.e., do not belong to the same recognized physical or chemical class or to the same art- recognized class and/or do not have a common use and/or do not share a substantial structural feature of a chemical compound and a use that flows from the substantial structural feature). The examiner should continue examination of the Markush claim to determine whether it meets all other requirements of patentability (e.g., 35 U.S.C. 101 and 112, nonstatutory double patenting, and proper Markush grouping).
Claims 1-2, 6, 10-11, 13, 15-18, 23-27, 29, 33, 42, and 46 are pending. Claims 13, 15-16, 39, 42, and 46 are withdrawn from further consideration as being directed towards nonelected species until a generic claim has been found allowable. Claims 1-2, 6, 10-11, 17-18, 23-27, 29, and 33 are examined on their merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statement filed on November 20th 2025, June 28th 2023, and January 19th 2023 are in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
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 17 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.
Claim 17 is indefinite for reciting:
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It appears as if an additional compound was added in the amendment to claim 17 in the response filed on November 20th 2025, but no such compound is found.
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.
Claims 1, 2, 6, and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nomura (U.S. Patent No. 7,902,367 issued on March 8th 2011).
The claims are directed towards a compound of the generic structure:
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Nomura teaches the compound,
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(Nomura, col. 131),
which is anticipatory of claims 1, 2, and 6.
Nomura additionally teaches pharmaceutical compositions of the compound (Nomura, col. 1), anticipating claim 23.
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.
Claims 1-2, 6, 18, 23-27, 29, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Petrukhin (U.S. Patent No. 9,944,644 issued on April 17th 2018) in view of Reilly (Reilly et al., J Med Chem. 2018 Jun 28;61(12):5367-5379) and Manka (Manka et al., Bioorg Med Chem Lett. 2013 Sep 15;23(18):5091-6).
Claims 1-2, 6, and 18 are directed towards compounds including,
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Petrukhin teaches the similar compound,
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(Petrukhin, col. 124, Example 55).
Petrukhin’s compound differs from applicant’s compound only in the center ring system, which stands as an octahydropyrrolo[3,4-c]pyrrole, and a 2,7-diazaspiro[4.4]nonane in applicant’s compound. One of ordinary skill in the art would have a reasonable expectation of success in substituting Petrukhin’s octahydropyrrolo[3,4-c]pyrrole for applicant’s 2,7-diazaspiro[4.4]nonane, because both are known in the art to be bioisosteres of piperazine.
For example, Reilly teaches that piperazines can successfully be replaced with diazaspiro cores and retain their pharmacological properties (Reilly, pg. 2, last paragraph; pg. 6, Conclusions; pg. 26, Figure 2). Additionally, Manka describes the bioisosteric relationship between piperazine and octahydropyrrolo[3,4-c]pyrrole:
One piperazine isostere of interest was the octahydropyrrolo[3,4-c]pyrrole. This particular ring system has been successfully employed in drug discovery research as an effective replacement for a piperazine ring in the past.14 Furthermore, the N-heteroaryl octahydropyrrolo[3,4-c]pyrrole chemotype has proven to be useful for the design of drug-like small molecules that interact with a number of CNS targets.
[Manka, pg. 2]
As one of ordinary skill in the art would recognize both cores as bioisosteres of piperazine, one would have a reasonable expectation of success in replacing Petrukhin’s core with applicant’s core in the process of drug development, and claims 1-2, 6, and 18 are thereby prima facie obvious.
Claim 23 is directed towards a pharmaceutical composition comprising the compound. Petrukhin teaches a pharmaceutical composition of the compound (Petrukhin, col. 146, claim 18), and claim 23 is prima facie obvious.
Claim 24 is directed towards a method for stabilizing TTR tetramers in a mammal comprising administration of the composition of claim 23. Petrukhin’s compounds act as antagonists of the RBP4-TTR interaction in mammals (Petrukhin, Figures 8-9), thus acting as stabilizers of the TTR tetramers, and claim 24 is thereby prima facie obvious.
Claims 25-27, 29, and 33 are directed towards the treatment of age-related macular degeneration via administration of the composition of claim 23 in an amount that lowers bisretiniod A2E levels. Petrukhin teaches the lowering of bisretinoid A2E levels and treatment of age-related macular degeneration with the compound (Petrukhin, col. 39), rendering claims 25-27, 29, and 33 prima facie obvious.
Nonstatutory 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, 2, 6, and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 9,944,644 in view of Reilly (Reilly et al., J Med Chem. 2018 Jun 28;61(12):5367-5379) and Manka (Manka et al., Bioorg Med Chem Lett. 2013 Sep 15;23(18):5091-6).
The reference patent claims compounds including:
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(reference patent, claim 5).
Said compound differs from applicant’s compound genus,
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in the replacement of the octahydropyrrolo[3,4-c]pyrrole with a 2,7-diazaspiro[4.4]nonane. For the teachings of Reilly and Manka as they relate to the replacement of octahydropyrrolo[3,4-c]pyrrole with a 2,7-diazaspiro[4.4]nonane (i.e. the shared bioisosterism with piperazine), see the above 103 rejections. The reference patent additionally claims pharmaceutical compositions of the compound (reference patent, claim 18).
Claims 1-2, 6, 23-27, 29, and 33 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,787,453 in view of Reilly (Reilly et al., J Med Chem. 2018 Jun 28;61(12):5367-5379) and Manka (Manka et al., Bioorg Med Chem Lett. 2013 Sep 15;23(18):5091-6).
The reference patent claims compounds including:
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(reference patent, claim 9).
Said compound differs from applicant’s compound genus,
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in the replacement of the octahydropyrrolo[3,4-c]pyrrole with a 2,7-diazaspiro[4.4]nonane. For the teachings of Reilly and Manka as they relate to the replacement of octahydropyrrolo[3,4-c]pyrrole with a 2,7-diazaspiro[4.4]nonane (i.e. the shared bioisosterism with piperazine), see the above 103 rejections. The reference patent additionally teaches the lowering of serum concentration of RBP4 via administration of the compound (i.e. demonstrating the same biological activity as the instant compounds) (reference patent, claim 1). Furthermore, the reference patent teaches the treatment of age-related macular degeneration with the compound (reference patent, claim 13).
Claims 1, 2, 6, and 23-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,440,486 in view of Reilly (Reilly et al., J Med Chem. 2018 Jun 28;61(12):5367-5379) and Manka (Manka et al., Bioorg Med Chem Lett. 2013 Sep 15;23(18):5091-6).
The reference patent claims compounds including:
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(reference patent, claim 11).
Said compound differs from applicant’s compound genus,
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in the replacement of the octahydropyrrolo[3,4-c]pyrrole with a 2,7-diazaspiro[4.4]nonane. For the teachings of Reilly and Manka as they relate to the replacement of octahydropyrrolo[3,4-c]pyrrole with a 2,7-diazaspiro[4.4]nonane (i.e. the shared bioisosterism with piperazine), see the above 103 rejections. The reference patent additionally teaches the lowering of serum concentration of RBP4 with the compound (i.e. demonstrating the same biological activity as the instant compounds) (reference patent, claim 4).
Claims 1, 2, 6, and 23-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of co-pending Application No. 19/257,683 in view of Reilly (Reilly et al., J Med Chem. 2018 Jun 28;61(12):5367-5379) and Manka (Manka et al., Bioorg Med Chem Lett. 2013 Sep 15;23(18):5091-6).
The reference application teaches administration of RBP4 antagonists of the generic formula:
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Which differs from applicant’s genus,
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in the replacement of the octahydropyrrolo[3,4-c]pyrrole with a 2,7-diazaspiro[4.4]nonane. For the teachings of Reilly and Manka as they relate to the replacement of octahydropyrrolo[3,4-c]pyrrole with a 2,7-diazaspiro[4.4]nonane (i.e. the shared bioisosterism with piperazine), see the above 103 rejections.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
Claims 10, 11, and 17 are free of the prior art.
Applicant has developed compounds of the generic formula,
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Such compounds act as antagonists of retinol-binding protein 4, thus stabilizing the transthyretin (TTR) complex and allowing for the treatment of various ocular diseases, such as macular degeneration.
Certain aspects of applicant’s generic formula have been found prima facie obvious (see the above 103 rejections. Specifically, the case wherein the center N-heterocycle is condensed with another to form a spiro-system. However, applicant’s particular compounds as described in claims 10, 11, and 17 are not found in the art, nor are they predictable from the art.
Claims 10, 11, and 17 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 17 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anthony Seitz whose telephone number is (703)756-4657. The examiner can normally be reached 7:30 AM ET - 5:00 PM ET M-F.
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, Jeffrey Lundgren can be reached at (571)272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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