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 .
Final Rejection
The Status of Claims:
Claims 1, 7,18, 23, 27-28, 35,42,49,56,62,151, 153,161,174-182 are pending.
Claims 1, 7,18, 23,151,153,161,174, 176-177, 179-182 are rejected.
Claims 178 is objected.
Claims 27-28, 35, 42, 49, 56, 62, 175 are withdrawn from consideration.
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 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.
Claim Objections
The objection of Claims 1, 9, 23, and 161 is withdrawn due to the modification of the claims.
Claim 178 is 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 Rejections - 35 USC § 112
Applicants’ argument filed 11/29/2025 have been fully considered, and some of them
are persuasive, while others are not persuasive.
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.
The rejection of Claims 1, 7,9,18, 23, 151,153,161,174 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn.
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.
The rejection of Claims 151,153,161,174 under 35 U.S.C. 112, first paragraph, is withdrawn due to the modification of the claims.
The rejection of Claims 151, 153, 161 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph,, is withdrawn.
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.
1. The rejection of Claim(s) 1, 7, 9 , 18 under 35 U.S.C. 102(a)(1) as being anticipated clearly by Alder et al(Berichte der DeutscheChemischen Gesellschaft Abteiluna B: Abhandlunaen 71.12 (1938): 2451-2461) is withdrawn due to the modification of the claim 1 and the cancellation of claim 9.
2. The rejection of Claim(s) 1, 7, 9 , 18 under 35 U.S.C. 102(a)(1) as being anticipated clearly by Manetti et al ( J. Med. Chem. 2019, 62, p. 1887-1901) is withdrawn due to the modification of the claim 1 and the cancellation of claim 9.
3. The rejection of Claim(s) 1, 7, 9 , 18, 22-23, 151,153,161,174 are rejected under 35 U.S.C. 102(a)(1) as being anticipated clearly by Dvela-Levitt et al (Cell 178, July 25,2019, 521–535) is withdrawn due to modification of the claim 1 and the cancellation of claim 9.
However, in view of the revised claims and finding a proper prior art , some103 rejections seem necessary in the followings:
Claim Rejections - 35 USC § 103
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.
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.
4. Claims 1, 7,18, 23,151,153,161,174, 176-177, 179-182 are rejected under 35 U.S.C. 103 as being unpatentable over Greka et al(WO 2020/257736 A1), which has a priority of US 62/865,096 (06/21/2019) and US 62/878,304 (07/24/2019).
Determination of the scope and content of the prior art
Greka et al discloses 2-endo-amino-3-exo-isopropylbicyclo[2.2. l ]heptane as shown in formula(II)
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(see page 48, formula (II)), which can be applied for a method of treating a toxic proteinopathy in the followings:
A method of treating or preventing a toxic proteinopathy with 2-endo-amino-3-exoisopropylbicyclo[2.2. l ]heptane or a pharmaceutically acceptable salt thereof as in claim 151.
6. A method for selecting a treatment for a toxic proteinopathy resulting from mutant protein accumulation in the early secretory pathway in a subject in need thereof, the method comprising:(a) identifying a subject as having or at risk of developing a toxic proteinopathy resulting from mutant protein accumulation in the early secretory pathway; and (b) selecting 2-endo-amino-3-exo-isopropylbicyclo[2.2. l ]heptane as in claim 179 (partially) as a treatment for the subject identified as having or at risk of developing a toxic proteinopathy resulting from mutant protein accumulation in the early secretory pathway as in claims 161 and 176-177.
7. The method of any one of claims 1-6, wherein the toxic proteinopathy is selected from the group consisting of a neurodegenerative disease, MDCI-associated kidney disease, autosomal dominant kidney disease caused by uromodulin mutations and a form of retinitis pigmentosa (RP) caused by a rhodopsin mutation as in claims 153.
8. The method of claim 7, wherein the toxic proteinopathy is MDCI-associated kidney disease(see page 144. Claims 1, 6-8)
36. A method of treating or preventing MDCI-associated kidney disease (MKD) in a subject in need thereof, the method comprising administering to the subject 2-endo-amino-3-exoisopropylbicyclo[2.2. l ]heptane or a pharmaceutically acceptable salt thereof as a first agent and a second agent selected from the group consisting of vitamin D, a phosphate binder, a blood pressure medication and a diuretic, thereby treating or preventing MKD in the subject as in claim 174.(see page 149. Claim 36)
38. The method of claim 37, wherein the proteinopathy is selected from the group consisting of MUC I-associated kidney disease, autosomal dominant kidney disease caused by uromodulin mutations, a form of retinitis pigmentosa (RP) caused by a rhodopsin mutation, and a neurodegenerative disease (e.g., Alzheimer's disease (AD) or other dementia; Parkinson's disease (PD) or a PD-related disorder; prion disease (including, e.g., Creutzfeldt-Jakob Disease, variant Creutzfeldt-Jakob Disease, Bovine Spongiform Encephalopathy, Kum, GerstmannStraussler-Scheinker disease, fatal familial insomnia (FFI), scrapie, or other animal TSE); motor neuron disease (MND; including, e.g., Amyotrophic Lateral Sclerosis (ALS), Primary Lateral Sclerosis (PLS), Progressive Bulbar Palsy (PBP), Pseudobulbar Palsy, Progressive Muscular Atrophy, Spinal Muscular Atrophy (Type 1, Type 2, Type 3, Type 4), or Kennedy's Disease); or spinocerebellar ataxia (SCA)) as in claims 180-182.(see page 150, claim 38)
The current invention, however, differs from the prior art in that the variable R1 of the claimed compound is t-butyl instead of isopropyl as the variable R1 of of the prior art compound.
Ascertainment of the difference between the prior art and the claims
The difference between the current application and the applied Greka et al art is that the applied Greka et al art does not expressly teach the variable R1 of the claimed compound being t-butyl.
Resolving the level of ordinary skill in the pertinent art.
Regarding the claims 1 and their dependent claims with respect to the lack of disclosing a methyl group attached to isopropyl group on the ring structure, the prior art is is silent. However, the distinction between the prior art and the claimed compound is hydrogen vs. methyl moiety; it is well-established that the substitution of methyl for hydrogen is a known compound is not a patentable modification absent unexpected or unobvious results. In re Wood, 582 F.2d 638, 199 U.S.P.Q. 137 (C.C.P.A. 1978); In re Hoke , 560 F. 2d 436, 195 U.S.P.Q. 148 (C.C.P.A. 1977). Furthermore, such a difference between the prior art and the claimed compound is a minor and can be expected to be prepared by the same method and to have generally the same or similar properties. This expectation is then deemed the motivation for preparing the methyl substituted compound. So, it would have been obvious to the skilled artisan in the art to be motivated to prepare the claimed compound as an alternative in the Greka et al method. This is because the skilled artisan in the art would expect such a selection and manipulation to be successful and feasible as guidance shown in the prior art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Greka et al expressly discloses 2-endo-amino-3-exo-isopropylbicyclo[2.2. l ]heptane as shown in formula(II)
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(see page 48, formula (II)), and it also does teach the method of treating a toxic proteinopathy with 2-endo-amino-3-exo-isopropylbicyclo[2.2. l ]heptane compound.
Although the prior art does not teach a methyl group attached to isopropyl group on the ring structure, the distinction between the prior art and the claimed compound is hydrogen vs. methyl moiety; it is well-established that the substitution of methyl for hydrogen is a known compound is not a patentable modification absent unexpected or unobvious results. In re Wood, 582 F.2d 638, 199 U.S.P.Q. 137 (C.C.P.A. 1978); In re Hoke , 560 F. 2d 436, 195 U.S.P.Q. 148 (C.C.P.A. 1977). Furthermore, such a difference between the prior art and the claimed compound is a minor and can be expected to be prepared by the same method and to have generally the same or similar properties. This expectation is then deemed the motivation for preparing the methyl substituted compound. So, it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to prepare the claimed compound as an alternative in the Greka et al method. This is because the skilled artisan in the art would expect such a selection and manipulation to be successful and feasible as guidance shown in the prior art.
5. Claims 1, 7,18 are rejected under 35 U.S.C. 103 as being unpatentable over Alder et al(Berichte der Deutschen Chemischen Gesellschaft Abteiluna B: Abhandlunaen 71.12 (1938): 2451-2461).
Alder et al discloses the following compounds:
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(see page 2452, compound# XIV)
The current invention, however, differs from the prior art in that the variable R1 of the claimed compound is isobutyl instead of propyl as the variable R1 of of the prior art compound.
Ascertainment of the difference between the prior art and the claims
The difference between the current application and the applied Alder et al art is that the applied Alder et al art does not expressly teach the variable R1 of the claimed compound being iso-butyl.
Resolving the level of ordinary skill in the pertinent art.
Regarding the claims 1 and their dependent claims with respect to the lack of disclosing a methyl group attached to the middle position of the propyl group on the ring structure, the prior art is silent. However, the distinction between the prior art and the claimed compound is hydrogen vs. methyl moiety; it is well-established that the substitution of methyl for hydrogen is a known compound is not a patentable modification absent unexpected or unobvious results. In re Wood, 582 F.2d 638, 199 U.S.P.Q. 137 (C.C.P.A. 1978); In re Hoke , 560 F. 2d 436, 195 U.S.P.Q. 148 (C.C.P.A. 1977). Furthermore, such a difference between the prior art and the claimed compound is a minor and can be expected to be prepared by the same method and to have generally the same or similar properties. This expectation is then deemed the motivation for preparing the methyl substituted compound. So, it would have been obvious to the skilled artisan in the art to be motivated to prepare the claimed compound as an alternative in the Alder et al preparation. This is because the skilled artisan in the art would expect such a selection and manipulation to be successful and feasible as guidance shown in the prior art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Alder et al discloses the following compound(XIV) as shown below:
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(see page 2452, compound# XIV).
Although the prior art does not teach a methyl group attached to attached to the middle position of the propyl group on the ring structure, the distinction between the prior art and the claimed compound is hydrogen vs. methyl moiety; it is well-established that the substitution of methyl for hydrogen is a known compound is not a patentable modification absent unexpected or unobvious results. In re Wood, 582 F.2d 638, 199 U.S.P.Q. 137 (C.C.P.A. 1978); In re Hoke , 560 F. 2d 436, 195 U.S.P.Q. 148 (C.C.P.A. 1977). Furthermore, such a difference between the prior art and the claimed compound is a minor and can be expected to be prepared by the same method and to have generally the same or similar properties. This expectation is then deemed the motivation for preparing the methyl substituted compound. So, it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to prepare the claimed compound as an alternative in the Alder et al preparation. This is because the skilled artisan in the art would expect such a selection and manipulation to be successful and feasible as guidance shown in the prior art.
Applicants argue the following issues:
Claims 1, 7, 9, and 18 stand rejected under 35 U.S.C. § 102(a)(l) as allegedly being anticipated by Alder et al. (Berichte der Deutschen Chemischen Gesellschaft Abteiluna B: Abhandlunaen 71.12 (1938): 2451-2461). The Examiner alleges that Alder et al. on pg. 2452 discloses several compounds (XIII & XIV) which are identical to the presently claimed compounds. Solely for the purpose of expediting prosecution, and without acquiescence to the rejection, claim 9 has been cancelled, and Applicants have amended claim 1 to recite that the R 1 substituent is isobutyl, t-butyl, trifluoromethyl, cycloalkyl, or thiophenyl. The compounds disclosed in Alder et al. do not comprise these substituents at the equivalent position. Therefore, claim 1 is novel over Alder et al. The remaining rejected claims depend from claim 1 and therefore incorporate all features of amended claim 1. Therefore, the claims as amended are novel over Alder et al.
Claims 1, 7, 9, and 18 stand rejected under 35 U.S.C. § 102(a)(l) as allegedly being anticipated by Manetti et al. (J. Med. Chem. 2019, 62: 1887-1901). The Examiner alleges that Manetti et al. on pg. 1890 discloses a substituted norbomene which anticipates the presently claimed compounds. Solely for the purpose of expediting prosecution, and without acquiescence to the rejection, claim 9 has been cancelled, and Applicants have amended claim 1 to recite that the R 1 substituent is isobutyl, t-butyl, trifluoromethyl, cycloalkyl, or thiophenyl. The compounds disclosed in Manetti et al. do not comprise these substituents at the equivalent position. Therefore, claim 1 is novel over Manetti et al. The remaining rejected claims depend from claim 1 and therefore ncorporate all features of amended claim 1. Therefore, the claims as amended are novel over Manetti et al.
Claims 1, 7, 9, 18, 22-23, 151, 153, 161, and 174 stand rejected under 35 U.S.C. § 102(a)(l) as allegedly being anticipated by Dvela-Levitt et al. (Cell, 2019, 178: 521-535). The Examiner argues that Dvela-Levitt et al., which discloses BRD4780 and its use in treating toxic proteinopathies, is inherently identical with the claims. Solely for the purpose of expediting prosecution, and without acquiescence to the rejection, claim 9 has been cancelled, and Applicants have amended claim 1 to recite that the R1 substituent is isobutyl, t-butyl, trifluoromethyl, cycloalkyl, or thiophenyl. The compounds disclosed in Dvela-Levitt et al. comprise an isopropyl group and do not comprise these substituents at the equivalent position. Claim 22 has been cancelled, and new claim 179 recites compounds not comprising an isobutyl, t-butyl, trifluoromethyl, cycloalkyl, or thiophenyl substituent. Therefore, claims 1 and 179 are novel over Dvela-Levitt et al. The remaining rejected claims depend from claim 1 and therefore incorporate all features of amended claim 1. Therefore, the claims as amended are novel over Dvela-Levitt et al. Accordingly, Applicants request reconsideration and withdrawal of the novelty rejections.
Applicants’ arguments have been noted and they are persuasive. However,
As indicated in the above, in view of the revised claims and finding a proper prior art , some 103 rejections seem necessary. Therefore, the application is not ready for allowance yet.
Conclusion
Claims 1, 7,18, 23,151,153,161,174, 176-177, 179-182 are rejected.
Claims 178 is objected.
Claims 27-28, 35, 42, 49, 56, 62, 175 are withdrawn from consideration.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAYLOR V OH whose telephone number is (571)272-0689. The examiner can normally be reached 8:00-5:00.
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/TAYLOR V OH/Primary Examiner, Art Unit 1625 6/18/2026
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