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 .
Election/Restrictions
Applicant's election with traverse of Group I, drawn to compounds represented by a chemical formula I, stereoisomers thereof or pharmaceutically acceptable salts thereof, and the compound 48 having the following structure:
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as the elected compound species are maintained.
Claim 12 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.
Expansion of Election of Species Requirement
A reasonable and comprehensive search of the elected compound species conducted by the Examiner determined that the prior art at the time of the present invention was such that it did not anticipate or render obvious the elected compound species:
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. In light of this discovery, the search is expanded to the subject matter of the compounds 1 to 368 recites in claim 8 in addition to the subgenus of chemical formula I having the structure of:
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,
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,
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and
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, such that it does not encompass the full scope of the compound represented by the chemical formula (I).
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on November 26, 2025, wherein claims 1-5 and 8-11 are amended; claims 6-7 and 13-15 are cancelled; claims 12 are unchanged.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-5 and 8-12 are pending. Claim 12 remain withdrawn.
Claims 1-5 and 8-11 are under examination in accordance with the elected species along with the expanded species sets forth in the Expansion of Species section above.
Priority
The instant application 17/614,967 filed on November 29, 2021 is a 371 of PCT/IB2020/055109 filed on May 29, 2020, which claims priority to, and the benefits of Foreign Application No.
KR10-2019-0064665 filed on May 31, 2019.
Declarations
The declarations under 37 CFR 1.132 filed on November 26, 2025 are sufficient to overcome the rejection of claims 1-2, 4-11 and 15 under 35 U.S.C. 103 as being unpatentable over Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021) as applied to claims 1-2, 4-7 and 9-11 above, and further in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176), because the declarants demonstrates the compound 31 of instant specification demonstrates unexpected properties (“excellent selective inhibitory activity against HDAC6”) when compared to compound 429 of Walji et al.
The declarations under 37 CFR 1.132 filed on November 26, 2025 are insufficient to overcome the rejection of claims 1-2, 4-7 and 9-11 under 35 U.S.C. 103 as being unpatentable over Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021), and the rejection of claims 1-7 and 9-11 under 35 U.S.C. 103 as being unpatentable over Walji et al. (WO 2017/222951 A1) as applied to claims 1-2, 4-7 and 9-11 above, and further in view of Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021), and the reasons are addressed in the response to arguments sets forth below.
The declarations under 37 CFR 1.132 filed on November 26, 2025 are insufficient to overcome the rejection of claims 1-2, 4-6 and 8-11 under 35 U.S.C. 103 as being unpatentable over Gallagher et al. (US 6,075,039), in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176), and the reasons are addressed in the response to arguments sets forth below.
Action Summary
Applicant’s amendment to the claims overcomes each and every objection previously sets forth in the Non-Final Office Action mailed on August 26, 2025.
All rejections pertaining to claims 6-7 are moot because the claims were cancelled in view of the amendments filed on November 26, 2025.
Claims 10-11 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph are maintained, but revisited and modified in view of the claim amendments.
Claims 5-6 and 8-11 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 are withdrawn in view of the claim amendments.
Claims 2 and 4 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends are withdrawn in view of the claim amendments.
Claims 1-11 rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives are maintained, but revisited and modified in view of the claim amendments.
Claim 10-11 rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives are withdrawn in view of the claim amendments.
Claims 1-2, 4-7 and 9-11 rejected under 35 U.S.C. 103 as being unpatentable over Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021) are maintained, but revisited and modified in view of the claim amendments.
Claims 1-7 and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021) as applied to claims 1-2, 4-7 and 9-11 above, and further in view of Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021) are maintained, but revisited and modified in view of the claim amendments.
Claims 1-2, 4-11 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021) as applied to claims 1-2, 4-7 and 9-11 above, and further in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176) are withdrawn in view of the declarations under 37 CFR 1.132 filed on November 26, 2025.
Claims 1, 4, and 8-11 rejected under 35 U.S.C. 103 as being unpatentable over Gallagher et al. (US 6,075,039), in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176), as evidenced by CAS Registry 201986-11-0 (Entered STN Registry on March 1, 1998) are withdrawn in view of the claim amendments.
Claims 1-2, 4-6 and 9-11 remain rejected and claim 8 is under 35 U.S.C. 103 as being unpatentable over Gallagher et al. (US 6,075,039), in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176) as applied to claims 1, 4, and 8-11 above, and further in view of Gallagher et al. (US 6,075,039) are maintained, but revisited and modified in view of the claim amendments.
Claim interpretation
Regarding the limitation of “wherein said pharmaceutical composition is used for treating histone deacetylase 6 activity-related diseases, wherein said histone deacetylase 6 activity-related diseases are at least one selected from the group consisting of neoplasm, respiratory diseases, digestive diseases, and musculoskeletal system and connective tissue diseases” in claim 10, and the limitation of “wherein histone deacetylase 6 activity-related diseases are at least one selected from the group
consisting of rheumatoid arthritis, inflammatory bowel disease, asthma, melanoma, multiple myeloma, lymphoma, breast cancer and lung cancer.” in claim 11, each of these limitations is reasonably construed by the Examiner as being drawn to the intended use of the pharmaceutical composition sets forth in claim 9, and these limitations do not create a structural difference to the pharmaceutical composition.
Claim Objections
Claim 4 is objected to because of the following informalities (newly applied as necessitated by amendment):
Regarding claim 4, the recitation of “[[, X or C1-C4 haloalkyl” includes left brackets without right backets in the claim, this appears to be a typographical error. It is noted that these left brackets are new to the claim without markings to indicate the changes.
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 10-11 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating rheumatoid arthritis, inflammatory bowel disease, asthma, melanoma, multiple myeloma, lymphoma, breast cancer and lung cancer, does not reasonably provide enablement for treating the entire scope of histone deacetylase 6 activity-related diseases instantly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and, (8) the quantity of experimentation necessary. All of the Wands factors have been considered and discussed below:
(1, 5) The breadth of the claims and the Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
Instant claim 10 recites “[t]he pharmaceutical composition according to claim 9, wherein said pharmaceutical composition is used for treating histone deacetylase 6 activity-related diseases, wherein said histone deacetylase 6 activity-related diseases are at least one selected from the group consisting of neoplasm, respiratory diseases, digestive diseases, and musculoskeletal system and connective tissue diseases”.
Instant claim 11 recites “[t]he pharmaceutical composition according to claim 10, wherein said histone deacetylase 6 activity-related diseases are at least one selected from the group consisting of rheumatoid arthritis, inflammatory bowel disease, asthma, melanoma, multiple myeloma, lymphoma, breast cancer and lung cancer”.
Therefore, the breadth of the claims cover treating the entire scope of histone deacetylase 6 activity-related diseases that are at least one selected from the group consisting of neoplasm, respiratory diseases, digestive diseases, and musculoskeletal system and connective tissue diseases, including the subgenus sets forth in claim 11.
(2, 3, 4) The state of the prior art, the level of skill in the art, and the predictability or lack
thereof in the art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the
art would have known, at the time the application was filed, about the subject matter to which the
claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art
refers to the skill of those in the art in relation to the subject matter to which the claimed invention
pertains at the time the application was filed.”
As discussed above, the instantly claimed invention pertains to a pharmaceutical composition comprising the compound represented by the chemical formula I suitable for preventing or treating each and every histone deacetylase 6 activity-related diseases.
At the time the application was filed, one skilled in the art would have known that the histone deacetylase 6 (HDAC6) inhibitor is useful for treating inflammatory disease such as rheumatoid arthritis, inflammatory bowel disease and asthma, as evidenced by Ran et al. (Thoracic cancer, 2019. Vol. 10(3): 405–412)(see e.g., ”Potential of HDAC6 inhibitors as treatments for inflammatory disease” section). One would have also known that selective histone deacetylase 6 (HDAC6) inhibitors are currently in clinical trials for treating melanoma, multiple myeloma, lymphoma, breast cancer and lung cancer, as evidenced by Li et al. (J Hematol Oncol, 2018. Vol. 11, 111)(see e.g., Table 2).
According to Di Bello et al. (CHIMIA, 2022. Vol. 76, no. 5: 448-453), FDA only approved five HDAC inhibitor for the treatment of hematological cancers so far, since they possess poor efficacy in solid tumors as single agent (see e.g., p. 452, left column, line 8-9). According to Ferreira et al. (J Biol Chem. 2017. Vol. 292(6): 2422-2440), although pan-HDAC inhibition in retina explants by TSA resulted in increased cell death and reduction in proliferation, the explants treated with apicidin (HDAC3i) had no difference in proliferation. Each of these findings demonstrate the level of skill and knowledge in the art with respect to using a HDAC inhibitor, including those that inhibits HDAC6, for treating the entire scope of the histone deacetylase 6 activity-related diseases, including any cancer species, is still underdeveloped due to the unpredictability of cancer treatment.
At the time the invention was made, the relative skill of those in the art tasked with identifying compounds that inhibits the biological activity of a mammalian histone deacetylase (HDAC) would have been high, as the ordinarily skilled artisan would have had an experience with screening techniques such as conducting high-throughput screening assays that measure HDAC activity in biochemical or cell-based formats, as evidenced by Hsu et al. (J Biomol Screen, 2016. Vol. 21(6): 643-652) (see e.g., p. 644, left column, 2nd paragraph).
Even though the HDAC6 inhibitor of the claimed invention, in this case, the compound represented by the chemical formula I, may play a role in treating rheumatoid arthritis, inflammatory bowel disease, asthma, melanoma, multiple myeloma, lymphoma, breast cancer and lung cancer by inhibiting the biological activity of HDAC6, it is uncertain whether the pharmaceutical composition comprising any compound species represented by the chemical formula I, stereoisomers thereof or pharmaceutically acceptable salts thereof can be used for treating the entire scope of histone deacetylase 6 activity-related diseases for the reasons set forth herein.
(6, 7, 8) The amount of guidance given, the presence of working example and the quantitation
of experimentation required:
In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the claimed invention. In the present case, the specification discloses the HDAC enzyme inhibitory activity of compound 1 to compound 368 (see e.g., Table 2), specifically HDAC1 and HDAC6; However, their biological activities against the full scope of histone deacetylase 6 activity-related diseases has not been disclosed. Therefore, one of the relative skill in the art armed with screening techniques could not reasonably predict which species of histone deacetylase 6 activity-related diseases encompassed by the claims could be treated by the compound represented by the chemical formula I based on the limited disclosure provided. As a result, it would require an undue experimentation as it is highly unpredictable that the pharmaceutical composition comprising any compound species represented by instant chemical formula I, stereoisomers thereof, or pharmaceutically acceptable salts thereof would, in fact, be usable across the entire scope of histone deacetylase 6 activity-related diseases with the intention to treat.
Accordingly, the pharmaceutical composition comprising any compound species represented by formula I, stereoisomers thereof or pharmaceutically acceptable salts thereof, with the intended use that covers preventing or treating the entire scope of histone deacetylase 6 activity-related diseases is not enabled by the instant specification. To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS. —Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends (newly applied as necessitated by amendments).
Regarding claim 4, the recitation of “X” in the list of substituents of R5, R6, R8, R10 and R11 fails to further limit the chemical formula I sets forth in claim 1, see below:
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, because said X has been removed from the previous chemical formula I after amendment. In addition, the recitation of “provided that Z5 to Z8…are consisting of CR2,CR3 and two Ns” fails to further limit ring
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in the chemical formula I sets forth in claim 1, because said ring can only be phenylene or pyridinylene, and that does not include a ring with 2 nitrogen atoms.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Arguments
Applicant's arguments filed on November 26, 2025 with respect to the rejection of claims 10-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, have been fully considered but they are not persuasive.
Applicant amends claim 10 from the recitation of “wherein said pharmaceutical composition is used for preventing or treating histone deacetylase 6 activity-related disease, wherein said pharmaceutical composition is used for preventing or treating hi stone deacetylase 6 activity-related diseases” to the recitation of “wherein said pharmaceutical composition is used for treating histone deacetylase 6 activity-related diseases, wherein said histone deacetylase 6 activity-related diseases are at least one selected from the group consisting of neoplasm, respiratory diseases, digestive diseases, and musculoskeletal system and connective tissue diseases”. Applicant further amends claim 11 from the recitation of “wherein said histone deacetylase 6 activity-related diseases are at least one selected from the group consisting of infectious diseases…deformities and chromosomal aberration” to the recitation of “rheumatoid arthritis, inflammatory bowel disease, asthma, melanoma, multiple myeloma, lymphoma, breast cancer and lung cancer”. Each of these findings demonstrate that the amendment changes the scope of the claims, and that necessitates a modification of the rejection on the record.
In Summary, applicant argues neoplasm, respiratory diseases, digestive diseases, and musculoskeletal system and connective tissue diseases fall within the scope of diseases that could be reasonably derived from rheumatoid arthritis, inflammatory bowel disease, asthma, melanoma, multiple myeloma, lymphoma, breast cancer, and lung cancer; and therefore, the claim amendments bear a reasonable correlation with the disclosure.
In response, applicant’s argument is not found persuasive. First, just because selective histone deacetylase 6 (HDAC6) inhibitors are known in the art to be capable of treating melanoma, multiple myeloma, lymphoma, breast cancer and lung cancer, it does not mean said compounds are capable of treating the entire scope of the genus (neoplasm). According to Di Bello et al. (CHIMIA, 2022. Vol. 76, no. 5: 448-453) cited above (see rejection above), FDA-approved HDAC inhibitors are known to show poor single-agent efficacy in solid tumors, which demonstrates the unpredictability surrounding the treatment of the entire scope of neoplasm. Same logic applies to other genus, such as respiratory diseases, digestive diseases, and musculoskeletal system and connective tissue diseases. Therefore, the rejection is maintained but revisited and modified in light of the claim amendments.
Claim Rejections - 35 USC § 112 - Improper Markush Grouping
Claims 1-5 and 8-11 remain rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature.
A Markush claim contains an “improper Markush grouping” if: (1) the species of the Markush group do not share a single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a "single structural similarity” when they belong to the same recognized physical or chemical class or to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent (see Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, p. 7166, left and middle columns, bridging paragraph).
The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons:
In the present case, instant claim 1 recites “[a] compound represented by a following chemical formula I, stereoisomers thereof or pharmaceutically acceptable salts thereof:
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”; and the instant claim 8 recites “[a] compound selected from the group consisting of compounds represented by following compounds 1 to 368, stereoisomers thereof or pharmaceutically acceptable salt thereof”. The Markush grouping of compounds with these different
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, R1, and
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moieties are improper, because the alternatives defined by the Markush grouping do not share a single structural similarities and the alternated compound species that do not share a common substantial structure feature that is essential for treating histone deacetylase 6-mediated disease. This moiety
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is the only portion of the chemical formula (I) and the only portion of compounds 1 to 368 that each species shares in common.
For instance, the Markush grouping of compounds represented chemical formula I and the Markush grouping of compounds 1 to 368 includes the following alternated compound species:
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(see compound 339); and
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(see compound 103) that do not share a substantial structure feature that is essential for inhibiting histone deacetylase 6. According to Gallagher et al. (US 6,075,039) sets forth in the 35 U.S.C. 103 rejection below, the compound 1-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]-1-ethyl]-3-[4-(5-methyl-1,2,4-oxadiazol-3-yl) phenyl] methyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride taught by the cited reference has the properties of binding to 5-HT receptors rather than inhibiting histone deacetylase 6. Please note the compound taught by Gallagher et al. has the structure of:
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, as evidenced by CAS Registry 201986-11-0. It is noted the compound species taught by Gallagher et al. and the claimed compound both have the 1,3,4-oxadiazole ring (
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) in the core; However, the compounds containing the 1,3,4-oxadiazole ring do not share the same properties. Therefore, one can reasonably conclude that the structure they have in common (the 1,3,4-oxadiazole ring) does not contribute to the desired properties instantly claimed.
Each of these findings demonstrates that not all members recited in this Markush grouping belong to the same recognized physical or chemical class, and the alternated compound species fail to share a substantial structural feature and a common use that flows from the substantial structural feature.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1) (emphasis provided).
Response to Arguments
Applicant's arguments filed on November 26, 2025 with respect to the rejection of claims 1-11 based on the judicially-created basis that it contains an improper Markush grouping of alternatives have been fully considered but they are not persuasive.
Applicant cancelled claims 6-7. Applicant amends the chemical formula I recites in claim 1, including the deletion of “C1-C4 alkyl” from R2 and R3 and the deletion of “C6-C12 aryl” from R4. Applicant further amends claim 8 by deleting the chemical formula I and now recites “[a] compound selected from the group consisting of compounds represented by following compounds 1 to 368”. Each of these findings demonstrate the amendment changes the scope of the claims, and that necessitates a modification of the rejection on the record.
In Summary, applicant argues the claim amendment changes the scope of the compounds of formula I by limiting the scope of the substituents; and therefore, the Markush grouping of compounds of formula I are supported by the compound species described in Example 1-368, and they shares both common structural features and a common use.
In response, applicant’s argument is not found persuasive. Even though the claim amendments narrow the scope of the compounds represented by formula I, the structure feature these compounds have in common is still the 1,3,4-oxadiazole moiety (
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), and does not constitute a significant portion of the compound as a whole. In the present case, the Markush grouping of compounds represented by the chemical formula I:
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, still includes
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(see compound 339); and
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(see compound 103), that do not share a substantial structure feature. The compound species embraced by each of these Markush groupings are substantially structurally different, because the only structure they have in common is the 1,3,4-oxadiazole ring (
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), and that does not represent a significant portion of the compound as a whole. There is an insufficient disclosure to provide adequate basis for concluding that the unexemplified compound species having the structure represented by the instant chemical formula I can selectively inhibit HDAC6 activity. For example, the disclosure fails to exemplify compound species of the instant chemical formula I, wherein
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, or
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all have the same desired properties of inhibiting HDAC6 activity; Therefore, the compound species embraced by instant chemical formula I are so varied such that each compound species of the Markush grouping do not share a substantial structure similarities and a common use that flows from the substantial structure feature.
Therefore, the rejection is maintained for same reasons on the record and for the reasons as set forth herein.
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.
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, 4-5 and 9-11 remain rejected under 35 U.S.C. 103 as being unpatentable over Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021).
Walji et al. teaches a compound 429, 3-(2-methoxyehtyl)-1-({5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl] pyridine-2-yl} methyl)-3,4-dihydroquinazolin-2(1H)-one, having the structure of:
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(see e.g., p. 214, compound 429). Walji et al. further teaches with the compound 429 has HDAC inhibitory activities, including HDAC6 (see e.g., Table 3, Ex. 429). Walji et al. further teaches pharmaceutical compositions comprising one or more compounds and a pharmaceutically acceptable carrier, which is useful for the manufacture of a medicament for treating or preventing a disease ameliorated by modulating HDAC activity, such as diabetes (see e.g., p. 36, line 29-30; claim 24). Please note diabetes taught by Walji et al. is a nutritional and metabolic disease, when the term “nutritional and metabolic disease” is reasonably construed in light of page 32 of the instant specification (see e.g., p. 32, line 14-15 of the instant specification).
Please note the compound 429 taught by Walji et al. is a compound represented by instant chemical formula I:
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excepts the 1,2,4-oxadiazole ring (
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), wherein
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is
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(Z1, Z2 and Z4 are each independently CRa and Ra is H; Z3 is N);
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is
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(
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is phenylene [C6 arylene]; R2 is H; R3 is H; Y is N; n is 1; K is O); R4 is
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(R4 is ethyl [C2 alkyl], in which one H of C2 alkyl is independently substituted with O-methyl [O-(C1 alkyl)]; and R1 is CF3.
For the present case, the difference between the compound 429 of Walji et al. and the claimed compound lies in the 1,2,4-oxadiazole ring attached to the pyridine ring indicated as follows (see shaded):
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; However, in the absence of showing unobvious results, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed when faced with compound 429 of Walji et al. to make the instantly claimed derivatives of a known product. The compound 429 of Walji et al. and the claimed compound are common derivatives known as isomers. Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09 (II) with regard to close structural similarity between chemical compounds (homologs, analogues, isomers).
Since the only structural difference between compound 429 of Walji et al. and the claimed compound represented by chemical formula I is the position of oxygen and nitrogen atom in the oxadiazole ring. Specifically, the compound 429 of Walji et al. has the 1,2,4-oxadiazole ring (
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) whereas the claimed compound has a 1,3,4-oxadiazole ring (
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) . Given that these chemical structures and properties (HDAC6 inhibiting activity) are sufficiently close, one of ordinary skill in the art would have been motivated to do so in order to make similar compounds that inhibiting HDAC for the treatment of diabetes.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Claims 1-5 and 9-11 remain rejected under 35 U.S.C. 103 as being unpatentable over Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021) as applied to claims 1-2, 4-5 and 9-11 above, and further in view of Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021).
The teachings of Walji et al. are set forth above and applied as before.
Walji et al. does not teach a compound as claimed in claim 3.
Walji et al. further teaches a compound of generic formula (I)
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, wherein X represents phenyl or a nitrogen containing six membered heteroaryl; Z is selected from the group consisting of, inter alia, -N-; R1 and R2 can combine together with the atoms to which they are attached to form a five to fifteen membered monocyclic, bicyclic or tricyclic heterocyclic aromatic, partially aromatic, or non-aromatic ring optionally interrupted by 1 to 2 heteroatoms selected from N, S, and O, said heterocyclic ring optionally substituted with 1 to 4 groups of Ra; Ra is selected from the group consisting of, inter alia, -(CH2)pC3-10heterocyclyl, and -C1-6alkylOR, said heterocyclyl is optionally substituted with 1 to 3 groups of Rb; Rb is selected from, inter alia, C1-6 alkyl; p is 0-4; R represents, inter alia, -C1-6 alkyl (see e.g., p. 2, line 30 to p. 4, line 5). Walji et al. further teaches heterocyclyl is preferably selected from, inter alia, piperidyl (see e.g., p. 25, line 20-21). Walji et al. further teaches in another subembodiment, Ra is selected from the group consisting of, inter alia, piperidinyl (see e.g., p. 13, line1-5).
Regarding the limitation of “each C2-C10 heterocycloalkyl in definitions of… R4…is independently
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…, in which W1 to W6 are each independently…N…, and a to d are each independently an integer of 1, 2, or 3” in claim 3, in this case, said limitation is taken to include the elected piperidyl ring (
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). The difference between the derivative of compound 429 of Walji et al. sets forth above and the claimed compound in claim 3 lies in the Ra moiety of the prior art compound, which is equivalent to instant R4 of the chemical formula I. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the modified compound 429 of Walji et al. sets forth above (
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) by replacing the (CH2)2-O-CH3 (i.e.,
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) with a piperidyl ring at the Ra position of the generic formula (I) taught by Walji et al. One would have been motivated to do so, because Walji et al. clearly teaches a list of Ra that can be added to the bicyclic heterocyclic ring form by R1 and R2 together includes -(CH2)pC3-10heterocyclyl such as piperidinyl, and -C1-6alkylOR such as
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. One would have reasonably expected that the further modified compound 429 of Walji et al. would have successfully inhibit HDAC activities, including HDAC6, and therefore, the said compound can reasonably incorporate into a pharmaceutical composition without any appreciable loss of activity.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant's arguments filed on November 26, 2025 with respect to the rejection of claims 1-2, 4-7 and 9-11 under 35 U.S.C. 103 as being unpatentable over Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021) have been fully considered but they are not persuasive for the reasons set forth below.
Applicant's arguments filed on November 26, 2025 with respect to the rejection of claims 1-7 and 9-11 under 35 U.S.C. 103 as being unpatentable over Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021) as applied to claims 1-2, 4-7 and 9-11 above, and further in view of Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021) have been fully considered but they are not persuasive for the reasons set forth below.
In Summary, applicant argues the rejection of claims 1-7 and 9-11 under 35 U.S.C. 103 as being unpatentable over Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021) as applied to claims 1-2, 4-7 and 9-11 above, and further in view of Walji et al. (WO 2017/222951 A1; cited in the IDS filed on November 29, 2021) still includes a compound with a 1,2,4 oxadiazole ring rather than a 1,3,4 oxadiazole ring as required by the present claims. Applicant further argues Walji et al. does not provide motivation to replace the 1,2,4-oxadiazole structure of the compound with the 1,3,4-oxadiazole structure. Applicant further argues based on the declarations under 37 CFR 1.132 filed on November 26, 2025, there would have been no reasonable expectation of success to arrive at the claimed invention, because one would not have expected to achieve more than tenfold higher selective HDAC6 inhibitory activity over HDAC1 by merely substituting one fluorine atom by a hydrogen atom in the -CF3 moiety. Applicant further directs attention to the results of experiments conducted on 368 test compounds in Table 2 of the instant specification.
In response, applicant’s argument is not found persuasive. First, with respect to applicant’s argument that the “resultant modified compound 429 still includes only a 1,2,4 oxadiazole ring and not a 1,3,4 oxadiazole ring as required by the present claims” (see page 53, line 10-11 of the response filed on November 26, 2025), the examiner noted that said rejection is form on the basis that one would further modify the derivates of compound 429 of Walji et al. sets forth in the previous rejection, which is the position isomer of compound 429 of Walji et al. For the sake of clarity, the examiner has recited the chemical structure of said compound
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in the body of the rejection (see page 27, line 14 of the previous Non-Final Office Action mailed on August 26, 2025). In other words, the derivates of compound 429 of Walji et al. clearly includes a 1,3,4 oxadiazole ring instantly claimed.
In response to applicant’s argument that there is no motivation to modify the 1,2,4-oxadiazole structure of the compound, the examiner recognizes that obviousness may be established by modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). According to MPEP 2144.09, “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities”; and “[c]ompounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) …are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also in re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978)”. In this case, the rejection is form on the basis that the 1,2,4-oxadiazole structure of the compound of Walji et al. and the 1,3,4 oxadiazole structure of claimed compound are position isomers, and each of these compounds have similar utilities (HDAC inhibiting effect, including HDAC6).
Second, the comparison data recites in the declaration under 37 CFR 1.132 filed on November 26, 2025 does not appear to be a true comparison between the claimed invention with the closest prior art. Specifically, the declaration compares the claimed compound 31 recites in claim 8 with the compound 429 of Walji et al., which requires the modification of -CF3 to -CF2H and the modification of 1,2,4-oxadiazole ring to 1,3,4-oxadiazole ring; However, the base rejections on the record are form on the basis that there is no modification needed for -CF3, but involves interchanging the position of oxygen and nitrogen atoms in the 1,2,4-oxadiazole ring, and then modify said compound in accordance with the formula I taught by Walji et al. (see rejections above). Since the data provided therein only compares the HDAC1/6 inhibiting effect of the claimed compound 31 to the compound 429 of Walji et al., it is not clear whether the changes in the HDAC1/6 inhibiting effect which applicant relies is attribute to the modification of 1,2,4-oxadiazole ring or the modification of -CF3; therefore, said comparison date fails to demonstrate changing the position of oxygen and nitrogen atom in the 1,2,4-oxadiazole ring alone leads to the unexpected results.
Furthermore, applicant’s assertion of unexpected results is not commensurate in scope with the claimed invention. Applicant argues unexpected results are demonstrated in the declarations under 37 CFR 1.132 filed on November 26, 2025. Specifically, said declaration compares the HDAC1/6 inhibiting effect of the compound 31 of instant application (
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) to the compound 429 of Walji et al. (
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), and noted that compound 31 has comparatively greater selectivity for HDAC6 inhibition over HDAC1 inhibition because said compound has no inhibitory activity against HDAC1 (see listed 9 in the declaration). The comparison data is specifically illustrated in the table shown below:
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.
In contrast, instant claim 1 recites “[a] compound represented by a following chemical formula I, stereoisomers thereof or pharmaceutically acceptable slats thereof:
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wherein, … R1 is CX3 or CX2H…X is an halogen atom”. It is noted that Applicant only exemplified unexpected results using compound 31 in the declaration, specifically the compound with CF2H at R1. Even though the HDAC 1/6 inhibitory effect of
Compound 1 to 368 are reported in Table 2 of the specification, the disclosure does not provide adequate basis for concluding that similar results would be obtained for other unexemplified compound species represented by chemical formula I, such as those with CX3 (e.g., CF3) at R1, other species of
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(e.g.,
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) and other species of
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(e.g.,
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) in the chemical formula I.
According to MPEP 716.02(d), “whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the ‘objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.’ In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”. In the present case, the declaration and the specification do not exemplify other compound species represented by chemical formula I as broadly encompassed by instant claim 1. It is noted that the declaration and the specification together only exemplify compound species with -CF2H at R1,
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or
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at
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,
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, or
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; and they are not commensurate in scope to include the each and every compound species represented by instant chemical formula I, such as those composed of different species of R1,
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and
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. These finding demonstrates that applicant’s assertion of unexpected results is not commensurate in scope with the claimed invention, thus, the argument is not persuasive.
Therefore, the rejection is maintained but revisited and modified in view of the claim amendments.
Claims 1-2, 4-5 and 8-11 remain rejected under 35 U.S.C. 103 as being unpatentable over Gallagher et al. (US 6,075,039) in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176).
Please note the foreign equivalent of Gallagher et al. (Foreign Patent Application No. JPH10-59962) has been cited under “Foreign Patent Documents”, desig. ID 14 in the IDS filed on June 21, 2023.
Gallagher et al. teaches 1-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]-1-ethyl]-3-[4-(5-methyl-1,2,4-oxadiazol-3-yl) phenyl] methyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (referred to herein as Compound 1) in Example 2 is an exemplary compound of formula (I):
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(see e.g., Col. 6, line 63-65; abstract). Please note the compound taught by Gallagher et al. has the structure of:
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, as evidenced by CAS Registry 201986-11-0. Gallagher et al. further teaches a pharmaceutical composition comprising as active ingredient a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, associated with a pharmaceutically acceptable excipient shown as follows:
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(see e.g., Col. 4, line 22-26; Example 6). Please note the active ingredient taught by Gallagher et al. is an effective component. Gallagher et al. further teaches the compound has selective affinity for the 5-HT receptors, and is useful for treating a variety of conditions, such as gastrointestinal disorder (see e.g., Col. 4, line 1-8). Gallagher et al. further teaches formula (I):
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, in which X is -CR’R” where R’ and R” are each hydrogen; Y is oxygen; R1, R2 and R7 are each selected from, inter alia, halo, C1-4 alkyl, heteroaryl; R3, R4, R5 and R6 are each hydrogen; n, m, and p are each 0, 1, 2 or 3; and salt and esters thereof (see e.g., Col. 1, line 9-30). Gallagher et al. further teaches C1-4 alkyl group is preferably methyl or ethyl (see e.g., Col. 1, line 53-54).
Gallagher et al. does not teach the compound represented by instant chemical formula I.
Patani et al. teaches bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents (see e.g., “introduction” section on p. 3147). Patani et al. further teaches a group of bioisosteres elicit similar biological activity, and have been classified as either classical or nonclassical, wherein the classical bioisosteres are a series of replacements defined by Grimm’s Hydride Displacement Law and Erlenmeyer’s definition of isosteres (see e.g., p. 3148-3149). Patani et al. further teaches the substitution of hydrogen by fluorine is one of the commonly employed monovalent isosteric replacement technique as these atoms are known to have similar steric parameters (see e.g., left column under “1. Fluorine vs Hydrogen Replacements” section on p.3149). Patani et al. further exemplified the replacement of the hydrogen with fluorine using a compound having the structure of:
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, and the said replacement results in enhanced receptor binding affinity (see e.g., right column on p.3149). Patani et al. further teaches replacing hydrogen for fluorine is an effective method of exploring the affinity of an agent to the target site (receptor or enzyme) by virtue of its greater electronegativity while other parameters such as steric size and lipophilicity are maintained (see e.g., left column, last paragraph under the section of “1. Fluorine vs Hydrogen Replacements” on p.3150). Patani et al. further teaches nonclassical bioisosteres includes the replacement of halogen with a stronger electron-withdrawing groups, such as a trifluoromethyl group (see e.g., p. 3172). Patani et al further exemplifies the said replacement using cholescystokinin-A receptor antagonists, and demonstrates that the analogues retain antagonistic activity shown as follows:
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(See e.g., p. 3172, left column, last paragraph to right column, Table 52).
In the present case, the difference between the compound 1 of Gallagher et al. and the claimed compound is that the prior art teaches the 1,3,4-oxadiazole ring is substituted with methyl rather than CX3 or CX2H (wherein X is a halogen atom), and the phenyl ring is substituted with fluoro rather than C1-C4 alkyl shown below (see shaded):
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. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to select the compound 1 of Gallagher et al. and then modify said compound by replacing the fluorine with a methyl at the R7 position of formula (I) of Gallagher et al., and then replacing the hydrogen atom(s) with a fluoro atom at the R1 position (
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) to arrive CF2H, and alternatively replace the fluoro atom with a trifluoromethyl to arrive CF3, as taught by Patani et al. One would have been motivated to do so, because Gallagher et al. teaches a list of R7, including halo that is preferably fluorine and C1-4 alkyl that is preferably methyl, to arrive a compound that binds to the 5-HT receptors; and Patani et al. teaches the replacement of hydrogen with fluorine is a bioisosteric replacement technique based on Grimm’s Hydride Displacement Law that can lead to greater receptor binding affinity; and the replacement of halogen with a trifluoromethyl group also retains biological activity. One would have reasonably expected that the modified compound 1 of Gallagher et al. in view of Patani et al. would have successfully bind to 5-HT receptor, and therefore, the said compound can successfully incorporate into a pharmaceutical composition without any appreciable loss of activity.
With respect to “wherein said pharmaceutical composition is used for treating histone deacetylase activity-related diseases…” in claim 10, and “wherein said histone deacetylase 6 activity-related diseases are at least one selected from the group…” in claim 11, these limitations are drawn to the intended use of the pharmaceutical composition instantly claimed. The intended use of the claimed pharmaceutical composition does not patentably distinguish the pharmaceutical composition per se, since such undisclosed use would naturally flow from the fact that the claimed pharmaceutical composition is obvious over the teachings of prior arts. In order to be limiting, the intended use must create a structural difference between the claimed pharmaceutical composition and the pharmaceutical composition taught by Gallagher et al. and Patani et al. In the present case, the pharmaceutical composition comprising the modified compound 1 of Gallagher et al. and Patani et al. renders obvious the limitation instantly claimed.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant's arguments filed on November 26, 2025 with respect to the rejection of claims 1-2, 4-6 and 8-11 under 35 U.S.C. 103 as being unpatentable over Gallagher et al. (US 6,075,039), in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176) as applied to claims 1, 4, and 8-11 above, and further in view of Gallagher et al. (US 6,075,039) are maintained, but revisited and modified in view of the claim amendments.
In the present case, applicant amends the chemical formula I recites in claim 1 such that R11 cannot be substituted with X, wherein X is an halogen atom. Given the base rejection on the record is form on the basis that R11 can be substituted with a halogen atom, said amendment necessitates a modification of the rejection on the record; therefore, the rejection has been revisited and modified in view of the claim amendments.
In Summary, applicant argues even though the substitution of hydrogen by fluorine in the compound of Patani et al. may result in no change in biological activity or an improvement of certain properties, it should not be concluded that such outcomes would be reproduced in the same manner for any compounds structurally different from the compounds of Patani et al and Gallagher et al. Applicant further argues one would not be motivate to modify the substituents of the compounds of Gallagher et al. in view of Patani et al., because the declaration filed on November 26, 2025 supports the disclosure of Patani et al. is not necessarily applicable to all compound structure.
In response, arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). In the present case, the declaration upon which applicant relies does not appear to be a true comparison, because it does not compare the claimed invention with the compound 1 of Gallagher et al. as the closest prior art. Specifically, the declarant compares the claimed compound 31 with the compound 429 of Walji et al., which requires two modifications shown below (see shaded):
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. In other words, the comparison disclosed therein does not modify the methyl to CF2 or CF3. If Applicant premises the substitution of hydrogen with fluorine does not reproduce the same outcomes in the same manner for any structurally different compounds, then the data for the compound 429 of Walji et al. in the declaration, which is a structurally different compound, is irrelevant to this rejection.
Therefore, the rejection is maintained but revisit and modified in view of the claim amendments.
Free of the Art
Claim 8 is free of the art.
Conclusion
No claims are allowed.
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 Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628