DETAILED ACTION
This office action is in response to applicant’s filing dated July 20, 2026.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 33 – 48 are pending in the instant application. Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on July 20, 2026 are acknowledged. Acknowledgement is made of Applicant's cancelation of claims 18 - 32 and addition of new claims 33 - 48. Claims 40 – 48 are withdrawn from consideration, as being drawn to a nonelected invention or species.
Claims 33 – 39 are under consideration in the instant office action.
Objections and/or Rejections and Response to Arguments
Applicants' arguments, filed on July 20, 2026, have been fully considered.
Acknowledgement is made of the Applicant’s cancelation of claims 18 – 23.
Accordingly, all Rejections and/or objections previously applied to claims 18 - 23 are hereby withdrawn.
The following rejections and/or objections are newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
New Objections and/or Rejections
Necessitated by Amendments
Claim Objections
The claims are objected to because the lines are crowded too closely together, making reading difficult. Substitute claims with lines one and one-half or double spaced on good quality paper are required. See 37 CFR 1.52(b).
Claim 38 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 § 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 33 – 37 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (US 2017/0305861 A1, cited in IDS, filed 06/18/2023, hereinafter Kim).
Instant claims are drawn to a compound of Formula I:
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, where Ring A is substituted or unsubstituted C6-C10 aromatic ring, or substituted or unsubstituted 3-10 membered heteroaromatic ring; ring B is substituted or unsubstituted C6-C10 aromatic ring, substituted or unsubstituted C3-C10 cycloalkane ring, substituted or unsubstituted 3-10 membered heterocycloalkane ring or substituted or unsubstituted 3-10 membered heteroaromatic ring; R1 is
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, R4 and R5 are independently hydrogen, n is 0 – 6, R6 is substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted C5-C10 heteroaryl; R2 is hydrogen, R3 is C1-C6 alkyl, C3-C8 cycloalkyl, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-10 membered heteroaryl. For example, compounds correspond to Formula I-6:
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. Exemplary compounds of Formula I are:
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,
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,
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. Instant claims are further drawn to a pharmaceutical composition, comprising compound of formula I and a pharmaceutically acceptable carrier. Said pharmaceutical composition is suitable for oral administration or administration by injection.
Kim teaches compound of Formula 1:
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, where
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refers to a single bond or double bond, a ring of Formula 1 comprises two to three double bonds; X is CH or N; Y is CH, N, or S; n is 1 or 2; L is C1-6 alkylene or linker (L) is -CH2-C(O)-; R1 is C6-14 aryl, such as phenyl, optionally further substituted with e.g. methyl, C5-20 heteroaryl; R2 to R4 are each independently hydrogen, amino (-NH2), substituted amino (NR’R”), R’ and R” are independently C1-6 alkyl; or R2 and R3 are positioned on adjacent carbon atoms and connected to each other to form a ring, where the ring is C6 to C14 aryl, C5 to C20 heteroaryl, C3 to C10 cycloalkyl, or C3 to C10 heterocycloalkyl, where the ring formed by R2 and R3 being positioned on adjacent carbon atoms and connected to each other is substituted with one or more substituents, such as C1-6 alkyl, where C3 to C10 heterocycloalkyl formed by R2 and R3 being positioned on adjacent carbon atoms and connected to each other may be piperidinyl (page 2, [0032] and [0033]). Kim defines alkyl as saturated, straight, or branched hydrocarbon moieties each containing 1 to 6 or 1 to 8 hydrocarbons in certain embodiments (e.g.: methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl) (page 2, [0025]). The term "heterocycloalkyl" refers to a non-aromatic 3-, 4-, 5-, 6-, or 7-membered ring or bi- or tri-cyclic group fused or unfused system, such as pyrrolidinyl, piperidinyl, where any of the rings may be fused to a benzene ring (pages 1-2, [008] – [0016] and [0021] – [0031]). The term "heteroaryl" refers to a mono- or poly-cyclic ( e.g., bi-, tri-cyclic, or higher) fused or unfused part or ring system, having at least one aromatic ring, and having 5 to 20 ring atoms wherein one of the ring atoms is selected from S, O, Se, and N, such as pyridinyl, pyrimidinyl or pyrrolyl (page 2, [0020]). One of the exemplary compounds taught by Kim, is compound of structure:
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(page 10, ex. 26). Kim further teaches a pharmaceutical composition, comprising compound of Formula 1 and a pharmaceutically acceptable carrier (page 5, [0050]). Said The pharmaceutical composition may be formulated in the form of a tablet, capsule, pill, granule, powder, injection etc. (page 5, [0052]).
Compound of Formula 1, taught by Kim, is equivalent to the instantly claimed compound of Formula I where in the Formula 1 of Kim:
X and Y are both carbons, n is 2; and corresponds to the ring A of instantly claimed Formula I;
(L) is -CH2-C(O)- and R1 is phenyl, optionally substituted with e.g. methyl, corresponds to the fragment
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of instantly claimed Formula I, where R1 corresponds to R6;
R4 is hydrogen and corresponds to R2 of instantly claimed Formula I;
ring formed by R2 and R3 positioned on adjacent carbon atoms and substituted with e.g. C1-6 alkyl corresponds to ring B and R3 of instantly claimed Formula I.
Thus, since Kim teaches compounds, where all the structural elements of the molecule are equivalent to those of instant claims, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to combine structural elements of the molecule taught by prior art, and make various compounds to arrive at claimed compounds. The one of ordinary skills would be motivated to do so in search of an active agent, possessing similar or better pharmaceutical properties for treatment of proliferative disease with the reasonable expectation of success.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues:
- The compounds of the present invention exhibit significant differences in the skeleton structure compared to the compound of formula 1 disclosed in the reference of Kim. In the compounds of the new claims 33-39 of the present invention, the R1 is
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, whereas the "L" in the compound of Formula 1 of Kim, corresponding to R1 in the compounds of the present invention has a structure "L" of C1-6 alkylene or C1-6 alkenylene. Among the compounds disclosed in Kim, only compounds of examples 25 and 26 have a -carbonyl-methylene-
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skeleton structure. Therefore, those skilled in the art, upon reviewing Kim, would only consider compounds of examples 25 and 26, which structures are significantly different from instantly claimed compounds, and would be unlikely to refer to the disclosed compounds of formula 1.
- The rejection does not establish why a person of ordinary skill, without knowledge of Applicant's disclosure, would have made the particular combination of structural selections required by the claims. The originally filed application identifies the common structural features shared by the disclosed species and expressly defines the permissible alternatives for rings A, B and C and substituents R1-R13. The rejection does not identify any teaching or suggestion in Kim to select compounds 25 or 26 as a starting point and then alter their fused-ring system, ring identities, substitution pattern, and R1-R3 arrangements to arrive at any compound within claims 33-38. These modifications are not a simple substitution of known equivalents, but require coordinated changes to multiple structural features.
- The compounds of the present invention can unexpectedly provide precision treatment for tumors exhibiting specific biological characteristics such as up-regulation of mitochondrial oxidative phosphorylation pathway, low activity of mitochondria permeability transition pore, low or no expression of NNMT gene, and/or high methylation level of DNA CpG site of NNMT gene (please see the Examples 1-112 of the description of the present invention). Moreover, the compounds of the present invention unexpectedly exhibit excellent liver stability. Since Kim does not teach any effect(s) on the precision treatment of tumors or liver stability, the skilled person would lack motivation to consult the compound(s) of Kim to develop the specific compound(s) of the presently claimed invention, which unexpectedly provide precision treatment for tumors with specific biological characteristics and exhibit excellent liver stability.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive because: as set forth above, instant claims are extremely broad regarding the scope of genus Formula I:
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, where ring A is any aromatic or heteroaromatic ring and B is any non-aromatic or aromatic carbo- or heterocycle. Both rings are somehow substituted with R1, R2 and R3.
Kim teaches compounds of the same genus formula, where all the corresponding structural elements are described (see the rejection section above). Thus, compounds disclosed in Kim are close structural analogs of the instantly claimed compounds, thereby rendering the claimed compounds obvious to one of ordinary skill in the art. Furthermore, compounds disclosed in Kim have the same utility (anti-cancer agents). The person of ordinary skills would have been motivated to modify prior art teachings, to make various structural analogs by selecting and combining known elements. Such a modification would be driven by a reasonable expectation of success that the resulting compounds would possess similar or improved chemical and biological properties. As states in MPEP 2143.I(B): “structural similarity can provide the necessary reason to modify prior art teachings. The Federal Circuit also addressed the kind of teaching that would be sufficient in the absence of an explicitly stated prior art-based motivation, explaining that an expectation of similar properties in light of the prior art can be sufficient, even without an explicit teaching that the compound will have a particular utility”.
Regarding the arguments about selecting specific compounds 25 or 26 as a starting point to arrive at instant invention, it is not persuasive because Kim teaches a compound of genus formula 1, where, as set forth above, all the structural elements are equivalent to the instantly claimed compound of genus Formula I. As noted in MPEP 2123: "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). Thus, the skilled artisan, when evaluating a series of compounds of common utilities and similar desired properties would consider not only the specific illustrated examples disclosed in the prior art reference, but also the generic structure of the compounds. In the instant case, the generic Formula I substantially overlaps with the genus Formula 1 taught by Kim.
Regarding the argument about biological properties of claimed compounds, it is not persuasive, because since Kim teachers structurally similar compounds, all necessary properties are inherently present, because compounds of identical or similar composition cannot exert mutually exclusive properties (see also MPEP 2112.01).
Therefore, Applicant’s arguments are not persuasive, and the rejection of claims 33 – 37 and 39 as obvious over teachings of Kim is maintained.
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 33 – 39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16 - 24, of copending Application No. 18/852,776 (reference application). (The examiner corrects here the reference application number, and thanks the applicant for pointing out the error).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims are directed to a compound of Formula I:
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, where Ring A is substituted or unsubstituted C6-C10 aromatic ring, or substituted or unsubstituted 3-10 membered heteroaromatic ring; ring B is absent or ring B is substituted or unsubstituted C6-C10 aromatic ring, substituted or unsubstituted C3-C10 cycloalkane ring, substituted or unsubstituted 3-10 membered heterocycloalkane ring or substituted or unsubstituted 3-10 membered heteroaromatic ring; R1 is
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, R4 and R5 are independently hydrogen, n is 0 – 6, R6 is substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted C5-C12 heteroaryl;
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, R10 and R11 are each independently hydrogen, R3 is none, hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-10 membered heteroaryl. Exemplary compounds of Formula I are:
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or
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. Instant claims are further drawn to a pharmaceutical composition, comprising compound of formula I and a pharmaceutically acceptable carrier.
Claims of copending application are directed to a drawn to a compound of Formula I:
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, where Ring A is substituted or unsubstituted C6-C16 aromatic ring, substituted or unsubstituted C3-C16 cycloalkane ring, substituted or unsubstituted 3-16 membered heterocycloalkane ring, or substituted or unsubstituted 3-16 membered heteroaromatic ring; ring B is absent; R1 is
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, R4 and R5 are independently hydrogen, n is 0 – 6, R6 is substituted or unsubstituted C6-C16 aryl, substituted or unsubstituted C5-C12 heteroaryl, substituted or unsubstituted 3-16 membered cycloalkyl or substituted or unsubstituted 3-16 membered heterocycloalkyl;
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, R10 and R11 are each independently hydrogen, R3 is none or hydrogen. Exemplary compounds of Formula I are:
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or
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. Copending claims are further drawn to a pharmaceutical composition, comprising compound of Formula I and a pharmaceutically acceptable carrier.
Although exemplary compounds of instant claims and copending claims are not identical, they are structural alternatives, encompassed by genus Formula I.
Thus, the compounds of copending claims would anticipate instantly claimed compounds.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant argues:
Applicant has filed a Terminal disclaimer over U.S. Application No. 18/852,776. Accordingly, Applicant respectfully submits that the nonstatutory double- patenting rejection has been overcome.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive because: the Terminal disclaimer filed by the applicant on July 20, 2026 has been disapproved by OPLC. Examiner suggests, the applicant files eTD (eTerminal Disclaimer) which 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.
Therefore, the provisional rejection of claims 33 – 39 on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/852,776 is maintained.
Conclusion
Claims 33 – 39 are rejected.
Claim 38 is objected to.
No claim is 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 ELENA V VISHNYAKOVA whose telephone number is (571)272-3781. The examiner can normally be reached 7:30am - 5pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, RENEE CLAYTOR can be reached at (571)272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/E.V.V./Examiner, Art Unit 1691
/SAVITHA M RAO/Primary Examiner, Art Unit 1691
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