DETAILED ACTION
This office action is in response to applicant’s filing dated November 10, 2025.
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant's submission filed on November 10, 2025 has been entered.
Status of claims
Claims 1, 6-8, 10-12, 14, 16-22, 24-30, 32- 35, 37-51, 58, and 59 are pending in the instant application. Claims 8, 10-12, 14, 16-22, 24-30, 32-35, 38-51 and 59 are withdrawn from consideration as being drawn to an unelected invention or species.
Acknowledgement is made of Applicant's amendment of claims 1, 6-8, 12, 18, 22, 28, 30, 34, 43, and 51 filed on November 10, 2025.
Claims 1, 6, 7, 37 and 58 are presently under examination as they relate to the elected species, a compound of formula
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Priority
The present application was filed on April 15, 2022. The present application is a 371 of PCT/US20/56048 and claims the benefit of priority to U.S. Provisional Application No. 62/916,018, filed October 16, 2019.
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, 6, 7, 37, and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Puerta et al (WO 2017/156194 A1, the reference is of record, hereinafter Puerta).
Instant claims are drawn to a compound of Formula Ia and Formula Ib
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correspondingly, where X in Formula Ia is oxygen or sulfur, in both genus formulas Ia and Ib Ra represents hydrogen, halo, or methyl; Ra’ represents hydrogen, halo, or alkyl; and Rb, Rc, and Rd are independently represent hydrogen, (C1-C15)alkyl, alkoxy, substituted alkoxy, 3-12 membered cycloalkyl, substituted cycloalkyl, 3-12 membered heterocycloalkyl, substituted heterocycloalkyl; provided that Ra, Rb, Rc, and Rd are not all hydrogen; and when Ra is hydrogen, Rc is not (C1-C15)alkyl. Instant claims are also directed to a pharmaceutical composition comprising a compound of Formula Ia or tautomer or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. One of the example compounds of Formula Ia or Formula Ib is the compound of formula:
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Puerta teaches a compound of formula (III)
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, where Y is O, R2, R3 and R4 are each independently hydrogen or substituted or unsubstituted heterocycloalkyl (page 2, [0008] and claim 1), wherein “heterocycloalkyl” is tetrahydrofuran-2-yl or tetrahydrofuran-3-yl (page 7, [0026]). Puerta further teaches a pharmaceutical composition including a described compound, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient (page 3, [0009]), where terms "pharmaceutically acceptable excipient" and "pharmaceutically acceptable carrier" refer to a substance that aids the administration of an active agent to and absorption by a subject (page 20, [0067]).
Since it is well-known in the art, that tropolone ring exists in two tautomeric forms, where C=O group and C-OH group (positions 1 and 2 of the tropolone cycle) easily interconvert by tautomeric proton transfer, as shown in following scheme:
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( Takegoshi et al J. Am. Chem. Soc. 1993, 115, 9747-9749) which makes positions 3 and 7 of the tropolone cycle equivalent. Thus, substituent R2 in compound of formula (III) of Puerta is attached to either position 7 or position 3 of tropolone cycle (
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). Thus, if R2 in Puerta’s compound of formula (III) is tetrahydrofuran-2-yl and both R3 and R4 are hydrogen, then the compound taught by Puerta is equivalent to the instantly claimed compound .
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. MPEP 2112.01.I states: Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product.
Thus, since Puerta teaches tropolone derivatives where position 3(7), (see the explanation above) of tropolone cycle is substituted with heterocycloalkyl such as tetrahydrofuran-2-yl, and instant claims disclose tropolone derivatives where tropolone cycle has a tetrahydrofuran-2-yl group in position 3(7), it would have been prima facies obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select particular substituents amongst given exemplified options and make various known tropolone derivatives to arrive at claimed compounds. The one of ordinary skills would be motivated to do so in search of a tropolone derivatives having similar or better desired properties with the reasonable expectation of success.
Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art before 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:
- Puerta does not disclose the compounds alleged in the Office Action, as variables may not be selected from a generic chemical formula to create a species without reason; convenient selections of variables in a generic formula does not render the species thereby arrived at prima facie obvious (Applicant refers to In re Baird, 16 F.3d 380, 382 (Fed. Cir. 1994);
- while Puerta teaches compounds of general formula (III), the structures of variables are very broad and encompass numerous compounds, so the one skilled in the art could not be led to select certain substituents to arrive at claimed compounds;
- the exemplary compounds within the general formula (III) of Puerta all but one have a methoxy group alpha to the carbonyl group on the tropolone ring, which compounds are not within the scope of any of Applicant’s claims, as in the instantly claimed compounds Ra (moiety in alpha position to the carbonyl of tropolone) represents hydrogen, halo or methyl; thus Puerta does not support a prima facie case of obviousness;
- the specification of Puerta’s reference disclose some compounds where one of the substituents is a phenyl group; none of Ra, Ra', Rb, Rc or Rd of instantly claimed compounds encompass phenyl group;
- the data disclosed in Puerta’s reference suggest that the presence of hydroxy group at the alpha position [of the tropolone ring] is quite desirable, as these compound exhibit high pharmacological activity, so there is no motivation for person skilled in the art to improve already advantageous compounds.
Examiner’s response:
Applicant's arguments have been fully considered, and Examiner agreed with the arguments, that broad genus structure, describing vast variety of possible structure of variables does not direct to select particular structure of substituents to create species, however:
regarding the arguments about broad disclosure of prior art, teaching compounds of genus formula (III), this argument is not persuasive because instant claims (e.g. claims 1, 6 and 7) describe possible structures of variables Ra, Ra’, Rb, Rc, and Rd in genus formulas Ia and Ib, which encompass enormous number of compounds, especially taking into account combinations of said variables. Detailed comparison between structure of compounds encompassed by genus formula (III) of Puerta and instantly claimed compounds, encompassed by Formula Ia, reveals apparent overlap of structural elements (see the rejection section above for details).
Regarding the argument about structure of variables taught by prior art and not encompassed by instant claims, this argument is not persuasive because amongst list of variables Puerta discloses the ones, encompassed by instant claims, such as alkyl, cycloalkyl, or heterocycloalkyl (e.g. tetrahydrofuran-2-yl), (see the rejection section above for details). MPEP 2123 states: "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).
Regarding the argument about absence of motivation for a person skilled in the art to improve already desirable structure of compound, this argument is not persuasive because, motivation to synthesize various tropolone derivatives is addressed above (see 103 rejection, section). MPEP 2145.X(B): An "obvious to try" rationale may support a conclusion that a claim would have been obvious where one skilled in the art is choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. " [A] person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense.
Therefore, Applicant’s arguments are not persuasive and the rejection of claims 1, 6, 7, 37, and 58 as obvious over teachings of Puerta 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 1, 6, 7, and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 7, 9, 11, 14, 16, 18, 24, 46 and 59 of copending Application No. 17/769,509 in view of Puerta et al (WO 2017/156194 A1, the reference of record).
Instant claims are directed to a compounds of genus formula Ia (
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or Ib (
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) where Ra represents hydrogen, halo, or methyl; Ra’ represents hydrogen, halo, or alkyl; and Rb, Rc, and Rd are independently represent hydrogen, (C1-C15)alkyl, alkoxy, substituted alkoxy, 3-12 membered cycloalkyl, substituted cycloalkyl, 3-12 membered heterocycloalkyl, substituted heterocycloalkyl; provided that Ra, Rb, Rc, and Rd are not all hydrogen; and when Ra is hydrogen, Rc is not (C1-C15)alkyl (claims 1 and 6). Instant claims are also directed to a pharmaceutical composition comprising a compound of Formula Ia or tautomer or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The copending claims are directed to compounds of formula Ia
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, where X is an oxygen, Ra, Rb, Rc, and Rd independently represent hydrogen, alkyl, aryloxy, substituted aryloxy, heteroaryl, substituted heteroaryl, heteroaryloxy or substituted heteroaryloxy; provided that Ra, Rb, Rc, and Rd are not all hydrogen and one of Ra, Rb, Rc, and Rd is heteroaryl, or substituted heteroaryl (claim 1). The copending claims are also directed to a pharmaceutical composition comprising a compound of Formula Ia or tautomer or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier (claim 46). Although instant claims do not require Ra, Rb, Rc, and Rd to represent aryloxy, substituted aryloxy, heteroaryl, substituted heteroaryl, heteroaryloxy or substituted heteroaryloxy as copending claims read, Puerta teaches compounds of formula (III)
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, where Y is oxygen, R2, R3 and R4 are independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, -OR3D or -OR4D, where R3D and R4D is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl (claim 1). Puerta defines “alkyl” as methyl (page 5, [0022]); “aryl” as polyunsaturated, aromatic, hydrocarbon substituent, which can be a single ring or multiple fused or covalently linked rings; “heteroaryl” refers to aryl groups (or rings) that contain at least one heteroatom such as N, O, or S (page 8, [0029]). Puerta further teaches a pharmaceutical composition including a described compounds, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient (page 3, [0009]).
Taken into consideration the compounds taught by prior art, where tropolone cycle contains linear or cyclic, aliphatic or aromatic, as well as non-aromatic heterocyclic and heteroaromatic (with N, O, S heteroatoms) substituents, it would be prima facie obvious to one of ordinary skill in the art to select particular substituents amongst given exemplified options and make a variety of known tropolone derivatives encompassed by formula Ia and Ib of instant claims, or compounds of formula Ia of copending claims to arrive at claimed compounds. The one of ordinary skills would be motivated to do so in search of a tropolone derivatives having similar or better desired properties with the reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant argues:
- claims of co-pending Application have been amended since the Office Action was issued, consequently, the outstanding rejection is inapplicable to the present claims; additionally, the rejection suffers from the same inadequacies in its allegations of what Puerta discloses as described above with respect to the rejection under 35 U.S.C. § 103.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive because: as set forth in the rejection above, claims disclosing compound of genus Formula Ia and Ib in examined application are considered obvious over claims of copending application No. 17/769,509, disclosing compound of genus Formula Ia, in view of teachings of Puerta, since structural elements of instantly claimed compounds of Formula Ia and Ib as well as structural elements of Formula Ia of copending claims fall within the scope of teachings of Puerta. (see the rejection section for details).
Therefore, applicant’s arguments are not persuasive and the provisional rejection of claims 1, 6, 7, and 58 on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No.17/769,509 in view of Puerta is maintained.
Conclusion
Claims 1, 6, 7, 37 and 58 are rejected. No claim is allowed.
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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/E.V.V./Examiner, Art Unit 1691
/SAVITHA M RAO/Primary Examiner, Art Unit 1691