DETAILED ACTION
A non-final Office action was mailed 20 August 2025 (“Office Action”).
Applicant’s reply was received 14 November 2025 (“Reply”).
Status of the Claims
The listing of claims filed with the Reply has been examined.
Claims 19–25 and 27–40 are pending. Claims 1–18 and 26 are canceled.
Claims 19, 20, 23, 24, and 29–33 are amended. Claims 38–40 are new.
Status of Rejections and Objections
The text of those sections of Title 35, U.S. Code and/or text providing the basis for non-statutory double patenting rejections not included in this action can be found in Office Action.
Unless repeated herein, any objection or rejection in Office Action is withdrawn.
Claim Objections
(i) Claim 19 is objected to for minor informalities: R variables in substructures are illegible. For example, claim 19 recites R2 =
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, and the text of the R variables attached to the ring structures is not clear.
Drawings in a patent claim must be reproducible for printing a patent, if granted.
(ii) Claim 29 is objected to because “Z is CH2” lacks antecedent basis.
Claim 29 depends from claim 19.
Claim 19 recites: “Z is -CD2-, -CF2-, -CHR3-, -NH-, or -S-; R3 is H . . .”
Claim 29 recites: “Z is CH2 or CHR3, wherein R3 is Me, or is selected from . . .”
Because claim 19 does not recite “Z is CH2,” claim 19 does not provide direct antecedent basis for “Z is CH2” in claim 29.
Examiner recommends an amendment consistent with the language of claim 19, such as: “Z is 3, wherein R3 is H, Me, or is selected from . . .”
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112
The following is a quotation of 35 U.S.C. § 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 19–25, 27, 28, and 32–40 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 19 recites R2 =
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, etc.
The R2 structures have R5 and R6 substituents, but claim 19 does not define what the options are for the substituents. The definition was deleted by amendment:
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The claim does not otherwise define the substituents. The wherein clause below merely requires at least one of the R5 and R6 substituents to be selected from the listed options:
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Because the R5 and R6 substituents are not defined, Examiner cannot update the prior art search to determine the patentability of claim 19.
Claims 20–25, 27, 28, and 32–40 are indefinite because they refer to claim 19, and therefore incorporate the limitations of claim 19, without curing the indefiniteness issue.
Appropriate correction is required.
To further prosecution, the previously cited prior art references were reconsidered.
Claim Rejections - 35 U.S.C. § 102
Claims 19, 21, 24, 27, 28, and 33–37 are rejected under 35 U.S.C. §§ 102(a)(2) as being anticipated by WO 2022/013728 (“Lee”).
Lee discloses compounds according to instant formula (I) as follows:
X and X’ are CH or CF; Y and Y’ are CH;
Z = CHR3; R3 = H;
B, D, E = N; A, M = C; R1 = H;
L = absent;
R2 =
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; R5 and R6 = H, halogen, and/or
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.
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(Lee, Table 1 spanning pp.13–39).
The claim 19 proviso does not apply because it is not directed to the scenario above in which variables B, D, E = N and A, M = C.
Additional compounds disclosed in Lee may read on the claimed Formula (I). Applicant is encouraged to review Lee and amend the instant claims accordingly.
Lee discloses pharmaceutical compositions comprising an excipient, including, e.g., a buffer, antioxidant, diluent, binder, etc., and the composition can be, e.g., a solid tablet for oral administration. (Id., 69:13–72:5).
Lee discloses HDAC6 inhibition and the treatment of a HDAC6-related disease. (Id., 69:22–71:4).
Lee discloses the use of the compounds with another drug that can be used to treat the same disease. (Id., 72:8–11).
Claim Rejections - 35 U.S.C. § 103
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.
Graham v. John Deere Co., 383 U.S. 1, 17 (1966); MPEP § 2141(II).
Claims 32 and 38–40 are rejected under 35 U.S.C. § 103 as being unpatentable over Lee in view of Chou, Ting-Chao, Pharmacological Review (2006), 58(3), 621–681 (“Chou”), Liang et al., J. Med. Chem. (2019), 62, 3898–3923 (“Liang”), and Suraweera et al., Frontiers in Oncology (2018), 8, Article 92 (15 pages) (“Suraweera”).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
The discussion of Lee in the above anticipation rejection is hereby incorporated by reference for this rejection.
Chou explains that drug combination therapy is commonly used to increase efficacy of the therapy in the treatment of various diseases, including cancer.
The use of multiple drugs may target multiple targets, multiple subpopulations, or multiple diseases simultaneously. The use of multiple drugs with different mechanisms or modes of action may also direct the effect against single target or a disease and treat it more effectively. The possible favorable outcomes for synergism include 1) increasing the efficacy of the therapeutic effect, 2) decreasing the dosage but increasing or maintaining the same efficacy to avoid toxicity, 3) minimizing or slowing down the development of drug resistance, and 4) providing selective synergism against target (or efficacy synergism) versus host (or toxicity antagonism). For these therapeutic benefits, drug combinations have been widely used and became the leading choice for treating the most dreadful diseases, such as cancer and infectious diseases, including AIDS.
(Chou, p.624).
Chou discloses bortezomib has been used in combination therapy to treat cancer. (Id., p.652).
Liang discloses a study of a combination therapy with a JAK inhibitor and a HDAC inhibitor. (Liang, p.3898).
Liang states, “the results confirm the therapeutic potential of JAK and HDAC dual inhibitors in hematological malignancies and provide valuable leads for further structural optimization and antitumor mechanism study. (Id., Abstract).
Suraweera discloses a review of HDAC inhibitors in combination therapy for the treatment of cancer. (Suraweera, p.1).
Suraweera discloses combination therapies with nivolumab and a HDAC inhibitor. (Id., pp. 8–9, Table 3).
Ascertaining the differences between the prior art and the claims at issue
Lee discloses the use of its HDAC6 inhibitor compounds in combination therapy, but does not specifically identify a particular co-therapeutic agent.
Resolving the level of ordinary skill in the pertinent art
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant application does not include examples or evidence directed to a combination therapy comprising a claimed compound and a claimed co-therapeutic agent.
The question of obviousness
Based on the above factors, it would have been obvious for a person having ordinary skill in the art, prior to the filing of the instant application, to combine the teachings of Lee, Choi, Liang, and Suraweera to arrive at the claimed composition comprising a compound according to claim 19 and a second therapeutic agent, such as bortezomib and nivolumab, because the use of combination therapy to treat cancer is established in the art, according to Choi. One of ordinary would have been motivated to combine the claimed HDAC inhibitors with bortezomib, a JAK inhibitor, or nivolumab because combinations comprising an HDAC inhibitor and the second agent are known in the art to improve treatments. One of ordinary skill in the art would have had a reasonable expectation of success at arriving at the claimed invention because combination therapies comprising an HDAC inhibitor and another therapeutic agent were established in the art. There is no evidence of secondary considerations in the applications.
Allowable Subject Matter
Claim 29 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.
Claims 30 and 31 are allowed.
Conclusion
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 C.F.R. § 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 C.F.R. § 1.17(a)) pursuant to 37 C.F.R. § 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.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached on 571-270-7674.
The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.M.N./Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623