DETAILED ACTION
Receipt of Arguments/Remarks filed on June 22 2026 is acknowledged. Claims 4-5, 7-8, 11-12, 16-17, 19, 25-30 were/stand cancelled. Claims 1, 3, 6, 15 and 18 were amended. Claims 33-35 were added. Claims 1-3, 6, 9-10, 13-15, 18, 20-24 and 31-35 are pending.
The response filed June 22 2026 requested reconsideration of the withdrawal of claims 13 and 20. Since the elected compound includes as B2 of guanine, and this is encompassed within the claims the claims should not be withdrawn. This argument is persuasive. Therefore, claims 13 and 20 are no longer considered withdrawn.
Claims 2-3, 6, 18, 24 and 31-35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 6 2026. Claims 1, 9-10, 13-15 and 20-23 are directed to the elected invention.
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 .
Withdrawn Objections/Rejections
The amendments to the specification filed June 22 2026 are sufficient to overcome the objection to the spacing of the specification.
The amendments to claim 1 filed June 22 2026 is sufficient to overcome the objection of the claim. The claim corrected the superscript to a subscript for consistency.
The amendments filed June 22 2026 are sufficient to overcome the rejection of claims 10 and 15 under 35 USC 112(b). The exemplary language was removed from the claims.
The arguments filed June 22 2026 are sufficient to overcome the rejection of claims 1, 9-10, 13-15, 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Altman et al. (WO2017027645, cited on PTO Form 1449) in view of Wu (WO2018085307). Specifically, page 16 of response (page 6 of remarks) correctly indicates that the structure skeleton is Altman is different and at least one of the bases is attached on the ring at the meta position.
However, upon further consideration, a new ground(s) of rejection is made in view of Yoshikawa et al. (WO2018100558). Thus, this rejection is second non-final.
The following represents all new grounds of rejections presented in this Office action.
Claim Rejections - 35 USC § 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 9-10, 13-15 and 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Yoshikawa et al. (WO2018100558) in view of Wu (WO2018085307).
Applicant Claims
The instant application claims a cyclic dinucleotide compound of formula II. Specifically elected compound is
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Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Yoshikawa et al. is directed to cyclic dinucleotides. Claimed are compounds of formula I (claim 1) wherein narrower embodiment is a compound of formula X having the following structure:
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(claim 3) wherein B2 includes
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(claim 20, page 341, second row first compound); and B1 includes:
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(claim 24, page 344, second row third compound) wherein this compound is also one of two choices for B1 (claim 26).
A specific compound taught is for example:
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(paragraph 1144). Treating cancer with compounds are claimed (claim 84, 88).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
The difference between the instantly elected compound and the specific compound taught in Yoshikawa et al. is the B1 and B2. However, Yoshikawa et al. claims the structure corresponding to instantly claimed B2 as B1 and is one of two choices and suggests the instantly claimed B1. Yoshikawa et al. does not expressly claim the B1 in combination with the B2. However, this deficiency is cured by Wu et al.
Wu is directed to prodrugs of clofarabine. Compounds taught include formula I:
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wherein R1 and R2 can be H (paragraph 0009). Taught are pharmaceutical composition comprising the compounds including those for topical use such as creams, ointments, etc. (paragraph 0062). The compounds are taught as treating cancer (claim 11). Clofarabine is known to inhibit DNA synthesis at two critical junctures: DNA polymerase I as well as RNA reductase (paragraph 0002). The structure of clofarabine is shown (page 27):
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Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Yoshikawa et al. and Wu and utilize clofarabine as one of the nucleotides in the cyclic dinucleotide. One skilled in the art would have been motivated to utilize clofarabine as it is known to be useful in treating cancer. Since Yoshikawa et al. also teaches the compositions for treating cancer and that the nucleotide corresponding to clofarabine can be one of the choices there is a reasonable expectation of success. Based on the teachings of Wu et al., one skilled in the art would have been motivated to select these specific substituents from the teachings of Wu et al. et al. to arrive at the instantly elected compound. Regarding the claimed stereochemistry, Yoshikawa et al. teaches that when compound (I) contains an isomer such as an optical isomer, a stereoisomer and the link, any isomer and a mixture thereof are also encompassed in the compounds (paragraph 1042). Exemplified compounds possess R stereochemistry (see examples) Rendering obvious claims 1, 9-10, 14-15 and 21.
Regarding claims 22-23, Yoshikawa et al. claims a pharmaceutical composition comprising the compound and a pharmaceutically acceptable excipient is claimed (claim 31). Wu et al. teaches compositions for topical administration. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Yoshikawa et al. and Wu and utilize the composition in a pharmaceutical composition in the form of topical administration as this type is expressly taught by Wu and is a conventional route of administration.
Response to Arguments
While the rejection above is new, the examiner is addressing several of the generic arguments with regards to patentability made by Applicants.
Applicants’ arguments filed June 22 2026 have been fully considered but they are not persuasive.
Applicants argue that (1) Table 1 and Figure 1 of Example 1 show that representative compounds of the present invention exhibited excellent activating effects on IFN-β secretion by THP-1 cells, showing comparable or even superior agonist activity compared to ADU-S100. Table 1 of Example 2 shows that compounds of the present invention had cytotoxic proliferation inhibitor activity against CT2g tumor cells while ADU-S100 did not. Example 3 and Figures 2A-2C show that in a mouse bilaterial transplantation tumor mol, compounds of the present invention exhibited superior tumor inhibitory ability. Example 5 and Figures 3A and 3B show the compounds of the present invention generated immune memory function in animals.
Regarding Applicants’ first argument, firstly, evidence that the claimed compounds work is not evidence of an unexpected effect. No where in the instant specification do the words unexpected or surprising appear. Looking to table 10, while compound 10 does have the designation A, which designation occurs for ADU-S100 as well. Furthermore, other compounds within the scope of claims have a B designation indicting a higher EC50. Looking at Table 2, while compound 10 has an A designation, so does clofarabine. As set forth in the rejection above, one of the dinucleotides corresponds to clofarabine. Therefore, it doesn’t appear that compound 10 is any better than clofarabine. In example 3, the specification states that the compounds of the invention showed equivalent or superior tumor inhibition activity to ADU-S100. Equivalent effect does not establish an unexpected effect. The fundamental requirement is that “any superior property must be unexpected to be considered as evidence of non-obviousness.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007). Therefore, the arguments are not persuasive as applicants have not actually demonstrated an unexpected effect. Even if, the effect for compound 10 were demonstrated as “unexpected”, the data is not commensurate in scope with the claims as the specification clearly teaches that some of the claimed compounds have a similar effect. 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) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110C and 130C. The court affirmed the rejection of claims 1-7 and 9-10 because the term "elevated temperatures" encompassed temperatures as low as 60C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.). Note: MPEP 716.02(d).
Applicants argue that (2) the prior art has an overall different inventive concept.
Regarding Applicants’ second argument, It is well settled that "any need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed." KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 420 (2007). As long as some suggestion to combine the elements is provided by the prior art as a whole, the law does not require that they be combined for the reason or advantage contemplated by the inventor. In re Beattie, 974 F.2d 1309, 1312 (Fed. Cir. 1992); In re Kronig, 539 F.2d 1300, 1304 (CCPA 1976). MPEP 2143.01 and 2144 (IV).
The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991)
In In re Lintner, the claimed invention was a laundry composition consisting essentially of a dispersant, cationic fabric softener, sugar, sequestering phosphate, and brightener in specified proportions. The claims were rejected over the combination of a primary reference which taught all the claim limitations except for the presence of sugar, and secondary references which taught the addition of sugar as a filler or weighting agent in compositions containing cationic fabric softeners. Appellant argued that in the claimed invention, the sugar is responsible for the compatibility of the cationic softener with the other detergent components. The court sustained the rejection, stating "The fact that appellant uses sugar for a different purpose does not alter the conclusion that its use in a prior art composition would be [sic, would have been] prima facie obvious from the purpose disclosed in the references." 173 USPQ at 562.
Thus, to render the instant claims anticipated or obvious, it is not necessary that the prior art teaches the formation of the same claimed compounds for the same claimed reasons, just that the formation of the claimed compounds is anticipated or obvious. Thus, it is not necessary that the prior art teaches intramolecular cytotoxic mechanism.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
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/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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