DETIALED 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 .
Status of Claims
Claims 1, 3 and 5-33 are pending in the instant application. Claims 1, 3 and 9-10 are amended, claims 32-33 are added and claims 2 and 4 are cancelled via the amendment filed April 22nd, 2026.
Priority
This is a 35 U.S.C. 371 National Stage filing of Application No. PCT/CN2021/110373 filed August 3rd, 2021, which claims priority to provisional Application No. 63/060,899, filed August 4th, 2020.
Withdrawn Objections
Applicant’s arguments and amendments, filed April 22nd, 2026, with respect to objection of claim 2 have been fully considered and are persuasive. The objection of claim 2 has been withdrawn.
Applicant has overcome this objection by replacing the previous pictures with clear pictures of each structure.
Applicant’s arguments and amendments, filed April 22nd, 2026, with respect to objection of claims 3 and 9 have been fully considered and are persuasive. The objection of claims 3 and 9 has been withdrawn.
Applicant has overcome this objection by amending the claims to be in proper dependent form.
Withdrawn Rejections
Applicant’s arguments and amendments, filed April 22nd, 2026, with respect to the 112(a) rejection of claims 1 and 9 have been fully considered and are persuasive. The 112(a) rejection of claims 1 and 9 has been withdrawn.
Applicant has overcome this rejection by amending claim 1 to delete “a progenitor or a stem cell or a cancer cell” and amending claim 9 to delete “preventing” and specify to the disorders to be treated.
Applicant’s arguments and amendments, filed April 22nd, 2026, with respect to the 112(b) rejection of claims 1-10 have been fully considered and are persuasive. The 112(b) rejection of claims 1-10 has been withdrawn.
Applicant has overcome these rejections by amending claim 1 to remove “particularly” and “a compound related to formula (I)”, also specifying the structure of the Afr1 inhibitor. Also, including proper antecedent basis of “Afr1 pathway” in claim 10.
Applicant’s arguments and amendments, filed April 22nd, 2026, with respect to the 35 U.S.C. 102 rejection of claims 1, 3-6 and 8-9 have been fully considered and are persuasive. The 35 U.S.C. 102 rejection of claims 1, 3-6 and 8-9 has been withdrawn.
Applicant has overcome this rejection by amending claim 1 to clearly specify the structure of the inhibitor targeting the Arf1 pathway.
Applicant’s arguments and amendments, filed April 22nd, 2026, with respect to the 35 U.S.C. 103 rejection of claims 1-9 have been fully considered and are persuasive. The 35 U.S.C. 103 rejection of claims 1-9 has been withdrawn.
Applicant has overcome this rejection by amending claim 1 to clearly specify the structure of the inhibitor targeting the Arf1 pathway. However, Applicant’s amendment has necessitated a new grounds rejection. Applicant’s arguments will be addressed in the response to remarks section as they apply to the new 35 U.S.C. 103 rejection.
Response to Remarks
Applicant’s arguments regarding the claim objections and 112(a), 112(b) and 102 rejections are moot as the objections and rejections have been overcome by Applicant’s amendments.
Applicant’s arguments regarding the 35 U.S.C. 103 rejection will be addressed below as the previous 35 U.S.C. 103 rejection has been altered to include the specific Afr1 pathway inhibitors clearly depicted in amended claim 1.
On p. 9-10 of the remarks, Applicant argues that Lang fails to teach or suggest the inhibitor targeting the Arf1 pathway as recited in amendment independent claim 1 of the present disclosure.
In response, Examiner acknowledges that Exo2 no longer is embraced by the inhibitors of instant claim 1. However, the newly altered 103 rejection cites Lang as way of showcasing that Exo2 has the ability to inhibit the Arf1 pathway and kill cancer cells. Thus, providing the necessary motivation to use the derivates of Exo2 as taught by Gutezoyan, that are embraced by amended instant claim 1, for the same utility of Exo2.
On p. 11-12 of the remarks, Applicant begins to cite figures and examples of the instant disclosure to show unexpected or surprising results of the instant invention. Applicant points to Figures 3-4 and 6, as well as Examples 2-15.
Examiner acknowledges the data in the instant specification and drawings, but respectfully disagrees.
Figure 3-4 and 6 of the instant disclosure do not disclose a concentration of the inhibitor . Example 2 merely discloses “a dose- dependent manner”, wherein a concentration of 0-21 uM was used of compound 109 and 110. Example 4 discloses that 50 mg/kg of Du 101 was used. Example 8 discloses that 25 mg/ml of Du101 was tested. Example 12 discloses that 10 uM Du 102 was tested.
Applicant refers to these alleged unexpected, surprising results; however, even if the results were considered unexpected, the results would not be commensurate in scope with the scope of the claims. The results provided do not occur over the entire claimed range (an unclaimed amount) and also that each compound of claim 1 was tested. The examples and figures are based on specific concentrations of Du101 and Du102, however, the present claims do not require a specific dosage amount and embrace more than 2 inhibitors.
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). See MPEP 716.02 (d) and MPEP 716.02 (e).
An affidavit or deceleration under 37 CFR 1.132 must compare the claimed subject matter with the closes prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
Regardless, Applicant has not compared the unexpected results provided to the prior art to effectively rebut the prima facie case of obviousness previously set forth.
Note also that there is no active step of administering in method claim 1.
Thus, the previous 35 U.S.C. 103 rejection was altered to embrace amended claim 1.
Response to Restriction/Election Requirement
Applicant’s election without traverse of Group I, drawn to a method, in the reply filed on October 1st, 2025 is acknowledged.
As the elected group has been found not allowable, claims drawn to the nonelected invention are held withdrawn from further consideration. As such, claims 11-31 have been withdrawn as being embraced by a nonelected invention.
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.
Claim(s) 1, 3, 5-10 and 32-33 stand or are newly rejected under 35 U.S.C. 103 as being unpatentable over Guetzoyan et al (Mol. BioSyst., 2010, 6, 2030–2038, as cited on the IDS dated 06/28/2024) in view Lang et al (Journal of Experimental & Clinical Cancer Research (2017) 36:112, as cited on the IDS dated 06/28/2024). The new rejections are necessitated by Applicant’s amendments.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Guetzoyan teaches the administration of the following compound to HeLa cells (Table 3):
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, wherein Ar is
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. This compound is compound 102 of instant claim 1.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Guetzoyan does not explicitly teach that the administration of the above compound kills a cancer cell and inhibits the Arf1 pathway.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Lang teaches the administration of Exo2 to DU145 and PC3 cells (page 4, right column, paragraph 2). Exo2 is of the following structure (Fig. 6):
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.
Lang further teaches that Exo2 inhibited cell migration and invasion and induced apoptosis in prostate cancer cells (page 4, right column, paragraph 2). Lang also teaches that Exo2 reduces Arf1 activation and effectively suppresses cell proliferation by blocking ERK1/2 activation. Exo2 also has other effects, inhibiting migration and invasion of PCa cells and inducing apoptosis (results).
Further, Guetzoyan teaches that the compound 102 of instant claim 1, is able to generate an Exo2-like morphological effect (page 2034, left column, paragraph 2). Guetzoyan also teaches that the compound is a clear candidate for an Exo2 derivative with reduced toxicity and differential specificity (page 2037, left column, paragraph 1).
Regarding claim 1, as Guetzoyan teaches a compound of formula (I) being administered to HeLa cells and Lang teaches that Exo2 inhibits cell migration and invasion and induced apoptosis in prostate cancer cells one of ordinary skill in the art would have a reasonable expectation of success of compound 102 being used in a method of killing a cancer cell as Guetzoyan teaches that the compound of formula (I) shows morphologically similar properties to Exo2, with improved properties. Note also that there is no active step of administering in method claim 1.
Regarding claim 3, as seen above, Lang teaches the administration of Exo2 to a PCa and DU145 cells, which inhibits Arf1 pathway activity.
Regarding claim 5, HeLa cells are cancer cells.
Regarding claim 6, as seen above, Exo2 induces cell apoptosis.
Regarding claim 7, one of ordinary skill in the art would have been motivated to carry out the process in vitro as the in vivo study presented promising results.
Regarding claim 8, as seen above, the administration of Exo2 and compound 102 is carried out in vivo.
Regarding claim 9, as seen above, Exo2 and compound 102 are administered as a way of treating cancer. Further, Gutezoyan teaches that the derivatives have been proposed as an attractive way to treat human disease (page 2031, left column, paragraph 1).
Regarding claim 10, Guetzoyan teaches the monitoring of the Arf1 GTPase pathway (Biological testing, page 2037, left column, paragraph 2).
Regarding claims 32-33, as seen above, Lang teaches the administration of Exo2 to a PCa and DU145 cells, which inhibits Arf1 pathway activity. PCa cells are prostate cancer cells and DU145 cells are brain cancer cells.
Conclusion
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.
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/A.G.K./Examiner, Art Unit 1626
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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