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 .
DETAILED ACTION
This Office Action is a response to Applicant’s Amendment and Remarks filed October 12, 2025.
Claims 9 and 16 have been amended.
Claims 9-16, 18 and 19 are pending in the present application.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 102/103
In the previous Office Action mailed April 11, 2025, claims 9-13 and 16 were rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Kamerkar et al. (Nature Vol. 546, pages 498-503 (2017)). This rejection is maintained for the reasons of record set forth in the previous Office Action mailed April 11, 2025.
Response to Arguments
In response to this rejection, Applicants traverse and argue that perineural invasion (PNI) is a distinct pathological phenomenon from general conceptions of "cancer progression" or metastasis. Applicants submit that the distinctiveness of PNI not only requires different research modalities but also different treatment modalities from those that seek to study or inhibit "cancer progression" or metastasis in general. Applicants argue that not only does Kamerkar not teach the claimed invention, but Applicant submits that Kamerkar would not have led one of skill in the art to develop the claimed invention.
In support of Applicant's position, Applicants rely on the § 1.132 Declaration of Dr. Mitchell Shirvan filed October 12, 2025 which supposedly provides evidence of the knowledge of the art that confirms that PNI and metastasis cannot be understood interchangeably and that treatments for one are not inherently useful for the other.
Applicant’s traversal has been fully considered, however it is not found persuasive. Further, the § 1.132 Declaration of Dr. Mitchell Shirvan has been considered in its entirely but similarly is not found persuasive. The issue is that the present Specification at DETAILED DESCRIPTION, part III, Compositions and Methods for Reducing Perineural Invasion explicitly discloses:
Disclosed herein is the observation that RNAi agents designed to specifically target KRAS G12D or KRAS G12C can, in an illustrative cancer cell line (the pancreatic cancer cell line MIA PaCa-2 which harbors a KRAS G12C mutation), significantly inhibit perineural invasion (PNI).
Kamerkar et al. teach siRNA targeting KRASG12D were administered to MIA PaCa-2 cells. See Extended Data, Figure 4q and 4u, for example. While the reference is silent as to any reduction in regional perineural invasion, the method of administration Kamerkar et al. is identical to the method steps associated with the PNI observation reported in Applicant’s Disclosure. Because the compositions and method steps for reducing perineural invasion of the instant invention are exactly identical to the disclosure of Kamerkar et al., the Examiner maintains that reduction of regional perineural invasion and pain associated with regional perineural invasion would naturally flow and be inherent to performing the administration step performed by Kamerkar et al. See MPEP 2112.
Note that the Patent Office does not have the facilities and resources to provide the factual evidence needed in order to determine properties between the instantly claimed method for reducing regional perineural invasion or method of reducing pain associated with regional perineural invasion and the method of administering siRNA targeting KRASG12D to MIA PaCa-2 cells taught by the prior art Kamerkar et al. The burden is upon the Applicant to prove that the method taught in the present invention and that which is disclosed in the prior art are different, thereby establishing patentable differences. The Examiner has considered Applicant’s traversal and the § 1.132 Declaration of Dr. Mitchell Shirvan, however they are not found to be persuasive since the method of administration of Kamerkar et al. is identical to method steps associated with the perineural invasion observation reported in Applicant’s Disclosure.
Further, the instant Specification serves as evidence of record establishing this inherency. Failure of those skilled in the art to contemporaneously recognize an inherent property (i.e. a biological mechanism of action) of a prior art reference does not preclude a finding of anticipation. Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342, 1349, 51 USPQ2d 1943, 1948 (Fed. Cir. 1999). See also Ex parte Novitski, 26 USPQ2d 1389 (Bd. Pat. App. & Inter. 1993).
For the reasons above, it is maintained that claims 9-13 and 16 are anticipated by and obvious over Kamerkar et al.
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In the previous Office Action mailed April 11, 2025, claims 9-16, 18 and 19 were rejected under 35 U.S.C. 103 as being obvious and unpatentable over Kamerkar et al. (Nature Vol. 546, pages 498-503 (2017)) in view of Golan et al. (Oncotarget Vol. 6, 24560-24570 (2015)). This rejection is maintained for the reasons of record set forth in the previous Office Action mailed April 11, 2025.
Response to Arguments
In response to this rejection, Applicants traverse and argue that as discussed above, the subject claims are non-obvious over Kamerkar because the reference neither inherently nor expressly teaches a method for treatment of regional PNI or pain arising from regional PNI. Applicants submit that Golan does not relate to PNI at all. Applicants conclude that the subject claims are non-obvious over the combination of Kamerkar and Golan.
Applicant’s traversal has been fully considered, however it is not found persuasive since the Examiner maintains that the method of administering siRNA targeting KRASG12D to MIA PaCa-2 cells taught by the prior art Kamerkar et al. would inherently reduce regional perineural invasion and pain associated with regional perineural invasion as discussed above.
The Examiner relied upon Golan et al. to teach the polymeric implant siG12D-LODERTM was well-tolerated and showed potential efficacy in patients with advanced pancreatic cancer.
Before the effective filing date of the claimed invention, a method of administering siRNA targeting KRASG12D to MIA PaCa-2 cells was known in the prior art of Kamerkar et al. It would have been obvious and a person of ordinary skill in the art would have been motivated to modify the teachings of Kamerkar et al. to include administration with the biopolymeric drug delivery device of Golan et al. for more efficient delivery of the siRNA molecule.
Turning to the facts, the presumption of obviousness applies here, and none of the means for rebutting it has been shown. In view of the foregoing, when all the evidence is considered, the totality of the rebuttal evidence of non-obviousness fails to outweigh the evidence of obviousness made of record. Thus, it is maintained that the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
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In the previous Office Action mailed April 11, 2025, claims 9-16, 18 and 19 were rejected under 35 U.S.C. 103 as being obvious and unpatentable over Author Unknown, “John Theurer Cancer Center Recruiting a Phase II Clinical Trial for Pancreatic Cancer”, February 8, 2019 in view of U.S. Patent No. 9080173. This rejection is maintained for the reasons of record set forth in the previous Office Action mailed April 11, 2025.
Response to Arguments
In response to this rejection, Applicants traverse and argue that the John Theurer Document is not available prior art since the reference was published less than one-year prior to Applicant's priority date. To support their arguments, Applicants point the Examiner to the evidence provided in the Declaration under 37 CFR § 1.130 by Dr. Mitchell Shirvan filed October 12, 2025. Applicants submit that the John Theurer Document is excluded from being prior art according to the provisions of 35 USC §102(b)(1)(A), and the rejection of the pending claims over the combination of the John Theurer Document and US 9,080,173 should be withdrawn.
Applicant’s traversal has been fully considered, however it is not found persuasive. Further, the § 1.130 Declaration of Dr. Mitchell Shirvan has been considered in its entirely but it is not found to be persuasive because the present application is a National Stage entry of PCT/IL2020/050537, International Filing Date: 05/17/2020. PCT/IL2020/050537 claims priority from Provisional Application 62849166, filed 05/17/2019. It should be noted that Provisional Application 62849166 does not have support for the present claims drawn to a method for reducing regional perineural invasion by a solid tumor or a method for reducing pain associated with regional perineural invasion of a solid tumor. While Provisional Application 62849166 supports a method for reducing pain, metastases, and local perineural invasion by a solid tumor, any method associated with regional perineural invasion is not supported.
Applicant should note that local and perineural invasion are not the same as evidenced by Google AI Overview downloaded from is regional perineural invasion and local perineural invasion the same - Google Search on October 27, 2025. Given this consideration, the present claims are afforded priority to PCT/IL2020/050537, International Filing Date: 05/17/2020. The John Theurer Document has a filing date February 8, 2019 and therefore was not published less than one year prior to Applicant’s priority date.
In conclusion, the § 1.130 Declaration of Dr. Mitchell Shirvan is not sufficient to disqualify The John Theurer Document as prior art.
Turning to the facts, the presumption of obviousness applies here, and none of the means for rebutting it has been shown. In view of the foregoing, when all the evidence is considered, the totality of the rebuttal evidence of non-obviousness fails to outweigh the evidence of obviousness made of record. Thus, it is maintained that the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims Rejection - Improper Markush
In the previous Office Action mailed April 11, 2025, claims 9-12, 14-16, 18 and 19 were rejected on the judicially-created basis that it encompasses an improper grouping of alternatives. This rejection is maintained for the reasons of record set forth in the previous Office Action mailed April 11, 2025.
Response to Arguments
In response to this rejection, Applicants traverse and argue that claims 9 and 16 have been amended to not be in the noted Markush format. Applicant respectfully requests withdrawal of this rejection. The Examiner notes the Amendment to claims 9 and 16 in their response filed October 12, 2025, however the amendment is not enough to overcome the instant rejection since it is maintained that the species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. For further explanation, see the previous Office Action mailed April 11, 2025 at pages 9 and 10.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. The rejection is maintained.
Double Patenting
In the previous Office Action mailed April 11, 2025, claims 9-16, 18 and 19 were rejected on the grounds of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-12 of U.S. Patent No U.S. Patent No. 9080173 in view of Author Unknown, “John Theurer Cancer Center Recruiting a Phase II Clinical Trial for Pancreatic Cancer”, February 8, 2019. This rejection is maintained for the reasons of record set forth in the previous Office Action mailed April 11, 2025.
Response to Arguments
In response to this rejection, Applicants traverse and argue the John Theurer Document is excluded from being prior art according to the provisions of 35 USC §102(b)(1)(A) as evidenced by the § 1.130 Declaration of Dr. Mitchell Shirvan filed October 12, 2025. Applicant respectfully requests withdrawal of this rejection.
Applicant’s traversal has been fully considered, however it is not found persuasive for the reasons discussed above. Specifically, the § 1.130 Declaration of Dr. Mitchell Shirvan is not sufficient to disqualify The John Theurer Document as prior art under §102(b)(1)(A). See § 35 U.S.C. 103 rejection above for further explanation.
The Examiner maintains that a terminal disclaimer disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 9,080,173 is required or some other appropriate action.
THIS ACTION IS MADE FINAL. 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 Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635