DETAILED 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 . 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.
Examiner’s Note
This application has been transferred to Fred Reynolds from Brendan Oliss.
Claims Status
Claims 1, 4-11, and 14-16 are pending.
Claims 1 and 16 have been amended.
Withdrawn Rejections
The rejection of claims 1-16 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph due to lack of enablement beyond PDAC is hereby withdrawn due to amendment.
The rejection of claims 1-16 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph over prevention of cancer is hereby withdrawn due to amendment.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
first rejection
Claims 1, 4-7, 9, 14, and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2018213631, hereinafter Nel et al with evidentiary support from Sugahara et al (Cancer Cell (2009) 16(6) p510-520, cited in IDS submitted with response)
With regard to claim 1, Nel et al. teach a method of treating cancer in a subject comprising administering to the subject an iRGD peptide or variant thereof or iRGD conjugate in combination with one or more immune checkpoint inhibitor (see [0064], [0083], and [0111]). Note that, as evidenced by Sugahara, a person of skill in the art would interpret iRGD peptide as CRGD(K/R)GP(D/E)C (abstract), which is a subgenus of the sequences of SEQ ID 3 of the examined claims. Nel et al. teach a method of treating cancer in a subject comprising administering to a subject in need thereof an effective amount of a nanovesicle drug carrier that is conjugated to an iRGD peptide and comprises an immune checkpoint inhibitor, specifically PD-1 and/or PD-L2 (see [0064], [0083], and [0111]). Nel et al. teach that the cancer is pancreatic duct adenocarcinoma (see [0091]).
With regard to claim 3, Nel et al. teach the method discussed above wherein the immune checkpoint inhibitor comprises a specifically PD-L1 and/or PD-L2 (see [0111]).
With regard to claim 4, Nel et al. teach the method discussed above wherein the one or more immune checkpoint inhibitor comprises PD-L1, PD-L2, PD-L3, PD-L4, CTLA-4, LAG3, B7-H3, B7-H4, KIR and/or TIM3 (see [0111]).
With regard to claims 5 and 6, Nel et al. teach the method discussed above wherein the immune checkpoint inhibitor comprises Pembrolizumab, Ipilimumab, or Nivolumab (see [0114], [0118]).
With regard to claim 7, Nel et al. teach that the cancer can be a metastatic cancer, particularly metastatic squamous neck cancer (see [0340]).
With regard to claim 9, Nel et al. teach that the immune activation of the PDAC microenvironment leads to the expression of checkpoint inhibitors (see [0824]).
With regard to claims 14 and 15, Nel et al. teach the method discussed above wherein there is an additional adjunct therapy treatment regime that is administered with the method above (see [0089]).
response to applicant’s arguments
Applicants argue that claim 1 has been amended to require SEQ ID 3, which Nel et al does not teach.
Applicant's arguments filed 15 June, 2026 have been fully considered but they are not persuasive.
Applicants have filed an IDS with their response with a reference that shows that the iRGD of Nel et al reads on SEQ ID 3 of the examined application.
second rejection
Claims 1 and 4-6 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by U.S. Patent No. 12,351,653, hereinafter Jarvelainen et al.
With regard to claim 1, Jarvelainen et al. teach a method for treating cancers in a subject in need thereof comprising administering an iRGD peptide (CEND-1) with chemotherapeutic agents, specifically immune checkpoint inhibitors PD-1, ipilimumab, pembrolizumab, and/or nivolumab (see column 2, lines 60-67 and column 3, lines 1-47).
With regard to claim 2, Jarvelainen et al. teach that the pharmaceutical composition comprises a structure that comprises the sequence of SEQ ID NO: 3 of the instant application (see claim 9).
With regard to claim 3-6, Jarvelainen et al. teach the method discussed above, wherein the immune checkpoint inhibitors include PD-1 inhibitors ipilimumab, pembrolizumab, and/or nivolumab (see column 3, lines 41-45).
response to applicant’s arguments
Applicants argue that they have amended the claims to avoid the PD-L1 inhibitors of this reference.
Applicant's arguments filed 15 June, 2026 have been fully considered but they are not persuasive.
Jarvelainen et al mention PD-1 inhibitors, not PD-L1 inhibitors.
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, 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.
first rejection
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2018213631, hereinafter Nel et al., as applied to claims 1, 3-7, 9, and 12-15 above, in view of US 20090246133 A1, hereinafter Ruoslathi et al.
Ruoslathi et al. teach peptides and methods for treating cancer. Specifically, they teach methods and compositions related to internalizing RGD peptides, and they teach the peptide of SEQ ID NO: 3 of the instant application in SEQ ID NO: 1 of the reference (see SEQ ID NO: 1, [0131]). They teach that, when tested for tumor binding in mouse models of prostate cancer, the sequence CRGDKGPDC dominated in the selection tools for internalizing the RGD for delivering treatment (see [0131]). Here, Ruoslathi et al. provide a clear motivation for the use of the RGD peptide of SEQ ID NO: 3 of the instant application in treating cancer by binding to tumors and internalizing the RGD. As such, given the fact that the peptide of SEQ ID NO: 3 was known for its usefulness in tumor binding in cancer treatments, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application, to use the peptide of SEQ ID NO: 3 in tumor targeting to treat cancer, particularly when already using an iRGD peptide as in Nel et al.
With regard to claim 16, Nel et al. teach the method discussed above, but they do not explicitly teach that the method sensitizes a cancer to immune checkpoint inhibitor immunotherapy. Nel et al. teach a method of treating cancer comprising administering to a subject an iRGD peptide in combination with a PD-L1 and/or PD-L2 (see [0064], [0083], and [0111]), and, as discussed above and in light of Ruoslathi et al., would have been obvious to use the iRGD peptide of SEQ ID NO: 3 in the composition (see [0131]). Here, administering products of identical chemical composition will necessarily yield the same result. In other words, a chemical composition and its function/properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. As such, the method discussed above would inherently sensitize a cancer to immune checkpoint inhibitor immunotherapy.
response to applicant’s arguments
Applicants argue that claim 16 is dependent on claim 1, which was not rejected here. Thus, the rejection is improper.
Applicant's arguments filed 15 June, 2026 have been fully considered but they are not persuasive.
The previous examiner formatted his rejections as additional claims rejected with the obviousness rejections (note “as applied to claims . . .” in the rejection above).
second rejection
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2018213631, hereinafter Nel et al., as applied to claims 1-7, 9, and 12-16 above, in view of Bear et al. (Bear, Adham S et al. “Challenges and Opportunities for Pancreatic Cancer Immunotherapy.” Cancer cell vol. 38,6 (2020): 788-802).
Nel et al. teach the method of treating cancer comprising administering to a subject an iRGD peptide in combination with a PD-L1 and/or PD-L2 (see [0064], [0083], and [0111]) discussed and applied above. Nel et al. do not, however, teach the method wherein the cancer is immunotherapy refractory. Nonetheless, Nel et al. do teach that the method is applied to pancreatic duct adenocarcinoma (see [0098]), which, according to Bear et al., is immunotherapy refractory in over 99% of cases (see page 788, paragraph 1). Nel et al. further teach that PDAC is an often-fatal and notoriously treatment-resistant disease (see [0819]). They teach that their nano-enabled approach offers distinct advantages over current immunotherapy strategies, particularly enhanced immune activation (see [0820]). Given that nearly all of the subjects in need of treatment in the method of Nel et al. are immunotherapy refractory, it would have been obvious to try to treat patients who are immunotherapy refractory with a reasonable expectation of success. The reasonable expectation of success is clear from the fact that Nel et al. teach that PDAC is notoriously treatment-resistant, but that their treatment offers distinct immune activation advantages over current treatments (see [0819]-[0820]). It would be obvious to try because there are only two options of patients to treat in Nel et al., those that are immunotherapy refractory and those that are not, and of these two options, over 99% are immunotherapy refractory (see Bear et al. page 788, paragraph 1).
response to applicant’s arguments
Applicants argue that they have amended the claims so Nel et al in view of Bear et al does not have all the limitations of claim 1.
Applicant's arguments filed 15 June, 2026 have been fully considered but they are not persuasive.
As noted in the first anticipation rejection, Sugahara et al shows that Nel et al anticipates claim 1.
third rejection
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2018213631, hereinafter Nel et al., as applied to claims 1-9, and 12-16 above, in view of Strobel et al. (Strobel, Oliver et al. “Optimizing the outcomes of pancreatic cancer surgery.” Nature reviews. Clinical oncology vol. 16,1 (2019): 11-26).
Nel et al. teach the method of treating cancer comprising administering to a subject an iRGD peptide in combination with a PD-L1 and/or PD-L2 (see [0064], [0083], and [0111]) discussed and applied above. As noted above, Nel et al. teach the method as applied to treating pancreatic duct adenocarcinoma (see [0098]). Although Nel et al. do teach that this method can be applied in the absence of surgical intervention (see [0394]), they do not explicitly teach the application of the method to unresectable cancers. According to Strobel et al., only 10% to 20% of PDAC patients have any resect ability (see Abstract). Given that Nel et al. teach that their method of treating PDAC can be used in the absence of surgery and that 80%-90% of PDAC cases are unresectable, it would have been obvious to try to treat unresectable PDAC cancers with a reasonable expectation of success. There is a reasonable expectation of success on account of the fact that Nel et al. teach that their method can be used on PDAC tumors in the absence of surgery anyway (see [0394]). It would be obvious to try because there are only two options of patients to treat in Nel et al., those with and without resect ability, and of those two options, 80%-90% are without resect ability (see Strobel et al. Abstract).
response to applicant’s arguments
Applicants argue that they have amended the claims so Nel et al does not have all the limitations of claim 1.
Applicant's arguments filed 15 June, 2026 have been fully considered but they are not persuasive.
As noted in the first anticipation rejection, Sugahara et al shows that Nel et al anticipates claim 1.
fourth rejection
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2018213631, hereinafter Nel et al., as applied to claims 1-10 and 12-16 above.
With regard to claim 11, Nel et al. teach methods of treating 4T1 cell lines, which are stage IV human breast cancer cells (see [0784]). They teach that there is high PD-1 expression in the 4T1 cells, which they note provides the motivation for treating these stage IV cells with immune checkpoint inhibitors, which resulted in significant tumor suppression (see [0483]). Given this motivation to treat stage IV cancer cells with the immune checkpoint inhibitor method of treating, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to apply the methods of treating cancer of Nel et al. to treat stage IV cancers. Beyond this, Nel et al. also teach treatments for models of metastatic PDAC (see [0810]).
response to applicant’s arguments
Applicants argue that they have amended the claims so Nel et al does not have all the limitations of claim 1.
Applicant's arguments filed 15 June, 2026 have been fully considered but they are not persuasive.
As noted in the first anticipation rejection, Sugahara et al shows that Nel et al anticipates claim 1.
New Rejections
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5 and 6 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 1, from which claims 5 and 6 depend, limit the checkpoint inhibitors to PD-1 and PT-L2 inhibitors. However, not all of the checkpoint inhibitors of claims 5 and 6 are PD-1 or PD-L2 inhibitors. For example, Savoia et al (Hum. Vacc. Immunotherapeut. (2016) 12(5) p1092-1101) states that ipilimumab is an anti CTLA-4 antibody (title). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Please note that this rejection is necessitated by amendment.
Conclusion
Applicant's submission of an information disclosure statement under 37 CFR 1.97(c) with the timing fee set forth in 37 CFR 1.17(p) on 15 June, 2026 prompted the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 609.04(b). 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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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