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 .
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for obtaining a desired pharmacologic and/or physiologic effect through administering compound(s) or composition(s), particularly alleviating pancreatic duct adenocarcinoma (PDAC) via administering an iRGD peptides or conjugates thereof in combination with one or more immune checkpoint inhibitor, does not reasonably provide enablement for treating or preventing all cancers. Specifically, the specification provides support for using an iRGD peptide in combination with gemcitabine and/or PD-L1 inhibitors in treating PDAC via injections. The examples provided do not, however, demonstrate preventing any cancers, and they do not demonstrate examples beyond treating or alleviating PDAC via injections in mouse models. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
With regard to the breadth of the claims, the nature of the invention, and the state of the prior art, claims 1-16 are directed at treating cancer in a subject, but the specification defines treating as including “preventing.” Here, the breadth of the claims would thereby include the prevention of any cancer of any cell/tissue/organ type in any organism. Given the nature of the invention as a method of treating comprising administering a peptide and given the state of the prior art not recognizing any peptide-based complete preventions of cancer, a person having ordinary skill in the art would not be enabled to make or use an invention that is recognized as impossible. With regard to the level of one of ordinary skill in the art, the level of predictability in the art, and the quantity of experimentation needed to make or use the invention based on the content of the disclosure, one of ordinary skill in the art would not know how to completely prevent any cancer using a peptide treatment and would thereby require extensive experimentation to develop a cancer prevention peptide. Moreover, based on the recognition in the state art of the impossibility of preventing all cancers with a peptide treatment, as well as the lack of guidance as to how to prevent cancers with the peptide in the disclosure, a person having ordinary skill in the art would not be enabled to make or use a prevention of this kind. The prior art does also provide support for using iRGD peptides in combination with immune checkpoint inhibitors in treating PDAC. Here, 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-L1 and/or PD-L2 (see [0064], [0083], and [0111]). Nel et al. teach that the cancer is pancreatic duct adenocarcinoma (see [0091]), but they do not provide support for treating, preventing, or alleviating other cancers using the method of the instant application. Moreover, as discussed below, Jarvelainen et al. provide support for using peptides of the instant application, specifically SEQ ID NO: 3 (see claim 9), in treating pancreatic cancer (see column 15, lines 38-45), but they do not provide support for treating or preventing other cancers/ With regard to the existence of working examples and the amount of direction given by the inventor, there are no working examples of completely preventing any cancer, and the inventor does not address the capability of the invention in any preventative form. As discussed above, the specification provides support through examples in mouse models for using an iRGD peptide in combination with gemcitabine and/or PD-L1 inhibitors in treating PDAC via injections. The examples provided do not, however, demonstrate preventing any cancers, and they do not demonstrate examples beyond treating or alleviating PDAC via injections in mouse models. Therefore, the disclosure has not enabled one having ordinary skill in the art to make and use the invention commensurate with the scope of the claims with regard to treating or preventing cancers outside of alleviating PDAC. It is advised that Applicant amend the claims to limit the scope of the invention to the embodiments that the disclosure enables, particularly ameliorating pancreatic duct adenocarcinoma.
Claims 1-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
As discussed above, the present disclosure claims a method of preventing all cancers via a peptide treatment. Applicant does not, however, provide any working examples of preventing any cancers, and the disclosure does not provide a representative sample of cancers that can be treated by the method. Specifically, Applicant only discloses embodiments for the treatment of pancreatic duct adenocarcinoma, and there are no examples of complete prevention of any cancer. As such, one having ordinary skill in the art would not reasonably conclude that Applicant had possession of preventions or treatments of all cancers. It is advised that Applicant amend the scope of the claims to encompass the embodiments for which the disclosure conveys possession of, particularly methods for ameliorating pancreatic duct adenocarcinoma.
Claim Rejections - 35 USC § 102
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 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.
Claims 1, 3-7, 9, and 12-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2018213631, hereinafter Nel et al.
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]). 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-L1 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 12 and 13, Nel et al. teach that the cancer can be PDAC (see [0098]).
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]).
Claims 1-6 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-L1 inhibitors ipilimumab, pembrolizumab, and/or nivolumab (see column 3, lines 41-45).
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.
Claims 2 and 16 are 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.
With regard to claim 2, 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 use of the peptide of SEQ ID NO: 3 of the instant application.
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.
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).
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).
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]).
Summary
Claims 1, 3-7, 9, and 12-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated. Claims 2, 8, 10-11, and 16 are rejected under 35 U.S.C. 103 as being unpatentable on the grounds of obviousness. Claims 1-16 are rejected under 35 U.S.C. 112(a) for scope of enablement and written description.
Conclusion
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/BRENDAN P. OLISS/Examiner, Art Unit 1658
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654