DETAILED ACTION
Notice of Pre-AIA or AIA
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-19 are under consideration
Rejections Withdrawn
The 35 USC § 112(b) rejections of claims 8, 10 and 16 have been withdrawn in view of claim amendments.
Rejections Maintained
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.
Claim(s) 1-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over McCreedy (McCreedy, et al., WO 2016/105542 A2; Published 06/30/2016, of record) and Molino (Molino, et al., ACS Nano. 2013 Nov 26; 7(11): 9743-9752, of record).
McCreedy discloses nanoparticle compositions that present biological ligands for modulating the activity of immune cells and methods of use (McCreedy, p 1, lines 7-8). Regarding claims 1, 2, 4, 7, 10-12 and 17, McCreedy discloses that the nanoparticles comprise tumor associated antigens such as cancer testis antigens (McCreedy, p 14, lines 21-24) conjugated to the surface of nanoparticle (McCreedy, p 35, lines 15-20). Regarding claims 5-6, 13-14 and 18, McCreedy discloses the cancer testis antigen NY-ESO-1 is bound to the surface of the nanoparticle (McCreedy, page 15, lines 6-7). Regarding claims 7, 11 and 19, McCreedy discloses that the functionalized nanoparticles of McCreedy are used in methods of treating cancer through via administration of the functionalized nanoparticles to activate T-cells and coupled with the administration of a PDL1 inhibitor (a checkpoint inhibitor) (McCreedy, p 25, lines 25-30). Regarding claim 9, McCreedy discloses that the administration of the nanoparticles of McCreedy induces an antigen-specific T cells in a patient (McCreedy, p 2, lines 1-3).
McCreedy does not teach that teach that the NY-ESO-1 surface-linked nanoparticle is an E2 subunit of a pyruvate dehydrogenase complex. McCreedy does not teach that that the E2 nanoparticle further comprises an adjuvant that is CpG, wherein the adjuvant is linked to the inside of the E2 nanoparticle. McCreedy does not teach that the linkage of NY-ESO-1 to the surface of E2 and the linkage of the adjuvant CpG to the inside of the E2 are responsive to the acidic and reducing environment of an endosome after dendritic cell uptake.
Molino teaches that E2 nonviral protein nanoparticles have the benefit of falling within the narrow size range of 20-45 nm, which is optimal for passive diffusion areas of high immune activity such as lymph nodes but do not possess any infectious ability or native function for entrance into mammalian cells (Molino, p 2 ¶ 2). Molino teaches that the E2 nanoparticles of Molino were internally functionalized with the adjuvant CpG (Molino, p 3, ¶ 3-5) and externally functionalized with a MHC I epitope antigen derived from ovalbumin to E2 that had already been internally functionalized with CpG (Molino, p 4, ¶ 3-4) and that these bonds are specifically triggered by the acidic and reducing environment of DC endosomes (Molino, p 7, ¶ 4). Molino teaches that the benefit of the antigen/adjuvant functionalized E2 nanoparticle delivery method is that it allows both the antigen and the adjuvant to reach the DC cell at the same time (Molino, p 7, ¶ 4) and that this results in enhanced DC activation compared with DC activator alone or antigen alone (Molino, p 7, ¶ 4). Molino also teaches another benefit of the functionalized E2 nanoparticles of Molino is that, upon internalization of the nanoparticles by DCs, release of both DC activator (adjuvant) and antigen is specifically triggered by the acidic and reducing environment of the endosome, with this controlled release of CpG adjuvant attenuating the systematic circulation of DC activators may result in inflammation and toxic side effects while weakening the antigen-specific response. (Molino, p 7, ¶ 4).
It would be prima facie obvious to combine the McCreedy’s teachings of administration of a PDL1 checkpoint inhibitor in conjunction with the NY-ESO-1 surface modified polymeric nanoparticles of McCreedy with the Molino’s teachings of E2 nanoparticles comprising internally linked with the adjuvant CpG and externally linked with an antigen, with both the CpG and antigen linkages being endosome labile following DC uptake. The net result would be a composition comprising: (1) a functionalized E2 nanoparticle therapeutic comprising: a) internally bound CpG adjuvant that is selectively released in DC endosomes following DC uptake and b) surface bound NY-ESO-1 antigen that is selectively released in DC endosomes following DC uptake and (2) a PDL1 inhibitor antibody. One of ordinary skill in the art would be motivated to do this in order to enhance the immunological response elicited in the method of McCreedy. One of ordinary skill in the art would have a reasonable expectation of success doing this because: 1) McCreedy teaches that administration of a PDL1 inhibitor in conjunction with nanoparticles with the TAA antigen NY-ESO-1 attached to the surface as a method of treating cancer via activation of an immune response against the TAA and 2) Molino’s bifunctionalized E2 nanoparticles constitute an improvement to the nanoparticles of McCreedy because they are optimized for delivery to and uptake by DCs, enhance the immune response to the antigen via simultaneous delivery of the NY-ESO-1 antigen and the CpG adjuvant/DC activator to DCs and avoid deleterious effects that could be caused by systemic adjuvant circulation.
Response to Arguments
Applicant's arguments filed 11/11/2025 have been fully considered but they are not persuasive.
Applicant first argues that regarding the differences between the nanoparticles taught by Molino and those of McCreedy operate by distinct biological pathways, with the nanoparticles of Molino acting via activation of natural APCs (such as dendritic cells), which, in turn, present the antigen to T cells, whereas the nanoparticles of McCreedy act as artificial APCs. Applicant argues that because the approaches of Molino and McCreedy operate by distinct biological pathways, one would not expect their combination to yield a predictable or beneficial outcomes.
These arguments are not persuasive because the modified method of McCreedy and Molino articulated in the rejection above comprises the E2-based nanoparticle delivery system of Molino (that works by activating natural APCs) only, with the only modifications coming from McCreedy being the NY-ESO adjuvant present on the surface of the nanoparticles and the PDL1 checkpoint inhibitor administered in conjunction. As such, the distinction between the biological mechanisms of the particles of Molino and the particles of McCreedy is not relevant, as the nanoparticles of McCreedy are not present in the modified method of McCreedy and Molino articulated in the rejection above.
Applicant also argues that the combination of a nanoparticle vaccine with an immune checkpoint inhibitor is counterintuitive because the checkpoint inhibitor inhibits checkpoints that could allow autoreactive cells to engage in autoimmune reactivity and possibly trigger cytokine storm due to prolonged immune cell activation releasing proinflammatory cytokines. Applicant also argues that arriving at the instant claimed method required extensive experimentation to arrive at alleged “unexpected results” with the inventors “surprisingly founding that the TAA nanoparticle vaccine may be combined with the ICIs without increased toxicity. These arguments are not persuasive because McCreedy specifically teaches nanoparticle-based, T cell-activating vaccines administered in conjunction with PDL1 checkpoint inhibitors and the modified E2 nanoparticles collectively taught by McCreedy and Molino above are also T cell- activating vaccines. Additionally, it is routine in the art to administer checkpoint inhibitors that are PDL1 antibodies in conjunction with T cell-based TAA vaccines because it is well-known in the art that PDL1 blockade enhances T cell-based immune responses.
Conclusion
Claims 1-19 are rejected.
No claims are allowed.
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 Sydney Van Druff whose telephone number is (571)272-2085. The examiner can normally be reached 10 am - 6 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SYDNEY VAN DRUFF/ Examiner, Art Unit 1643
/JULIE WU/ Supervisory Patent Examiner, Art Unit 1643