DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendments of 09/15/2025 have been entered in full. Claims 14-28 are pending.
All prior objection/rejections not specifically maintained in this Office action are hereby withdrawn in view of Applicants’ amendment and/or arguments filed 09/15/2025.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Australia on 31 July 2013. It is noted, however, that applicant has not filed a certified copy of the 2013902846 application as required by 37 CFR 1.55. In the absence of a certified copy of AU 2013902846, the priority date of the instant disclosure is July 30, 2014, the filing date of application 14/447532.
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.
Claims 14-28 are rejected under 35 U.S.C. 103 as being unpatentable over Baz Morelli et al, (Journal of Medical Microbiology, 01 July 2012, Vol. 61, pages 935-943) (hereinafter ‘Baz Morelli’), US 20080199485 (Kundig), and US 20090075886 (Brasel). All references are of record.
The instant claims 14-16 are drawn to methods of treating a tumor in a subject, protecting a subject against development of a tumor, or inducing an immune response against a tumor, each method comprising administering to the subject a composition comprising at least one tumor antigen, a saponin-based adjuvant, a TLR ligand, and a FIt3 ligand. Newly added claims 17-28 are dependent from claim 14 and they variously recite species of saponin-based adjuvant, TLR ligand, and FIt3 ligand.
This same combination of references was previously cited with respect to claims 14-16. Applicant’s arguments filed 09/15/2025 generally attacks each reference individually as failing to teach the complete combination of a saponin-based adjuvant, a TLR ligand, and a FIt3 ligand. It is maintained, however, that the combined teachings of the references would have suggested the claimed combination to one of skill in the art.
As noted previously, Baz Morelli teaches that the saponin-based adjuvant, ISCOMATRIX™ , consistently stimulates robust and readily detectable CD4+ and CD8+ T-cell responses to various antigens, including tumor antigens in mice and humans. Baz Morelli teaches (p.940 last paragraph) that combining ISCOMATRIX adjuvant with TLR agonists or other adjuvants simultaneously engages multiple signaling pathways leading to synergistic effects. Baz Morelli cites a prior art example of this type of synergy obtained by combining ISCOMATRIX with CpG ODN (a TLR 9 ligand as in claims 27 and 28). Baz Morelli teaches that synergies are found by combining ISCOMATRIX adjuvant with other TLR agonists as well as with aluminum salts for both Ab responses and CD4+ or CD8+ T-cell responses. Baz Morelli reviews prior art evidence showing that MPL (a TLR 4 ligand as in claims 21 and 22), CpG, Poly IC (a TLR 3ligand as in claims 19 and 20), Flagellin (a TLR 5 ligand as in claims 24 and 24), and R848 (a TLR 7/8 ligand as in claims 25 and 26) are known to induce or enhance T cell and antibody responses, thereby suggesting the combined use of each of these ligands with ISCOMATRIX™. Baz Morelli teaches that the combined use of a TLR ligand and an Flt3 ligand was already known in the prior art (page 937, column 1). It is maintained that knowing that ISCOMATRIX can be advantageously combined with TLR ligands, and that TLR ligands can be advantageously combined with Flt3 ligands, would prompt one of skill in the art to envision combining ISCOMATRIX, TLR ligands, and a Flt3 ligand.
As noted previously, Kundig teaches compositions for enhancing immunization and vaccination [0002], particularly for optimizing CD8+ T cell responses [0005]. The compositions comprise an immunogen plus an immunopotentiator or biological response modifier [0007]. The immunogen can be a tumor antigen [0014]. The immunopotentiator or biological response modifier may be any of the TLR ligands recited in the instant claims, such as CpG, poly I:C, LPS, imiquimod, monophosphoryl lipid A (MPL), a saponin or saponin derivative, [0015][0018][0063-0064][0066][0069]. The biological response modifier may be an Flt3 ligand [0067]. In remarks filed 09/15/2025, Applicant takes issue with the fact that these agents are listed in the alternative (immunopotentiator or biological response modifier) with no suggestion to use combinations. This is not persuasive because Kundig, like Baz Morelli, teaches that TLR ligands and Ttl3 ligands are all usable for the same general purpose of enhancing immune responses to an antigen. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
As noted previously, Brasel teaches a method for augmenting a tumor-specific immune responses by increasing the number of dendritic cells in a patient having a cancerous or neoplastic disease, comprising administering flt3-ligand to the patient in an amount sufficient to generate an increase in the number of the patient's dendritic cells and administering a tumor antigen to the patient, wherein the tumor antigen is specific for said disease and wherein the resulting dendritic cells augment specific immune response to said tumor in said patient (see claim 20). Thus, Brasel teaches that, as a vaccine adjuvant, flt3-ligand can generate large quantities of dendritic cells and other intermediate cells in vivo to more effectively present the antigen. The overall response is a stronger and improved immune response and more effective immunization to the antigen [0008]. The flt-3 ligand can be a soluble fusion form of the protein [0018], as recited in pending claim 18.
In remarks filed 09/15/2025, Applicant takes issue with the fact that Brasel does not teach the combined use of the flt-3 ligand with either a saponin or a TLR ligand. This is not persuasive because Brasel teaches that the flt-3 ligand is useful for the same purpose taught in Kundig, and Baz Morelli for saponins and TLR ligands, i.e. enhancing immune responses to an antigen (In re Kerkhoven). In fact, Brasel describes flt-3 ligand as an adjuvant and further teaches that it may be combined with other adjuvants [0040]. Furthermore, one of skill in the art would recognize the mechanism of Ftl3 ligand to increase the number of the patient's dendritic cells disclosed in Brasel as being distinct from the activating pathways stimulated by saponins or TLR agonists. Consequently, the person of skill in the art would reasonably expect that a Ftl3 ligand would be complementary to, and possibly synergistic with, saponins or TLR agonists. Therefore, more than merely envisioning the combination of ISCOMATRIX, TLR ligands, and a Flt3 ligand in view of Baz Morelli, as noted above, the person of skill in the art would have a reasonable expectation that the inclusion of a Flt3 ligand would improve the effectiveness of the triple combination, as compared to any combination comprising merely two recited agents.
In summary, each component of the composition recited for administration in the methods of claims 14-28 has been generically or specifically taught in Baz Morelli, Kundig, or Brasel, to be useful, alone or in various combinations, for stimulating immune responses against tumor antigens. Therefore, it is predictable that the claimed combination of elements can be administered together to achieve the intended results of the claimed methods.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. US 20080131466 and US 20070212329 teach subcombinations of adjuvants recited in the pending claims.
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 DANIEL C GAMETT, Ph.D., whose telephone number is (571)272-1853. The examiner can normally be reached on M-W. Please note the examiner’s part-time schedule. 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, Joanne Hama can be reached on 5712722911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANIEL C GAMETT/Primary Examiner
Art Unit 1647