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 .
Claims Status
The Amendment filed on 19May2026 is acknowledged in which claim(s) 9 and 11 were canceled and claim(s) 22-34 are new.
Applicant’s election without traverse of (A) TLR4, (B) PGPC, (C) whole tumor cell lysate and (D) checkpoint inhibitors species in the reply filed on 05Nov2025 is acknowledged.
Claim(s) 3, 10, 21, 27 and 34 is/are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05Nov2025.
Claim(s) 1-2, 4-8, 10-20, 22-26, and 28-33 is/are presented for examination on the merits.
Response to Amendment and Arguments
The objection(s) to the specification have been withdrawn in view of the Amendment filed on 19May2026.
All previous rejection(s) of claim(s) 10 are moot in view of claim withdrawal as being drawn to a non-elected invention in view of the Amendment filed on 19May2026.
All other previously presented rejection(s) and objection(s) are maintained in modified form, or NEW, as necessitated by the claim Amendment filed on 19May2026, which added new limitations to the claims. For reasons below, Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
New/Maintained Rejections, Modified as Necessitated by Claim Amendments
Claim Rejections - 35 USC § 103
The rejection(s) of claim(s) 1-2, 4-8, 11-20, 22-26, and 28-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/067302 A2 (hereinafter “WO302”), in view of Zanoni et al. (2017, Immunity 47, 697–709; Oct 17, 2017; hereinafter “Zanoni”), is/are maintained in modified form as necessitated by amendment for the reasons set forth below.
Regarding instant claim(s) 1-2, 4-8, 11, 16, 22-26, WO302 teaches a method of inducing or enhancing an adaptive immune response to treat cancer (such as TNBC) in a subject comprising administering a tumor antigen (e.g., cancer immunogen) that is a tumor lysate [e.g., title; abstract; ¶ 0010-0011, 0089, 0095, 0126-0128, 0194], MPLA TLR4 ligand [e.g., ¶ 0039], and oxPAPC (e.g., non-canonical inflammasome activating lipid) [e.g., ¶ 0012].
Regarding instant claim(s) 12-13, 28-29, WO302 further teaches the hyperactivated cells are human [e.g., ¶ 0040, 0116, 0195-0196; fig. 8].
Regarding instant claim(s) 14, 30, WO302 further teaches that the composition is made from biocompatible FDA-approved materials (e.g., a pharmaceutical composition) [e.g., ¶ 0006, 0113, 0117, 0195, 0224].
Regarding instant claim(s) 15, WO302 further teaches the composition can be used to prevent inflammatory conditions (e.g., prophylactic treatment of cancer) [e.g., ¶ 0119].
Regarding instant claim(s) 17, WO302 further teaches hyperactivated DCs induce T cell activation [e.g., ¶ 0057, 0080, 0252, 0267-0269; fig. 25, 48].
Regarding instant claim(s) 18-20, 31-33, WO302 further teaches combination therapy with checkpoint inhibitors [e.g., ¶ 0269].
WO302 does not expressly teach a method of inducing or enhancing an adaptive immune repose to a cancer in a subject comprising administering (1) tumor lysate, LPS TLR4 ligand, and PGPC wherein (a) the subject is human, (b) the tumor lysate, LPS and PGPC are part of a pharmaceutical composition, (c) the immune response is prophylactic, (d) the immune response is therapeutic, (e) the immune response comprises T cell activation, (e) treatment further comprises the administration of one or more checkpoint inhibitors, or (f) the therapeutic interventions are co-administered or sequentially administered.
Zanoni teaches that PGPC and LPS together induce hyperactivation of dendritic cells (DC) and macrophages, whereas oxPAPC only induced DC hyperactivation [e.g., pgs. 703-704, “Specific oxPAPC components Hyperactivate…” ].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the TLR4 ligand MPLA and the non-canonical activating lipid oxPAPC in the method of inducing or enhancing adaptive immune response to treat cancer as taught by WO302, with the LPS TLR4 ligand and the PGPC non-canonical activating lipid as taught by Zanoni, in the context of designing and developing a TLR4 directed cancer therapy. A PHOSITA would have been motivated to substitute the TLR4 ligand MPLA and the non-canonical activating lipid oxPAPC in the method of inducing or enhancing or inducing adaptive immune response to treat cancer as taught by WO302, because WO302 teaches the base therapeutic method and Zanoni teaches that the advantages of LPS and PGPC together include hyperactivation of both DCs and macrophages, whereas oxPAPC was only shown to hyperactivate DCs. Further, WO302 teaching the administration of the composition to a subject and that the composition comprises biocompatible FDA-approved materials necessarily teaches a pharmaceutical composition. Additionally, WO302’s teachings of administration to a subject as well as teaching examples in human cells necessarily teaches the subject is a human. There would have been a reasonable expectation of success for a PHOSITA to substitute the TLR4 ligand MPLA and the non-canonical activating lipid oxPAPC in the method of inducing or enhancing or inducing adaptive immune response to treat cancer as taught by WO302 because WO302 teaches the base therapeutic method and Zanoni teaches that the application of LPS and PGPC together induced hyperactivation in both DCs and macrophages. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Further, it would have been obvious to a PHOSITA to modify the modified method of inducing or enhancing adaptive immune response to treat cancer as taught by WO302 and Zanoni (see above) to include the (1) the immune response is prophylactic, (2) the immune response is therapeutic, (3) the immune response comprises T cell activation, (4) treatment further comprises the administration of one or more checkpoint inhibitors, or (5) the therapeutic interventions are co-administered or sequentially administered as taught by WO302, because WO302 and Zanoni teach the modified method, and WO302 teaches the base method as well as variations to the method. Further, WO302’s teaching of the composition for cancer therapy necessarily teaches the immune response is therapeutic, and the teachings of the administration of the composition and a checkpoint inhibitor necessarily meets the limitations “co-administered or sequentially administered” because those are the only two options that are possible (co-administered means at the same time; sequentially administered means at different times). There is an expectation of success for a PHOPSITA to substitute the modified method of inducing or enhancing adaptive immune response to treat cancer as taught by WO302 and Zanoni (see above) to include the method variants as further taught by WO302, because WO302 and Zanoni teach the modified method, and WO302 teaches the base method as well as variations to the method. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues:
Reviews that WO302, as the office notes does not teach a method of inducing or enhancing adaptive immune response to cancer comprising administering PGPC, as in the instant claims. Nothing in WO302 would lead a PHOSITA to combine TLR ligand and PGPC as in the instant claim. WO302 contains a single passing reference to oxPAPC in the specification, as one of several possible small molecule TLR modulators to be encapsulated within a particle, with no indication of how it should or should not be combined with other components, or used to induce or enhance adaptive immune responses to treat cancer.
In response, WO302 was not relied upon to teach PGPC administration. PGPC administration and benefits thereof, was taught by Zanoni (see rejection above for details). Applicant arguments directed to oxPAPC are directed to the unelected species and are therefore was not examined for the limitations recited in the arguments above. However, in the interest of a complete response, WO302 expressly teaches oxPAPC as one of four total options [e.g., ¶ 0012; claim 8]. Therefore, WO302 is considered to expressly teach oxPAPC.
There is no teaching or suggestion in WO302 that adding a non-canonical inflammasome activating lipid such as PGPC into the particle would be possible or suitable for such a therapeutic cancer vaccine.
In response to 2, WO302 was not used to teach PGPC administration (see response above for details). Additionally, WO302 expressly teaches that both the first and second lipid may be chosen from the phosphocholine family of lipids, and while it does not expressly teach PGPC, a skilled artisan would understand PGPC is within phosphatidylcholine family, which is part of the broader phosphocholine family as taught by WO302 for liposomal particles.
Zanoni doesn’t teach administering any type of therapeutic, nor any reason to have expected that the combination of a TLR ligand, PGPC, and a cancer immunogen would have induced or enhanced an adaptive immune response to a cancer as in the instant invention.
In response, WO302 was relied upon to teach therapeutic methods, whereas Zanoni was relied upon to teaches that PGPC and LPS together induce hyperactivation of dendritic cells (DC) and macrophages (e.g., a benefit in treating cancer; induced adaptive immune cells; see rejection above for details).
For reasons above, WO302 and Zanoni would hot yield predictable results as neither reference alone nor in combination would provide a PHOSITA reasonable expectation of success, and the reconstruction is based on hindsight. Example provided of the instant invention method resulting in a significant delay in tumor growth and strong protection again re-challenge.
In response, the preceding arguments were not persuasive for the reasons provided above. Additionally, the arguments regarding results of the instant method are not claimed limitations and therefore have not been examined on the merits. Additionally, Applicant is advised to consult MPEP 2112 (I).
Unexpected results: (a) "These mice completely rejected a lethal re-challenge with Bl6OVA cells and remained tumor free 300 days post initial tumor challenge."; (b) In contrast, no protective immunity was observed for mice that were unimmunized or immunized with WTL alone or WTL+LPS. See, specification as originally filed, e.g., at page 79, lines 8-12; and Figure 3A. Similar results were observed in additional cancer models as well (see, specification as originally filed, e.g., at page 81, lines 12-20; and Figure 9B) and using alternative TLR ligands (see, specification as originally filed, e.g., at page 81, lines 21-23; and Figure 3G).
In response, applicant arguments regarding unexpected results are drawn to limitations not claimed (e.g., protective immunity). In the interest of complete response, briefly, it is noted that while the results of Fig 9B are recited (LPS vs LIP+PGPC), that there is no control with LPS and other phosphocholine lipids. Further, the results in Fig 9A that include LPS+OxPAPC as well as LPS+PGPC groups would be expected based on the teachings of Zanoni (e.g., that LPS+PGPC activated DCs and Macrophages, whereas LPS+OxPAPC was only found to activate DCs) and the methods of WO302 (see rejections and responses to arguments above for details). Additionally, Applicant is further advised to consult MPEP 2112(I). For these reasons, the results provided are not considered to be unexpected in view of the teachings of WO302 and Zanoni.
Applicant arguments have been thoroughly reviewed but are not persuasive. The rejection(s) of claim(s) 1-2, 4-8, 11-20, 22-26, and 28-33 are maintained.
Conclusion
No claims are currently allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
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