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 .
Response to Amendment
In the amendment filed on 12/16/2025 Applicant amended claims 1, 11 and 23. Claims 1-3, 5-7, 9, 11-13, 20, 23-26, 28-30, 32 and 35 are pending; claims 24-26, 28-30, 32 and 35 remain withdrawn from prosecution for being drawn to non-elected subject matter. Claims 1-3, 5-7, 9, 11-13, 20 and 23 are examined.
Priority
Applicant’s arguments regarding priority were persuasive and the priority is recognized to Provisional Patent Application No. 62/946,934, filed on December 11, 2019.
Withdrawn claim objection/rejections
The objection to claim 11 is withdrawn in view of the amendment to the claim.
The rejection of claims 1-3 and 20 under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. is withdrawn in view of the amendments to the claims.
Maintained and new claim rejections necessitated by amendment
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 7, 9, 12, 13 and 23 remain and 1-3, 11 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang in view of Wu et al. and Clappaert et al. (all cited in the previous Office action).
The claims are drawn to a personalized tumor vaccine comprising:
(a) a phagocytosis stimulating agent,
(b) an immunostimulatory adjuvant, and
(c) attenuated cancer cells,
wherein the phagocytosis stimulating agent is integrated into a cell membrane of the
attenuated cancer cells, wherein the personalized tumor vaccine, when administered to an individual in need thereof, is effective to activate an immune response. The attenuated cancer cells are obtained from a solid or liquid tumor of the individual. The phagocytosis stimulating agent may be a mannan, wherein the mannan is conjugated to a BAM. The immunostimulatory adjuvant may be a R-848, a poly (I:C), an LTA, or an anti-CD40 antibody
Zhang teaches cancer vaccines utilizing autologous tumor cells from patients (thus personalized) (p.260). These cancer vaccines may comprise:
(a) structures that attract phagocytosis markers (comprise scaffolds or
microparticles carrying or associated with tumor cells, which may be attached to PEG) (p. 261, p.266);
(b) an adjuvant to stimulate an immune reaction co-located or administered with the processed tumor cells (p.264);
(c) irradiated (attenuated) autologous tumor cells (p. 260, p. 261, p.264).
The source of autologous cells are solid tumor (Table 1). Anti-CD40 may be used for improved targeting specificity, but also for the capacity to enhance antigen cross-presentation (p. 262).
The teachings of Zhang were silent about the phagocytosis stimulating agent being integrated into a cell membrane of the attenuated cancer cells, (a) a mannan, wherein the mannan is conjugated to a BAM, (b) a R-848, a poly (l:C), and an
LTA.
Wu discloses a novel ligand, mannan-PEG-PE (abstract) conjugated to
a BAM (PEG-phosphatidyl ethanolamine) conjugated to mannan, wherein PEG-PE is identified as a membrane linker suitable as a BAM in [0062] of the instant application (p. 1). Thus, the mannan-PEG-PE of Wu , by its structure, would be able to be anchored in the cell membrane.
Clappaert discloses a TLR7/8 agonist, R848, a poly (l:C), a potent TLR3 agonist,
and LTA (an TLR2/6 agonist) and an anti-CD40 antibody to activate macrophages and
antigen-presenting cells. (pages 4-6).
It would have been obvious for a person of ordinary skill in the art, at the time of the invention was filed to have modified the vaccine as disclosed by Zhang to incorporate a mannan conjugated to a BAM, as taught by Wu, with a reasonable expectation of success. This is because Zhang discloses a phagocytosis stimulating agent, Wu discloses a mannan ligand that increases phagocytosis of nanoparticles to which it is conjugated and may be integrated in the cell membrane, and this combination would provide the capability of targeting phagocytotic cells for which mannan would stimulate phagocytosis of the tumor cells. Further, a person of ordinary skill in the art, at the time of the invention was filed, to have modified the vaccine as disclosed by Zhang to incorporate R-848, poly l:C, LTA, and an anti-CD40 antibody, as taught by Clappaert with a reasonable expectation of success. This is because Zhang disclose immunostimulatory adjuvants, Clappaert discloses the synergistic benefit of an immunostimulatory cocktail of TLR agonists, including R-848, poly l:C, and LTA, and the immunostimulatory effect of anti-CD40 agonist antibodies, and this combination would provide the capability of using these adjuvants to improve the immune response to the tumor cell vaccine. A skilled artisan would thus use knowledge know in the art to try obtaining a personalized vaccine composition and would have a reasonable expectation of success in doing so. This is because the elements of the vaccine compositions were known and used in the art for vaccination purposes. A person of ordinary skill in the art is always motivated to pursue the known options within her or his technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
On page 8 of the Remarks Applicant argues that: “In fact, Zhang is a review article of discussing several different vaccine platforms including: DNA, mRNA, peptide, DC vaccines, tumor cell vaccines, nanoparticle based systems, scaffolds, etc. Given that Zhang does not disclose a single embodiment of "a personalized tumor vaccine," and its recited elements, Zhang cannot anticipate claims 1-3 and 20”.
The arguments were carefully considered but not found persuasive because as indicated in the Non-Final rejection, the reference teaches cancer vaccines utilizing autologous tumor cells from patients (p.260).
These cancer vaccines may comprise:
(a) structures that attract phagocytosis markers (comprise scaffolds or
microparticles carrying or associated with tumor cells, which may be attached to PEG) (p. 261, p.266);
(b) an adjuvant to stimulate an immune reaction co-located or administered with
the processed tumor cells (p.264);
(c) irradiated (attenuated) autologous tumor cells (p. 260, p. 261, p.264).
The source of autologous cells (hence individualized vaccines) are solid tumor (Table 1). Anti-CD40 may be used for improved targeting specificity, but also for the capacity to enhance antigen cross-presentation (p. 262).
Further (on pages 9-10), Applicant argued against the Wu et al. and Clappaert et al. references individually: “…there is no prima facie case of obviousness based on Zhang in view of Wu and Clappaert because none of the references teach the structure of attenuated tumor cells having an immunostimulatory agent integrated into the cell membrane as recited in amended claims 1 and 23. Further, Wu discloses gene delivery using nanoparticle to specific cell types (i.e., liver macrophages), which is unrelated to a tumor vaccine”.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The arguments were carefully considered but not found persuasive because all the component elements of the composition claimed were known in the art and used for personalized vaccine. The limitation added to claims 1 and 23, that the phagocytosis stimulating agent is integrated into a cell membrane of the attenuated cancer cells, is present in the teaching in the sense that a mannan conjugated to a BAM having the same structure as claimed instantly, is indeed used by Wu for use with nanoparticles, However, due to the same structure, the mannan-BAM of Wu et al. would be expected to behave similarly and integrate in the cell membrane.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (cited supra) in view of Wu and in further view of Hege et al. (al cited in the previous Office actions).
The claim add the limitation that
wherein the attenuated cancer cells are prepared by:
(a) harvesting cancer cells from a biopsy of a site of tumor from the individual,
(b) culturing the harvested cancer cells to a therapeutically relevant amount, and
(c) irradiating the cultured cancer cells.
The teachings of Zhang and Wu were presented supra and they were silent about harvesting the cancer cells to a therapeutically relevant amount, and irradiating the cultured cancer cells.
Hege discloses establishing actively replicating tumor cell cultures prior to retroviral transduction (page 329), and irradiating the tumor cells after genetic modification, which in turn took place after culturing (p. 329).
Regarding claim 6, which claims a range of cell concentration between 103-107, it is submitted the concentration is considered routine optimization and it would have been within the skill of an ordinary artisan.
It would have been obvious to a person of ordinary skill in the art, at the time of filing, to have modified the vaccine as disclosed by Zhang together with the teachings of Wu and incorporate culturing the harvested cancer cells to a therapeutically relevant amount and irradiating the cultured cancer cells, as taught by Hege, as Zhang discloses a vaccine composed of autologous tumor cells, Hege discloses a vaccine composed of autologous tumor cells that have been cultured and irradiated, and this combination would provide the capability of using a small amount of initial cells to create a larger therapeutic dose, and to allow additional doses if necessary.
On page 11 of the Remarks Applicant argues that: “Hege does not cure the deficiencies described above with respect to Zhang. Specifically, Zhang does not disclose the recited tumor vaccine as recited in amended claims 1 and 23. Hege does not disclose the recited elements of amended claims 1 and 23. Accordingly, claims 1 and 23 along with their dependent claims are patentable over the cited references”.
The arguments were carefully considered but not found persuasive because the references must be considered together and not individually. As shown above, claims 1 and 23 are obvious in view of Zhang and Wu. The limitation added by the instant claims is covered by Hege, which shows that the tumor cells that are irradiated are viable albeit attenuated.
Conclusion
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.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647