DETAILED ACTION
Status of the Claims
Claims 1-3 and 6-18 are pending in the instant application. Claims 12 and 15-17 have been withdrawn based upon Restriction/Election as discussed below. Claims 1-3, 6-11, 13-14 and 18 are being examined on the merits in the instant application.
Advisory Notice
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
All rejections and/or objections not explicitly maintained in the instant office action have been withdrawn per Applicants’ claim amendments and/or persuasive arguments.
Priority
The U.S. effective filing date has been determined to be 06/16/2020, the filing date of PCT/CN2020/096302. Applicant's claim for a foreign priority date of, 03/26/2020, the filing date of document CN202010223563.2, is acknowledged, however no English translation of said foreign priority document has been provided such that the examiner can confirm written description (112(a)) support therein. Accordingly, foreign priority to this document cannot be afforded at this time.
Information Disclosure Statement
The information disclosure statements submitted on 11/26/2025 was filed after the mailing date of the first office action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the Examiner.
Claim Objections
Claim 10 is objected to because the claim recites three Markush groups (1) organic synthetic polymer, (2) natural polymer materials, and (3) inorganic materials. Item (1) organic synthetic polymer fails to include a proper conjunction between the last two elements (e.g. “polyamino acid and synthetic peptides”). Appropriate correction is required.
Claim 12 is objected to because the claim has been withdrawn based on Restriction/Election, as previously discussed1, however the status identifier does not reflect the claim status as withdrawn (MPEP §714 – 37 CFR §1.121(c)).
Claim Rejections - 35 USC § 112(d)
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 13 and 18 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 1 has been amended to recite “wherein the solubilizer is urea or guanidine hydrochloride” and claim 13 recites “water solution containing a solubilizer or an organic solvent” which are broader than base claim which limited “the water-insoluble components are converted to be soluble in water solution containing a solubilizer before loading; wherein the solubilizer is urea or guanidine hydrochloride.”
Claim 13 is further rejected as depending from subsequent claim 18. MPEP 608.01(n)(III) requires a claim in dependent form to “reference a claim previously set forth”. When examining a dependent claim, the examiner should determine whether the claim complies with 35 U.S.C. 112(d), which requires that dependent claims contain a reference to a previous claim in the same application, specify a further limitation of the subject matter claimed, and include all the limitations of the previous claim. If the dependent claim does not comply with the requirements of 35 U.S.C. 112(d), the examiner should reject the dependent claim under 35 U.S.C. 112(d) as unpatentable rather than objecting to the claim. See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92, 79 USPQ2d 1583, 1589-90 (Fed. Cir. 2006).
Claim 1 has been amended to recite “wherein the solubilizer is urea or guanidine hydrochloride” and claim 18 recites “water solution containing a solubilizer or organic solvent” (in line 8) which are broader than base claim which limited “the water-insoluble components are converted to be soluble in water solution containing a solubilizer before loading; wherein the solubilizer is urea or guanidine hydrochloride.”
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Arguments:
Applicant's arguments filed 11/26/2025 have been fully considered but they are not persuasive.
Applicant’s indication that claim 13 has been amended to depend from claim 18 does nothing to resolve the fact that “a solublizer or an organic solvent” is broader in scope than the base claim 1 which requires a solubilizer that is urea or guanidine HCl. Additionally, it improper for a claim to depend from a subsequent claim, particularly MPEP 608.01(n)(III) requires a claim in dependent form to “reference a claim previously set forth”.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3, 6-11, 13-14 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over FUCHS (US 2013/0302409; published November, 2013) in view of Nam et al. (“Lysozyme Microencapsulation Within Biodegradable PLGA Microspheres: Urea Effect on Protein Release and Stability,” 2000; John Wiley & Sons; Biotechnology and bioengineering Vol. 70, No. 3, pp. 270-277) Mueller et al. (“Coencapsulation of tumor lysate and CpG-ODN in PLGA-microspheres enables successful immunotherapy of prostate carcinoma in TRAMP mice,” 2012; ELSEVIER; Journal of Controlled Release, Vol. 162, pp. 159-166) Iranpour et al. (“Enhanced stimulation of anti-breast cancer T cells response by dendritic cells loaded with poly lactic-co-glycolic acid (PLGA) nanoparticle encapsulated tumor antigens,” 2016; BioMed Central; Journal of Experimental & Clinical Cancer Research, Vol. 35, No. 168, pp. 1-11) and Kuwada et al. (“Insoluble Fraction of Tumor Cell Homogenate Is a Useful Material for Eliciting Cytotoxic T Lymphocytes: A Unique Method for Protein Solubilization,” 2011; Anticancer Research, Vol. 31, pp. 881-892).
Applicants Claims
Applicant claims a whole-cell components delivery system comprising of a nano-sized or micron-sized particle and whole-cell components loaded on the particle, wherein the whole-cell components are water-soluble components and water-insoluble components of a whole cell in a cell or tissue; wherein the water-soluble components comprise a supernatant of a cell lysate from the whole cell;, wherein the water-insoluble components are a precipitate portion prepared by centrifuging the cell lysate, wherein the water-soluble components are components which can be dissolved in pure water or water solution without a solubilizer; wherein the water-insoluble components are converted to be soluble in a water solution containing a solubilizer before loading; wherein the solubilizer is urea or guanidine hydrochloride; wherein the cell or tissue is cancer cell or tumor tissue (instant claim 1).
With regard to the process steps of claims 1-2 and 13, “Even though product-by process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” See MPEP § 2113.
Determination of the scope
and content of the prior art (MPEP 2141.01)
FUCHS teaches methods and compositions for cancer immunotherapy (title, see whole document) including “a method for treating an abnormal cellular proliferation in a patient comprises the steps of (a) administering at or near the site of the abnormal cellular proliferation an effective amount of a composition that promotes a therapeutic immune response to the abnormal cellular proliferation comprising (i) a polymeric particle; and (ii) optionally one or more therapeutic agents encapsulated in or incorporated on or into the polymeric particle; and (b) ablating the abnormal cellular proliferation.” (abstract).
FUCHS teaches that: “The present invention is based, at least in part, on the discovery that biodegradable nanoparticles engineered to function as immunological adjuvants stimulate the T cell response to cancer in vivo by activating antigen-presenting cells (APCs) in the tumor microenvironment and by ferrying antigens into APCs for processing and presentation to tumor reactive T cells.” ([0004]).
FUCHS teaches that: “In certain embodiments, the polymeric particle comprises poly lactide (PLA), polyglycolide (PGA), poly (lactic-co-glycolic acid) (PLGA) or co-polymers thereof. In a specific embodiment, the polymeric particle is PLGA.” ([0008]).
FUCHS teaches that: “In other embodiments, the compositions of the present invention further comprise one or more immunological adjuvants encapsulated in or incorporated on or into the polymeric particle.” ([0009]).
FUCHS teaches that: “In a more specific embodiment, the one or more therapeutic agents is an antigen preferentially expressed by the abnormally proliferating cell.” ([0009]). FUCHS teaches that: “Moreover, tumor antigens can be (a) full length molecules associated with cancer cells, (b) homologs and modified forms of the same, including molecules with deleted, added and/or substituted portions, (c) fragments of the same, and (d) extracts or lysates of tumor cells.” [emphasis added]([0054])(instant claim 1, “wherein the cell or tissue is cancer cell or tumor tissue.”). FUCHS claims a method including administering at or near the cancer site an effective amount of a composition that promotes a therapeutic immune response to the cancer (claim 1), wherein the composition comprises (a) a polymeric particle; and (b) optionally one or more therapeutic agents encapsulated in or incorporated on or into the polymeric particle (claim 5) the polymer being PLGA (claims 6-7), “the composition further comprises one or more immunological adjuvants encapsulated in or incorporated on or into the polymeric particle.” (claim 8), and “the one or more therapeutic agents is a cancer antigen.” (claim 17).
FUCHS teaches hot melt encapsulation and solvent removal technique both result is spheres ([0043]-[0044])(instant claim 11).
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of FUCHS is that FUCHS does not expressly teach using urea in their compositions.
Nam et al. teaches that: “Lysozyme was encapsulated within biodegradable poly(D,L-lactide-co-glycolide) microspheres by a double emulsion solvent evaporation method for studying its release mechanism associated with protein stability problems. When urea, a protein unfolding agent, was added into the incubation medium lysozyme release rate from the microspheres increased with the increase in urea concentration. The enhanced lysozyme release was attributed to the suppression of protein aggregation, to the facilitated diffusion of unfolded lysozyme by an efficient reptile motion of unfolded protein molecules through porous channels in microspheres, and to the largely decreased extent of nonspecific protein adsorption onto the enlarged surface area of degrading polymer microspheres in the presence of urea. Encapsulating lysozyme in an unfolded form within PLGA microspheres was attempted by using urea as an excipient. This new urea-based formulation exhibited a more sustained lysozyme release profile than the control formulation, and released lysozyme from the microspheres showed a much less amount of lysozyme dimer population while maintaining a correct conformation after refolding in the incubation medium. This study provides new insights for the formulation of protein encapsulated PLGA microspheres.” (abstract, see whole document).
Nam et al. concludes that: “It has been demonstrated that the addition of urea into the incubation medium dramatically increased the release rate of lysozyme from PLGA microspheres. The incomplete release behavior of lysozyme from microspheres was due to protein stability problems such as protein–protein aggregation and protein adsorption onto polymer surface. The increased lysozyme release in response to urea was attributed to the reptation-mediated diffusion of unfolded lysozyme through microporous channels within the polymer matrix and the reduced protein–polymer interaction. A better understanding of the fundamental aspects of incomplete protein release mechanism from microspheres led to a new urea-based formulation. This new formulation significantly suppressed the protein aggregation during formulation and achieved a more sustained release capability of lysozyme, with improved retention of biological activity after release.” (p. 276, col. 2, §Conclusion).
Iranpour et al. teaches that: “Cancer immunotherapy and vaccines are new therapeutic approaches which offer a promising treatment against cancer with minimum adverse effects. Cell-mediated immune mechanisms have been determined in breast cancers. These immune responses are induced by breast tumor cells and thus lead to a systemic anti-tumor immunity and regression of breast cancer. Therefore, immunotherapy may be effective in treating patients with breast cancer. This kind of therapy concentrates on the induction and enhancement of immune responses against tumors. In a limited number of malignancies in which tumor-associated antigens have been determined, antitumor vaccine strategies have proven to be partially effective, predominantly based on the loading of professional antigen-presenting cells (APCs), including DCs [7]. APCs are a group of cells that can process antigens of both endogenous (normal cell proteins, tumor or viral antigens) and exogenous origin (extracellular antigens). Using DCs which are the most potent APCs with the unique capability to induce primary immune responses against tumor-associated antigens in cancer treatment is a promising approach. In addition, vaccines act through DCs that induce, regulate and maintain T-cell immunity. Ex-vivo loaded DC based cancer vaccines study has been shown that this strategy is safe, well tolerated and capable of inducing cellular immune responses. DCs and macrophages are highly phagocytic cells, capable of taking up any particles with similar dimensions to the pathogens (up to 10 µm). Therefore, both large ‘micro-’ and small ‘nano-’ particles can efficiently be taken up by both cell types.” (p. 2, col. 1, 1st paragraph).
Iranpour et al. further teaches that: “In the recent years, biodegradable polymers, such as Poly (D,L-lactic-co-glycolic acid) (PLGA), have been studied for the fabrication of drug delivery systems and administration of vaccine antigens. PLGA is a FDA approved biodegradable polymer that have been widely used in production of biodegradable surgical sutures and the sustained delivery of drugs into humans. In this study, the effect of breast tumor lysate antigen encapsulated within PLGA NPs to enhance DC maturation and antigen-loaded mature DC stimulated T-cell immune responses against breast cancer have been investigated.” (p. 2, col. 1, 2nd paragraph).
Iranpour et al. teaches that: “NPs encapsulated with tumor lysate were able to stimulate specific T cells to produce larger quantities of Th1 and Th2-based cytokines including IFN-γ and IL-4, respectively. The higher concentrations of IFN-γ and IL-12 were detected in NPs encapsulated tumor lysate compared to tumor lysate and NPs alone. The results of this study provide evidence of principle that the whole tumor lysates can stimulate T cell-released cytokines, when delivered to DC in a particulate form.” [emphasis added](p. 10, col. 1, 3rd paragraph)(instant claim 1, “wherein the cell or tissue is cancer cell or tumor tissue.”).
Iranpour et al. further teaches that: “PLGA-NPs are attractive vehicles for protein antigen delivery for an effective stimulation and maturation of DCs, allowing not only an enhancement in antigen processing and immunogenicity or improvement of antigen stability, but also they improve the targeted delivery and slow release of antigens. Matured and stimulated DCs display the strong enhancement in their capacity to stimulate naive autologous T helper cells and secret the amount of the cytokines.” (p. 10, §Conclusions).
Mueller et al. teaches that: “In this study we used PLGA-MS with co-encapsulated tumor lysates and CpG oligodeoxynucleotides (CpG-ODN) as well as microencapsulated polyI:C in order to elicit anti-tumor responses. Immunization of mice with such mixtures of MS yielded substantial cytotoxic T cell (CTL) responses and interfered with tumor growth in TRAMP mice, a pre-clinical transgenic mouse model of prostate carcinoma, which has previously resisted dendritic cell-based therapy. As an important step towards clinical application of PLGA-MS, we could show that γ-irradiation of PLGA-MS sterilized the MS, without reducing their efficacy in eliciting CTL and anti-tumor responses in subcutaneous tumor grafts. Since PLGA is approved for clinical application, sterilized PLGA-MS containing tumor lysates and TLR ligands hold promise as antitumor vaccines against prostate carcinoma in humans.” (abstract, see whole document).
Mueller et al. teaches that: “An approach using lysate of melanoma tumors was pioneered in 1988 by Mitchell and colleagues. The tumor lysates were applied together with DETOX, a water-in-oil emulsion containing immunostimulatory adjuvants derived from bacteria. The vaccine Melacine® was launched by Corixa Corporation with a significant increase in relapse free survival in melanoma patients in first trials.” (p. 159, col. 2, 1st paragraph). And that: “The approach to deliver PCa tumor lysate pursued in this study relies on co-encapsulation of the lysates in biodegradable poly(D,L-lactide-co-glycolide) microspheres (PLGA-MS). The PLGA-MS system compares favorably with IFA and has been proven to be effective in vitro and in immunotherapy of syngeneic model tumors in mice. Antigens and TLR ligands microencapsulated in PLGA-MS are taken up by human and murine dendritic cells and macrophages very efficiently in vitro and in vivo without negatively influencing cardinal properties like migratory capacity, cytokine secretion or antigen presentation. The co-encapsulation of protein or peptide antigens and TLR ligands into PLGA-MS protects them from degradation and provides a long lasting depot for sustained and prolonged immune responses.” (p. 159, col. 2, 2nd paragraph).
Mueller et al. teaches that: “We and others could show that the co-encapsulation of the model antigen ovalbumin and CpG oligodesoxynucleotides (ODN) yields substantial cytotoxic T lymphocyte (CTL) responses as well as striking anti-tumor responses. These are excellent prerequisites for efficient in vivo loading of professional antigen presenting cells (APC) and priming of CTL mediated anti-tumor responses. In 2007 it was shown, that encapsulation of tumor cell lysate and subsequent injection leads to delayed tumor occurrence, even without the usage of any immune-stimulatory adjuvant. Other laboratories could show that encapsulation of endogenous antigens can break tolerance and that co-encapsulated tumor lysates with CpG-ODN led to impaired tumor growth in mice [19].We could further improve this system by adding a second Toll like receptor (TLR) ligand, separately encapsulated. This has been shown to influence DCs in terms of T helper (Th) cell polarization. (p. 160, col. 1, 1st paragraph).
Mueller et al. teaches that: “The best characterized mouse model to test immunotherapy of PCa is the transgenic adenocarcinoma mouse prostate (TRAMP) model. TRAMP mice are transgenic for the SV40 large T antigen expressed after puberty under the control of the rat probasin regulatory elements. Male TRAMP mice remain healthy until puberty (weeks 4 to 5). In the weeks thereafter TRAMP mice progressively develop prostate intraepithelial neoplasia, with documented progression to invasive carcinoma of epithelial origin, closely resembling the pathology of human PCa and subsequent metastasis formation.” (p. 160, col. 1, 2nd paragraph). And that: “Attempts to limit or abrogate tumor growth in male TRAMP mice with immunotherapy have been met with limited success. In particular, cellular immunotherapy with dendritic cells failed to elicit significant cytolytic responses when applied at the age of 9 weeks i.e. after the onset of tumor growth which was most likely due to the T cell tolerizing capacity of TRAMP tumors. In this study, we show that immunization of male TRAMP mice with PLGA-MS containing TRAMP prostate tumor lysate (PTL) and CpG oligonucleotides and PLGA-MS containing polyI:C at the age of 10 weeks is able to prevent or strongly reduce the growth of PCa in TRAMP mice. Given that PLGA is a material approved for clinical application and that PCa tissue from patients is often available, this approach holds promise to be tested in the clinical setting.” (p. 160, col. 1, 3rd paragraph).
Mueller et al. concludes that: “We have shown in a PCa mouse model, which very closely reflects the human disease, that immunotherapy with PLGA-MS containing autologous tumor lysates and TLR ligand is feasible, reproducible, and effective. As PLGA is a material approved for clinical application, as resected autologous PCa tissue is often available, and as sterilization by γ-irradiation is applicable, this straight forward approach deserves to be tested in a phase I clinical trial.” (p. 165, §Conclusions).
Kuwada et al. teaches that: “Dendritic cell (DC)-based cancer immunotherapy using tumor homogenate has been evaluated. In all previously reported cases, DCs have been pulsed with a soluble fraction (lysate) of the tumor homogenate. The aim of this study was the evaluation of DCs pulsed with solubilized insoluble fraction of tumor cells.” (abstract, see whole document).
Kuwada et al. teaches that: “Many methods for refolding of recombinant proteins have been developed, especially in the case of Escherichia coli expression systems. However, these methods are suitable only for specific target proteins and another device is necessary to accomplish solubilization of a mixture of proteins. A material was sought for solubilization from biogenic substances because these substances would show a low toxicity to DCs. The peptide bond frame forms hydrogen bonds with different parts of the frame and nucleotides form hydrogen bonds between the bases. The urea molecule then breaks the hydrogen bond between the nucleotide bases. When refolding of denatured protein is desired, it is usually temporarily dissolved in urea or guanidine hydrochloride solution. When the protein is continuously dialyzed against a physiological buffer, in many cases it reverts to an insoluble form. This phenomenon led the authors to believe that materials able to form hydrogen bonds must play a key role in solubilization. Therefore, it was hypothesized that monomeric nucleotides may interact with proteins and render them soluble in a physiological solution.” (p. 882, col. 1, 2nd paragraph). And further that: “For solubilization of the insoluble fraction of cell homogenates, precipitate was dissolved in 8 M urea-PBS and the efficacy of solubilization was estimated by protein assays […].” (p. 883, col. 2, 2nd paragraph). Kuwada et al. teaches that: “We expect that electroloading DCs with the insoluble fraction of tumor cells will be a powerful tool for manipulating the immune system. This evidence suggests the usefulness of the tumor insoluble fraction for DC vaccination therapy, such as helper T-cell function and/or antitumor effect using a mouse model in vivo, to be tested in future clinical studies.” (p. 890, col. 2).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce a PLGA micro- or nano-particle composition encapsulating a tumor cell lysate containing antigens and further including surface antigens on the particle for cancer immunotherapy, as suggested by FUCHS, and further to incorporate urea, a protein unfolding agent, for improved stability and release characteristics (“formulation significantly suppressed the protein aggregation during formulation and achieved a more sustained release capability of lysozyme, with improved retention of biological activity after release”), and further to incorporate an antigen in the particle to improved the immunotherapy response, as suggested by Mueller et al., the particle being suitable targeted delivery and slow release of antigens, as suggested by Iranpour et al., for cancer immunotherapy, and further to include whole cell lysate including the insoluble fraction (e.g. precipitate) solubilized by urea or guanidine HCl, as suggested by Kuwada et al.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention to produce a tumor cell lysate incorporating urea (a known protein unfolding agent/solubilizer) and subsequent incorporation into a PLGA micro- or nano-particle for cancer immunotherapy. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
Response to Arguments:
Applicant's arguments filed 11/26/2025 have been fully considered but they are not persuasive.
The examiner acknowledges Applicants amendments however Applicants arguments do not clearly indicate any distinction over the cited combination of prior art. Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-3, 6-11, 13-14 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-16 and 19 of copending Application No. 18/028,084 (hereafter ‘084).
Instant claim 1 is discussed above.
Copending ‘084 claim 1 recites a targeting delivery system loaded with whole-cell components, wherein it is nano-sized or micron-sized particles with a targeting head on surface thereof, and the particles are loaded with whole-cell components of cancer cells or tumor tissues wherein, the whole-cell components are water-soluble components and water-insoluble components of whole cells in the cells or tissues; the water-insoluble components are solubilized with a solubilizer or a solubilizing solution containing a solubilizer; the targeting head bonds to molecules on the surface of specific cells or tissues to assist the particles to enter cells or tissues. ‘084 claim 2 recites the solublizer can be selected from one or more of urea, guanidine hydrochloride […].
The difference between the instantly rejected claims and the claims of copending ‘084 is that the claim of copending ‘084 do not expressly limit the solubilizer to urea or guanidine hydrochloride.
It would have been prima facie obvious before the effective filing date of the claimed invention that the instantly rejected claims are an obvious variant of the claims of copending ‘084 because urea and guanidine hydrochloride are suggested solubilizers. The skilled artisan would have been motivated to modify the claims of copending ‘084 and produce the instantly rejected claim because it would have been prima facie obvious to selected recited solubilizers. Furthermore, the skilled artisan would have had a reasonable expectation of success in producing the invention of the instantly rejected claims because it would have required no more than an ordinary level of skill in the art to utilize a known solubilizer such as urea and/or guanidine hydrochloride.
This is a provisional obviousness-type double patenting rejection.
Claims 1-3, 6-11, 13-14 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of copending Application No. 18/718,623 (hereafter ‘623) in view of FUCHS (US 2013/0302409; published November, 2013) in view of Nam et al. (“Lysozyme Microencapsulation Within Biodegradable PLGA Microspheres: Urea Effect on Protein Release and Stability,” 2000; John Wiley & Sons; Biotechnology and bioengineering Vol. 70, No. 3, pp. 270-277) Mueller et al. (“Coencapsulation of tumor lysate and CpG-ODN in PLGA-microspheres enables successful immunotherapy of prostate carcinoma in TRAMP mice,” 2012; ELSEVIER; Journal of Controlled Release, Vol. 162, pp. 159-166) Iranpour et al. (“Enhanced stimulation of anti-breast cancer T cells response by dendritic cells loaded with poly lactic-co-glycolic acid (PLGA) nanoparticle encapsulated tumor antigens,” 2016; BioMed Central; Journal of Experimental & Clinical Cancer Research, Vol. 35, No. 168, pp. 1-11) and Kuwada et al. (“Insoluble Fraction of Tumor Cell Homogenate Is a Useful Material for Eliciting Cytotoxic T Lymphocytes: A Unique Method for Protein Solubilization,” 2011; Anticancer Research, Vol. 31, pp. 881-892).
Instant claim 1 is discussed above.
Copending ‘623 claim 1 recites a dendritic cell cancer vaccine, wherein the dendritic cell cancer vaccine is obtained by activating dendritic cells in vitro with delivery particles loaded with cell components, wherein the delivery particles are nanoparticles and/or microparticles, the cell components are derived from water-soluble components and/or non-water-soluble components of cancer cells and/or tumor tissues, and the activating is co-incubating the delivery particles loaded with the cell components with the dendritic cells. ‘623 claim 5 recites the dendritic cell cancer vaccine according to claim 1, wherein the non-water-soluble components are loaded to the delivery particles after solubilization, and a solubilizer used is selected from at least one of urea, guanidine hydrochloride […]. ‘623 claim 6 recites the dendritic cell cancer vaccine according to claim 1, wherein immunopotentiating adjuvants are loaded inside the delivery particles, and/or the immunopotentiating adjuvants are loaded on the surfaces of the delivery particles.
The difference between the instantly rejected claims and the claims of copending ‘623 is that the claim of copending ‘623 do not expressly claim the species of particle (nanoparticles and/or microparticles), the adjuvants, the size/shape.
FUCHS teaches methods and compositions for cancer immunotherapy, as discussed above and incorporated herein by reference.
Nam et al. teaches Lysozyme was encapsulated within biodegradable poly(D,L-lactide-co-glycolide) microspheres by a double emulsion solvent evaporation method, and including urea, a protein unfolding agent, added into the incubation medium lysozyme, as discussed above and incorporated herein by reference.
Iranpour et al. teaches cancer immunotherapy and vaccines are new therapeutic approaches which offer a promising treatment against cancer with minimum adverse effects, as discussed above and incorporated herein by reference.
Mueller et al. teaches PLGA-MS with co-encapsulated tumor lysates and CpG oligodeoxynucleotides (CpG-ODN) as well as microencapsulated polyI:C in order to elicit anti-tumor responses, as discussed above and incorporated herein by reference.
Kuwada et al. teaches Dendritic cell (DC)-based cancer immunotherapy using tumor homogenate, as discussed above and incorporated herein by reference.
It would have been prima facie obvious before the effective filing date of the claimed invention that the instantly rejected claims are an obvious variant of the claims of copending 623 because it would have been prima facie obvious to utilize an established biodegradable polymer such as PLGA for the particles therein. The skilled artisan would have been motivated to modify the claims of copending ‘623 and produce the instantly rejected claim because one would have necessarily selected a material for the particles and PLGA was know. Furthermore, the skilled artisan would have had a reasonable expectation of success in producing the invention of the instantly rejected claims because it would have required no more than an ordinary level of skill in the art to produce a PLGA nano- or micro-particle composition encapsulating a cancer cell lysate (cell components including dendritic cells) in order to produce a cancer vaccine.
This is a provisional obviousness-type double patenting rejection.
Response to Arguments:
Applicant's arguments filed 11/26/2025 have been fully considered but they are not persuasive.
The examiner acknowledges Applicants amendments however Applicants arguments do not clearly indicate any distinction over the reference Application and/or the cited combination of prior art. Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Conclusion
Claims 1-3, 6-11, 13-14 and 18 are pending and have been examined on the merits. Claims 10 and 12 are objected to. Claims 13 and 18 are rejected under 35 U.S.C. 112(d); claims 1-3, 6-11, 13-14 and 18 are rejected under 35 U.S.C. 103; and claims are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim of copending Application Nos. 18/028,084 and 18/718,623. No claims allowed at this time.
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 IVAN A GREENE whose telephone number is (571)270-5868. The examiner can normally be reached M-F, 8-5 PM PST.
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/IVAN A GREENE/Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
1 Non-Final Rejection dated 08/27/2025, p. 2.