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 .
Applicant's amendment and remarks, filed 11/25/25, are acknowledged.
Claims 1-7, 11, 18, and 20 have been amended.
Claims 22-25 have been added.
Claims 1-8, 10-13, 15-16, 18, and 20-25 are pending and are under examination.
Acknowledgment is made of applicant's claim for domestic priority under 35 U.S.C. 119(e). However, the provisional application USSN 62/937,075 upon which priority is claimed fails to provide adequate support under 35 U.S.C. 112 for the present claims. The ‘075 application discloses culturing dendritic cells with a non-canonical inflammasome activating lipid, but dos not disclose “priming the dendritic cells with a TLR ligand ex-vivo”, or the genus of TLR ligands encompassed in the present claims. Consequently, the claims have been accorded the priority of the filing date of the PCT application, i.e. 11/18/20.
Applicant’s arguments filed 11/25/25 have been fully considered, but they are not persuasive.
Applicant argues that the claims are entitled to priority since the ‘075 application discloses priming with a TLR ligand on pages 41, 46, 51-52. However, in the pages cited the Applicant, the ‘075 application teaches using LPS in certain experiments, while the present claims encompass any TLR ligand. LPS is species of TLR ligand, but it is well established that a species does not provide adequate support for the broader genus of TLR ligands encompassed by the present claims. Consequently, the claims have been accorded the priority of the filing date of the PCT application, i.e. 11/18/20.
The rejections under 112b are withdrawn in view of Applicant’s claim amendments.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-7, 10-13, 15-16, 18, and 20-24 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2021071977 (of record).
WO 2021071977 teaches a method of generating a population of dendritic cells used for therapy, wherein the method comprises culturing immature dendritic cells with a TLR agonist, such as LPS (i.e. priming), followed by culturing with an inflammation activating lipid to produce mature, hyperactivated dendritic cells (see page 21-22, in particular). WO 2021071977 teaches that the immature dendritic cells are living cells obtained from a donor (see page 18, in particular). WO 2021071977 teaches further contacting the dendritic cells with an antigen prior to, during, or subsequent to maturation (see page 26, in particular). WO 2021071977 teaches that the inflammation activating lipid can be one or more of oxPAPC, PGPC, KOdiA-PC, HOOA-PC or KOOA-PC (See page 9 and 25, in particular). WO 2021071977 teaches that the antigen can be a tumor antigen, tumor cell lysate, or viral or bacterial antigen (see page 26, in particular). WO 2021071977 teaches that the tumor antigen or whole tumor lysate can be from a biopsy sample of a cancer patient and that the dendritic cells can be autologous dendritic cells (i.e. autologous, cancer immunogen See page 27, in particular). WO 2021071977 teaches that the resulting dendritic cells can be administered to induce an immune response to treat cancer in a subject (see page 28, 34-36, in particular). WO 2021071977 teaches administering the dendritic cells to the treat human subjects (See page 4, 30, 35, 37, in particular). WO 2021071977 teaches obtaining the immature dendritic cells by isolation from the blood (i.e. harvesting in vivo differentiated dendritic cells), or by harvesting progenitor cells from a donor, including bone marrow (i.e. bone marrow derived), and culturing the progenitor cells to induce differentiation into immature dendritic cells (see page 18, in particular). WO 2021071977 teaches combination treatment of cancer comprising administering the dendritic cells in combination with chemotherapy drugs (see page 37, in particular). WO 2021071977 teaches an embodiment wherein the LPS and inflammatory activating lipid can be added to the dendritic cells simultaneously (See page 38,40 in particular). Regarding claims 23-24, WO 2021071977 teaches that the immature dendritic cells can be provided by enrichment from peripheral blood by density gradient centrifugation, and this would inherently include all DC types present in the blood, including cDC1.
Applicant’s arguments filed 11/15/25 have been fully considered, but they are not persuasive.
Applicant argues that the claims are entitled to a priority date of 11/18/19, and therefore the reference is not prior art because WO 2021071977 has a filing date of 10/7/20, and the provisional application, filed 10/8/19, upon which priority is claimed in WO 2021071977, does not disclose PGPC, as recited in amended claim 1. Regardless of what the provisional application in the prior art may or may not disclose, the present claims are given a priority date of 11/18/20 for the reasons set forth above. WO 2021071977 has a filing date of 10/7/20, which is before the effect filing date of the instant application. Thus, the reference still qualifies as prior art as of its filing date under 102 (a)(2) and the rejection is maintained.
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.
Claim 1-7, 10-13, 15-16, 18, and 21-22 is/are rejected under 35 U.S.C. 103 as being unpatentable WO 2004/076651, in view of Zanoni, 2017 (of record) and US (of record).
WO 2004/076651 teaches a method of producing a population of therapeutic dendritic cells comprising obtaining a population of living dendritic cells from a donor, culturing the dendritic cells with LPS ex-vivo to induce maturation, and loading the dendritic cells with an antigen (i.e. an immunogen, see pages 7, 14, in particular). WO 2004/076651 teaches administering the dendritic cells to a subject to induce an immune response or to treat cancer in a subject (see page 18, 20, in particular). WO 2004/076651 teaches that the subject is a human subject, and that the dendritic cells are obtained from a donor by harvesting monocytes (i.e. progenitor cells) and culturing said monocytes ex vivo under conditions to induce differentiation (see paragraph 29 and pages 9-11, in particular). WO 2004/076651 teach that the antigen is a bacterial antigen, a viral antigen, a whole tumor cell lysate or antigens isolate from tumors (see page 15, in particular). WO 2004/076651 teaches that the antigen is from a biopsy sample form a cancer patient and that the dendritic cells are also from the cancer patient (i.e. autologous, see pages 10 and 16, in particular). WO 2004/076651 teaches that dendritic cells can also be isolated directly from peripheral blood (i.e. from in vivo differentiated dendritic cells, see page 2, in particular). WO 2004/076651 also teaches bone marrow derived dendritic cells (see paragraph 5, in aprticualr0> and 17WO 2004/076651 teaches that combination therapy can be performed for treating cancer, including using chemotherapy (See paragraph 12, in particle).
The reference differs from the claimed invention in that it does not explicitly teach culturing the dendritic cells with oxPAPC.
Zanoni teaches that oxPAPC promotes activation of LPS matured dendritic cells, leading to dendritic cell hyperactivation with retained viability and release of inflammatory cytokines (see page 698 and 700, in particular). Zanoni teach treating dendritic cells with LPS first (i.e. priming) and subsequently contacting dendritic cells with oxPAPC, or alternatively, simultaneously contacting dendritic cells with said LPS and oxPAPC (see pages 698-700 and 708 in particular). Zanoni teach dendritic cells that are isolated from the spleen (i.e. in vivo differentiated), or differentiated from progenitor cells (see page 700-702). Zanoni teaches oxPAPC includes PGPC and POVPC (See page 704, in particular). Zanoni teach that LPS and oxPAPC are superior induces of adaptive immunity than LPS alone (see page 708, in particular).
The ’414 publication teaches that oxPAPC induces responses within dendritic cells that promote their survival and ability to activate T cells (see page 1, in particular). The ‘414 publication teaches that oxPAPC synergizes with microbial products, such as TLRs, which function together to hyperactive dendritic cells leading to induce a more robust activation of antigen specific T cells (See page 1, in particular). The ‘414 publication teaches that said oxPAPC can be used as immunogenic compositions with an immunogen to elect an immune response and activate dendritic cells in a human subject (See pages 1-2, in particular). The ‘414 publication teaches oxPAPC includes HOdiA-PC (see page 2, in particular). The ‘414 publication teaches immunogens including viral antigens or tumor antigens and treating human subjects (see page 2 and 7, in particular). The ‘414 publication exemplifies the dendritic cell activation using living dendritic cells obtained from a donor that are cultured with LPS (priming) and subsequently treated with oxPAPC (see page 14-19, in particular). The ’414 publication also teaches an embodiment wherein the dendritic cells are co-treated at the same time (i.e. simultaneously) with LPS and oxPAPC (See page 19, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include oxPAPC simultaneously with, or after LPS maturation, as taught by the ‘414 publication and Zanoni, in the method of providing LPS matured dendritic cells of WO 2004/076651. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because Zanoni and the ’414 publication teaches that oxPAPC induces responses within dendritic cells that promote their survival and ability to activate T cells and that oxPAPC synergizes with microbial products, such as TLRs, which function together to hyperactive dendritic cells leading to induce a more robust activation of antigen specific T cells. Regarding claims 23-24, the references teach using spleen dendritic cells or dendritic cells provided from peripheral blood by density gradient centrifugations, and this would include all DC types present in the blood or spleen, including cDC1.
Applicant’s arguments filed 11/15/25 have been fully considered, but they are not persuasive.
Applicant argues that the references do not teach priming the dendritic cells with a TLR ligand ex-vivo and culturing the primed dendritic cells with PGPC.
Zanoni and the ‘414 publication both teach a priming step with oxPAPC/PGPC that can be performed in vitro/ex-vivo to increase dendritic cell activation. For example, Zanoni teaches isolating dendritic cells and contacting them ex-vivo a TLR agonist and culturing the primed dendritic cells with oxPAPC, and teaches that oxPAPC types include PGPC. Zanoni teaches the advantages of doing so, including that it promotes survival and T cell activation by the dendritic cells, leading to more robust activation of antigen specific T cells. Therefore, the ordinary artisan would be motivated to include a oxPAPC/PGPC activation step in the method of producing dendritic cells ex-vivo for cancer therapy taught by WO 2004/076651 to achieve the advantages taught by Zanoni and the ‘414 publication.
Applicant argues that the present application describes how hyperactive dendritic cells can be generated ex-vivo and used for adoptive cell therapy to induce an anti-tumor immune response.
As an initial matter, at least claim 1 does not require adoptive cell therapy. Regardless, the cited refences make obvious administration of dendritic cells for inducing an anti-tumor immune response and for cancer therapy for the reasons set forth above.
Claim 8 is rejected under 35 U.S.C. 103(a) as being unpatentable over WO 2021071977, OR over WO 2004/076651, Zanoni and US 2018/0318414, as applied to claim 1 above, and further in view of Santin, 2008
The teachings of WO 2021071977, or WO 2004/076651, in view of Zanoni and US 2018/0318414 are discussed above.
They do not explicitly teach HPV antigens.
Santin teach that dendritic cells can be loaded the HPV antigens, which are antigens from an infectious agent associated with development of cervical cancer. Santin teach that HPV loaded dendritic cells are useful as a vaccine.
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to apply the teachings of Santin, and use HPV as antigen/immunogen in the method of WO 2021071977, or in the method made obvious by WO 2004/076651, in view of Zanoni and US 2018/0318414. One of ordinary skill in the art at the time the invention was made would have been motivated to do so, and have a reasonable expectation of success, because Santin teaches that said HPV antigens are useful for loading dendritic cells for producing a vaccine.
Applicant argues that the claims are not obvious for the reasons set forth above.
The claims stand rejected for the same reasons set forth above.
The following are new grounds of rejection necessitated by Applicant’s’ claim amendments
Claim 22-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2010/0272700, in view of Zanoni, 2017 (of record) and US 2018/0318414 (of record).
The ‘700 publication teaches a method of producing a population of therapeutic dendritic cells comprising obtaining a population progenitor cells from a subject (i.e. living cells from a cell donor) and culturing the progenitor cells ex-vivo withFlt3-L under conditions under which the progenitor cells differentiate into dendritic cells, and further treating the dendritic cells with an agent that promotes DC1 polarization, such as TLR agonists including LPS (i.e. “priming”, see paragraphs 1-14, 27, 85, 88-92, Fig. 5, 19 and 29). The ‘700 publication teaches that said dendritic cells are conventional dendritic cells (cDC) and as the reference teaches they are also DC1 polarized, this meets the limitation of cDC1 as recited in claim 24. The ‘700 publication teaches loading the dendritic cells with a tumor antigen (i.e. cancer immunogen, see paragraphs 94-96, in particular). The ‘700 publication teaches that the progenitor cells are derived from bone marrow, i.e. the dendritic cells are bone marrow derived, see paragraph 63, in particular).
The reference differs from the claimed invention in that it does not explicitly teach culturing the dendritic cells with oxPAPC.
Zanoni teaches that oxPAPC promotes activation of LPS matured dendritic cells, leading to dendritic cell hyperactivation with retained viability and release of inflammatory cytokines (see page 698 and 700, in particular). Zanoni teach treating dendritic cells with LPS first (i.e. priming) and subsequently contacting dendritic cells with oxPAPC, or alternatively, simultaneously contacting dendritic cells with said LPS and oxPAPC (see pages 698-700 and 708 in particular). Zanoni teach dendritic cells that are isolated from the spleen (i.e. in vivo differentiated), or differentiated from progenitor cells (see page 700-702). Zanoni teaches oxPAPC types including PGPC or POVPC (See page 704, in particular). Zanoni teach that LPS and oxPAPC are superior induces of adaptive immunity than LPS alone (see page 708, in particular).
The ’414 publication teaches that oxPAPC induces responses within dendritic cells that promote their survival and ability to activate T cells (see page 1, in particular). The ‘414 publication teaches that oxPAPC synergizes with microbial products, such as TLRs, which function together to hyperactive dendritic cells leading to induce a more robust activation of antigen specific T cells (See page 1, in particular). The ‘414 publication teaches that said oxPAPC can be used as immunogenic compositions with an immunogen to elect an immune response and activate dendritic cells in a human subject (See pages 1-2, in particular). The ‘414 publication teaches oxPAPC includes HOdiA-PC (see page 2, in particular). The ‘414 publication teaches immunogens including viral antigens or tumor antigens and treating human subjects (see page 2 and 7, in particular). The ‘414 publication exemplifies the dendritic cell activation using living dendritic cells obtained from a donor that are cultured with LPS (priming) and subsequently treated with oxPAPC (see page 14-19, in particular). The ’414 publication also teaches an embodiment wherein the dendritic cells are co-treated at the same time (i.e. simultaneously) with LPS and oxPAPC (See page 19, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include oxPAPC simultaneously with, or after LPS/TLR maturation, as taught by the ‘414 publication and Zanoni, in the method of providing dendritic cells of the ‘700 publication. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because Zanoni and the ’414 publication teaches that oxPAPC induces responses within dendritic cells that promote their survival and ability to activate T cells and that oxPAPC synergizes with microbial products, such as TLRs, which function together to hyperactive dendritic cells leading to induce a more robust activation of antigen specific T cells.
Claim 22-25 is/are rejected under 35 U.S.C. 103 as being unpatentable WO 2021071977, in view of US 20030077263.
The teachings of WO 2021071977 are described above.
The reference differs from the claimed invention in that it does not explicitly teach FLT3-L.
The ‘263 publication teaches that dendritic cells can be differentiated ex-vivo for use as tumor vaccines, and that FLT3-L can be used as a dendritic cell differentiation factor for producing dendritic cells from CD34+ bone marrow derived cells (See paragraphs 6, 18-20, and 30, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use FLT3-L, as taught by the ‘263 publication, as a dendritic cell differentiation agent for in the method of WO 2021071977 wherein dendritic cells are differentiated from bone marrow progenitor cells. Doing so would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385). Furthermore, using FLT3-L to provide bone marrow derived dendritic cells, are made obvious above, would also provide cDC1 dendritic cells, since the instant specification discloses that this is a latent property that flows naturally from differentiation of bone marrow precursors in the presence of FLT3-L.
No claim is 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker, can be reached at telephone number 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644