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 6/18/26, are acknowledged.
Claims 2, 7-8, and 17 have been amended.
Claims 2, 7-8, and 17 are pending and are under examination.
In view of Applicant’s’ claim amendments and 1.132 declarations, the previous grounds of rejection are withdrawn.
The following are new grounds of rejection necessitated by Applicant’s amendment
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 7-8, and 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 is directed a multivalent DC vaccine comprising ex-vivo generated mature DC loaded with a tumor complex antigen, wherein the tumor complex antigen comprises (a) a tumor cell lysate of B95-8 LCLS and (b) a lysate of C666-1 cells. The claims explicitly recite that the tumor complex antigens comprises two components (a) and (b), and that the DC vaccine comprises dendritic cells loaded with the tumor complex antigen. This would appear to at least some dendritic cells in the vaccine be loaded with both (a) and (b) lysates. However, the claim also recites product by process limitations wherein a first population of DCs are loaded with (a) and a second population of DCs are loaded with (b) and the two populations are mixed in equal amounts to provide the multivalent DC vaccine. This would appear to encompass a DC vaccine comprising DCs loaded with a) lysate only mixed with DCs loaded with b) lysate only. However, this is at odds with the above limitations, which seemingly require DCs loaded with a) and b). Therefore, the scope of the claim is unclear and indefinite. For the purposes of examination, the claims are being interpreted as encompassing dendritic cells loaded with lysates of both (a) and (b), as specifically recited in lines 2-6 of claim 2, but also encompassing a dendritic cell vaccine comprising an equal mixture of mature dendritic cells loaded with (a) only and mature dendritic cells loaded with (b) only.
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 2, 7-8, and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Herr, 2000, in view of Zyl, Feb. 2019, Tyagi, 2017, and WO 02/053176 (all of record).
Herr teaches mature dendritic cells that have been loaded with lysates from EBV infected B-LCL cells for use as a vaccine to treat patients suffering from EBV associated tumor such as nasopharyngeal carcinoma (i.e. a method of use of a tumor lysate in preparation of a drug, see pages 1857 and 1863, in particular). Herr teaches that the B-LCL cells are immortalized by transformation with B95.8 EBV strain (see page 1858, in particular). Herr teaches producing the dendritic cells by culturing PBMC with GM-CSF and IL-4 for 5 days to generate immature dendritic cells and co-cultivating the immature dendritic cells with the lysate and adding TNF-alpha to mature the dendritic cells, wherein the cells are co-cultivated for 48 hours (See materials and methods). Herr teach that the TNF-alpha matures the dendritic cells (See page 1858, in particular). Herr teach producing a cell lysate from 109 B-LCL cells (See page 1858, in particular). Herr teaches that the use of tumor lysates as a source of antigen for loading dendritic cells is attractive, since it can activate a broad repertoire of antigen specific T cells to multiple tumor antigens present in the lysate (see page 1863, in particular). Herr teaches that the strategy can be extrapolated to using tumor cell lines for generating lysates (see page 1863, in particular).
The reference differs from the claimed invention in that it does not explicitly teach a lysate of EBV positive C666-1 cells.
Tyagi teaches EBV infected nasopharyngeal carcinoma tumor cell line C666-1, and that lysates derived from said C666-1 tumor cells can be used as source of tumor antigens for loading into dendritic cells as a therapeutic vaccine for EBV associated nasopharyngeal carcinoma (see page 861, in particular).
Zyl teaches that a cocktail of EBV antigens from different EBV strains might be able to achieve a higher level of protection against EBV and the malignant consequences of EBV infection (see page 8, in particular).
WO 02/053176 teaches using a mixture of lysates from different tumor cells lines as an antigen for loading dendritic cells for producing a vaccine (see pages 3-4). WO teaches that doing so is advantageous since it provides for a large number of different antigens from different cell lines which will enhance the T cell response. WO 02/053176 teaches that the dendritic cells are matured by treatment with TNF-alpha (See page 8-9, in particular). WO 02/053176 teaches the use of said loaded dendritic cells as a vaccine for cancer, including lymphoma and carcinoma (see pages 6-8, 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 combine the lysates from Herr and Tyagi, as taught by Zyl and WO 02/053176, for loading the dendritic cells. The ordinary artisan at the time the invention was made would have been motivated to do so, because Zyl teaches that a cocktail of EBV antigens from different EBV strains might be able to achieve high level of protection against infection and its malignant consequences and WO 02/053176 teaches that using a mixture of lysates from different tumor cells lines as an antigen source for loading dendritic cells is advantageous since it provides for a large number of different antigens from different cell lines. Furthermore, the ordinary artisan would have a reasonable expectation of success, since Tyagi and Herr both the lysates can be used for loading dendritic cells for inducing therapeutic immune responses for treating nasopharyngeal carcinoma.
The present claims are directed to a multivalent DC vaccine comprising ex-vivo generated mature DCs loaded with a tumor complex antigen, wherein the tumor complex antigen comprises lysates (a) and (b). The cited references, which make obvious loading dendritic cells the lysate of Herr, i.e. lysate (a) of the present claims, and the lysate of Tyagi, i.e. lysate (b) of the present claims, is within the scope of the instant claims. Regarding the product by process limitations, the patentability of a product does not depend on its method of production in the absence of a structural difference. The cited references render obvious all the structural features required in the claim. It is also noted that the product by process limitations do not require that first population is loaded with tumor lysate (a) only, or that the second population is loaded with tumor lysate (b) only. The claims recite that the DC vaccine “comprises” dendritic cells load with tumor complex antigen wherein the “antigen comprises” (a) and (b). The term comprises is an open term that does not exclude unrecited steps or elements. For example, the product by process limitations would encompass separately co-culturing a first and second DC population, each DC population being co-cultivated with both antigens (a) and (b). The resulting two (identical) populations, when mixed in equal amounts would be identical to the dendritic cell population made obvious above in the cited prior art.
Applicant’s augments filed 6/18/26 have been fully considered, but they are not persuasive.
Applicant argues that claim 2 does not encompass a dendritic cell vaccine loaded with a mixture or cocktail of lysates. Applicant argues that the cited references do not suggest dividing iDCs into separate portions and loading one portion with B-LCL lysate and another portion with a C666-1 lysate, and then mixing the two portions in equal amounts.
As noted above, these are product by product limitations. Claim 2 specifically recites a DC vaccine comprising ex-vivo generated mature DC loaded with a tumor complex antigen comprising lysate (a) and lysate (b). Furthermore, the claims would not exclude performing the product by process steps by separately incubating portions of iDC with both lysates and mixing the two populations, as noted above.
Claim 2, 7-8, and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Herr, 2000 (of record), in view of Tyagi, 2017 (of record), Bachleitner-Hofmann, 2009 and Salcedo, 2005.
Herr teaches mature dendritic cells that have been loaded with lysates from EBV infected B-LCL cells for use as a vaccine to treat patients suffering from EBV associated tumor such as nasopharyngeal carcinoma (i.e. a method of use of a tumor lysate in preparation of a drug, see pages 1857 and 1863, in particular). Herr teaches that the B-LCL cells are immortalized by transformation with B95.8 EBV strain (see page 1858, in particular). Herr teaches producing the dendritic cells by culturing PBMC with GM-CSF and IL-4 for 5 days to generate immature dendritic cells and co-cultivating the immature dendritic cells with the lysate and adding TNF-alpha to mature the dendritic cells, wherein the cells are co-cultivated for 48 hours (See materials and methods). Herr teach that the TNF-alpha matures the dendritic cells (See page 1858, in particular). Herr teach producing a cell lysate from 109 B-LCL cells (See page 1858, in particular). Herr teaches that the use of tumor lysates as a source of antigen for loading dendritic cells is attractive, since it can activate a broad repertoire of antigen specific T cells to multiple tumor antigens present in the lysate (see page 1863, in particular). Herr teaches that the strategy can be extrapolated to using tumor cell lines for generating lysates (see page 1863, in particular).
The reference differs from the claimed invention in that it does not explicitly teach a lysate of EBV positive C666-1 cells.
Tyagi teaches EBV infected nasopharyngeal carcinoma tumor cell line C666-1, and that lysates derived from said C666-1 tumor cells can be used as source of tumor antigens for loading into dendritic cells as a therapeutic vaccine for EBV associated nasopharyngeal carcinoma (see page 861, in particular).
Bachleitner-Hofmann teaches populations of DCs loaded with different tumor cell lysates from different tumor cell lines, and combined treatment of cancer using said different tumor lysate pulsed DC (see page 1588 and Fig. 1, in particular) Bachleitner-Hofmann explains that each tumor cell lysate has a different antigen profile and using multiple lysates provides a broad spectrum of different antigens, increasing the versatility of the DC vaccine to induce an anti-tumor T cell response in individual patients (see page 1590, in particular). Bachleitner-Hofmann teaches combining different tumor lysate pulsed DCs into one vaccine, which can increase likelihood of a tumor response due to delivery of a broader spectrum of antigens (see page 1591, in particular). Bachleitner-Hofmann teaches that the dendritic cells are produced by culturing PBMC with GM-CSF and IL-4 for 5 days and loading with each tumor cell lysate for 12 hours and then maturing by adding TNFa (see page 1586, in particular). See also Salcedo, which teaches methodology for combining dendritic cells loaded with different antigens, wherein dendritic cells are loaded with different antigens and then mixed in equal numbers prior to administration as a vaccine (See page materials and methods, 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 combine the lysate loaded dendritic cells of Herr and the lysate loaded dendritic cells taught by Tyagi, in equal numbers to provide a combination dendritic cell vaccine, as taught by Bachleitner-Hofmann and Salcedo. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, since Bachleitner-Hofmann teaches combining different tumor lysate pulsed DCs into one vaccine can increase likelihood of a tumor response due to delivery of a broader spectrum of antigens.
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 2, 7-8, and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,419,912, in view of Bachleitner-Hofmann, 2009 and Salcedo, 2005..
The ‘912 patent claims a method of treating an EBV associated infectious disease comprising administering a dendritic cell based vaccine loaded with EBV antigen composites, wherein the antigen composite comprises lysates of human immortalized B lymphoblastoid cell lines (B-LCLs) B95-8-LCL, GD1-LCL, M81-LCL, HKNPC1-LCL to HKNPC9-LCL, SNU-719-LCL, YCCEL1-LCL, and lysates of EBV positive infected cells C666-1, HNE1, and EB-3. The ‘912 patent claims that the dendritic cell vaccine is made by a process comprising co-cultivating dendritic cells with said EBV antigen composite and TNF-alpha,, and a method of using an EBV antigen/lysate composition in preparation of a vaccine (i.e. a drug). The ‘912 patent claims that the amount of the lysate is from 2 x 107 cells.
Regarding the product by process limitations of the instant claims, the claims encompass a dendritic cells vaccine loaded with the EBV composite for the same reasons set forth above. Alternately, it would be obvious, based on the teachings of Bachleitner-Hofmann, 2009 and Salcedo, 2005 that one could provide the dendritic cell vaccine loaded with the EBV antigen composites claimed in the ‘912 patent, combining different tumor lysate pulsed DCs into one vaccine in equal amounts, as taught by Bachleitner-Hofmann, 2009 and Salcedo, 2005 for the reasons set forth above.
Regarding claims 8 and 17, although not specifically claimed in the ‘912 patent, it would be obvious to use the dendritic cell based vaccine for treating a nasopharyngeal carcinoma, since Herr and Tyagi teach that dendritic cells loaded with B-LCL B95-8 lysate or C666-1 lysate can be used for therapeutic vaccination to treat EBV associated nasopharyngeal carcinoma.
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, Misook Yu can be reached on 571-272-0839. 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
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