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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Priority
The instant application, filed 02/17/2023, is a 371 filing of PCT/US2021/047139, filed 08/23/2021, and claims domestic benefit to US provisional application 63/068,733, filed 08/21/2020.
Status of Claims/Application
Applicant’s preliminary amendment of 02/17/2023 is acknowledged. Claims 4-7 and 10-13 are amended. Claims 1-13 are currently pending and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/17/2023, 04/18/2024, and 08/25/2025, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Drawings
The drawings filed on 02/17/2023 are objected to because they contain low resolution images that are difficult to read. For instance, see Figures 1A, 4A, 4B, 8, 9A, 9B, 10, 12, 14A, 17, and 18.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification Objection
The specification recites “Taxol” which is a registered trademark. In the specification, Taxol is recited as “taxol” without appropriate capitalization or symbol. For instance, see pages 1, 2, 12, and 32.
The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The Figure 11 description in the specification references a purple line and a blue line (page 4, lines 2327) but the drawings are in black and white/grayscale. As such, the description does not properly delineate between the different lines on the plot in Figure 11. It is also noted that Figure 11 comprises 5 different data lines but not all are identified.
Duplicate Claim Warning
Applicant is advised that should claim 6 be found allowable, claim 8 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Both claims 6 and 8 are drawn to methods of treating cancer in a subject comprising administration of at least one oncodriver pulsed dendritic cell and a FMT from a pCR donor or a CDK inhibitor. The claims are the same in scope and are, therefore, duplicates of each other.
Claim Interpretation
Claim 3 recites the limitation that the oncodriver pulsed dendritic cell is activated with IL-12 “prior to administration”. Claim 3 depends on claim 1 which is drawn to an anti-cancer combination therapy, which is a product and does not recite administration of a therapy. In the instant office action, the limitation of the dendritic cell being activated with IL-12 prior to administration is interpreted as an intended use of the claimed product. See MPEP 2111.02.
Claim Objections
Claims 2 and 9 are objected to because of the following informalities: on line 2, the claims recite “(HER) 1(HER 1)”. The claims are missing a space between the “1” and the “(HER1)”. Appropriate correction to “(HER) 1 (HER1)” is required.
Claims 2 and 9 recite “estrogren” receptor (ER) which is an incorrect spelling of “estrogen”. Correction of “estrogren” to “estrogen” is required.
Claim Rejections - 35 USC § 112(b)
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 5, 7, and 10-11 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.
Claims 5 and 11 contain the trademark/trade name “Taxol”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the anticancer drug Taxol, which comprises the drug paclitaxel, and, accordingly, the identification/description is indefinite.
Claim 7 is dependent on claim 1 and recites the preamble “The method of treating a cancer of claim 1”. There is insufficient antecedent basis for this recitation in the claim. Claim 1 is drawn to an anti-cancer combination therapy and does not recite a method of treating cancer. Appropriate correction is required.
Claims 10 and 11 are dependent on claim 8 and recite the preamble “The anti-cancer combination therapy of claim 8”. There is insufficient antecedent basis for this recitation in the claim. Claim 8 is drawn a method of treating cancer in a subject, not to an anti-cancer combination therapy. In so far as the recitation could apply to the combination of i) and ii) recited in claim 8, it is unclear if claims 10 and 11 encompass the method of claim 8 or only the combination therapy recited therein. Appropriate correction is required.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2 and 4-13 are rejected under 35 U.S.C. 103 as being unpatentable over US 2017/0216421A1 (Czerniecki, B.J. and G.K. Koski) 3 Aug 2017 in view of Yu, B., et al (2003) Effective combination of chemotherapy and dendritic cell administration for the treatment of advanced-stage experimental breast cancer Clinical Cancer Research 9; 285-294.
US’421 teaches that dendritic cells are white blood cells that acquire protein antigens from microbes or even cancerous cells and show, or “present” these antigens to T cells. The T cells, thus activated by the DCs, then initiate systemic immune response to challenge the threat (page 1, [0003]). Popular steps for cancer vaccines include: extracting DCs from cancer patients, loading them with tumor antigens in vitro, supplying unique activation signals to the cells, then re-administering them to the body. This ensures proper DC activation removed from the influence of the tumor microenvironment. When returned to the body, the DCs can then interact with T cells and initiate powerful anti-tumor immunity (page 1, [0004]).
US’421 teaches compositions and methods for producing an FDA-approved injectable multi-dose antigen pulsed dendritic cell vaccine for the personalized treatment of cancer or other disorders (page 4, [0033]). US’421 further teaches that the antigen suitable for loading into the APC is a tumor antigen including transformation related molecules, such as the oncogene HER-2/Neu/ErB-2 (pages 11-12, [0145]-[0147]). US’421 also exemplifies DCs pulsed with HER2 (page 20, [0236]).
US’421 teaches a method of enhancing the immune response in a mammal comprising the steps of: generating immature DCs from monocytes obtained from a mammal, e.g., a patient; pulsing the immature DCs with a composition comprising an antigenic composition; activating the antigen loaded DCs with at least one TLR agonist; cryopreserving the activated antigen loaded DCs; thawing the activated, antigen loaded DCs and then administering the activated, antigen loaded DCs to a mammal in need thereof (page 15, [0189]). US’421 teaches that the embodiments include a cell that has been exposed or otherwise “pulsed” with an antigen. For example, an APC, such as a DC, may become Ag-loaded in vitro, for instance by culturing the cell ex vivo in the presence of an antigen, or in vivo by exposure to an antigen (page 10, [0128]). US’421 further teaches that the mammalian recipient may be a human and the cells can be autologous with respect to the recipient (page 16, [0190]).
US’421 further teaches that the present embodiments provides an effective therapy to treat cancer wherein the therapy induces changing the immune response to the tumor so that the immune cells in the tumor site are more effective in attacking the tumor cells. In some instances, the effective therapy includes improving the migration and activity of immune cells in the tumor site (page 17, [0205]). US’421 further teaches that the disclosed methods can be used to treat breast cancer (page 17, [0210]).
US’421 teaches that the vaccines of the disclosure can be provided in a treatment regimen in combination with another cancer medicament for the treatment of cancer in subjects (page 17, [0208]). US’421 teaches the addition of chemotherapeutic agents including taxanes. The taxanes affect cell structures called microtubules that are important in cellular functions. In normal cell growth, microtubules are formed when a cell starts dividing, but once the cell stops dividing, the microtubules are disassembled or destroyed. Taxanes prohibit the microtubules from breaking down such that the cancer cells become so clogged with microtubules that they cannot grow and divide. US’421 teaches that paclitaxel is an exemplary taxane (page 18, [0218]). US’421 further teaches that the brand name for paclitaxel is TAXOL (page 19, left column).
US’421, however, does not exemplify the combination of the pulsed DCs with paclitaxel (Taxol). Additionally, US’421 does not teach that the pulsed DCs are administered intratumorally, as recited in instant claims 7 and 13.
Yu investigated the treatment of advanced stage breast cancer using a combination of chemotherapy and dendritic cell administration (abstract, purpose). Yu teaches that previous experiments established proof-of-concept that the combination of the intratumoral placement of ex vivo generated autologous DCs in concert with apoptosis inducing therapy might lead to a generation of systemic antitumor immunity. Yu used a tumor model of mammary adenocarcinoma DA3. DC administration was combined with 3 cycles of paclitaxel at a dose that induces apoptosis and moderate immune suppression. It was found that such combined treatment induces significant antitumor immune response that was associated with a marked antitumor effect (page 286, left column, paragraph 1).
Yu teaches that combined treatment resulted in the induction of HA-specific CD8-mediated responses in all nine of the tested mice, and CD4-mediated responses in four of six treated mice. These effects were only observed if DCs were injected into the tumor site, but not when injected by i.v. No specific responses were found in mice treated with either chemotherapy or DCs alone (abstract, results). Yu further teaches that combined treatment increased median survival from 29 days in the control group to 45 days (page 291, right column, paragraph 2; Figure 6).
Yu teaches that paclitaxel (Taxol) was selected because, together with its analogue Taxotere (docetaxel), it is the most frequently used drug in breast cancer with proven apoptotic effect on tumor cells (page 287, left column, paragraph 4).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to combine the HER2 antigen pulsed DCs of US’421 with paclitaxel (Taxol) and to administer the pulsed DCs intratumorally based on the teachings of Yu. An ordinarily skilled artisan would have been motivated to administer paclitaxel with the HER2 pulsed DCs and to administer the DCs intratumorally as Yu teaches that when pulsed DCs are administered intratumorally in combination with paclitaxel, significant antitumor immune responses are observed which are associated with a marked antitumor effect and prolonged survival. An ordinarily skilled artisan would have had a reasonable expectation of success as US’421 teaches combination of the disclosed HER2 pulsed DCs with paclitaxel as a potential additional therapy. Additionally, both US’421 and Yu teach the administration of dendritic cells as a means to induce immune response for the treatment of breast cancer.
Regarding claims 4 and 10, the combination of US’421 and Yu teach the alternative therapy of recited in claims 1 and 8 of a CDK inhibitor (Taxol). None of claims 1, 4, 8, or 10 require that the second therapy be a fecal microbial transplant. Therefore, the teaching of the alternative therapy also renders the instant claims obvious.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over US 2017/0216421A1 (Czerniecki, B.J. and G.K. Koski) 3 Aug 2017 in view of Yu, B., et al (2003) Effective combination of chemotherapy and dendritic cell administration for the treatment of advanced-stage experimental breast cancer Clinical Cancer Research 9; 285-294 as applied to claim 1 above, and in further view of Grohmann, U., et al (1998) IL-12 acts directly on DC to promote nuclear localization of NF-κB and primes DC for IL-12 production Immunity 9; 315-323.
The combination of US’421 and Yu teach the anti-cancer combination of claim 1 as discussed in detail above.
As discussed in detail above, US’421 teaches methods in which DCs are supplied unique activation signals before re-administration to the body. US’421 further teaches that the DCs can be activated by a cytokine and/or a toll like receptor ligand (page 9, [0111]). Traditional DC-based vaccines comprise of matured DCs generated from using a cytokine cocktail mixture including combinations of TNF, IL-6, PGE2, and IL-1β. The embodiments disclosed by US’421 utilize TLR agonists to mature the DCs and stimulate production of signal (page 12, [0152]). The stimulation of DCs with a combination of TLR ligands leads to the production of increased amounts of IL-12 (page 12, [0153]).
The combination of US’421 and Yu do not disclose that the DCs are activated with IL-12.
Grohmann teaches that DC are the most potent cellular initiators of the immune response and, in particular, are responsible for the induction of primary antigen-specific immune reactions. In keeping with this notion is their ability to secret IL-12 and to direct the development of Th1 cells from naïve CD4+ T cells. Based on previous findings that recombinant IL-12 will prime purified DC cultures pulsed with a tumor peptide in vitro for effective sensitization in vivo, the present study investigated the possible expression of an IL-12 receptor by DC. The results indicate that DC express an IL-12R and that IL-12 signaling in these cells may involve early events that differ from those operating in T lymphocytes, including nuclear localization of the NF-κB family. These events may ultimately lead to functional responses that are independent of the presence of IFNγ, including increased expression of MHC class II antigens and priming of DCs for LPS-induced production of IL-12 (paragraph bridging page 315).
The studies of Grohmann demonstrate that DC express a single class of high-affinity IL-12R on their surface and that IL-12 binding on DC transduces activation signals via nuclear localization of p50 and relB, two members of the NF-κB family. This unique feature of IL-12 effects on DC may confer unique actions on the target cells, including increased class II antigen expression and enhanced production of endogenous IL-12 (page 321, left column, paragraph 3).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method taught by US’421 for activating the DCs to either further include IL-12 with the disclosed cytokines and/or TLR ligand, or, alternatively, to substitute the disclosed cytokines and/or TLR ligand with IL-12, based on the teachings of Grohmann. An ordinarily skilled artisan would have been motivated to make these modifications as Grohmann teaches that DCs express a high-affinity IL-12R on their surface and that IL-12 increases antigen expression and enhances production of endogenous IL-12. An ordinarily skilled artisan would have had a reasonable expectation of success as Both US’421 and Grohmann teach the activation of DCs and the expression of IL-12 by activated DCs.
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 § 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.
18/021,847
Claims 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/021,847. Although the claims at issue are not identical, they are not patentably distinct from each other.
App’847 claims an anti-cancer combination therapy comprising i) at least one oncodriver pulsed dendritic cell and ii) a FMT from a pCR donor or a CDK inhibitor; further comprising an immunoregulatory molecule (claim 1). The claims further recite that the oncodriver is selected from HER1, HEr2, HER3, EGFR, c-MET, BRAF, KIT, AR, ER, KRAS, TP53, and APC (claim 2) and that the oncodriver pulsed dendritic cell is activated with IL-12 prior to administration. App’847 further claims that the FMT is enriched Anaerosporobacter, and that the CDK inhibitor is abemaciclib, ribociclib, palbociclib, Trilaciclib, or Taxol (claims 4-5). App’847 further clams a method of treating cancer comprising administering the anti-cancer combination and that the DC is administered intratumorally (claims 7-8). App’847 claims that the DC are removed from the subject and pulsed with the oncodriver ex vivo (claim 14).
The claims of App’847 differ from the instant claims in that App’847 teaches an additional immunoregulatory molecule in the combination/treatment.
The instant claims are drawn to combinations and methods using “comprising” language. The instant specification defines “comprising” as meaning that the compositions, methods, etc. include the recited elements, but do not exclude others (page 8, lines 7-16). A definition which is consistent with that of MPEP 2111.03 I. As the instant claims encompass combinations and methods that include the recited elements as well as additional, unrecited elements, the claims of App’847 are a species of the instantly claimed combination and method and; therefore, anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AUDREY L BUTTICE whose telephone number is (571)270-5049. The examiner can normally be reached M-Th 8:00-4:00.
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/AUDREY L BUTTICE/Examiner, Art Unit 1647
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693