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 .
Claims Status
The Amendment filed on 27Feb2026 is acknowledged in which claim(s) 11, 16, 23-24, 26, 28, 31-32, 39-56, 61 were canceled, and claim(s) 88-91 are new.
Claim(s) 1-10, 12-15, 17-22, 25, 27, 29-30, 33-38, 57-60, 62, 64-65, 69, 74-75, 80-81, 84, 86, and 88-91 is/are currently pending and presented for examination on the merits.
Response to Amendment and Arguments
All previous rejections and/or objections of claim(s) 11, 23-24 are moot in view of claim cancelation.
The objection(s) to the specification have been withdrawn in view of the Amendment filed on 27Feb2026.
The rejection(s) of claim(s) 4,33, 37-38, 57-60, 62, 84, under 35 U.S.C. § 112(b), of claim(s) 1-3, 10, 15, 17, 21, 33, 35, 64-65, 69, 74-75, 80-81, 86 under 35 U.S.C. § 102, of claim(s) 27-31, 34, 36 under 35 U.S.C. § 102/103 and of claim(s) 4-9, 11-14 under 35 U.S.C. § 103 have been withdrawn in view of the recent claim amendment filed on 27Feb2026, which added new limitation(s) to the base claim that were not previously considered.
As all previously presented rejection(s) and/or objection(s) have been withdrawn, Applicant arguments are not addressed herein.
New Rejections/Objections Necessitated by Claim Amendments
Claim Objections
Claim(s) 33, 89 (and dependent claim 91) is/are objected to because of the following informalities: “MAGE A1” is missing a hyphen (e.g., hyphenated in dependent claim 91). Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
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.
Claim(s) 1-10, 12-15, 17-22, 25, 27, 29-30, 33-38, 57-60, 62, 64-65, 69, 74-75, 80-81, 84, 86, 88-91 is/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.
Regarding claim(s) 1-10, 12-15, 17-22, 25, 27, 29-30, 33-38, 57-60, 62, 64-65, 69, 74-75, 80-81, 84, 86, and 88-91, recitation of the phrase "similar to" in claim 1(a) renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "similar to"), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d).The instant disclosure does not define what “molecules similar to” or “similar to” means. For the purposes of compact prosecution “similar to” an antigen present on the cancer afflicting the individual is considered to mean any extracellular antigen (e.g., because any cell can become cancerous), ligand(s) thereto, or neoantigen derived molecules. This rejection may be overcome by amending claim 1 to clearly recite the limitation(s) of the instant invention. Claim(s) 2-10, 12-15, 17-22, 25, 27, 29-30, 33-38, 57-60, 62, 64-65, 69, 74-75, 80-81, 84, 86, and 88-91 can overcome this rejection by amending claim 1 as described above.
Claim Rejections - 35 USC § 112(a)
Claim(s) 37-38 is/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for adjuvants known in the art, does not reasonably provide enablement for adjuvants comprising a TLR (e.g., a TLR as an adjuvant). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation."' (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (A) The nature of the invention; (B) The breadth of the claims; (C) The amount of direction provided by the inventor; (D) The existence of working examples; (E) The state of the prior art; (F) The level of predictability in the art; (G) The quantity of experimentation needed to make or use the invention based on the content of the disclosure and (H) The level of one of ordinary skill. While all of these factors are considered, a sufficient amount for amount for a prima facie case are discussed below.
The nature of the invention
Claims 37 are drawn to a method for treating cancer comprising the administration of a TLR as an adjuvant.
The breadth of the claims
The claim is broad in that it includes TLRs as adjuvants. Specifically, claim 37 is inclusive of ALL TLRs as adjuvants and claim 38 specifically recites TLR2, TLR3, TLR4, TLR7, TLR9, and TLR9 as adjuvants.
The amount of direction provided by the inventor/the existence of working examples
The instant disclosure recites TLRs as adjuvants but does not provide any examples of reduction to practice of administration of TLRs as adjuvants, nor does it provide any reference(s) for evidence of TLRs are adjuvants in the prior art at the time of filing.
The state of the art/the level of predictability in the art
No prior art was found to disclose TLRs are adjuvants, nor was art after the filing date found to teach TLRs as adjuvants. However, at the time of filing, US 2011/0212090 A1 (hereinafter “US090”) taught TLR ligands such as LPS, lipoproteins, lipopeptides, flagellin, dsRNA, unmethylated CpG islands, etcetera were known to act as immune adjuvants.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
In order to practice the invention as claimed, one of ordinary skill in the art would have to perform undue experimentation to develop a method to (1) determine how to stabilize each and every known TLR devoid of a cell (e.g., because the claims require TLR administration, not a cell comprising a TLR), and (2) test every stabilized TLR receptor to determine which (if any) act as an adjuvant upon administration. Applicant is enabled for administration of adjuvant (e.g., only those known in the art).
Conclusion
In view of the Wands factors as discussed above, one of ordinary skill in the art would have to engage in undue experimentation to practice the full scope of the instant claimed invention. As such, instant claims 37-38 were determined to not meet the scope of enablement requirement of 35 USC § 112(a).
Enablement can be met by amending claims 37-38 to recite TLR ligand(s).
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-10, 12-15, 17, 21, 25, 27, 29-30, 34-36, 57-60, 62, 69, 74-75, 80-81, 88 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2011/0212090 A1, as evidenced by Rousseau et al. (BLOOD, 15Feb2006, Vol. 107, No. 4; hereinafter “Rousseau”), Alkasalias et al. (Int. J. Mol. Sci. 2018, 19, 1532; hereinafter “Alkasalias”), Tito (Mol Biotechnol. 2019 Mar;61 (3):209-220.; hereinafter "Tito"), Schattner et al. (Blood, Vol 91, No 8 (April 15), 1998: pp 2689-2697; hereinafter “Schattner”), Hostager and Bishop (Front. Immunol., 14 November 2013, Vol. 4 – 2013; hereinafter “Hostager”), Hanissian and Geha (Immunity, Vol. 6, 379–387, April 1997; hereinafter “Hanissian”), and Tchao and Turka. (American Journal of Transplantation 2012; 12: 1079-1090; hereinafter "Tchao").
Regarding instant claim(s) 1, 25, 35-36, 57-58, 80-81, 88, US090 teaches methods of treating leukemia in the “Treating High Risk Leukemia with CD40 Ligand and IL-2 Gene Modified Tumor Vaccine” embodiment comprising administering a tumor vaccine comprising CD40L (e.g., tumor associated protein, see 112(b) above), and modified autologous skin fibroblasts [e.g., abstract; ¶ 0156; tbl. S]. US090 teaches cancer vaccines refers to a vaccine that treats an existing cancer (e.g., a composition capable of inducing cancer cell death) [e.g., ¶ 1042]. The disclosure of “treating” leukemia with the fibroblast vaccine above is considered to require a “therapeutically effective amount” of fibroblast cells. US090 further teaches vaccines (e.g., of the embodiment above) administered in combination with adjuvants (e.g., a composition capable of augmenting antigen presentation) [e.g., ¶ 0670, 0736], and that adjuvants comprise TLR ligands or mimics [e.g., ¶ 1037-1038].
Regarding instant claim(s) 2-9, 12, 14, US090 further teaches that treatment (e.g., vaccine and adjuvant) may be given repeatedly, more than once in the same day, daily, or weekly (e.g., repeated administration is considered to teach all recited combinations of orders of steps a-d) [e.g., ¶ 1073, 1074].
Regarding instant claim(s) 10, US090 further teaches the vaccine may be administered alone [e.g., ¶ 0670].
Regarding instant claim(s) 13, US090 further teaches that treatment (e.g., vaccine) may be given repeatedly, more than once in the same day, daily, or weekly (e.g., repeated administration is considered the recited combinations of orders of steps a-b) [e.g., ¶ 1073, 1074].
Regarding instant claim(s) 15, 17, normal fibroblasts administered in the methods of US090 (see above) to treat cancer would naturally possess anti-inflammatory activity comprising suppressing TNFa production in the TME (e.g., relative to cancer associated fibroblasts), as evidenced by Alkasalias [e.g., pg. 3, “2.2”; pg. 5, “3.1”].
Regarding instant claim(s) 21, fibroblasts administered in the methods of US090 (see above) to treat cancer would naturally express GDF-11, as evidenced by Tito [e.g., abstract].
Regarding instant claim(s) 27, administration of the CD40 Ligand and IL-2 Gene Modified Tumor Vaccine taught by US090 (see above) induces expansion of anti-leukemic T cells, as evidenced by Rousseau [e.g., abstract].
Regarding instant claim(s) 29, CD40 Ligand is expressed on leukemia cells (e.g., derived from histologically similar cancer), as evidenced by Schattner [e.g., title, abstract].
Regarding instant claim(s) 30, the CD40 Ligand and IL-2 Gene Modified Tumor Vaccine taught by US090 (see above) comprises patient derived leukemic blasts admixed with the engineered fibroblasts (e.g., derived from ), as evidenced by Rousseau [e.g., abstract]. Therefore, antigen(s) or molecule(s) of the tumor lysate therefore could reasonably be expected be part of the vaccine composition.
Regarding instant claim(s) 34, the CD40 Ligand and IL-2 Gene Modified Tumor Vaccine taught by US090 (see above) is autologous (e.g., self-derived and therefore HLA matched), as evidenced by Rousseau [e.g., pg. 133, col. 2, “recipient-derived vaccine preparation”].
Regarding instant claim(s) 59-60, the CD40L (e.g., of the vaccine taught by US090) is known to bind the CD40 receptor, which is known to result in the canonical activation of NFKb (e.g., by degradation/inhibition of I kappa B), as evidenced by Hostager [e.g., abstract].
Regarding instant claim(s) 62, the CD40L (e.g., of the vaccine taught by US090) is known to bind the CD40 receptor, which is known to activate the JAK/STAT pathway, as evidenced by Hanissian [e.g., abstract].
Regarding instant claim(s) 69, US090 further teaches the vaccine can be administered with one or more drugs [e.g., ¶ 0670], and that the anti-cancer drug comprises busulfan/Busulfex (e.g., chemotherapy) for leukemia [e.g., ¶ 0860].
Regarding instant claim(s) 74-75, US090 further teaches the vaccine can be administered with one or more drugs [e.g., ¶ 0670], and that the anti-cancer drug comprises fludarabine (e.g., lymphodepleting drug that induces lymphopenia) for leukemia [e.g., ¶ 0889]. One having ordinary skill in the art would understand lymphodepleting agents are administered prior to therapeutic agent(s) (e.g., vaccines). It is well recognized within the art that lymphopenia induces compensatory hemostatic proliferation of T cells (lymphocytes), as evidenced by Tchao [e.g., abstract].
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claim(s) 18-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0212090 A1, as evidenced by Rousseau et al. (BLOOD, 15Feb2006, Vol. 107, No. 4; hereinafter “Rousseau”), Alkasalias et al. (Int. J. Mol. Sci. 2018, 19, 1532; hereinafter “Alkasalias”), Tito (Mol Biotechnol. 2019 Mar;61 (3):209-220.; hereinafter "Tito"), Schattner et al. (Blood, Vol 91, No 8 (April 15), 1998: pp 2689-2697; hereinafter “Schattner”), Hostager and Bishop (Front. Immunol., 14 November 2013, Vol. 4 – 2013; hereinafter “Hostager”), Hanissian and Geha (Immunity, Vol. 6, 379–387, April 1997; hereinafter “Hanissian”), and Tchao and Turka. (American Journal of Transplantation 2012; 12: 1079-1090; hereinafter "Tchao"), as applied to claim(s) 1 above, and further in view of Sziksz et al. (Mediators of Inflammation, Volume 2015, Article ID 764641; hereinafter "Sziksz"), as evidenced by Hanahan and Weinberg (Cell, Vol 144, Issue 5, 04mar2011, Pgs. 646-67 4; hereinafter "Hanahan").
The teachings of US090 as recited above apply for claim(s) 1.
US090 does not expressly teach culturing fibroblasts in IL10 resulting in decreased TNFa production.
Regarding instant claim(s) 18-20, Sziksz teaches the role of IL10 in inflammatory diseases including cancer [e.g., title; abstract; pg. 7, "6. Therapeutic Targets…”]. Sziksz further teaches characteristics of IL10, including that IL10 responsive genes include suppressor of cytokine signaling 3 (SOCS3), whose induction is correlated with decreased expression of TNFa [e.g., pg. 3, "4. Characteristic of the IL-10 Cytokine Family']. Sziksz further teaches TNFa is a proinflammatory cytokine associated with inflammatory diseases [e.g., pg. 7, "6. Therapeutic Targets ... "; pg. 5, col 1, ¶ 1; pg. 5, col 2, ¶ 2-3]. One of ordinary skill in the art would understand that tumor-promoting inflammation is a hallmark of cancer that function as an enabling characteristic thereof, as evidenced by Hanahan [e.g., fig. 3].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to combine the methods of treating cancer comprising administering a CD40 Ligand and IL-2 Gene Modified Tumor Vaccine (e.g., comprising fibroblasts) as taught by US090 (see above), with the methods of culturing fibroblasts in IL10 as taught by Sziksz, to arrive at the instant invention of the CD40 Ligand and IL-2 Gene Modified Tumor Vaccine, wherein the fibroblasts are cultured in IL10 and result in reduced TNFa. A PHOSITA would have been motivated to combine the method of treating leukemia comprising administering a CD40 Ligand and IL-2 Gene Modified Tumor Vaccine (e.g., comprising fibroblasts) as taught by US090 (see above), with the methods of culturing fibroblasts in IL10 as taught by Sziksz, because US090 teaches administering a vaccine comprising fibroblasts to treat cancer, which is an inflammatory disease, and Sziksz teaches that culturing fibroblasts in IL10 results in decreased TNFa production and thereby lowers inflammation (e.g., beneficial in treating an inflammatory disease). There would have been a reasonable expectation of success for a PHOSITA to combine the method of treating leukemia comprising administering a CD40 Ligand and IL-2 Gene Modified Tumor Vaccine (e.g., comprising fibroblasts) as taught by US090 (see above), with the methods of culturing fibroblasts in IL10 as taught by Sziksz, because administering a fibroblast that reduces TNFa is beneficial in treating inflammatory diseases (e.g., cancers). This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0212090 A1, as evidenced by Rousseau et al. (BLOOD, 15Feb2006, Vol. 107, No. 4; hereinafter “Rousseau”), Alkasalias et al. (Int. J. Mol. Sci. 2018, 19, 1532; hereinafter “Alkasalias”), Tito (Mol Biotechnol. 2019 Mar;61 (3):209-220.; hereinafter "Tito"), Schattner et al. (Blood, Vol 91, No 8 (April 15), 1998: pp 2689-2697; hereinafter “Schattner”), Hostager and Bishop (Front. Immunol., 14 November 2013, Vol. 4 – 2013; hereinafter “Hostager”), Hanissian and Geha (Immunity, Vol. 6, 379–387, April 1997; hereinafter “Hanissian”), and Tchao and Turka. (American Journal of Transplantation 2012; 12: 1079-1090; hereinafter "Tchao"), as applied to claim(s) 1, 88-89 above, and further in view of US 2002/0131960 A1 (hereinafter "US960").
The teachings of US090 as recited above apply for claim(s) 1.
US090 does not expressly teach fibroblasts comprise the expression of Flu peptides
Regarding instant claim(s) 22, US960 teaches artificial antigen presenting cells (AAPCs) and methods of use thereof [e.g., title, abstract]. US960 teaches fibroblasts are retrovirally transduced with a single HLA peptide complex along with accessory molecules, resulting in stable AAPCs that are "readily engineered for any HLA molecule and any specific peptide" [e.g., ¶ 0003]. US960 teaches peptides that trigger T cell responses can be derived from foreign peptides including viruses, and specifically flu peptides [e.g., ¶ 0009, 0033, 0057; table 1; figs. 38, 9]. US960 further teaches the administration of AAPCs for the treatment of cancer, specifically including glioma and meningioma (e.g., types of brain cancer) [e.g., ¶ 0019, 0104].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to combine the method of treating cancer comprising administering a CD40 Ligand and IL-2 Gene Modified Tumor Vaccine (e.g., comprising CD40L+/IL2+ fibroblasts) as taught by US090 (see above), with the Flu peptide expressing fibroblasts taught by US960, to arrive at a method of treating cancer comprising administering a CD40 Ligand and IL-2 Gene Modified Tumor Vaccine (e.g., comprising CD40L+/IL2+/Flu peptide+ fibroblasts). A PHOSITA would have been motivated to combine the of treating cancer comprising administering a CD40 Ligand and IL-2 Gene Modified Tumor Vaccine (e.g., comprising CD40L+/IL2+ fibroblasts) as taught by US090 with the Flu peptide expressing fibroblasts taught by US960, because both US090 and US960 teach compositions comprising fibroblasts for the treatment of cancer, and US960 further teaches fibroblasts comprising flu peptide are T-cell immunogenic (e.g., desirable for cancer vaccines). There would have been a reasonable expectation of success for a PHOSITA to combine the of treating cancer comprising administering a CD40 Ligand and IL-2 Gene Modified Tumor Vaccine (e.g., comprising CD40L+/IL2+ fibroblasts) as taught by US090 with the Flu peptide expressing fibroblasts taught by US960 because US090 teaches the base method and vaccine composition comprising fibroblasts for the treatment of cancer, and US960 further teaches engineering fibroblasts to express Flu peptides as effective cancer therapy. This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 33, 89 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0212090 A1, as evidenced by Rousseau et al. (BLOOD, 15Feb2006, Vol. 107, No. 4; hereinafter “Rousseau”), Alkasalias et al. (Int. J. Mol. Sci. 2018, 19, 1532; hereinafter “Alkasalias”), Tito (Mol Biotechnol. 2019 Mar;61 (3):209-220.; hereinafter "Tito"), Schattner et al. (Blood, Vol 91, No 8 (April 15), 1998: pp 2689-2697; hereinafter “Schattner”), Hostager and Bishop (Front. Immunol., 14 November 2013, Vol. 4 – 2013; hereinafter “Hostager”), Hanissian and Geha (Immunity, Vol. 6, 379–387, April 1997; hereinafter “Hanissian”), and Tchao and Turka. (American Journal of Transplantation 2012; 12: 1079-1090; hereinafter "Tchao"), as applied to claim(s) 1, 88 above, and further in view of Hou et al. (Blood Cancer Journal (2015) 5, e331, Doi: 10.1038/bcj.2015.59; hereinafter “Hou”).
The teachings of US090 as recited above apply for claim(s) 1, 88.
US090 does not expressly teach the tumor associated protein is a p53 mutant.
Regarding instant claim(s) 33, 89, Hou teaches TP53 (p53) mutations are frequently detected in leukemia patients [e.g., title, abstract].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to combine the method of treating cancer comprising administering a vaccine comprising CD40L+/IL2+ fibroblasts as taught by US090 (see above), with the mutant p53 peptides as taught by Hou, to arrive at a method of treating cancer comprising administering a vaccine comprising CD40L+/IL2+ fibroblasts and p53 mutant peptides. A PHOSITA would have been motivated to combine the method of treating cancer comprising administering a vaccine comprising CD40L+/IL2+ fibroblasts as taught by US090 (see above), with the mutant p53 peptides as taught by Hou, because US090 teaches the base method and vaccine composition for treating leukemias, and Hou further teaches mutant p53 peptides are frequently detected in leukemic patients. Therefore, a PHOSITA would recognize that including tumor antigens that are expressed ‘frequently’ (e.g., in the tumors of more subjects than not), that the vaccine may be effective for a broader range of leukemia patients. There would have been a reasonable expectation of success for a PHOSITA to combine the method of treating cancer comprising administering a vaccine comprising CD40L+/IL2+ fibroblasts as taught by US090 (see above), with the mutant p53 peptides as taught by Hou because US090 teaches the base method and vaccine, and Hou teaches p53 mutant peptide as a frequently detected leukemia associated antigen. This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 64-65 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0212090 A1, as evidenced by Rousseau et al. (BLOOD, 15Feb2006, Vol. 107, No. 4; hereinafter “Rousseau”), Alkasalias et al. (Int. J. Mol. Sci. 2018, 19, 1532; hereinafter “Alkasalias”), Tito (Mol Biotechnol. 2019 Mar;61 (3):209-220.; hereinafter "Tito"), Schattner et al. (Blood, Vol 91, No 8 (April 15), 1998: pp 2689-2697; hereinafter “Schattner”), Hostager and Bishop (Front. Immunol., 14 November 2013, Vol. 4 – 2013; hereinafter “Hostager”), Hanissian and Geha (Immunity, Vol. 6, 379–387, April 1997; hereinafter “Hanissian”), and Tchao and Turka. (American Journal of Transplantation 2012; 12: 1079-1090; hereinafter "Tchao"), as applied to claim(s) 1, 35-36 above, and further in view of US 2017/0196951 A1 (hereinafter “US951”).
The teachings of US090 as recited above apply for claim(s) 1, 88.
US090 does not expressly teach GM-CSF activated dendritic administration.
Regarding instant claim(s) 64-65, US951 teaches anti-tumor fibroblast vaccines [e.g., title, abstract]. US951 further teaches “priming” a patient with in vivo GM-CSF activation of dendritic cells (DCs) [e.g., ¶ 0026]. US951 further teaches DCs interact with T cells in vivo causing them to recognize and destroy cells (e.g., cancer cells).
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to combine the method of treating cancer comprising administering a fibroblast vaccine as taught by US090, with the in vivo GMC-CSF priming of dendritic cells as taught by US951, to arrive at the method of treating cancer comprising administering a fibroblast vaccine wherein DCs are primed in vivo. A PHOSITA would have been motivated to combine the method of treating cancer comprising administering a fibroblast vaccine as taught by US090, with the in vivo GMC-CSF priming of dendritic cells as taught by US951, because US090 teaches the base method and cancer vaccine, both US090 and US951 teach anti-cancer fibroblast vaccines, and US951 further teaches that DCs promote T cell killing (e.g., enhance anti-cancer activity). There would have been a reasonable expectation of success for a PHOSITA to combine the method of treating cancer comprising administering a fibroblast vaccine as taught by US090, with the in vivo GMC-CSF priming of dendritic cells as taught by US951 because US090 teaches the base method and cancer vaccine, both US090 and US951 teach anti-cancer fibroblast vaccines, and US951 further teaches that DCs promote T cell killing (e.g., enhance anti-cancer activity). This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 84 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0212090 A1, as evidenced by Rousseau et al. (BLOOD, 15Feb2006, Vol. 107, No. 4; hereinafter “Rousseau”), Alkasalias et al. (Int. J. Mol. Sci. 2018, 19, 1532; hereinafter “Alkasalias”), Tito (Mol Biotechnol. 2019 Mar;61 (3):209-220.; hereinafter "Tito"), Schattner et al. (Blood, Vol 91, No 8 (April 15), 1998: pp 2689-2697; hereinafter “Schattner”), Hostager and Bishop (Front. Immunol., 14 November 2013, Vol. 4 – 2013; hereinafter “Hostager”), Hanissian and Geha (Immunity, Vol. 6, 379–387, April 1997; hereinafter “Hanissian”), and Tchao and Turka. (American Journal of Transplantation 2012; 12: 1079-1090; hereinafter "Tchao"), as applied to claim(s) 1, 88-89 above, and further in view of Kumazoe et al. (FEBS Letters 587 (2013) 3052-3057; hereinafter “Kumazoe”).
The teachings of US090 as recited above apply for claim(s) 1.
Regarding instant claim(s) 84, US090 teaches the vaccine may be administered with another drug.
US090 does not expressly teach the administration of a PDE-5 inhibitor.
Regarding instant claim(s) 84, Kumazoe teaches PDE-5 sensitizes leukemia to apoptosis [e.g., ¶ title, abstract].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to combine the method of treating cancer comprising administering a fibroblast vaccine with another drug as taught by US090, with the PDE-5 inhibitor as taught by Kumazoe, to arrive at a method of treating cancer comprising administering a fibroblast vaccine and a PDE-5 inhibitor. A PHOSITA would have been motivated to combine the method of treating cancer comprising administering a fibroblast vaccine as taught by US090 with the PDE-5 inhibitor as taught by Kumazoe, because US090 teaches the base method for treating leukemia and vaccine composition therefor may be combined with other anti-cancer drugs, and Kumazoe teaches PDE-5 is an is a drug that sensitizes leukemia to apoptosis. There would have been a reasonable expectation of success for a PHOSITA to combine the method of treating cancer comprising administering a fibroblast vaccine as taught by US090 with the PDE-5 inhibitor as taught by Kumazoe, because US090 teaches the base method for treating leukemia and vaccine composition therefor may be combined with other anti-cancer drugs, and Kumazoe teaches PDE-5 is an is a drug that sensitizes leukemia to apoptosis. This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 86 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0212090 A1, as evidenced by Rousseau et al. (BLOOD, 15Feb2006, Vol. 107, No. 4; hereinafter “Rousseau”), Alkasalias et al. (Int. J. Mol. Sci. 2018, 19, 1532; hereinafter “Alkasalias”), Tito (Mol Biotechnol. 2019 Mar;61 (3):209-220.; hereinafter "Tito"), Schattner et al. (Blood, Vol 91, No 8 (April 15), 1998: pp 2689-2697; hereinafter “Schattner”), Hostager and Bishop (Front. Immunol., 14 November 2013, Vol. 4 – 2013; hereinafter “Hostager”), Hanissian and Geha (Immunity, Vol. 6, 379–387, April 1997; hereinafter “Hanissian”), and Tchao and Turka. (American Journal of Transplantation 2012; 12: 1079-1090; hereinafter "Tchao"), as applied to claim(s) 1, 88-89 above, and further in view of Chonan et al. (Neuro-Oncology 17(11), 1453–1462, 2015; hereinafter “Chonan”).
The teachings of US090 as recited above apply for claim(s) 1.
US090 does not expressly teach the treatment of brain tumor(s).
Regarding instant claim(s) 22, Chonan teaches glioblastomas (e.g., brain tumors) express CD40L and that augmenting CD40 signaling enhances vaccine efficacy [e.g., title, abstract].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the cancer indication in the method of treating leukemia comprising administering a fibroblast vaccine as taught by US090, with the glioblastoma indication as taught by Chonan, to arrive at a method of treating glioblastoma comprising administering a fibroblast vaccine. A PHOSITA would have been motivated to substitute the cancer indication in the method of treating leukemia comprising administering a fibroblast vaccine as taught by US090, with the glioblastoma indication as taught by Chonan, because US090 teaches the base method and vaccine composition comprises fibroblasts engineered to express CD40L, and Chonan teaches that glioblastomas express CD40L and further that augmenting CD40 signaling (e.g., via CD40L+ fibroblast vaccine) enhances the efficacy of vaccinations against glioma models. There would have been a reasonable expectation of success for a PHOSITA to substitute the cancer indication in the method of treating leukemia comprising administering a fibroblast vaccine as taught by US090, with the glioblastoma indication as taught by Chonan, because US090 teaches the base method and vaccine composition comprises fibroblasts engineered to express CD40L, and Chonan teaches that glioblastomas express CD40L and further that augmenting CD40 signaling (e.g., via CD40L+ fibroblast vaccine) enhances the efficacy of vaccinations against glioma models. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 90-91 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2011/0212090 A1, as evidenced by Rousseau et al. (BLOOD, 15Feb2006, Vol. 107, No. 4; hereinafter “Rousseau”), Alkasalias et al. (Int. J. Mol. Sci. 2018, 19, 1532; hereinafter “Alkasalias”), Tito (Mol Biotechnol. 2019 Mar;61 (3):209-220.; hereinafter "Tito"), Schattner et al. (Blood, Vol 91, No 8 (April 15), 1998: pp 2689-2697; hereinafter “Schattner”), Hostager and Bishop (Front. Immunol., 14 November 2013, Vol. 4 – 2013; hereinafter “Hostager”), Hanissian and Geha (Immunity, Vol. 6, 379–387, April 1997; hereinafter “Hanissian”), and Tchao and Turka. (American Journal of Transplantation 2012; 12: 1079-1090; hereinafter "Tchao") in view of Hou et al. (Blood Cancer Journal (2015) 5, e331, Doi: 10.1038/bcj.2015.59; hereinafter “Hou”), as applied to claim(s) 1, and/or 88-89 above, and further in view of Schadendorf (Seminars in Oncology, Vol 29, No 5 (October), 2002: pp 503-512).
The teachings of US090 and/or Hou as recited above apply for claim(s) 1 and/or 88-89.
US090 and Hou do not expressly teach a method of treating melanoma comprising administration of a fibroblast vaccine (e.g., of claim 88) comprising p53 mutant and gp100 peptides.
Regarding instant claim(s) 90-91, Schadendorf teaches malignant melanomas comprise p53 mutant proteins and gp100 proteins [e.g., pg. 508 “gene transfer…”; pg. 509 “genetic immunizations”].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the cancer indication, and combine the cancer antigen target(s) in the method of treating leukemia comprising administering a fibroblast vaccine comprising mutant p53 as taught by US090 and Hou (see above), with the melanoma indication and mutant p53 and gp100 melanoma expressed antigens as taught by Schadendorf, to arrive at a method of treating melanoma comprising administering a fibroblast vaccine comprising mutant p53 and gp100 antigens . A PHOSITA would have been motivated to substitute the cancer indication, and combine the cancer antigen target(s) in the method of treating leukemia comprising administering a fibroblast vaccine comprising mutant p53 as taught by US090 and Hou (see above), with the melanoma indication and mutant p53 and gp100 melanoma expressed antigens as taught by Schadendorf, because US090 and Hou teach the base method of treating cancer comprising administering a fibroblast vaccine comprising p53 mutant peptide, and Schadendorf teaches p53 mutant antigen as well as gp100 mutant antigen is/are expressed in melanomas. One of ordinary skill in the art would understand that additional tumor antigen peptide(s) in the vaccine would necessarily make the vaccine effective for a wider number of patients with the specific cancer (e.g., melanoma) because there is heterogeneity in antigen expression even within a solid tumor (e.g., therefore more antigens commonly expressed in a tumor type result in more effective vaccines). There would have been a reasonable expectation of success for a PHOSITA to substitute the to substitute the cancer indication, and combine the cancer antigen target(s) in the method of treating leukemia comprising administering a fibroblast vaccine comprising mutant p53 as taught by US090 and Hou (see above), with the melanoma indication and mutant p53 and gp100 melanoma expressed antigens as taught by Schadendorf, because US090 and Hou teach the base method of treating cancer comprising administering a fibroblast vaccine comprising p53 mutant peptide, and Schadendorf teaches p53 mutant antigen as well as gp100 mutant antigen is/are expressed in melanomas. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141) and/or applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are currently 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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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