DETAILED ACTION
This action is in reply to papers filed 9/22/2025. Claims 1-15 and 17-20 are pending and examined herein.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the as-filed specification.
Withdrawn Rejection(s)
Unless otherwise indicated, previous objections/rejections that have been rendered moot in view of the amendment will not be reiterated.
Rejection(s) Necessitated by Amendments
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.
Prior Art Rejection 1
Claim(s) 1-3 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Wolter et al. (WO2008051852A2, Published 5/2/2008, Filed 10/19/2007, previously cited), Hare et al. (PgPub US20190038742A1, Published 2/07/2019, previously cited), Pallaoro et al. (PgPub US20110052716A1, Published 3/3/2011, previously cited) and Pittman, P. (Vaccine. 2002 May 31:20 Suppl 3:S48-50.).
Claim interpretation: In the absence of an explicit definition in the specification, the recitation “sex risk level”, when taken in context with claim 1, is interpreted to mean the likelihood of a negative therapeutic outcome based on the sex of the subject in whom the adjuvant is administered to. In other words, the adjuvant is administered to a subject based on the likelihood of a positive therapeutic outcome in said subject.
Regarding claim 1, in-part, Wolter teaches a custom composition suitable for use as a cancer vaccine comprising: an immunogenic amount of a cancer antigen preparation of interest; and a cancer vaccine adjuvant, wherein said cancer vaccine adjuvant comprises a preparation characteristic of an extracellular matrix (ECM) material (Pg. 8, para. 28), wherein the ECM upon which autologous (Pg. 11,para. 39) fibroblasts (as in claim 2 and claim 3 (the instant specification at para. 8 states immune system stem cells includes fibroblast cell)) (Pg. 12, para. 47) have been grown and subsequently removed may be collected. At Pg. 33, para. 149, Wolter teaches this conditioned ECM may be used as a vaccine or vaccine adjuvant. Wolter teaches these conditioned-ECM preparations possess a relatively concentrated combination of cell and tissue secreted factors/peptides/organic and inorganic molecules anticipated to provide much if not all of the beneficial anti-cancer and anti-tumor growth properties of the whole cell-containing preparations (Pg. 10, para. 36). Wolter adds that the ECM preparation further comprises T-cell suppressors and/or CpG oligonucleotides (as further in claim 1) (Pg. 10, para. 37).
However, Wolter fails to teach the cell medium comprises an allogenic stem cell line (as further in claim 1).
Before the effective filing date of the claimed invention, Hare et al. taught a method of enhancing an immune response to a vaccine by administering a vaccine and a population of isolated allogeneic human mesenchymal stem cells (as further in claim 1) (Abstract). Hare teaches that surprisingly, despite the reports of mesenchymal stem cells having a suppressive effect on aspects of the immune system, they have discovered a method of enhancing a subject's immune response to a vaccine or of inducing an immune response in a non-responding subject (Pg. 2, para. 13).
However, neither Wolter nor Hare teach synthesizing the oligonucleotide-based adjuvant with a second adjuvant (as further in claim 1).
Before the effective filing date of the claimed invention, Pallaoro et al. taught a process for preparing an immunogenic composition comprising a step of mixing (i) an adjuvant of the invention and (ii) an immunogen (Pg. 1, para. 8). With respect to the adjuvant, Pallaoro teaches a process for preparing the immunological adjuvant of the invention, comprises a step of mixing an aluminium salt (as in claim 15) with the oligonucleotide and then the polymer is added (Pg. 1, para. 9). Note that Pallaoro identifies the aluminum salt as an adjuvant (Pg. 1, para. 12) (as further in claim 1).It is further noted that Pallaoro teaches the oligonucleotide to be a adjuvant and comprising a CpG motif (Pg. 2, para. 20). Pallaoro teaches adjuvant compositions of the invention can be administered in combination with immunogens to induce an immune response in a cancer patient (Pg. 4, para. 58).
However, none of Wolter nor Hare nor Pallaoro teach the synthesized adjuvant comprises an enhanced adjuvant calculated as a function of sex risk level (as further in claim 1).
Before the effective filing date of the claimed invention, Pittman taught anthrax vaccine, adsorbed (AVA) is a vaccine containing aluminum hydroxide that is administered as six subcutaneous (SQ) doses over 18 months. Pittman teaches that it is the only aluminum hydroxide licensed for SQ administration. To optimize the vaccination schedule and route of administration, a prospective pilot study comparing the use of fewer doses administered intramuscularly (IM) as well as SQ with the licensed schedule and route was performed. Data from that study on injection site reactions were extracted for this report. Erythema and induration occurred more commonly when the vaccine was administered SQ compared to IM.
Pittman teaches local adverse events such as SQ nodules, erythema and induration were more common in women and associated with the SQ route of administration (Abstract; ). This teaching by Pittman reads on the synthesized adjuvant (CpG Oligonucleotides-based adjuvant of Wolter as a first adjuvant and an aluminum adjuvant of Pallaoro as a second adjuvant) comprising an enhanced adjuvant as Pittman teaches an enhanced therapeutic effect in men as compared to women ~ sex risk level (as further in claim 1).
When taken with the teachings of Wolter et al., wherein Wolter teaches a vaccine derived from the medium of fibroblasts seeded on an ECM material, wherein said medium possesses anti-cancer and anti-tumor growth properties, one of ordinary skill in the art would have found it prima facie obvious to also include the allogeneic stem cells of Hare et al. with a reasonable expectation of success. The skilled artisan would have also found it prima facie obvious to do so because Hare specifically teaches enhancing an immune response to a vaccine by administering a vaccine and a population of isolated allogeneic human mesenchymal stem cells. Additionally, one of ordinary skill in the art would have found it prima facie obvious to synthesize the ECM CpG Oligonucleotides-based adjuvant of Wolter with an aluminum adjuvant because Pallaoro teaches the suitability of this composition for treating cancer. Moreover, the skilled artisan would have found it prima facie obvious to use this vaccine, as combined by the teachings of Wolter et al., Hare et al., and Pallaoro et al., in men as Pittman teaches SQ nodules, erythema and induration were more common in women and associated with the SQ route of administration.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
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Prior Art Rejection 2
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Wolter et al. (WO2008051852A2, Published 5/2/2008, Filed 10/19/2007, previously cited), Hare et al. (PgPub US20190038742A1, Published 2/07/2019, previously cited) Pallaoro et al. (PgPub US20110052716A1, Published 3/3/2011, previously cited) and Pittman, P. (Vaccine. 2002 May 31:20 Suppl 3:S48-50.) as applied to claims 1-3 and 15 above and further in view of Allen et al. (PgPub US20060147437A1, Published 2/27/2006, previously cited).
The teachings of Wolter et al., Hare et al., Pallaoro et al. and Pittman are relied upon as detailed above. However, none of Wolter et al., Hare et al., Pallaoro et al. and Pittman teach the cultured medium is conditioned by retinal cells (as in claim 4).
Before the effective filing date of the claimed invention, Allen et al. teach their invention is based on the discovery that retinal pigmented epithelial (RPE) cells secrete Fas L and are capable of functioning outside of the structural confines of the retina to produce an immune privileged site (Pg. 1, para. 6). To test this theory, Allen teaches freshly isolated human fetal thymocytes were incubated in fresh medium or RPE cell conditioned-medium (as in claim 4) for 6-12 hours (Pg. 7,para. 58- 60). Allen teaches apoptosis in the thymocytes incubated in fresh medium (not exposed to RPE cells) was approximately 12%. However, when the Fas L concentration of the RPE CM had reached its highest value, i.e., 13 ng/100 ul of conditioned medium, the apoptotic value had risen to 24% or to approximately twice that of the control medium (Pg. 8, para. 69).
When taken with the teachings of Wolter et al. in view of Hare et al., Pallaoro et al. and Pittman, wherein the combination teaches a male-specific vaccine comprising an ECM material comprising a NP CpG oligonucleotide adjuvant synthesized with an aluminium adjuvant and an allogeneic stem cell line, wherein said vaccine possesses anti-cancer and anti-tumor growth properties, one of ordinary skill in the art would have found it prima facie obvious to also seed retinal cells on the ECM of Wolter prior to its use as a vaccine. The skilled artisan would have found it prima facie obvious to do so in order to include the anti-cancer and anti-tumor secreted factors Allen observed in retinal cell conditioned medium on the ECM. A reasonable expectation of success was present as Wolter observed success when deriving secreted factors by culturing cells from a rat tumor on an ECM material (Pg. 12, para. 46)
The Courts have consistently held that "it is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose;" wherein the "idea of combining them flows logically from their having been individually taught in prior art." In re Kerkhoven, 205 USPQ 1069 (C.C.P.A. 1980).
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Prior Art Rejection 3
Claims 5-7, 9-11, 17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Wolter et al. (WO2008051852A2, Published 5/2/2008, Filed 10/19/2007, previously cited), Hare et al. (PgPub US20190038742A1, Published 2/07/2019, previously cited) Pallaoro et al. (PgPub US20110052716A1, Published 3/3/2011, previously cited) and Pittman, P. (Vaccine. 2002 May 31:20 Suppl 3:S48-50.) as applied to claims 1-3 and 15 above and further in view of Tam et al. (PgPub US20040013649A1, Published 1/22/2004,previously cited) and Kallen et al. (PgPub US20190054164A1, Published 2/21/2019,previously cited).
The teachings of Wolter et al., Hare et al., Pallaoro et al. and Pittman are relied upon as detailed above. However, none of Wolter, Hare et al., Pallaoro et al. and Pittman teach the oligonucleotide-based adjuvant comprises an antisense oligonucleotide (as in claim 5), the antigen comprises a nucleotide (as in claim 6), wherein the antigen comprises of a protein fragment of a bacterium (as in claim 17) or wherein the oligonucleotide-based adjuvant comprises a hexamer oligonucleotide (as in claim 19). Further, none of Wolter, Hare, Pallaoro and Pittman teach generating a vaccine schedule (as in claim 9).
Before the effective filing date of the claimed invention, Tam et al. taught when compared to known adjuvants, the present invention provides improved adjuvants comprising combinations of lipids and nucleic acids that act synergistically to stimulate enhanced, Th-1 biased immune responses. Tam teaches such compositions of the present invention comprise a nucleic acid component and a lipid component. Preferably the nucleic acid component comprises at least one oligonucleotide (Pg. 8, para 94), such an antisense oligonucleotide (as in claim 5) (Pg. 9, para. 104) or a hexamer oligonucleotide (as in claim 19) (Pg. 26, para. 274). In addition, Tam teaches the cancer vaccine comprising, inter alia, the adjuvant also comprises a target antigen (Pg. 8, para. 91), wherein such antigen is a nucleic acid encoding (as in claim 6) a peptide or protein in a form suitable for expression in a subject and presentation to the immune system of that subject (Pg. 15, para. 147 and 151) and wherein such antigen is derived from the bacterium Helicobacter pylori (as in claim 17) (Pg. 15, para. 152). Tam notes that for treatment of a patient, depending on activity of the compound, manner of administration, purpose of the immunization (i.e., prophylactic or therapeutic), nature and severity of the disorder, age and body weight of the patient (as in claim 10 and claim 11), different doses may be necessary. Tam teaches the administration of a given dose can be carried out both by single administration in the form of an individual dose unit or else several smaller dose units. Multiple administration of doses at specific intervals of weeks or months apart (i.e. vaccine schedule) (as in claim 9) is usual for boosting the antigen-specific responses (Pg. 18, para. 183).
And while none of Wolter, Hare, Pallaoro, Pittman nor Tam teach the antigen comprising nucleotide comprises mRNA (as in claim 7), this is remedied by Kallen et al. Indeed, Kallen teaches a vaccine comprising at least one mRNA encoding at least one antigen (as in claim 7) for use in the prophylaxis and/or treatment of a disease in newborns and/or infants, wherein the treatment elicits an immune response in said newborn or infant (Pg. 32, para. 237). Kallen explains that by antigen synthesis in transfected host cells, mRNA vaccines directly introduce antigen into cellular antigen processing and presentation pathways, granting access to MHC molecules and triggering T cell responses, irrespective of the hosts MHC haplotype. This enables the induction of polyclonal T cell responses that may act synergistically with other immune responses, including B cells (Pg. 4, para. 21).
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Wolter et al., Hare et al. ,Pallaoro et al. and Pittman., wherein the combination teaches a male-specific vaccine comprising an ECM material comprising a NP CpG oligonucleotide adjuvant synthesized with an aluminium adjuvant and an allogeneic stem cell line, wherein said vaccine possesses anti-cancer and anti-tumor growth properties, with the teachings of Tam et al., wherein Tam teaches improved adjuvants comprising combinations of lipids and nucleic acids that act synergistically to stimulate enhanced, Th-1 biased immune responses, with a reasonable expectation of arriving at the claimed invention.
That is, one of ordinary skill in the art would have found it prima facie obvious to modify the synthesized adjuvant of Wolter et al., Hare et al., Pallaoro et al. and Pittman such that it include elements of the adjuvant of Tam as Tam teaches their adjuvants are improved over what is known in the art. Additionally, given Wolter’s concern regarding vaccine safety (see Wolter at Example 7, Pg. 24+), the skilled artisan would found it prima facie obvious to look to Tam because Tam provides guidance on determining a vaccination schedule based on, inter alia, the age of the vaccine recipient.
Finally, one of ordinary skill in the art would have found it prima facie obvious to use an antigen-encoding mRNA because Kallen explains that by antigen synthesis in transfected host cells, mRNA vaccines directly introduce the antigen into cellular antigen processing and presentation pathways, granting access to MHC molecules and triggering T cell responses.
Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Prior Art Rejection 4
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Wolter et al. (WO2008051852A2, Published 5/2/2008, Filed 10/19/2007, previously cited), Hare et al. (PgPub US20190038742A1, Published 2/07/2019, previously cited) Pallaoro et al. (PgPub US20110052716A1, Published 3/3/2011, previously cited) and Pittman, P. (Vaccine. 2002 May 31:20 Suppl 3:S48-50.) as applied to claims 1-3 and 15 above and further in view of Furch et al. (PgPub US20180140717A11, Published 5/24/2018, previously cited).
The teachings of Wolter et al., Hare et al., Pallaoro et al. and Pittman are relied upon as detailed above. However, none of Wolter, Hare et al., Pallaoro et al., and Pittman teach the delivery of the vaccine comprises a targeting system to specific receptor sites (as in claim 8).
Before the effective filing date of the claimed invention, Furch et al. taught a method of preferentially delivering an active agent, including vaccines (Pg. 6, para. 56), to cells of a mammalian subject, including a human that expresses surface receptors enabling receptor-mediated uptake of a targeted nanocarrier so as to deliver its therapeutic payload into said cell (as in claim 8) (Pg. 3, para. 19).
When taken with the teachings of Wolter et al. ,Hare et al., Palloro et al., and Pittman wherein the combination teaches a male-specific vaccine comprising an ECM material comprising a NP CpG oligonucleotide adjuvant synthesized with an aluminum adjuvant and an allogeneic stem cell line, wherein said vaccine possesses anti-cancer and anti-tumor growth properties, one of ordinary skill in the art would have found it prima facie obvious to use the carrier system of Furch et al., with a reasonable expectation of arriving at the claimed invention. The skilled artisan would have found it prima facie obvious to do so because Furch teaches system delivers the payload directly to the targeted cell expressing surface receptors.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Prior Art Rejection 5
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Wolter et al. (WO2008051852A2, Published 5/2/2008, Filed 10/19/2007, previously cited), Hare et al. (PgPub US20190038742A1, Published 2/07/2019, previously cited) Pallaoro et al. (PgPub US20110052716A1, Published 3/3/2011, previously cited) and Pittman, P. (Vaccine. 2002 May 31:20 Suppl 3:S48-50.) as applied to claims 1-3 and 15 above and further in view of Drexler et al. (Cancer Res (1999) 59 (19): 4955–4963., previously cited).
The teachings of Wolter et al., Hare et al. Pallaoro et al. and Pittman are relied upon as detailed above. However, none of Wolter et al., Hare et al., Pallaoro et al. or Pittman teach the antigen comprises a modified carrier virus (as in claim 12).
Before the effective filing date of the claimed invention, Drexler et al. taught vaccination with tumor-associated antigens is a promising approach for cancer immunotherapy. Because the majority of these antigens are normal self-antigens, they may require suitable delivery systems to promote their immunogenicity. Towards this end, Drexler teaches a recombinant vector based on the modified vaccinia virus Ankara (MVA) was used for expression of human tyrosinase, a melanoma-specific differentiation antigen (as in claim 12) and evaluated for its efficacy as an antitumor vaccine. Drexler notes that the tyrosinase-specific CTL responses were significantly augmented by repeated vaccination with MVA-hTyr. Concluding, Drexler teaches these findings demonstrate that HLA-restricted CTLs specific for human tumor-associated antigens can be efficiently generated by immunization with recombinant MVA vaccines. The results are an essential basis for MVA-based vaccination trials in cancer patients (Abstract; Pg. 4961, Col. 2, last paragraph).
When taken with the teachings of Wolter et al., Hare et al., Palloro et al., and Pittman wherein the combination teaches a male-specific vaccine comprising, inter alia, a cancer antigen of interest, one of ordinary skill in the art would have found it prima facie obvious to modify the antigen such that it is contained in the modified recombinant vector of Drexler. The skilled artisan would have found it prima facie obvious to do so because Drexler observed success when MVA was used for expression of a melanoma-specific differentiation antigen.
Thus, for the same benefit, the modification would have been prima facie obvious.
Prior Art Rejection 6
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Wolter et al. (WO2008051852A2, Published 5/2/2008, Filed 10/19/2007, previously cited), Hare et al. (PgPub US20190038742A1, Published 2/07/2019, previously cited) Pallaoro et al. (PgPub US20110052716A1, Published 3/3/2011, previously cited) and Pittman, P. (Vaccine. 2002 May 31:20 Suppl 3:S48-50.) as applied to claims 1-3 and 15 above and further in view of Kang et al. (Oncotarget. 2015 Sep 29; 6(29): 27751–27762. , previously cited) and Ji et al. (Metab Eng. 2020 Jan; 57: 193–202. , previously cited)
The teachings of Wolter et al., Hare et al., Pallaoro et al. and Pittman are relied upon as detailed above. However, none of Wolter et al., Hare et al., Pallaoro et al. Pittman teach the oligonucleotide-based adjuvant is received from a user and purified in a cell line (as in claim 13).
Before the effective filing date of the claimed invention, Kang et al. evaluated the use of a human (a user) pancreatic cancer derived protein, pancreatic adenocarcinoma upregulated factor (PAUF), as a novel DC vaccine adjuvant (as in claim 13, in-part). Kang shows that PAUF can induce activation and maturation of DCs and activate NFkB by stimulating the Toll-like receptor signaling pathway. Furthermore, vaccination with PAUF treated DCs pulsed with E7 or OVA peptides leads to generation of E7 or OVA-specific CD8+ T cells and memory T cells, which correlate with long term tumor protection and antitumor effects against TC-1 and EG.7 tumors in mice (Abstract; paragraph bridging Pg. 27753 and 27754). Kang adds that to keep the cost of producing this adjuvant reasonable, E. coli can be used to produce recombinant protein (Pg. 27758, Col. 1).
Towards this end, Ji et al. report the engineering of an Escherichia coli strain (a strain is a subpopulation of a cell line) (as in claim 13) for in situ production and accumulation of MPLA. Furthermore, Ji established a succinct method for purifying MPLA from the engineered E. coli strain (as further in claim 13). Ji shows that the purified MPLA (named EcML) stimulates the mouse immune system to generate antigen-specific IgG antibodies similarly to commercially available MPLA, but with a dramatically reduced manufacturing time and cost (Abstract; Pg. 6, last paragraph).
When taken with the teachings of Kang et al., one of ordinary skill in the art would have found it prima facie obvious to derive an adjuvant for the male-specific vaccine of Wolter in view of Hare, Pallaoro and Pittman et al. from a male human user/patient. The skilled artisan would have found it prima facie obvious to do so in order to provide a personalized adjuvant treatment. Moreover, one of ordinary skill in the art would have found it prima facie obvious to produce said adjuvant in an E. Coli strain because Ji observed success in producing an adjuvant and with substantially reducing manufacturing time and cost. Thus, for these advantages, the modification would have been prima facie obvious.
Prior Art Rejection 7
Claims 1 and 14 are rejected under 35 U.S.C. 103 as being unpatentable Wolter et al. (WO2008051852A2, Published 5/2/2008, Filed 10/19/2007, previously cited), Hare et al. (PgPub US20190038742A1, Published 2/07/2019, previously cited), Bigdeli et al. (Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1603-1609, previously cited) and Wang et al. (Environ Toxicol Pharmacol. 2017 Jun:52:193-199.).
Claim interpretation: In the absence of an explicit definition in the specification, the recitation “sex risk level”, when taken in context with claim 1, is interpreted to mean the likelihood of a negative therapeutic outcome based on the sex of the subject in whom the adjuvant is administered to. In other words, the adjuvant is administered to a subject based on the likelihood of a positive therapeutic outcome in said subject.
Regarding claim 1,in-part, Wolter teaches a custom composition suitable for use as a cancer vaccine comprising: an immunogenic amount of a cancer antigen preparation of interest; and a cancer vaccine adjuvant, wherein said cancer vaccine adjuvant comprises a preparation characteristic of an extracellular matrix (ECM) material (Pg. 8, para. 28), wherein the ECM upon which autologous (Pg. 11,para. 39) fibroblasts (Pg. 12, para. 47) have been grown and subsequently removed may be collected. At Pg. 33, para. 149, Wolter teaches this conditioned ECM may be used as a vaccine or vaccine adjuvant. Wolter teaches these conditioned-ECM preparations possess a relatively concentrated combination of cell and tissue secreted factors/peptides/organic and inorganic molecules anticipated to provide much if not all of the beneficial anti-cancer and anti-tumor growth properties of the whole cell-containing preparations (Pg. 10, para. 36). Wolter adds that the ECM preparation further comprises T-cell suppressors and/or CpG oligonucleotides (as further in claim 1) (Pg. 10, para. 37).
However, Wolter fails to teach the cell medium comprises an allogenic stem cell line (as further in claim 1).
Before the effective filing date of the claimed invention, Hare et al. taught a method of enhancing an immune response to a vaccine by administering a vaccine and a population of isolated allogeneic human mesenchymal stem cells (as further in claim 1) (Abstract). Hare teaches that surprisingly, despite the reports of mesenchymal stem cells having a suppressive effect on aspects of the immune system, they have discovered a method of enhancing a subject's immune response to a vaccine or of inducing an immune response in a non-responding subject (Pg. 2, para. 13).
However, neither Wolter nor Hare teach synthesizing the oligonucleotide-based adjuvant with a second adjuvant (as further in claim 1).
Before the effective filing date of the claimed invention, Bigdeli et al. teach silver (as further in claim 1 and claim 14) nanoparticles are one of the most attractive metal nanoparticles which have antimicrobial, adjuvanticity, and anti-tumour properties. Moreover, silver-based nanoparticles have attracted attention, because they show enhanced physicochemical and biological characteristics based on the type of additional elements used in the nanoparticle preparations (Pg. 1603, Col. 2, para. 1). Towards this end, Bigdeli et al. teach the mechanism of synthesized silver chloride nanoparticles (AgClNPs) in apoptosis induction against human breast cancer cells was investigated at both transcriptional and translational levels. Bigdeli teaches in vitro cell viability assay clearly indicated AgClNPs were severely toxic to human breast cancer cells even more than AgNPs. Moreover, an increase in the percentage of apoptotic cells, measured by flow cytometry, plainly clarified an induction of programmed cell death in the cancer cells after treatment with AgClNPs (paragraph bridging Pg. 1607 and Pg. 1608).
However, none of Wolter nor Hare nor Bigdeli teach the synthesized adjuvant comprises an enhanced adjuvant calculated as a function of sex risk level (as further in claim 1).
Wang et al. teach silver nanoparticles (AgNPs) have been used in medical products and industrial coatings, due to their antimicrobial properties. However, Wang cautions that excessive use of AgNPs can have adverse effects on the human body, however, their toxicity characteristics to human sperm and the potential mechanisms are not entirely clear. In this study, Wang exposed human sperm to different doses of AgNPs (0, 50 μg ml−1, 100 μg ml−1, 200 μg ml−1 or 400 μg ml−1) for various times (15 min, 30 min, or 60 min), followed by analyses of the sperm viability, motility and the ratio of abnormal to normal sperm. Then, transmission electron microscopy(TEM) was used to explore the sperm ultrastructural characteristics. The results showed a dose- and time-dependent decline in sperm viability and motility and an increased ratio of abnormal to normal sperm after 30 min and 60 min of exposure to AgNPs at 200 μg ml−1 and 400 μg ml−1. The most common abnormalities were sperm heads with disrupted chromatin or absent acrosomes, bent tails, and curved mid-pieces. The ultrastructural characteristics of AgNP-treated sperm included disrupted, swollen, granular and vacuolar defects of the chromatin. In addition, ROS(reactive oxygen species)production and DNA fragmentation were markedly increased after 60 min of exposure to AgNPs at 200 μg ml−1 and 400 μg ml−1. Wang’s results indicated that AgNPs caused detrimental changes in human sperm characteristics, and the excessive use of AgNPs should be carried out with caution (Abstract; Fig. 2, Fig. 3; Pg. 196, Col. 2). This teaching by Wang reads on the synthesized adjuvant (CpG Oligonucleotides-based adjuvant of Wolter as a first adjuvant and an silver adjuvant of Bigdeli as a second adjuvant) comprising an enhanced adjuvant as Wang teaches an enhanced therapeutic effect in women as compared to men ~ sex risk level (as further in claim 1).
When taken with the teachings of Wolter et al., wherein Wolter teaches a vaccine derived from the medium of fibroblasts seeded on an ECM material, wherein said medium possesses anti-cancer and anti-tumor growth properties, one of ordinary skill in the art would have found it prima facie obvious to also include the allogeneic stem cells of Hare et al. with a reasonable expectation of success. The skilled artisan would have also found it prima facie obvious to do so because Hare specifically teaches enhancing an immune response to a vaccine by administering a vaccine and a population of isolated allogeneic human mesenchymal stem cells. Additionally, one of ordinary skill in the art would have found it prima facie obvious to synthesize the ECM CpG Oligonucleotides-based adjuvant of Wolter with an silver adjuvant because Bigdeli teaches silver has anti-tumor activity. Moreover, the skilled artisan would have found it prima facie obvious to use this vaccine, as combined by the teachings of Wolter et al., Hare et al., and Bigdeli et al., in women as Wang teaches human sperm can be negatively affected by exposure to silver nanoparticles.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Prior Art Rejection 8
Claims 18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Wolter et al. (WO2008051852A2, Published 5/2/2008, Filed 10/19/2007, previously cited), Hare et al. (PgPub US20190038742A1, Published 2/07/2019, previously cited), Pallaoro et al. (PgPub US20110052716A1, Published 3/3/2011, previously cited) and Pittman (Proc Natl Acad Sci USA. 2013 Dec 3;110(49):19902-7.) as applied to claims 1-3 and 15 above and further in view of Klemke et al. (WO2021163222A1, Published 8/19/2021, previously cited).
The teachings of Wolter et al., Hare et al., Pallaoro et al. and Pittman are relied upon as detailed above. However, none of Wolter et al., Hare et al., Pallaoro et al. and Pittman teach the immune system cells comprise of mast cells (as in claim 18) and are cryopreserved (as in claim 20).
Before the effective filing date of the claimed invention, Klemke et al. taught methods of making and delivering vaccine compositions using an enucleated cell-based platform (Abstract). Specifically, Klemke teaches a therapeutic fluid comprising conditioned media in which cytoplasts are stored (Pg. 96-97,para. 223-224). Klemke teaches the cytoplast is derived from an immune cell, such as a mast cell (as in claim 18) (Pg. 31, para. 71; Pg. 97,para. 227). Klemke teaches the mast cells are cryopreserved (as in claim 20) prior to use (Pg. 101,para. 238; Pg. 129, para. 457). Klemke adds that such enucleated cell-based platform reduces the vaccine development timeline as compared with conventional biological vaccines, and improves vaccine efficacy.
When taken with the teachings of Wolter et al., Hare et al., Pallaoro et al., and Pittman wherein the combination teaches a male-specific vaccine comprising an ECM material comprising a CpG oligonucleotide adjuvant and aluminium adjuvant and an allogeneic stem cell line, wherein said vaccine possesses anti-cancer and anti-tumor growth properties, one of ordinary skill in the art would have found it prima facie obvious to also include mast cells on the ECM material prior to its use as a vaccine. The skilled artisan would have found it prima facie obvious to do because Klemke teaches conditioned media derived from mast cells contain cytoplasts which possess therapeutic benefits.
The Courts have consistently held that "it is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose;" wherein the "idea of combining them flows logically from their having been individually taught in prior art." In re Kerkhoven, 205 USPQ 1069 (C.C.P.A. 1980).
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
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Conclusion
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).
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/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632