DETAILED ACTION
Status of Claims
Claims 1-15 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Office Action: Non-Final
Claim Objections
The following claims are objected to because of the following informalities:
A. Claim 6 is objected to because the claim should read:
6. ([…]) The composition for enhancing immunogenicity according to claim 1, wherein the immuno-stimulating factor is a ligand or agonist binding to a Toll-like receptor (TLR), a NOD-like receptor (NLR), a RIG-like receptor,
B. Claim 9 is objected to because the claim should read:
9. ([…]) The composition for enhancing immunogenicity according to claim 1, wherein a number-average molecular weight of the amphiphilic polymer is 500 to 100,000 by [[(]]molar ratio[[)]].
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112, First Paragraph - Enablement
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 the first paragraph of pre-AIA 35 U.S.C. § 112:
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 of carrying out his invention.
Claims 13 and 15 are rejected under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Scope of Enablement
Claims 13 and 15 are rejected under 35 U.S.C. § 112(a), because the specification, while being enabling for treating some kinds of cancer, does not reasonably provide enablement for “preventing” said cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. Specifically, the method of preventing cancer, has not been sufficiently taught to enable the full scope of the claims. In this regard, the application disclosure and claims have been compared per the factors indicated in the decision In re Wands, 8 USPQ 2d 1400 (Fed. Cir., 1988) as to undue experimentation. The factors include:
(1) the nature of the invention;
(2) the scope or breadth of the claims;
(3) the state of the prior art;
(4) the predictability or unpredictability of the art;
(5) the relative skill of those skilled in the art;
(6) the presence or absence of working examples;
(7) the amount of direction or guidance presented and,
(8) the quantity of experimentation necessary.
The relevant factors are addressed below on the basis of comparison of the disclosure, the claims and the state of the prior art in the assessment of undue experimentation.
(1) Nature of the Invention & (2) Scope or Breadth of the Claims:
Instant claims 13 and 15 recite:
13. ([…]) A vaccine for treatment and/or prevention of cancer, containing the composition for enhancing immunogenicity according to claim 1, as an active ingredient.
[…]
15. ([…]) A method for treating and/or preventing cancer, comprising administering the composition for enhancing immunogenicity according to claim 1 to a subject.
However, the instant specification as originally filed lacks adequate guidance, direction or discussion to apprise the skilled artisan of how to prevent cancer. The claims are broad in that they claim a method for preventing cancer, the breadth of which exacerbates the complexity of the invention. The term “preventing” is a potent and absolute term indicating that the method of prevention will necessarily prevent the onset of any cancer, regardless of the cause, and in every instance by the administration of the instant composition. Since the instant specification provides no limiting definition of the term “preventing,” the term has been interpreted expansively. The term “preventing” encompasses a wide range of situations, from preventing a disease from occurring to preventing it from progressing. Nor is the term limited by any time frame.
Applicant is claiming a method of “preventing” cancer in claims 13 and 15. Prevention, as defined by Merriam-Webster Dictionary, is to keep from happening or existing, which implies taking advance measures against something possible or probable. Furthermore, the act of preventing embraces complete 100% inhibition. Thus, the burden of enablement in the assertion of this claim is much higher than would be the case of enabling simply the treatment of the condition. As for the instant application in relation to the prior art, neither the prior art nor the instant application enable for prevention of cancer. Nowhere in the instant application has the efficacy of the instant composition been enabled to prevent the occurrence of cancer. Since absolute success in preventing most diseases/conditions is not reasonably possible, the specification, which lacks an objective showing that cancer can actually be prevented, is viewed as lacking an adequate written description of the same.
The claim is thus extremely broad insofar as it suggests that following administration of the claimed composition, one will not experience cancer; that should one already have said cancer, it will not worsen; and that it will not recur in any other cells of the body. For instance, the full scope of the claim encompasses the situation where administration of the instant composition necessarily requires that any cell of the body on that individual will never experience cancer from the time of the administration forward. While such prevention might theoretically be possible under strictly controlled laboratory conditions, as a practical matter it is nearly impossible to achieve in the “real world” in which patients live.
(3) State of the prior art
The composition of the instant claims, particularly for use as treating cancer is known. See, for instance, US 2011/0300223 A1 by Nishio et al., as discussed below. Thus, the state of the art with regard to using the instant composition to prevent cancer is essentially non-existent, and has not been described in the art.
(4) Degree of Predictability or Unpredictability in the Art
The ability to prevent cancer assumes that one is able to know where said cancer will occur before it occurs. Accurate, reliable, and reproducible prediction of where said cancer will occur on a mammal has not been demonstrated and is therefore highly unpredictable at this time.
(5) Relative Skill Possessed by Those in the Art
In view of the discussion of the state and predictability of the prior art, and the scope of the claims, which are drawn to a method of preventing cancer, the level of skill in the art is high and is at least that of a medical doctor or Ph.D. scientist with several years of experience in the field(s) of oncology.
(6) Presence or Absence of Working Examples
No working examples of preventing cancer were provided in applicant’s specification
(7) Amount of Guidance or Direction Provided
In considering the guidance provided in the specification, the use of the instant composition is described in the instant published application, US 2024/0374716 A1, at par. [0122]-[0128], for induction of mouse bone marrow-derived dendritic cell, and enhancing immunogenicity, not preventing cancer in the absolute meaning of “prevent,” noted above. In this respect, no guidance is presented as to how one determines what cells are expected to experience cancer. This is particularly important regarding the term “preventing” since it is not within the skill of the ordinary artisan to accurately predict which cells will have experience said cancer. Thus, in the absence of such guidance in the specification, the ordinary artisan would not know how to identify cells that may experience said cancer.
(8) Quantity of Experimentation Required to Make and Use the Invention
In view of the factors discussed above, the state of the art with regard to preventing cancer, in general, is fairly complex and sufficiently unpredictable such that the skilled artisan would have been required to undertake undue experimentation to determine the exact conditions and manner and/or process of execution to arrive at those conditions amenable to actually preventing said cancer in the absence of detailed guidance to this effect. Absent such direction or guidance as to how the skilled artisan would go about preventing said cancer, one of ordinary skill in the art would have no alternative recourse but to undertake an exhaustive, and, thus, unduly burdensome search of methods to practice the claimed invention.
Claim Rejections – 35 U.S.C. § 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. § 103(a) 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 C.F.R. § 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 1-15 are rejected under 35 U.S.C. § 103 as being unpatentable over NISHIO (US 2011/0300223 A1, Publ. Dec. 8, 2011; on 02/27/2024 IDS; hereinafter, “Nishio”), in view of KOSHI (US 2016/0256543 A1, Publ. Sep. 8, 2016; on 02/27/2024 IDS; hereinafter, “Koshi”).
Nishio is directed to:
IMMUNOGENIC COMPOSITION
ABSTRACT
An immunogenic composition includes as an effective ingredient an antigen-adjuvant microparticle complex containing an antigen encapsulated in an adjuvant microparticle composed of an amphiphilic polymer(s) whose hydrophobic segment is a poly(hydroxy acid), or a particle composed of the antigen-adjuvant microparticle complex associated together, can induce a high immune response against the antigen even with a small amount of the antigen and a small number of doses, so that the immunogenic composition is useful as a vaccine effective for therapy and prophylaxis of infectious diseases, cancer and the like.
Nishio, title & abstract. In this regard, Nishio teaches an “Antigen-Adjuvant Microparticle” complex of “dextran-poly(lactic-co-glycolic acid) (PLGA)” with “CEA (carcinoembryonic antigen)” and “immune-activating substance (CpG)”:
Example 3
Preparation of Antigen-Adjuvant Microparticle
Complexes Using Dex-g-PLGA Polymers (Dex-g-PLGA
particles (1)-(28))
[0099] In 100 μl of dimethyl carbonate, 5 mg of dextran-poly(lactic-co-glycolic acid) (PLGA) (Compounds (12)-(23)) in Example 1 was dissolved, to prepare a 50 mg/ml polymer solution. To this polymer solution, 20 μl of tert-butanol was added, and 50 μl of the encapsulated antigen ((OVA (ovalbumin) (Sigma) or CEA (carcinoembryonic antigen) (COSMO BIO Co., Ltd.)) and/or immune-activating substance (CpG) shown in Table 3 was/were added to the concentration(s) described, and the resulting mixture was stirred with a vortex mixer, to produce a reversed-phase emulsion. As the Cpg, 5′-gggggggCGACGATCGTCAgG-3′ (lowercase letters represent phosphorothioate-modified bases) (contract synthesis by Sigma-Genosys) was used.
[0100] The reversed-phase emulsion was subjected to prior freezing with liquid nitrogen, and freeze-dried using a freeze dryer (EYELA, FREEZE DRYER FD-1000) at a trap cooling temperature of −45° C. at a degree of vacuum of 20 Pa for 24 hours. The obtained solids were dispersed in the dispersion medium in the amount shown in Table 3, to prepare an S/O suspension. The S/O suspension was added dropwise to 2 ml of an aqueous 10% Pluronic F-68-containing solution, and the resulting mixture was stirred/emulsified by the stirring method described in Table 3, to prepare an S/O/W emulsion. From the S/O/W emulsion, the water-immiscible organic solvent was removed by solvent evaporation, to provide an antigen-adjuvant microparticle complex dispersion. The dispersion was subjected to prior freezing with liquid nitrogen, and freeze-dried using a freeze dryer (EYELA, FREEZE DRYER FD-1000) at a trap cooling temperature of −45° C. at a degree of vacuum of 20 Pa for 24 hours, to obtain dry powder of an antigen-adjuvant microparticle complex (average particle size, 0.4 μm) and a particle (average particle size, 5 to 40 μm) formed by association of the antigen-adjuvant microparticle complex. The result of calculation of the average particle size of the obtained particle by observation with a scanning electron microscope (SEM: S-4800 manufactured by Hitachi, Ltd.) is shown in Table 3.
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Nishio, par. [0099]-[0100], Ex. 3 & Table 3.
Regarding independent claim 1 and the requirements:
1. ([…]) A composition for enhancing immunogenicity, containing, as an active ingredient, a mixture of a particle and an immuno-stimulating factor, wherein the particle comprises an amphiphilic polymer in which a hydrophobic segment is poly(hydroxy acid) and a hydrophilic segment is β-glucan, and an antigen.
Nishio clearly teaches “Particle ID” “(13)” of an “Antigen-Adjuvant Microparticle” complex of “dextran-poly(lactic-co-glycolic acid) (PLGA)” with “CEA (carcinoembryonic antigen)” and “immune-activating substance (CpG)” (Nishio, par. [0099]-[0100], Ex. 3 & Table 3), WHEREBY it is noted:
“immune-activating substance (CpG)” (Nishio, par. [0099], Ex. 3 & Table 3) is an “immuno-stimulating factor” of independent claim 1;
“dextran-poly(lactic-co-glycolic acid) (PLGA)” (Nishio, par. [0099], Ex. 3 & Table 3) is “an amphiphilic polymer(s) whose hydrophobic segment is a poly(hydroxy acid)” (Nishio, abstract), which relates to “an amphiphilic polymer in which a hydrophobic segment is poly(hydroxy acid) and a hydrophilic segment is β-glucan” of claim 1, as well the requirements of claim 5 for:
5. ([…]) The composition for enhancing immunogenicity according to claim 1, wherein the poly(hydroxy acid) is poly(lactic-co-glycolic acid), polylactic acid, or polyglycolic acid.
but for “β-glucan”; and
“CEA (carcinoembryonic antigen)” (Nishio, par. [0099], Ex. 3 & Table 3) in an “antigen” of claim 1;
wherein “Antigen-Adjuvant Microparticle” complex of “dextran-poly(lactic-co-glycolic acid) (PLGA)” with “CEA (carcinoembryonic antigen)” (Nishio, par. [0099], Ex. 3 & Table 3) relates to a “particle” comprising “amphiphilic polymer” and “antigen” of claim 1.
However, it is noted that although Nishio teaches the “amphiphilic polymer is a graft amphiphilic polymer composed of a polysaccharide backbone and a poly(hydroxy acid) graft chain” (Nishio, par. [0012]), wherein “[t]he hydrophilic segment of the amphiphilic polymer is not restricted, and preferably a biocompatible polymer,” inter alia, “refractory polysaccharides ( e.g., cellulose, chitin, chitosan, gellan gum, alginic acid, hyaluronic acid, pullulan and dextran)” (Nishio, par. [0038]), Nishio, however, DOES NOT EXPRESSLY TEACH a “hydrophilic segment [that] is β-glucan” of the “amphiphilic polymer” required by claim 1, or the requirements of claims 3-4 and 9 for:
3. ([…]) The composition for enhancing immunogenicity according to claim 1, wherein the β-glucan is a polymer of glucose linked by one or more β-1,3 bonds and/or one or more β-1,6 bonds.
4. ([…]) The composition for enhancing immunogenicity according to claim 1, wherein the β-glucan is black yeast glucan, curdlan, pachyman, laminaran, lichenan, schizophyllan, lentinan, scleroglucan, or pachymaran.
[…]
9. ([…]) The composition for enhancing immunogenicity according to claim 1, wherein a number-average molecular weight of the amphiphilic polymer is 500 to 100,000 (molar ratio).
which is well within the purview of the ordinarily skilled artisan.
Koshi, for instance, is directed to:
IMMUNOPOTENTIATOR
ABSTRACT
There is provided an immunopotentiator comprising, as an active ingredient, a modified β-glucan which β-glucan and poly(hydroxy acid) are covalently bonded. The immunopotentiator can potently enhance the immunopotentiating effect of β-glucan.
Koshi, title & abstract. In this regard, Koshi discloses claim embodiments directed to a “a modified β-glucan which β-glucan and poly(hydroxy acid) are covalently bonded,” wherein the “poly(hydroxy acid) is a poly(lactic-co-glycolic acid)”:
1. An immunopotentiator comprising, as an active ingredient, a modified β-glucan which β-glucan and poly(hydroxy acid) are covalently bonded.
2. The immunopotentiator according to claim 1, wherein β-glucan is a polymer of glucose linked by at least one β-1,3 bond and/or at least one β-1,6 bond.
3. The immunopotentiator according to claim 1, wherein modified β-glucan is a graft type polymer composed of the main chain of β-glucan and the side chain of poly(hydroxy acid).
4. The immunopotentiator according to claim 1, wherein the proportion of β-glucan segments is 1% to 50% (w/w).
5. The immunopotentiator according to claim 1, wherein β-glucan is curdlan, pachyman, laminaran, lichenan, sizofiran, lentinan, scleroglucan, Aureobasidium pullulans glucan, or pachymaran.
6. The immunopotentiator according to claim 1, wherein the number average molecular weight of β-glucan is 500 to 100,000.
7. The immunopotentiator according to claim 1, wherein poly(hydroxy acid) is a poly(lactic-co-glycolic acid), polylactic acid, or polyglycolic acid.
(Ksohi, claims 1-7), which encompasses a “β-glucan” claims 1 and 3-4, for an “amphiphilic polymer” of claims 1 and 9. See MPEP § 2144.05 (I) regarding the obviousness of prior art overlapping claimed numerical ranges. Further in this regard, Koshi teaches that “When a modified β-glucan was used, the expression level of CD86 was higher than that when modified dextran (15) was used, revealing that modified β-glucan has potent dendritic cell activation capacity”:
Example 15
In Vitro Stimulation Test 2 of Modified β-Glucans
(Modified Pachyman (16), Modified Sizofiran (17),
Modified Aureobasidium pullulans Glucan (18),
Modified Pachymaran (22)) in Murine Bone Mar-
row-Derived Dendritic Cells (BMDC)
<Methods>
[0182] After 10 mg of a modified β-glucans obtained in Example 11 (modified pachyman (16), modified sizofiran (17), modified Aureobasidium pullulans glucan (18), modified pachymaran (22)) were weighed, they were dissolved in 1 ml of acetonitrile to obtain a polymer solution. By dropping of the polymer solution (corresponding to 1 mg of polymer) (100 μl) into a 12-well plate and drying the plate, a polymer coated plate was obtained. On the polymer coated plate, the dendritic cells obtained in Reference Example 1 were seeded together with a culture medium so that the number of cells was 3×105 per well. The seeded plate was incubated for 2 days in a CO2 incubator, and then the cells were strongly suspended using a micropipette to collect only cells not adhered on the plate. The collected cells were centrifuged at 1,500 rpm for 5 minutes to precipitate the cells, the supernatant was removed, and the cells were suspended in 100 μl of an RPMI medium. To the cell suspension, FITC-labeled anti-CD86 antibodies and PE-labeled anti-CD11c antibodies were added, and the suspension was allowed to stand at 4° C. for 15 minutes to perform antibody labeling reaction. After completion of the antibody labeling reaction, the expression level of an activation marker (CD86) in the dendritic cells (CD11c-positive cells) was assessed based on mean fluorescence intensity (MFI) by flow cytometry.
[0183] As Comparative Example, using a plate on which modified dextran (15) obtained in Comparative Example 1 was coated in the same manner, the expression level of the activation marker was compared in the same manner. As another Comparative Example, 1 mg of unmodified β-glucans (pachyman hydrolysate (7), sizofiran hydrolysate (8), Aureobasidium pullulans glucan hydrolysate (9), pachymaran hydrolysate (13)) obtained in Example 11 or 100 μg of poly I:C (Sigma-Aldrich Co. LLC.) with known immunopotentiating capacity were/was added to a culture medium, and the expression level of the activation marker was compared in the same manner.
<Results>
[0184] Mean fluorescence intensity (MFI), an index of the expression level of CD86, an activation marker of dendritic cells, is shown in FIG. 20. When a modified β-glucan was used, the expression level of CD86 was higher than that when modified dextran (15) was used, revealing that modified β-glucan has potent dendritic cell activation capacity. When an unmodified β-glucan was used, the expression level of CD86 was lower than that when modified β-glucan was used, revealing that modification of poly(hydroxy acid) to β-glucan is important for immunopotentiating capacity. Not only linear modified β-glucans (Example 4, modified curdlans (9) to (12); present Example, modified pachyman (16)) but also branched modified β-glucans (present Example: modified sizofiran (17), modified Aureobasidium pullulans glucan (18)) and derivatized modified β-glucan (present Example: modified pachymaran (22)) were found to have immunopotentiating capacity.
Koshi, par. [0182]-[0184], Ex. 15.
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to formulate Nishio’s “Particle ID” “(13)” (Nishio, par. [0099]-[0100], Ex. 3 & Table 3) and substituting “dextran-poly(lactic-co-glycolic acid) (PLGA)” (Nishio, par. [0099]) with “a modified β-glucan which β-glucan and poly(hydroxy acid) are covalently bonded” per Koshi (Koshi, abstract). One would have been motivated to do so with a reasonable expectation of success since both Nishio and Koshi are concerned with similar problems in the art, namely the formulation of immunological compositions. Nishio, abstract; Koshi, abstract. Further, it is well within the skill of the ordinary artisan to select suitable polysaccharide hydrophilic segment (Nishio, par. [0038]) for an “graft amphiphilic polymer composed of a polysaccharide backbone and a poly(hydroxy acid) graft chain” (Nishio, par. [0012]). See MPEP § 2144.07 stating that the selection of a known material based on its suitability for its intended use is prima facie obvious, which cites Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945), wherein “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle.” Doing so amounts to no more than combining prior art elements according to known methods to yield predictable results, namely the formulation of Nishio’s “Particle ID” “(13)” (Nishio, par. [0099]-[0100], Ex. 3 & Table 3) with “a modified β-glucan which β-glucan and poly(hydroxy acid) are covalently bonded” per Koshi (Koshi, abstract) in order to obtain the advantage of a “modified β-glucan” with “potent dendritic cell activation capacity” that is “higher than that when modified dextran” (Koshi, par. [0184], Ex. 15).
Thus, the prior art renders claims 1, 3-5 and 9 obvious.
Regarding claim 2 and the requirements:
2. ([…]) The composition for enhancing immunogenicity according to claim 1, wherein the mixture comprises each of the particle and the immuno-stimulating factor in an independent state.
Nishio teaches that “[t]he immune-activating substance may be either contained in the outside of the adjuvant microparticle or encapsulated therein”:
[0085] The immunogenic composition contains as an effective ingredient the antigen-adjuvant microparticle complex or the particle formed by association of the complex, and hence has an adjuvant capacity, but, by further inclusion of an immune-activating substance, a higher immune-activating capacity can be realized. The immune-activating substance may be either contained in the outside of the adjuvant microparticle or encapsulated therein, and the substance is preferably encapsulated in the adjuvant microparticle. The immune-activating substance is not restricted as long as it may function as an immune-activating substance, and examples thereof include oils, aluminum salts, calcium salts, gel-forming polymers, immune-activating cytokines and TLR receptor ligands, among which immune-activating cytokines and TLR receptor ligands are preferred.
(Nishio, par. [0085]), which encompasses “wherein the mixture comprises each of the particle and the immuno-stimulating factor in an independent state” of claim 2 (as well as par. [0096] of the instant published application, US 2024/0374716 A1, describing, “[i]n a mixture of the particle and the immune-stimulating factor, which is an active ingredient of the composition for enhancing immunogenicity of the present invention, each of the particle and the immuno-stimulating factor may be comprised in an independent state (namely, the immuno-stimulating factor may be comprised as a separate structure from the particle)”). See MPEP § 2123 [R-5] regarding the obviousness of rearranging a reference according to the teachings of that same reference.
Thus, the prior art renders claim 2 obvious.
Regarding claims 6-8 and the requirements:
6. ([…]) The composition for enhancing immunogenicity according to claim 1, wherein the immuno-stimulating factor is a ligand or agonist binding to a Toll-like receptor (TLR), a NOD-like receptor (NLR), a RIG-like receptor or a C-type lectin receptor (CLR), or a stimulator of interferon gene (STING).
7. ([…]) The composition for enhancing immunogenicity according to claim 6, wherein the ligand or agonist binding to the Toll-like receptor (TLR) is a ligand or agonist binding to TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, TLR9, or TLR11.
8. ([…]) The composition for enhancing immunogenicity according to claim 6, wherein the ligand or agonist binding to the Toll-like receptor (TLR) is any of the following (i) to (vii):
(i) a ligand or agonist binding to TLR2 selected from the group consisting of peptidoglycan, lipoprotein, lipopolysaccharide, and zymosan;
(ii) a ligand or agonist binding to TLR3 selected from the group consisting of poly(I:C) and poly(A:U);
(iii) a ligand or agonist binding to TLR4 selected from the group consisting of lipopolysaccharide (LPS), HSP60, RS09, and MPLA;
(iv) flagellin as a ligand or agonist binding to TLR5;
(v) a ligand or agonist binding to TLR7 or 8 selected from the group consisting of an imidazoquinoline compound and single-strand RNA;
(vi) a ligand or agonist binding to TLR9 selected from the group consisting of bacterial DNA, unmethylated CpG DNA, hemozoin, ODN1585, ODN1668, and ODN1826; and
(vii) a ligand or agonist binding to TLR11 selected from the group consisting of profilin and uropathogenic bacteria.
Nishio teaches suitable “immune-activating substance[s],” inter alia, “TLR receptor ligands” including “flagellin”:
[0085] The immunogenic composition contains as an effective ingredient the antigen-adjuvant microparticle complex or the particle formed by association of the complex, and hence has an adjuvant capacity, but, by further inclusion of an immune-activating substance, a higher immune-activating capacity can be realized. The immune-activating substance may be either contained in the outside of the adjuvant microparticle or encapsulated therein, and the substance is preferably encapsulated in the adjuvant microparticle. The immune-activating substance is not restricted as long as it may function as an immune-activating substance, and examples thereof include oils, aluminum salts, calcium salts, gel-forming polymers, immune-activating cytokines and TLR receptor ligands, among which immune-activating cytokines and TLR receptor ligands are preferred.
[…]
[0087] Examples of the TLR receptor ligands include lipoproteins; double-stranded RNAs such as poly I:C and poly I:CLC; flagellin; single-stranded RNAs; CpG; profilin; MPL; QS21; and TDM, among which nucleic acids such as double-stranded RNAs, single-stranded RNAs and CpG are preferred, and CpG is more preferred. The CpG herein means unmethylated CpG (cytosine-guanine)-motif DNAs existing in viruses, bacteria and the like (see Japanese Translated PCT Patent Application Laid-open No. 2001-503254). Various effective sequences are reported as CpG motifs, and the type of the sequence is not restricted as long as it has an immune-activating capacity, and the sequence may be prepared using a base analogue or may be selected from various types of modified products.
(Nishio, par. [0085] & [0087]), which is at least “(iv) flagellin as a ligand or agonist binding to TLR5” of claim 8, a “ligand or agonist binding to the Toll-like receptor (TLR)” of claims 6-8, and “immuno-stimulating factor” of claim 6. See MPEP § 2123 [R-5] regarding the obviousness of rearranging a reference according to the teachings of that same reference.
Thus, the prior art renders claims 6-8 obvious.
Regarding claim 10 and the requirements:
10. ([…]) The composition for enhancing immunogenicity according to claim 1, wherein an average particle size of the particle is 0.1 to 50 μm.
Nishio teaches “Particle ID” “(13)” of an “Antigen-Adjuvant Microparticle” complex of “dextran-poly(lactic-co-glycolic acid) (PLGA)” with an average particle size of 5 μm (Nishio, par. [0099], Ex. 3 & Table 3). See MPEP § 2144.05 (I) regarding the obviousness of prior art overlapping claimed numerical ranges.
Thus, the prior art renders claim 10 obvious.
Regarding claims 11-13 and the requirements:
11. ([…]) A medicine containing the composition for enhancing immunogenicity according to claim 1, as an active ingredient.
12. ([…]) A vaccine containing the composition for enhancing immunogenicity according to claim 1, as an active ingredient.
13. ([…]) A vaccine for treatment and/or prevention of cancer, containing the composition for enhancing immunogenicity according to claim 1, as an active ingredient.
Nishio teaches that “[t]he immunogenic composition can be used as a vaccine for therapy and/or prophylaxis of infectious diseases, cancer and the like” (Nishio, par. [0134]), relates to a medicine of claim 11, and vaccine of claims 12-13. It is further noted that the requirements of claims 11-13 for “enhancing immunogenicity,” and claim 13 for “treatment and/or prevention of cancer” are recitations of intended use. In this regard, it is noted that recitations of intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it reads on the claim. See MPEP § 2103 (I)(C)). Since Nishio teaches a“vaccine for therapy and/or prophylaxis of infectious diseases, cancer and the like” (Nishio, par. [0134]), as well as the structure of a “composition for enhancing immunogenicity according to claim 1,” as discussed above, then it reasonably follows that the prior art composition would be capable of performing the intended use recited in the instant claims.
Thus, the prior art renders claims 11-13 obvious.
Regarding claims 14-15 and the requirements:
14. ([…]) A method for enhancing immunogenicity, comprising administering the composition for enhancing immunogenicity according to claim 1, to a subject.
15. ([…]) A method for treating and/or preventing cancer, comprising administering the composition for enhancing immunogenicity according to claim 1 to a subject.
Nishio teaches “[t]he immunogenic composition can be used as a vaccine for therapy and/or prophylaxis of infectious diseases, cancer and the like” (Nishio, par. [0134]), which meets the active step requirements of claims 14-15 for “administering” for “enhancing immunogenicity” and “treating and/or preventing cancer” of claims 14-15.
Thus, the prior art renders claims 14-15 obvious.
Claim Rejections - Nonstatutory 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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-15 are rejected on the ground of nonstatutory double patenting over claims 1-10 of US Patent 10,556,004 B2 to Koshi et al., hereinafter “‘004 Patent,” matured from copending Application No. 15/028,266, in view of the disclosure of NISHIO (US 2011/0300223 A1, Publ. Dec. 8, 2011; on 02/27/2024 IDS; hereinafter, “Nishio”).
Although the conflicting claims are not identical, they are not patentably distinct because the instant claims as well as the copending claims are drawn to a particle composition comprising an antigen, and a modified-glucan in which β-glucan and poly (hydroxy acid) are covalently bonded. However, to the extent that the ‘004 Patent DOES NOT TEACH an immuno-stimulating factor such as a “Toll-like receptor (TLR),” bound or independent, per the requirements of claims 1-2 and 6-8, the incorporation thereof would be obvious for similar reasons as discussed above, per the disclosure of Nishio.
Thus, the ‘004 Patent per Nishio render claims 1-15 obvious.
Claims 1-8 and 10-15 are provisionally rejected on the ground of nonstatutory double patenting over claims 1, 3-7, 10-12 and 14-19 of copending Application No. 18/687,149 (‘149 Application). This is a provisional double patenting rejection since the conflicting claims have not in fact been patented.
Although the conflicting claims are not identical, they are not patentably distinct because the instant claims as well as the copending claims are drawn to a composition for enhancing immunogenicity, containing, as an active ingredient, a mixture of a particle and an immuno-stimulating factor, wherein the particle comprises an amphiphilic polymer and an antigen.
Claim 1 is obvious per claims 1 and 4 of the ‘149 Application. See MPEP § 2123 [R-5] regarding the obviousness of rearranging a reference according to the teachings of that same reference.
Claim 2 is anticipated by claim 3 of the ‘149 Application.
Claim 3 is anticipated by claim 5 of the ‘149 Application.
Claim 4 is anticipated by claim 6 of the ‘149 Application.
Claim 5 is anticipated by claim 7 of the ‘149 Application.
Claim 6 is anticipated by claim 10 of the ‘149 Application.
Claim 7 is anticipated by claim 11 of the ‘149 Application.
Claim 8 is anticipated by claim 12 of the ‘149 Application.
Claim 10 is anticipated by claim 14 of the ‘149 Application.
Claim 11 is anticipated by claim 15 of the ‘149 Application.
Claim 12 is anticipated by claim 16 of the ‘149 Application.
Claim 13 is anticipated by claim 17 of the ‘149 Application.
Claim 14 is anticipated by claim 18 of the ‘149 Application.
Claim 15 is anticipated by claim 19 of the ‘149 Application.
Claims 1-8 and 10-15 are provisionally rejected on the ground of nonstatutory double patenting over claims 1, 3-7 and 10-19 of copending Application No. 18/692,396 (‘396 Application). This is a provisional double patenting rejection since the conflicting claims have not in fact been patented.
Although the conflicting claims are not identical, they are not patentably distinct because the instant claims as well as the copending claims are drawn to a composition for enhancing immunogenicity, containing, as an active ingredient, a mixture of a particle and an immuno-stimulating factor, wherein the particle comprises an amphiphilic polymer and an antigen.
Claim 1 is obvious per claims 1 and 4 of the ‘396 Application. See MPEP § 2123 [R-5] regarding the obviousness of rearranging a reference according to the teachings of that same reference.
Claim 2 is anticipated by claim 3 of the ‘396 Application.
Claim 3 is anticipated by claim 5 of the ‘396 Application.
Claim 4 is anticipated by claim 6 of the ‘396 Application.
Claim 5 is anticipated by claim 7 of the ‘396 Application.
Claim 6 is anticipated by claim 10 of the ‘396 Application.
Claim 7 is anticipated by claim 11 of the ‘396 Application.
Claim 8 is anticipated by claim 12 of the ‘396 Application.
Claim 10 is anticipated by claim 14 of the ‘396 Application.
Claim 11 is anticipated by claim 15 of the ‘396 Application.
Claim 12 is anticipated by claim 16 of the ‘396 Application.
Claim 13 is anticipated by claim 17 of the ‘396 Application.
Claim 14 is anticipated by claim 18 of the ‘396 Application.
Claim 15 is anticipated by claim 19 of the ‘396 Application.
Conclusion
Claims 1-15 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOMINIC LAZARO whose telephone number is (571)272-2845. The examiner can normally be reached on Monday through Friday, 8:30am to 5:00pm EST; alternating Fridays out.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, BETHANY BARHAM can be reached on (571)272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DOMINIC LAZARO/Primary Examiner, Art Unit 1611
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