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 .
Claim Status
The preliminary amendment filed February 5, 2024 has been received and entered.
Claims 3-8 and 11-12 have been amended.
Claims 1-12 are pending and under consideration.
Priority
This application is a 371 of PCT/JP2022/030202 filed August 5, 2022, which claims the benefit of Japan Application No. 2021-130022 filed August 6, 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
However, support for the claimed invention cannot be determined because the foreign priority documents provided for Application No. JP 2021-130022 are not in English. Applicant cannot rely upon the certified copy of the foreign priority application to overcome any prior art rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216. Failure to provide a certified translation may result in no benefit being accorded for the non-English application. Accordingly, the PCT/ JP2022/030202 filing date of August 5, 2022 will be used for the purpose of applying prior art.
Information Disclosure Statements
The information disclosure statements (IDSs) submitted March 5, 2025 and January 6, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 6-7 are objected to because of the following informalities:
Claims 6-7 (line 2) - should read “the nucleic acid structure according to claim 1…”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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.
WRITTEN DESCRIPTION
Claims 1-4 and 5-12 are rejected under 35 U.S.C. 112(a), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See MPEP § 2163.
Claim 1 is drawn to a nucleic acid structure comprising a polynucleotide encoding a SNARE protein and a polynucleotide encoding an allergen.
The claims encompass a large genus of structurally distinct polynucleotides encoding for a SNARE protein.
The specification discloses that the SNARE protein belongs to a family of proteins that are classified into four subfamilies of QA-SNARE, QB-SNARE, QC-SNARE, and R-SNARE, based on the characteristics of amino acid residues of the SNARE motif. SNARE proteins are localized in cellular fractions such as endoplasmic reticula, golgi bodies, endosomes, vacuoles, and cytoplasmic membranes, as well as exosomes, which each function in the process of membrane fusion in a specific intracellular transport pathway [0004].
The instant specification only demonstrates the results for 21 types of SNARE polynucleotides fused with a nucleic acid encoding ovalbumin. The specification further discloses the resulting SNARE-Ova fusion polypeptides induce CD4+ T cells to produce IFNg which is correlated with suppression of Th2-type immune response associated with exposure to an allergen. However, as shown in Figure 1, not all 21 SNARE-Ova polypeptides demonstrated an increase in IFNg compared to the control. In fact, almost half (9/21) fusion polypeptides resulted in little to no increase in IFNg compared to the control. Further, only VAMP7-Ova demonstrated an antigen-specific Th1-type immune response and an antigen-specific cellular immune response [Figures 6-7, and 10].
It is well understood in the art that SNARE proteins share the common function of docking of vesicles with the target compartment. However, Jahn et al. (Mol Cell Bio, 2006; cited IDS 3/5/2025) teaches that there are 36 human SNARE proteins comprised of different amino acid sequences that carry out vastly different roles. For example, SNARES are involved in both endocytosis (e.g. vesicle transport) and exocytosis (hormone secretion) [Introduction]. Therefore, the properties of one SNARE cannot be applied to other SNARES as evidenced by Applicant’s own experiments in which only some of the SNARE fusions demonstrated an increase of IFNg indicative of a Th1-type response and only one (VAMP7-Ova) demonstrated a cellular immune response. Thus, one cannot readily extrapolate the properties of one SNARE protein to the SNARE proteins encompassed by claim 1, as the properties of the claimed SNARE proteins are not predictive of the full genus of proteins.
The instant application has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of polynucleotides encoding for SNARE proteins encompassing various structures, specificities and functions. Further, the Court has interpreted 35 U.S.C. § 112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe, Inc., 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002). In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 48 USPQ2d 1398 (Fed Cir. 1997)).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with
reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession
of the invention. The invention is, for purposes of the 'written description’ inquiry, whatever is now
claimed." (See Vas-Cath, p. 1117). The specification does not "clearly allow persons of ordinary skill in
the art to recognize that [he or she] invented what is claimed." (See Vas-Cath, p. 1116). Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., Inc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
Meeting the written description threshold requires showing that the applicant was in
“possession” of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support
need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein
v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning —
i.e., what the written description and knowledge in the art would lead one to speculate as to
modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Ariad points out, the written description requirement also
ensures that when a patent claims a genus by function, the specification recites sufficient materials to
accomplish that function - a problem that is particularly acute in biological arts." Ariad, 598 F.3d at 1352-3.
Given the claimed broadly class of polynucleotides, in the absence of sufficient disclosure of relevant identifying characteristics, the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims. There is insufficient written description of the required kind of structure- identifying information about the corresponding makeup of the claimed polynucleotides to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). Thus, one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
Claims 2-4 and 6-12 are included in the rejection because they depend from a rejected claim and fail to resolve the issue.
ENABLEMENT #1
Claims 1-12 are rejected under 35 U.S.C. 112(a), 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.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP § 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(1) The nature of the invention and (5) The breadth of the claims:
Claim 1 is drawn to a polynucleotide encoding for a SNARE protein and an allergen.
Claim 5 limits the SNARE proteins to one of 14 SNAREs.
Samanthi et al. (www.differencebetween.com/what-is-the-difference-between-v-snare-and-t-snare, 2022) teaches SNARE is a large protein family that mediates the fusion of vesicles with target membranes. There are 60 different SNARES that have been identified in mammalian cells. Generally, SNARES are classified as v-SNAREs and t-SNARES. V-SNARE proteins are associated with the membrane of transport vesicle during the process of budding that mediates exocytosis. t-SNARE proteins form stable subcomplexes and function as a guide for v-SNARE [Conclusion]. Samanthi further teaches VAMP7 and VAMP 8 are two main types of v-SNARE while Syntaxin 1 and SNAP-25 are two main types of t-SNARE [pg. 4].
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
Ungar et al. (Annu Rev Cell Dev Biol, 2003) teaches the relationship between SNARE complex assembly and membrane fusion is complex. The structure of SNARE proteins vary, with some SNAREs having two SNARE motifs contained within the same polypeptide chain, while some SNAREs lack a C-terminal transmembrane anchor [pg. 496]. Further, many SNARE proteins have autonomously folding N-terminal domains that regulate assembly [pg. 497].
Given the lack of predictability of SNARE function (i.e. endocytosis or exocytosis) combined with the varying structure of SNARE proteins, one of ordinary skill in the art would have to engage in undue experimentation to identify which SNARE proteins when fused to an allergen that would elicit a Th1-type immune reaction.
6) the amount of direction or guidance provided by the inventor; 7) the existence of working examples;
The instant specification sets forth the results for only 21 SNARE proteins fused with a single allergen, ovalbumin. A Th1-type response is associated with the suppression of the Th2-type immune response elicited with exposure to an allergen. Of the 21 fusion peptides tested, 9 did not elicit an increase in IFNg, which is indicative of a Th1-type response capable of suppressing the Th2-type allergic reaction. Further, claim 5 recites 14 SNAREs, however, not all were shown to elicit a response. For example, Figure 1 clearly shows that the STX6-Ova construct did not elicit any IFNg release, with levels equivalent to control constructs. Further, only one SNARE protein, VAMP7, was shown to elicit a cellular immune response or to treat ovalbumin associated allergic reaction. Thus, it would be difficult for one of ordinary skill in the art to envisage any SNARE protein would also have the same properties as recited in the instant claims.
Thus, based on the unpredictability of the art and the breadth of the claims, the instant
specification must provide a sufficient and enabling disclosure commensurate in scope with the instant
claims. It would require enormous amount of trial and error in order to obtain a SNARE polynucleotide that when linked with a nucleic acid encoding for an allergen that would elicit an enhanced Th1-type immune response. This is not in commensurate in scope with the instant claims, which encompass fusing any SNARE polypeptide with an allergen to treat an allergic reaction. Thus, it would require undue experimentation to practice the full scope of the claimed method. Specifically, one cannot envisage all SNARE proteins to have the same properties as recited in the instant claims. However, the explicit examples provided in the instant specification fall within a genus that is not fully enabled.
Claims 2-4 and 6-12 are included in the rejection because they depend from a rejected claim and fail to resolve the issue.
ENABLEMENT #2
Claim 11 is rejected under 35 U.S.C. 112(a) because the specification, while being enabling for treating an allergy; does not reasonably provide enablement for preventing an allergy as broadly claimed.
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.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP § 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(1) The nature of the invention and (5) The breadth of the claims:
Claim 11 is drawn to a nucleic acid vaccine comprising a SNARE protein fused with an allergen via a linker that is administered for the prevention or treatment of an allergy.
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
Regarding allergies in general, Royal et al. (Yale J Bio and Med, 2020) teaches allergic conditions remain a cause of significant morbidity and healthcare expenditure and, while manageable with chronic treatment, to a large degree have no cure [Background]. Regarding prevention of food allergies, Royal teaches that no benefit was found when restricting common food allergens among pregnant women including dairy, egg, wheat, and peanut. Although studies have suggested that maternal fish consumption during pregnancy is protective for allergy outcomes in their offspring, a systematic review failed to validate this association. Furthermore, although a higher maternal intake of dairy products has been shown to reduce the risk of atopic dermatitis and asthma, it has not yet prevented these disorders. Importantly, it was concluded that dietary interventions during pregnancy may compromise maternal and fetal health [pg. 690]. In addition, Royal teaches various studies wherein introduction of egg proteins in infants reduced the incidence of, but did not prevent egg allergy [pg. 693].
Given the lack of predictability in the treatment of allergies, one of skill in the art would have to engage in undue experimentation to identify what SNARE protein would be applicable to treat a specific allergy.
6) the amount of direction or guidance provided by the inventor; 7) the existence of working examples;
The instant specification sets forth in vitro examples testing the ability of 21 SNARE-Ova fusion peptides to induce an IFNg reaction that is correlated with a Th1-type immune response. Of the 21 polypeptides, only 12 demonstrated an increase in IFNg [Fig. 1]. The VAMP7-Ova polypeptide was chosen for further characterization. Figure 9 shows that Ova-sensitized mice treated with an VAMP7-Ova mRNA construct did not succumb to lower body temperature, which is associated with an anaphylactic reaction. However, the in vivo experiments only suggest (i.e. via body temperature) that allergy to ovalbumin can be treated with the recited construct, not prevent it. Therefore, the only embodiment that is enabled is treatment of an allergy. One of skill in the art would be required to engage in extensive, difficult experimentation to first develop criteria for identification of types of SNARE protein and allergy to which the method can apply which is known to be unpredictable as indicated above. This required experimentation is undue.
In conclusion, the claimed invention does not provide enablement for prevention of an allergen. Thus for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
ENABLEMENT #3
Claim 12 is rejected under 35 U.S.C. 112(a), first paragraph, because the specification, while being enabling for administering a nucleic acid vaccine parenterally; does not reasonably provide enablement for administering a nucleic acid vaccine orally.
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.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP § 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(1) The nature of the invention and (5) The breadth of the claims:
Claim 12 is drawn to a nucleic acid vaccine comprising a polynucleotide encoding for a SNARE protein and an allergen that is administered orally or parenterally.
Abramson et al. (Matter, 2022; 5(3):975-987) teaches nucleic acids are enabling a new generation of therapeutics and vaccines to treat and prevent a range of diseases [Summary]. Nucleic acid-based therapeutics have been shown to improve clinical outcomes in patients with hereditary transthyretin-mediated amyloidosis and homozygous familial hypercholesterolemia. In addition, experimental nucleic acid-based vaccines have recently been developed for cancer and Zika virus, and nucleic acid-based vaccines for COVID-19 have been approved for clinical use. Abramson further teaches that mRNA vaccines are attractive because they can be developed more rapidly than other vaccine types [Introduction].
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
Regarding the current state of the art in nucleic acid therapeutics and vaccines, Abramson et al. (Matter, 2022; 5(3):975-987) teaches that they are only available as injectable formulations because these therapeutic molecules cannot survive passage through the gastrointestinal tract [Highlights]. Therefore, even though patients prefer oral dosage forms over injections, nucleic acids are generally administered intravenously, intramuscularly, or subcutaneously because the gastrointestinal tract naturally prohibits biomacromolecule uptake. When administered orally, nucleic acids rapidly degrade after ingestion, thus limiting cellular permeation and reducing bioavailability. Parenteral delivery methods enable rapid systemic uptake and ensure that therapies reach organs receiving large amounts of blood flow, such as the liver, lungs, and kidneys [Introduction].
To enhance GI uptake, target a specific organ, promote transfection, and/or prevent off-target effects, nucleic acid- and other macromolecule-based medications have often turned to permeation enhancers and specially designed nanoparticles. Still, nucleic acid-based therapeutics continue to have low oral bioavailability [Introduction].
Given the predictability of low bioavailability when orally administrating therapeutic nucleic acid vaccines, one of ordinary skill in the art would have to engage in undue experimentation to identify alternative methods (i.e., nanoparticles or robotic injection pills) to deliver a SNARE + allergen complex to effectively treat a patient when administered orally.
6) the amount of direction or guidance provided by the inventor; 7) the existence of working examples;
The instant specification sets forth in vivo results wherein a VAMP7-Ova polynucleotide is administered intramuscularly to ovalbumin sensitized mice. Challenged mice treated with the vaccine demonstrated less body temperature loss associated with anaphylactic shock than control mice. However, there are no examples wherein the nucleic acid vaccine is administered orally. Therefore, the only embodiment that is enabled is parenteral delivery. One of skill in the art would be required to engage in extensive, difficult experimentation to first develop methods to achieve oral bioavailability which is known to be challenging as indicated above. This required experimentation is undue.
In conclusion, the claimed invention does not provide enablement for oral administration of a nucleic acid vaccine comprising a polynucleotide encoding a SNARE protein and an allergen. Thus for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
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.
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Tureci et al. (US 8,178,653) (“Tureci”) in view of Lacombe (British Society Immunol, 2017; https://www.immunology.org/policy-and-public-affairs/briefings-and-position-statements/allergy) (“Lacombe”).
The instant claims are drawn to a nucleic acid structure, which is a plasmid vector, mRNA or a virus vector, administered parenterally, comprising a polynucleotide encoding a SNARE protein and a polynucleotide encoding an allergen, wherein the polynucleotide encoding an allergen is linked downstream of the polynucleotide encoding a SNARE protein via a polynucleotide encoding a linker. The SNARE protein is selected from the group consisting of VAMP7, GOSR2, STX10, STX18, BNIP1, STX7, VTI1A, STX16, STX5, GOSR1, STX8, STX12, VAMP8 and SEC22B. The claimed polynucleotide induces a Th1-type immune response and an allergen-specific cellular response for the treatment of allergy.
Tureci teaches methods for inducing an immune response in a mammal by administering nucleic acid fusion constructs encoding for an antigen and a SNARE molecule [col. 1]. Tureci teaches that the efficacy of recombinant vaccines is dependent upon optimal stimulation of CD4+ and CD8+ lymphocytes, however, only very poor or even no stimulation of CD4+ lymphocytes can be achieved with recombinant vaccines based on nucleic acids. Tureci teaches that vaccines can be modified to maximize the immune response by increasing antigen presentation and thus immunogenicity in relation to a particular antigen by administering fusion peptides [col. 2].
Specifically, Tureci teaches nucleic acids which code for a fusion molecule comprising an antigen and a SNARE protein, such as syntaxin-5, syntaxin-8, syntaxin-10, VTI1A, and VAMP-7 (instant claims 1, 5). Targeted transport of the antigen into a defined compartment ( e.g. lysosomes and endosomes) is possible by fusing an antigen to a SNARE protein at the C terminus of the SNARE protein (instant claim 2). The fusion molecule further comprises a transmembrane linker of 80-120 amino acids between the SNARE and the antigen (instant claim 3) [col. 5, Fig. 7]. The fusion molecule is administered and expressed on antigen presenting cells, particularly dendritic cells, monocytes, and macrophages, which increases the antigen-presenting activity of such cells which in turn enhances the primary activation of CD4 + and CD8+ T cells [col. 6].
Tureci teaches the fusion molecule can be used for the treatment, vaccination, or immunization against various antigens (instant claim 8, 11). The nucleic acid construct is recombinant mRNA that is introduced into the host cell using a plasmid or viral vector (instant claim 4) [col. 12, 14]. The therapeutic agent can be administered by injection or by infusion (instant claim 12) [col. 18].
Experimental results show that the fusion molecules lead to an enhanced stimulation and expansion of antigen-specific CD4+ and CD8+ lymphocytes and are 100x more potent in relation to the expansion of antigen-specific CD8+ lymphocytes. Further, the immunogenic peptides have a stronger effect on the expansion of antigen-specific CD4+ T cells, even at a 100x lower dose [col. 25-26]. Importantly, the constructs induced a maximum level of antigen-specified IFNg secretion when incubated with autologous dendritic cells from antigen-positive donors (instant claims 6-7, 9-10) [col. 23].
The teachings of Tureci differ from the present invention in that although a nucleic acid vaccine construct encoding for a SNARE protein linked to an antigen which induces a cellular immune response is taught, the antigen is not explicitly taught as being an allergen.
Lacombe teaches allergens are proteins called antigens found in a non-infectious allergy-causing substance (for example pollens or dust mites), which ultimately trigger the immune system to respond in a way that can be harmful, causing tissue damage and serious disease. These harmful immune responses are termed hypersensitivities and often cause a number of undesirable reactions which can lead to wheezing, coughing, edema (swelling), or, in extreme circumstances, anaphylaxis. IgE-mediated allergy is broadly characterized as a Type 1 hypersensitivity [pg. 3-4].
Given that Lacombe teaches that allergens are a specific type of antigen that causes a Type 1 hypersensitive immune response, one of ordinary skill in the art would have a reasonable expectation of success in using an allergenic peptide instead of an antigen in the construct taught by Tureci.
Section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalents for the same purpose. The court has held that it is obvious to combine two elements each of which is taught by the prior art to be useful for the same purpose. No specific teaching or suggestion is needed for combination – the idea of combining them flows logically from their having been individually taught in the prior art as useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the invention as a whole was prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention.
Double Patenting
Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 13 of U.S. Application No. 18/681,254 in view of Lacombe (British Society Immunol, 2017; https://www.immunology.org/policy-and-public-affairs/briefings-and-position-statements/allergy) (“Lacombe”).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to the identical nucleic acid vaccine construct comprising a polynucleotide encoding a SNARE protein and recite the exact claim language describing the immunogenic properties of said polynucleotide construct as recited in the instant claims. The instant claims differ from the copending claims only in that the term “allergen” is used in place of an antigen. However, copending claim 5 discloses that the antigen can be a fungal antigen, which would also be considered an allergen as fungal antigen can trigger an allergic reaction.
Furthermore, Lacombe teaches that allergens are a specific type of antigen that causes a Type 1 hypersensitive immune response (pg. 3-4). Therefore, one of ordinary skill in the art would have a reasonable expectation of success in using an allergenic peptide instead of an antigen in the construct recited in the copending claims.Section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalents for the same purpose. The court has held that it is obvious to combine two elements each of which is taught by the prior art to be useful for the same purpose. No specific teaching or suggestion is needed for combination – the idea of combining them flows logically from their having been individually taught in the prior art as useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. As such, the instant claimed invention is an obvious modification of the copending claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 12, and 14 of U.S. Application No. 18/681,277 in view of Lacombe (British Society Immunol, 2017; https://www.immunology.org/policy-and-public-affairs/briefings-and-position-statements/allergy) (“Lacombe”).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to the identical nucleic acid structure with the same immunogenic properties for prevention or treatment of an allergy comprising a polynucleotide encoding a SNARE protein and an antigen, wherein the antigen is selected from a group of allergens.
Although the copending claims do not recite any examples of an allergen, Lacombe teaches allergens are antigens found in a non-infectious allergy-causing substance (for example pollens or dust mites), which ultimately trigger a Type I hypersensitive response [pg. 3-4].
Given that Lacombe teaches that allergens are a specific type of antigen that causes a Type 1 hypersensitivity, one of ordinary skill in the art would have a reasonable expectation of success in using an allergenic peptide in the construct recited in the copending claims.
Section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalents for the same purpose. The court has held that it is obvious to combine two elements each of which is taught by the prior art to be useful for the same purpose. No specific teaching or suggestion is needed for combination – the idea of combining them flows logically from their having been individually taught in the prior art as useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results.
As such, the instant claimed invention is an obvious modification of the copending claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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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/MAUREEN VARINA DRISCOLL/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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