DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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.
Election/Restrictions
Applicant’s election without traverse of Group II, claims 9-12 in the reply filed on 6 July 2026 is acknowledged.
Claims 1-8 and 13-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6 July 2026.
Applicant’s election of the species of a nucleic acid vaccine in the reply filed on 6 July 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
No claim is withdrawn due to the species election.
Specification
The instant specification discloses the following on the paragraph bridging pages 1-2, which is reproduced below.
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As such, applicant cites reference #8 as supporting the idea that adjuvants are included in mRNA vaccines to enhance their immunogenicity. However, looking to reference #8, this reference has the following title, as of page 30 of the specification.
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As such, reference #8 would appear to relate to DNA vaccination, which would not appear to support the idea that adjuvants are included in mRNA vaccine formulations to enhance their immunogenicity. As such, the specification appears to be in error in that it cites reference #8 as supporting the idea that reference #8 supports the idea that adjuvants are included in mRNA vaccines.
Claim Interpretation
Instant claim 9 recites the term “buffer.” The examiner notes that the term “buffer” does not appear to have been defined in the instant specification. Nevertheless, the term “buffer” is commonly used in this art area to refer to an aqueous solution comprising a salt dissolved therein, wherein the salt dissolved therein helps resist dramatic pH changes caused by the addition of solutes and thereby buffers the pH in a particular range. This is commonly achieved by using a salt whose cations or anions have a pKa (i.e. negative logarithm of the acidity constant) in the range of the desired pH.
A general overview of the science of pH buffers has been provided at LibreTexts (“6.8: pH Buffers” https://chem.libretexts.org/@go/page/372205 accessed 14 July 2026, pages 6.8.1-6.8.4); with that being said, the claims are not understood to be limited to the specific buffers discussed in LibreTexts. The buffering effect is well-described in figure 6.8.2 of LibreTexts, which is reproduced below.
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The examiner clarifies that the term “buffer” as recited is understood to refer to aqueous solutions rather than organic solutions.
The instant claims recite the terms “DOTAP” and “Quil-A.” These abbreviations are defined as of the instant specification on page 2, relevant text reproduced below.
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The examiner notes that at the time of filing, “DOTAP” was a well-known cationic lipid and Quil-A a well-known vaccine adjuvant.
Claim Rejections - 35 USC § 112(b) – Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 12 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 12 recites the abbreviation “DTOP.” It is unclear how this term further limits the claim scope. The abbreviation “DTOP” is not defined by the instant specification and the skilled artisan would not have known “DTOP” to have been a well-known abbreviation.
As best understood by the examiner, “DTOP” appears to be a typographical error, and the term that should have been recited is “DOTAP.” As such
in order to overcome this rejection, the examiner suggests removing “DTOP” and replacing it with “DOTAP”; and
for the purposes of examination under prior art, the examiner will interpret the term “DTOP” as if it recited “DOTAP.”
Claim Interpretation – Issues Regarding 35 U.S.C. 112(f)
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that use the word “means” or “step” but are nonetheless not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph because the claim limitation(s) recite(s) sufficient structure, materials, or acts to entirely perform the recited function. Such claim limitation(s) is/are: “comprising the steps of” in claim 9, as well as claims 10 and 12, which further reference “step (i)”.
Because this/these claim limitation(s) is/are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are not being interpreted to cover only the corresponding structure, material, or acts described in the specification as performing the claimed function, and equivalents thereof.
If applicant intends to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to remove the structure, materials, or acts that performs the claimed function; or (2) present a sufficient showing that the claim limitation(s) does/do not recite sufficient structure, materials, or acts to perform the claimed function.
Claim Rejections - 35 USC § 103 – Obviousness
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 9-10 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mehravaran et al. (Iran Journal of Immunology, Vol. 12(4), 2015, pages 274-287) in view of Cho et al. (US 2022/0287970 A1) and Esener et al. (US 2016/0303236 A1).
Mehravaran et al. (Iran Journal of Immunology, Vol. 12(4), 2015, pages 274-287), which is drawn to cationic immune stimulating complexes, as of Mehravaran, page 274, title and abstract. Mehravaran teaches the following method of making this composition, as of the last paragraph of page 276, relevant text reproduced below.
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Mehravaran appears to differ from the claimed method for at least the following reasons. In the claimed method, a solution of DOTAP in [aqueous] buffer and a solution of Quil-A in aqueous buffer are separately prepared, then combined. In contrast, in the above-reproduced method, DOTAP is first dissolved in chloroform, the chloroform evaporated to form a solid film. Then an aqueous buffer solution comprising Quil-A in phosphate buffered saline (PBS) was prepared and mixed with the solid DOTAP film. As such, the method of Mehravaran does not include a step of producing a solution of DOTAP dissolved in a buffer in the absence of Quil-A.
Cho et al. (hereafter referred to as Cho) is drawn to a combination of saponin with cationic liposomes for reducing hemolysis, as of Cho, title and abstract. Cho teaches mixing a liposome with saponin, as of paragraph 0006, relevant text reproduced below.
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The examiner understands the above-reproduced text to teach mixing a liposome, which is necessarily present in an aqueous environment rather than in an organic solvent, with saponin; see also the title of Cho. Cho teaches liposome in HEPES buffer, as of paragraph 0100.
For the purposes of this rejection, the examiner takes the position that Cho does not teach a vaccine, and that the purpose of combining the cationic liposome and saponin of Cho differs from that of the instant invention. This is because, in the instant invention, the cationic liposome and saponin are being combined to make a vaccine, whereas they are being combined to reduce red blood cell hemolysis in Cho.
It would have been prima facie obvious for one of ordinary skill in the art to have modified the method of Mehravaran to have first combined the cationic lipid in an aqueous buffer to form a liposome, then to have later added saponin Quil-A. Mehravaran is drawn to a method of making a composition that includes both a liposome made from a cationic lipid and a saponin. Mehravaran teaches that an aqueous buffer comprising saponin is added to a film containing the cationic lipid. However, Cho teaches that a cationic liposome in a buffer may be combined with a saponin, also separately in an aqueous phase. As such, the skilled artisan would have been motivated to have modified the method of Mehravaran to have first formed a cationic liposome by adding aqueous buffer to the lipids including DOTAP followed by later adding Quil-A saponin in order to have predictably formed a composition with both a cationic lipid and a saponin for predictable use in a vaccine, as taught by Mehravaran, with a reasonable expectation of success.
Neither Mehravaran nor Cho teach the required vortexing step.
Esener et al. (hereafter referred to as Esener) is drawn to nanoparticles for drug delivery, as of Esener, title and abstract. Esener teaches mixing of lipids and a dye to be encapsulated by vortexting for 15 seconds, as of Esener, paragraph 0162.
Esener does not teach a cationic lipid or Quil-A.
It would have been prima facie obvious for one of ordinary skill in the art to have used the vortexing method of Esener to have mixed the lipids and Quil-A of Mehravaran and Cho. Both Mehravaran and Cho teach mixing a cationic lipid and Quil-A, but do not teach how this mixing is conducted. Esener teaches that vortexing for 15 seconds is useful to mix lipids with payload materials. As such, the skilled artisan would have been motivated to have vortexed the DOTAP and Quil-A of Mehravaran and Cho to have predictably mixed these ingredients with a reasonable expectation of success.
As to claim 9, part (i), Mehravaran teaches mixing Quil-A in phosphate-buffered saline, which is abbreviated as PBS. As best understood by the examiner, Mehravaran teaches a concentration of 8 mg of Quil-A in 4 mL of PBS, as of Mehravaran, page 276, relevant text reproduced above, which appears to be 2 mg/mL of Quil-A. Assuming a density of 1 g/mL (or 1000 mg/mL), which is the density of water, this would appear to be 2 mg Quil A per 1000 mg total, or 0.2% Quil-A. This appear to be higher than the claimed amount. Nevertheless, generally, differences in concentration between the claimed invention and prior art will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144.05(II)(A). In this case, no evidence of criticality has been provided. Additionally, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A). In this case, the general conditions of forming a liposome by mixing Quil-A with DOTAP have been taught by the prior art. As such, it would not have been inventive for the skilled artisan to have discovered the optimum or workable concentration of DOTAP via routine experimentation.
Also as to claim 9, step (i), The examiner further takes the position that the difference between hydrating a DOTAP containing film with a buffer comprising a saponin, as taught by Mehravaran, as compared with first forming DOTAP liposomes in aqueous buffer followed by later adding saponin would appear to be a difference in the order of steps. Selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results; also, selection of any order of mixing ingredients is prima facie obvious. See MPEP 2144.04(IV)(C).
As to claim 9, step (ii), Mehravaran appears to teach a 2:2:1 ratio of DOTAP, Quil-A and cholesterol, as of Mehravaran, page 276, relevant text reproduced above. This appears to indicate that the amount of DOTAP taught by Mehravaran is the same as that of Quil-A, which would appear to be 0.2% DOTAP. This appear to be higher than the claimed amount. Nevertheless, generally, differences in concentration between the claimed invention and prior art will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144.05(II)(A). In this case, no evidence of criticality has been provided. Additionally, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A). In this case, the general conditions of forming a liposome by mixing Quil-A with DOTAP have been taught by the prior art. As such, it would not have been inventive for the skilled artisan to have discovered the optimum or workable concentration of DOTAP via routine experimentation. The examiner also notes that Mehravaran also teaches 6.7 mg/mL total lipids; however, this appears to be the total lipid concentration in chloroform, which is not relevant because the chloroform is removed by evaporation. In contrast, the claimed concentration is drawn to the lipid concentration in an aqueous buffer, not in chloroform.
As to claim 9 part (iii), Cho teaches combining Quil-A with DOTAP in solution, and Esener teaches vortexing for 15 seconds.
As to claim 9 part (iv), Mehravaran teaches that the mixture with stand prior to injection, as of page 276, relevant text reproduced above. This is understood to read on the required incubation step.
As to claim 10, Mehravaran teaches a Soluble Leishmania Antigen as a payload, as of Mehravaran, page 276, second paragraph.
As to claim 12, the rationale applied by the examiner in view of MPEP 2144.05(II)(A) regarding claim 9 is also understood to be applicable to claim 12.
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mehravaran et al. (Iran Journal of Immunology, Vol. 12(4), 2015, pages 274-287) in view of Cho et al. (US 20220287970 A1) and Esener et al. (US 2016/0303236 A1), the combination further in view of Fotin-Mleczek et al. (US 2018/0207295 A1).
Mehravaran is drawn to combining DOTAP of Quil-A for the purposes of acting as a vaccine adjuvant. See the rejection above over Mehravaran in view of Cho and Esener.
Mehravaran differs from the claimed invention because Mehravaran appears to be drawn to a protein antigen vaccine wherein a protein is the payload rather than an mRNA vaccine wherein mRNA is the payload.
Fotin-Mlezcek et al. (hereafter referred to as Fotin) is drawn to an RNA containing composition for treatment or prevention of tumors, as of Fotin, title and abstract. Fotin teaches that this is a vaccine containing antigen encoding mRNA, as of Fotin, paragraphs 0032-0033. Fotin teaches the inclusion of adjuvants in general, as of paragraphs 0026-0027. The adjuvant of Fotin may be Quil-A, as of Fotin, paragraph 0802. Fotin also teaches a cationic liposome comprising DOTAP in paragraph 0651.
Fotin is not anticipatory at least because DOTAP and Quil-A are selected from a long list of cationic lipids and adjuvants, and are not present together in the same embodiment.
It would have been prima facie obvious for one of ordinary skill in the art to have used the Quil-A and DOTAP combination of Mehravaran to have delivered mRNA, as of Fotin. Fotin is drawn to the delivery of mRNA for vaccination, and teaches that the mRNA can be administered with an adjuvant, which may be Quil-A, along with a cationic lipid nanoparticle. Mehravaran is drawn to a method of making a cationic lipid nanoparticle comprising Quil-A, with DOTAP as the cationic lipid. As such, the skilled artisan would have been motivated to have used the formulation made by the method of Mehravaran to have delivered an mRNA which encodes an antigen in order to have predictably enhanced the immune response to said antigen with a reasonable expectation of success.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ISAAC SHOMER whose telephone number is (571)270-7671. The examiner can normally be reached 7:30 AM to 5:00 PM Monday Through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at (571)272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612
Prosecution Insights