DETAILED ACTION
Applicants’ arguments, filed 8 June 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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) 24, 35-38 and 41-43 is/are rejected under 35 U.S.C. 103 as being unpatentable over Benenato et al. (WO 2021/055835 A1).
Benenato et al. (hereafter referred to as Benenato) is drawn to carbonate containing lipid compounds, as of Benenato, title and abstract. Benenato teaches various compounds including compound 22 on page 16, which is reproduced below.
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As to claim 24, the chemical structure of Benenato appears to differ from the following claimed structure
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only by the length of various carbon chains; specifically, those between the carbonate groups and the central tertiary amine nitrogen atom. As such, the instant claims are not anticipated by Benenato. Nevertheless, the instant claims appear to be prima facie obvious over Benenato. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." See MPEP 2144.09(I). In this case, both the compounds of Benenato and those of the instantly claimed invention are ionizable cationic lipids usable for the formation of lipid nanoparticles for delivery of nucleic acids. As such, the subject matter of Benenato appears to be sufficiently similar to the claimed subject matter to render the claimed compound prima facie obvious based upon structural similarity. Additionally, compounds which are … homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. See MPEP 2144.09(II).
As to claim 35, Benenato teaches a lipid nanoparticle in the abstract, which reads on the required delivery system.
As to claim 36, Benenato teaches mRNA as of pages 81-82, paragraph 00263.
As to claim 37, Benenato teaches a mRNA vaccine in at least page 90, paragraphs 00286-00287.
As to claim 38, Benenato teaches a cancer vaccine as of page 42, paragraph 00130.
As to claim 41, Benenato teaches mRNA as of pages 81-82, paragraph 00263. The mRNA reads on the required bioactive substance.
As to claims 42-43, Benenato teaches the following lipid nanoparticle, as of page 85, top paragraph, relevant text reproduced below.
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These formulations would appear to read on the claimed structure.
Note Regarding Reference Date: Benenato was published on 25 March 2021. This is less than a year prior earlier than the earliest possible effective filing date of the instant application, which is 7 July 2021, based upon a foreign priority claim. As such, Benenato is prior art under AIA 35 U.S.C. 102(a)(1). Benenato was also effectively filed earlier than the effective filing date of the instant application and is thereby prior art under AIA 35 U.S.C. 102(a)(2). There are no common inventors, and there does not appear to be a common assignee between Benenato et al. (WO 2021/055835 A1) and the instantly claimed invention. As such, the AIA exceptions would not appear to be applicable here.
Claim(s) 39-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Benenato et al. (WO 2021/055835 A1) in view of Schoenmaker et al. (International Journal of Pharmaceutics, Vol. 601, 2021, Article 120586, pages 1-13).
Benenato is drawn to a lipid nanoparticle for delivery of mRNA comprising a particular lipid. See the rejections above over Benenato by itself.
Benenato does not teach a SARS-CoV-2 vaccine.
Schoenmaker et al. (hereafter referred to as Schoenmaker) is drawn to commercially available COVID-19 (i.e. SARS-CoV-2) vaccines formed from mRNA and lipids, as of Schoenmaker, page 1, title and abstract. Schoenmaker teaches mRNA for vaccination against SARS-CoV-2, as of Schoenmaker, page 3, figure 1, reproduced below.
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Schoenmaker also teaches the use of lipid nanoparticles to deliver said mRNA, and emphasizes the importance of using ionizable cationic lipids, as of Schoenmaker, page 1, title and abstract as well as elsewhere in the document.
Schoenmaker differs from the claimed invention because Schoenmaker does not teach an L1 and/or L2 which is -O(C=O)O; in contrast, the L1 and/or L2 taught by Schoenmaker is an ester rather than a carbonate, as of Schoenmaker, page 8, relevant structure reproduced below with annotation by the examiner of the portions of the structures of Schoenmaker that render Schoenmaker different from the claimed structure.
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It would have been prima facie obvious for one of ordinary skill in the art to have substituted the ionizable cationic lipid of Benenato in place of that of Schoenmaker in a lipid nanoparticle for delivering mRNA for vaccination against SARS-CoV-2, as taught by Schoenmaker. Schoenmaker is drawn to a lipid nanoparticle comprising an ionizable cationic lipid for delivery of mRNA that acts as a vaccine against SARS-CoV-2. As both Schoenmaker and Benenato teach ionizable cationic lipids for the formation of lipid nanoparticles for delivery of mRNA, the skilled artisan would have been motivated to have substituted the ionizable cationic lipid of Benenato in place of that of Schoenmaker for predictable delivery of an mRNA active agent which can be used for vaccination with a reasonable expectation of success.
As to claim 39, the mRNA of Schoenmaker vaccinates against SARS-Cov-2 (i.e. COVID-19), which is a coronavirus, as of Schoenmaker, page 1.
As to claim 40, the mRNA of Schoenmaker vaccinates against SARS-Cov-2 (i.e. COVID-19), which is a coronavirus, as of Schoenmaker, page 1.
Note Regarding Reference Date: Schoenmaker was published on 9 April 2021. See the bottom of page 1 of Schoenmaker for information regarding the publication date. This is less than a year earlier than the earliest effective filing date of the instant application, which is 7 July 2021. As such, Schoenmaker is prior art under AIA 35 U.S.C. 102(a)(1).
Response to Arguments
Applicant has presented arguments in the previously applied rejection, as of applicant’s response on 8 June 2026 (hereafter referred to as applicant’s response). These arguments are addressed below to the extent that the arguments are applicable to the currently pending rejection.
Applicant cites various case law as of applicant’s response, starting on the last two lines of page 6 and onto page 7. One case cited by applicant is Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 83 USPQ2d 1169 (Fed. Cir. 2007), which has been discussed in MPEP 2143(I)(E), Example 4. Looking at the cited case, it appears that in the cited case, there was an example of the prior art teaching away from the recited modifications. See MPEP 2143(I)(E), Example 4, last paragraph in section, relevant text reproduced below.
Accordingly, Office personnel should recognize that the obvious to try rationale does not apply when the appropriate factual findings cannot be made. In Takeda, there was a recognized need for treatment of diabetes. However, there was no finite number of identified, predictable solutions to the recognized need, and no reasonable expectation of success. There were numerous known TZD compounds, and although one clearly represented the closest prior art, its known disadvantages rendered it unsuitable as a starting point for further research, and taught the skilled artisan away from its use.
The above-reproduced text speaks the fact that in the cited case, the prior art taught disadvantages with the claimed invention. This appears to be a case of teaching away. In contrast in the fact pattern of the instant application, there is no such indication of teaching away. As such, the cited case does not appear to relate to the fact pattern of the instant application.
Applicant additionally cited Procter & Gamble Co. v. Teva Pharm. USA, Inc., 566 F.3d 989, 90 USPQ2d 1947 (Fed. Cir. 2009). This case is discussed as of MPEP 2143(I)(B), Example 10, wherein relevant text has been reproduced below.
The Federal Circuit affirmed the district court’s decision. The Federal Circuit did not deem it necessary in this case to consider the question of whether 2-pyr EHDP had been appropriately selected as a lead compound. Rather, the Federal Circuit reasoned that, if 2-pyr EHDP is presumed to be an appropriate lead compound, there must be both a reason to modify it so as to make risedronate and a reasonable expectation of success. Here, there was no evidence that the necessary modifications would have been routine, so there would have been no reasonable expectation of success.
Two issues stand out from the above-reproduced text from the MPEP. First, the above-reproduced text would appear to indicate that in a lead-compound analysis, any compound in the prior art may be selected as a lead compound for the purpose of an obviousness analysis. Secondly, nothing in the above-reproduced paragraph would appear to preclude the examiner relying upon MPEP 2144.09 to determine what modifications would have been routine.
Additionally, the explanation provided by the MPEP of the cited case calls into question whether the lead compound analysis is actually appropriate in all compound cases. See MPEP 2143(I)(B), Example 10, last paragraph in section, relevant text reproduced in part below.
It should be noted that the lead compound cases do not stand for the proposition that identification of a single lead compound is necessary in every obviousness rejection of a chemical compound. For example, one might envision a suggestion in the prior art to formulate a compound having certain structurally defined moieties, or moieties with certain properties. If a person of ordinary skill would have known how to synthesize such a compound, and the structural and/or functional result could reasonably have been predicted, then a prima facie case of obviousness of the claimed chemical compound might exist even without identification of a particular lead compound. … Thus, Office personnel should recognize that in certain situations, it may be proper to reject a claimed chemical compound as obvious even without identifying a single lead compound.
As such, this case would appear to indicate that a lead compound analysis may not be necessary to establish a prima facie case of obviousness.
Applicant argues that the skilled artisan would not have been motivated to have selected the above-indicated compound of Benenato as a lead compound, as of applicant’s response, page 7, bottom paragraph, reproduced below.
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This argument is not persuasive. The fact that Benenato teaches the above-indicated compound would itself appear to be sufficient for the skilled artisan to have selected this particular compound as a lead compound. See the examiner’s analysis of MPEP 2143(I)(B), Example 10, fourth paragraph, as set forth above. The fact that the majority of compounds taught by Benenato have structurally distinct features as compared with compound 22 of Benenato is not sufficient to make the case that the skilled artisan would not have used compound 22 of Benenato as a lead compound.
Applicant then makes the following arguments, as of page 8 of applicant’s response, wherein relevant text has been reproduced below.
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The examiner disputes the idea that the skilled artisan would not have been able to have predicted whether a specific modification would have resulted in a compound with a similar property. Benenato is clearly drawn to ionizable cationic lipids for the delivery of RNA, as of Benenato, abstract. The prior art as a whole recognizes the utility of such compounds. In support of this position, the examiner notes Schoenmaker, which teaches the following, as of page 4, left column, section 2.2, relevant text reproduced below.
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As such, the skilled artisan would have expected that compounds meeting the requirement of being both ionizable cationic (e.g. having a non-quaternary amine group) and lipids (e.g. having a non-polar long alkyl tail and a polar head) would have had a reasonable expectation of successfully being useful for the delivery of nucleic acids. As such, modifications that would have rendered the compound to have been an ionizable cationic lipid would have had a reasonable expectation of successfully delivering a nucleic acid payload when included in a lipid nanoparticle. Obviousness requires a reasonable expectation of success, not absolute predictability. See MPEP 2143.02(II).
The examiner does not necessarily dispute applicant’s position that the skilled artisan would not have been able to have predicted which ionizable cationic lipids would have been the most effective and which ionizable cationic lipids would have been the least effective. See e.g. Lowe (https://www.science.org/content/blog-post/rna-vaccines-and-their-lipids accessed 19 October 2022, pages 1-15), which is discussed in greater detail below. Nevertheless, the standard for determining obviousness is a reasonable expectation of success, not absolute predictability. See MPEP 2143.02(II). In this case, there would have been a reasonable expectation that a compound that can be considered an ionizable cationic lipid could have successfully delivered nucleic acid when in a lipid nanoparticle. While there would have been no absolute predictability that particular modifications would have resulted in improved properties, such absolute predictability is not needed in order to establish a prima facie case of obviousness.
Applicant then refers to compound 22 of Benenato as prophetic, as of applicant’s response, page 9, top paragraph. This is not persuasive. Nothing in Benenato indicates that this compound is a prophetic example. Furthermore, even if, purely en arguendo, compound 22 would accurately be considered a prophetic example, this is insufficient to overcome the prima facie case of obviousness. Patents are relevant for all they contain. See MPEP 2123.
In the alternative, if applicant’s argument that compound 22 of Benenato is a prophetic example is taken as an argument that Benenato is not enabling prior art, this is not persuasive. MPEP 2121 states that when the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. Nothing in applicant’s response is sufficient to rebut the presumption of operability.
Applicant then cites the following case law, as of applicant’s response, page 9, relevant text reproduced below.
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In response, the examiner notes that during the course of examination, the examiner must rely upon the MPEP. The above-cited case does not appear to be in the MPEP. As such, the relevance of the above-cited case regarding the patentability determination is unclear to the examiner. With that being said, applicant provides the following explanation of the case on page 10 of applicant’s response, wherein relevant text has been reproduced below.
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It is the examiner’s position that the issues pertaining to antipsychotic activity, as in the cited case, differ from the issues pertaining to ionizable cationic lipids in the instant applications because of differences in their technologies. In regard to ionizable cationic lipids, the skilled artisan could have identified a chemical structure as an ionizable cationic lipid simply by looking at the structure. The presence of an ionizable cationic group and of a hydrophobic tail could have readily been identified by one of ordinary skill in the art area of organic chemistry. However, the determination of antipsychotic activity from looking at a chemical structure would not have been readily apparent to one of ordinary skill in the art. As such, the fact pattern as it relates to ionizable cationic lipids is not the same as the fact pattern relating to antipsychotic drugs because antipsychotic drugs are more unpredictable than ionizable cationic lipids.
In support of the position that there would have been predictability regarding cationic lipids at the time of filing, the examiner cites Lowe (https://www.science.org/content/blog-post/rna-vaccines-and-their-lipids accessed 19 October 2022, pages 1-15). Lowe teaches the following on page 3, relevant paragraph reproduced below.
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Lowe then goes on to teach the following on page 4, relevant paragraph reproduced below.
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The above-reproduced paragraphs indicate that lipid nanoparticles comprising ionizable cationic lipids are useful for delivering nucleic acids. The above-reproduced text indicates that it is unpredictable as to which formulation comprising which ionizable cationic lipid would have been the most effective. However, the above-reproduced text would appear to indicate that there would have been a reasonable expectation that a lipid nanoparticle comprising an ionizable cationic lipid would have successfully delivered a nucleic acid. In order to set forth a prima facie case of obviousness, it is incumbent the examiner to show that there would have been a reasonable expectation that a particular formulation would have been successful; see MPEP 2143.02. It is not incumbent upon the examiner to show that a particular formulation would have been the best possible formulation in order to set forth a prima facie case of obviousness. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use. See MPEP 2145(X)(D)(1). As such, even if, purely en arguendo, the teachings of Lowe are interpreted as showing that the claimed formulation is somewhat inferior to a different ionizable cationic lipid for the formulation of a lipid nanoparticle for the delivery of nucleic acids (and the examiner does not believe that Lowe actually teaches this), these are not sufficient to overcome the previously applied rejection.
The examiner clarifies that Lowe is not part of the statement of rejection, and has been newly cited herein in order to best respond to applicant’s arguments.
Applicant then cites alleged unexpected results, as of applicant’s response, page 10, bottom half of page. Applicant cites figures 25-28 in applicant’s response. Applicant takes the position that the comparative testing shows a comparison between the lipid nanoparticles with the claimed lipids and lipid nanoparticles with the ionizable cationic lipids ALC-0315 and SM-102. These comparative ionizable cationic lipids are the ionizable cationic lipids found in the Pfizer-BioNTech COVID-19 vaccine and Moderna COVID-19 vaccine respectively.
As an initial matter, the claimed invention must be compared with the closest subject matter that actually exists in the prior art. See MPEP 716.02(e). In this case, applicant appears to have compared a lipid nanoparticle comprising the claimed lipid against a comparative example that is at least as close of that of the prior art. The examiner presents the following rationale in support of this position.
The chemical identity of Samples 9-12 is the following, as of page 15 of the specification.
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The cationic lipids described in the above-reproduced text have been discussed on page 14 of the specification, which is reproduced below.
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As such, Samples 9 and 10 appear to be inventive examples, and Samples 11 and 12 appear to be comparative examples.
In this case, the lipid nanoparticles of the Pfizer-BioNTech COVID-19 vaccine and Moderna COVID-19 vaccine appear to reasonably be considered the closest subject matter to actually exist in the prior art. This is because these lipid nanoparticles comprise all of the required ingredients including an ionizable cationic lipid, and differ from the claimed invention only in regard to the chemical identity of the ionizable cationic lipid.
The claimed invention must show unexpected results with respect to the comparative example. In this case, applicant cites figures 26 and 27 in applicant’s response. These figures show the following, and are reproduced below.
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The above-reproduced figures show that Samples 9 and 10 avoid particle aggregation during storage, whereas Samples 11 and 12 undergo particle aggregation during storage. Samples 9 and 10 are lipid nanoparticles comprising the claimed lipids, whereas Samples 11 and 12 are lipid nanoparticles comprising comparative lipids.
With that being said, the data presented in figures 26 and 27 do not represent the full scope of data in the application. In contrast, applicant also presents data from Table 2 on pages 14-15 of the specification, which is reproduced below.
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In the above-reproduced table, Samples 1 and 2 are examples made from the inventive lipid, whereas Samples 3 and 4 are examples made from the comparative lipid. In the above-reproduced table, it appears that Sample 2, which is an inventive example, has a worse particle size distribution as compared with Samples 3 and 4, which are comparative examples. Similarly, Sample 5, which is an inventive example, has a particle size distribution that is worse than that of Samples 7 and 8, which are comparative examples.
Unexpected results must be commensurate in scope with the claimed invention. See MPEP 716.02(d). In this case, the data in Table 2 would appear to indicate that the unexpected results are not commensurate in scope with the claimed invention. This is because the unexpectedly superior results apply only to the comparison between Samples 9-12, and not to the comparison between Samples 1-4 and Samples 5-8. As such, this would appear to indicate that the data presented by applicant in the specification applies only to certain lipid formulations (e.g. those in Samples 9-11) but not to other lipid formulations (e.g. those in Samples 1-8).
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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