DETAILED ACTION
Applicants’ arguments, filed 18 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 Interpretation
Claim 19 recites that aluminum phosphate has the abbreviation “ALPO” and aluminum hydroxide has the abbreviation “ALOH.” The examiner clarifies that these abbreviations are interpreted as not limiting the molar ratio of aluminum to phosphate or hydroxide and are not interpreted as chemical formulas. The examiner clarifies that aluminum hydroxide has the chemical formula Al(OH)3 because aluminum ions are trivalent and positively charged and hydroxide ions are monovalent and negatively charged; as such, three hydroxide ions are needed to balance the charge of one aluminum ion. Regarding phosphate, the examiner notes that both aluminum and phosphate are trivalent; as such, only one phosphate anion is needed to balance the charge of one aluminum cation. However, phosphate is a polyatomic anion having a formula of PO33-; as such, aluminum phosphate has the chemical formula of AlPO3. As such, the examiner interprets the abbreviations of ALPO and ALOH as not limiting the ratio of phosphorus to oxygen in the phosphate ion in aluminum phosphate and not limiting the ratio of hydroxide to aluminum in aluminum hydroxide. As such, the claims that recite these formulas are not rejected as indefinite.
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) 1-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fairman et al. (US 2020/0054739 A1).
Fairman et al. (hereafter referred to as Fairman) is drawn to a conjugated vaccine, as of Fairman, title and abstract.
As to part (a) of claim 1, Fairman teaches protein-antigen conjugates wherein the antigens are polysaccharides, which would have resulted in a protein-polysaccharide conjugate, as of Fairman, paragraph 0014. Fairman teaches non-natural amino acids in the abstract, and teaches at least two non-natural amino acids in paragraph 0008.
As to part (b) of claim 1, Fairman teaches an aluminum adjuvant as of at least paragraphs 0517-0518.
As to part (c) of claim 1, Fairman teaches phosphate buffer in paragraph 0313 and 0325; this appears to refer to a non-aluminum phosphate salt. Fairman teaches disodium phosphate dehydrate in paragraph 0530 and sodium phosphate in paragraph 0531.
As to part (d) of claim 1, Fairman teaches 0.9% sodium chloride in paragraph 1276.
As to claim 1, the claim requires less than 200 mM of sodium chloride. Fairman teaches 0.9% sodium chloride in paragraph 1276. As best understood by the examiner, this is 0.154 M or 154 mM sodium chloride, which is less than 200 mM sodium chloride.
As to claim 1, the claim requires a pH of between about 5.5 and 7. Fairman teaches multiple pH values in the table on page 123 of Fairman; these include pH values of 6.7, as of the first entry on the table, which is within the claimed range. Even if, purely en arguendo, Fairman does not teach the required pH range (e.g. possibly because the teachings of Fairman regarding pH refer to the pH of an intermediate product rather than the final product), this is not sufficient to overcome the applied rejection. 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 a vaccine comprising a polysaccharide-polypeptide conjugate in the form of an aqueous solution have been taught by the prior art. As such, it would not have been inventive for the skilled artisan to have determined the optimum or workable ranges of pH via routine experimentation.
As to claim 1, Fairman appears to teach all of the claimed requirements, albeit in separate embodiments. While the prior art teaches all of the claimed components, the prior art is not anticipatory insofar as these components must be selected from various lists/locations in the prior art reference. It would have been prima facie obvious; however, to have selected the recited components from various lists/locations in the prior art reference and to have combined them together. This is because such a modification would have represented nothing more than the predictable use of prior art components according to their established functions. Combining separate prior art components (from a single prior art reference) according to known methods to yield predictable results is prima facie obvious. See MPEP 2143, Exemplary Rationale A.
As to claim 2, Fairman teaches a surfactant in paragraph 0533; this reads on the required emulsifier.
As to claim 3, Fairman teaches 2-amino-3-(4-azidophenyl)propanoic acid substitution in paragraph 0116.
As to claim 4, Fairman teaches a carrier protein as of at least paragraph 0040.
As to claim 5, Fairman teaches a capsular polysaccharide as of the abstract.
As to claim 6, Fairman teaches a capsular polysaccharide from Streptococcus pneumoniae in paragraph 0013.
As to claim 7, Fairman teaches a capsular polysaccharide from Streptococcus pneumoniae in paragraph 0013.
As to claim 8, Fairman teaches the following as of paragraphs 0029-0031, reproduced below.
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As to claim 9, the teachings from paragraphs 0029-0031 of Fairman which are reproduced above are understood to read on the claim requirement.
As to claim 10, Fairman teaches the following antigens as of paragraph 0234, relevant text reproduced below.
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These are understood to read on the claimed requirement. The examiner notes that the serotypes are not listed in the same order in Fairman as in the instant claims, with 7F being listed before 7C; nevertheless, the teachings of Fairman would appear to read on the requirements of instant claim 10.
As to claim 11, Fairman teaches a cell wall polysaccharide as of paragraphs 0260-0261.
As to claim 12, Seq. ID #1 of Fairman is understood to read on the required unsubstituted sequence because none of the natural amino acids are substituted with unnatural amino acids. This sequence is reproduced in part below from page 133 of Fairman; the sequence goes on to the top of page 135 of Fairman.
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Note the lack of “Xaa” amino acids in this sequence.
As to claim 13, Fairman teaches a sequence that is substituted with pAMF at multiple positions, as of paragraph 0104 of Fairman; the acronym pAMF refers to 2-amino-3-(4 (azidomethyl)phenyl) propanoic acid, as of paragraph 0010 of Fairman.
As to claim 14, the sequence described in paragraph 0104 of Fairman would appear to have at least two pAMF substitutions.
As to claim 15, Fairman teaches an exemplary modified CRM may include substitution of a nnAA (e.g. pAMF) at each of K33, K212, K244, K264, K385, and K526; this has six substitutions of the same non-natural amino acid.
As to claims 16-17, Seq ID #1 of Fairman, as of pages 133-135 of Fairman and reproduced above in the rejection of claim 12, would appear to read on the required sequence.
As to claim 18, Fairman teaches the following, as of Sequence #14, relevant text reproduced below from page 144 of Fairman.
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The examiner notes that the substitutions at sites 34, 213, 245, 386, and 527 appear to be the same substitution sites as in instant Seq. ID #2. While Fairman does not appear to specify a pAMF substitution in the text of the sequence ID, the skilled artisan would have been motivated to have used a pAMF substitution in view of at least the teachings of Fairman, paragraph 0104.
As to claims 19-20, Fairman teaches aluminum phosphate as of at least paragraphs 0518 and 0520-0521.
As to claim 21, Fairman teaches an aluminum concentration of ≤1 mg per mL, as of paragraphs 0523. This appears to overlap with the claimed concentration range. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
In the alternative as to claim 21, Fairman teaches an aluminum phosphate adjuvant, but teaches a different concentration as compared with what is required by the instant claims. Nevertheless, generally, differences in concentration between the prior art and claimed invention 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 condition of a vaccine comprising an aluminum phosphate adjuvant has been taught by the prior art. As such, it would not have bene inventive to have discovered the optimum or workable ranges of this ingredient via routine experimentation.
As to claim 22, Fairman teaches 15 mM potassium phosphate as of paragraph 1256. This appears to be within the claimed range.
As to claim 23, Fairman teaches 15 mM potassium phosphate as of paragraph 1256. This is slightly different from the 17 mM phosphate concentration required by the claim. Nevertheless, generally, differences in concentration between the prior art and claimed invention 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 presented. 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 a composition comprising a polypeptide, an aluminum adjuvant, a non-aluminum phosphate salt, and sodium chloride have been taught by the prior art. As such, it would not have been inventive for the skilled artisan to have determined the optimum or workable ranges of these ingredients via routine experimentation.
As to claim 24, the claim requires about 150 mM of sodium chloride. Fairman teaches 0.9% sodium chloride in at least paragraph 1275. As best understood by the examiner, this is 0.154 M or 154 mM sodium chloride. This is understood to read on the claimed requirements.
As to claim 25, Fairman teaches compositions with pH values of 6.7 as of the first two lines of the table on page 123. However, elsewhere in the document, Fairman teaches a pH adjusting agent, as of Fairman, paragraph 0529, and also teaches a lower pH value of 5.5, as of Fairman, paragraph 0748. While the pH values taught by Fairman appear to differ from the claimed pH values, this is not sufficient to overcome the prima facie case of obviousness. 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 a composition comprising a polypeptide, an aluminum adjuvant, a non-aluminum phosphate salt, and sodium chloride have been taught by the prior art. As such, it would not have been inventive for the skilled artisan to have determined the optimum or workable ranges of the pH of the composition via routine experimentation.
As to claim 26, Fairman teaches that the aluminum salt adjuvant is in the form of a suspension, as of paragraph 0534; otherwise, the composition is in a solution, as of paragraph 0524.
As to claim 27, Fairman teaches that aluminum adjuvants for stable porous aggregates of 1-10 microns in diameter, as of Fairman, paragraph 0524. As such, there would have been a reasonable expectation that the D50 of the aluminum adjuvants would have been 1-10 microns in diameter.
Note Regarding Reference Date: The instant application appears to have an earliest possible effective filing date of 2 September 2021, which is the filing date of provisional application 63/240,244. Fairman was published on 20 February 2020. As such, Fairman was published over a year earlier than the earliest effective filing date of the instant application. As such, Fairman is prior art under AIA 35 U.S.C. 102(a)(1). As Fairman was published over a year earlier than the effective filing date of the instant application, the exceptions under AIA 35 U.S.C. 102(b)(1)(A) and 102(b)(1)(B) would not appear to be applicable.
Response to Arguments
Applicant has presented arguments regarding the previously applied rejection, as of applicant’s response on 18 June 2026 (hereafter referred to as applicant’s response). These arguments have been addressed below.
In applicant’s response, applicant makes the following arguments, as of the paragraphs bridging pages 2-3.
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This is not persuasive. Objective evidence, such as that intended to support a position that an obviousness rejection should be withdrawn on the grounds of unexpected results, must be supported by actual proof. See MPEP 716.01(c)(I); see also MPEP 716.02(b). An assertion in applicant’s arguments that there is an unexpected benefit to vaccine stability does not meet the standard of providing actual proof. Additionally, applicant did not point to direct or indirect comparative testing, which would appear to be needed to establish patentability based upon unexpected results; see MPEP 716.02(b)(III).
Applicant then makes the following argument, as of page 3 of applicant’s response, relevant text reproduced below.
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One argument in the above-reproduced paragraph relates to the issue of whether there would have been a reasonable expectation that a combination of antigen, aluminum adjuvant, phosphate salt, and sodium chloride at the recited pH would have had a reasonable expectation of successfully being “stabilized”, e.g. as recited by the preamble of claim 1. In response, the examiner notes that obviousness requires a reasonable expectation of success, not absolute predictability. See MPEP 2143.02, especially MPEP 2143.02(II). In this case, the fact that Fairman teaches all of the required components in what appears to be a stable vaccine composition is sufficient to result in a reasonable expectation of success.
The examiner notes that according to the heading of MPEP 2143.02(II), applicant may present evidence showing that there was no reasonable expectation of success. Nevertheless, nothing in the above-reproduced paragraph constitutes such evidence. In contrast, the above-reproduced paragraph is argument rather than evidence. Attorney argument cannot take the place of evidence on the record; see MPEP 716.01(c)(II) and MPEP 2145(I).
Additionally, the relevance of the discussion of aluminum-antigen interactions in the above-reproduced paragraph is unclear to the examiner. This is because the instant claims do not appear to require that the aluminum adjuvant and the antigen interact. (As best understood by the examiner, the term “interact” in this case refers to engaging in intermolecular non-covalent chemical interactions such as hydrogen bonding, ion-ion interactions, ion-dipole interactions, dipole-dipole interactions, van der Waals forces, or London dispersion forces). In contrast, the instant claims merely require that these components be together in the same composition. If, purely en arguendo, applicant is arguing that the prior art fails to teach that the aluminum adjuvant and the antigen interact, this argument is not persuasive because applicant appears to be arguing subject matter not actually recited by the instant claims.
In view of the fact that applicant discussed the issue of interactions between aluminum and the antigen, the examiner conducted an additional search regarding this issue. Reference found in such a search are discussed in the section below entitled “Additional Cited Prior Art Regarding Aluminum-Antigen Interactions.” The examiner clarifies that these newly cited references are not part of the statement of rejection, and were found by the examiner to address an issue that was first brought up in applicant’s response on 18 June 2026.
Applicant then makes the following arguments, as of applicant’s response, page 3, relevant text reproduced below.
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Applicant has not pointed to evidence showing a reduction in flocculation and improved suspension stability. As such, applicant’s arguments that there is a reduction in flocculation and improved suspension stability are not persuasive. Attorney argument cannot take the place of evidence on the record; see MPEP 716.01(c)(II) and MPEP 2145(I).
Additionally, applicant’s argument that there is no reasonable expectation that the recited antigen could have been successfully formulated into a stable formulation is not persuasive. This is because Fairman teaches the same antigen that is required by the instant claims and appears to have successfully formulated this antigen into a stable formulation. That Fairman formed a stable formulation would appear to go against applicant’s position that there would have been no reasonable expectation of successfully formulating the claimed antigen.
Applicant then presents an argument asserting that the examiner used impermissible hindsight reasoning, as of applicant’s response, page 3, 4th to last line and 3rd to last line on page. This is not persuasive. Any judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper. See MPEP 2145(X)(A). In this case, applicant did not point to the examiner having used knowledge gleaned only from applicant’s disclosure. As such, applicant’s arguments are not persuasive.
Relevant Prior Art – No Rejection
As relevant prior art, the examiner cites Fairman et al. (US 2018/0333484 A1). This reference appears to teach most of what is taught by Fairman et al. (US 2020/0054739 A1).
In selecting the references to be used in rejecting the claims, the examiner should carefully compare the references with one another and with the applicant’s disclosure to avoid an unnecessary number of rejections over similar references. The examiner is not called upon to cite all references that may be available, but only the "best." (See 37 CFR 1.104(c).) Multiplying references, any one of which is as good as, but no better than, the others, adds to the burden and cost of prosecution and should therefore be avoided. See MPEP 904.03. In this case, Fairman et al. (US 2018/0333484 A1) does not appear to be the best reference because, as best understood by the examiner, Fairman et al. (US 2018/0333484 A1) does not appear to teach a sequence which reads on Seq. ID #2, as required by instant claim 19. As such, no rejection over Fairman et al. (US 2018/0333484 A1) has been written by the examiner.
Additional Cited Prior Art Regarding Aluminum-Antigen Interactions
In applicant’s response on 18 June 2026, applicant discussed the issue of interactions between aluminum and the antigen, as of applicant’s response, page 3, second full paragraph. In view of this, the examiner has conducted an additional search regarding these issues, and references found from such a search are discussed below.
As relevant prior art, the examiner cites HogenEsch (Frontiers in Immunology, Vol. 3, January 2013, pages 1-13). HogenEsch teaches beneficial effects of antigens adsorbing to aluminum on page 1, abstract and page 4, left column, bottom paragraph. However, HogenEsch teaches that adsorption that is too tight can have a negative effect on vaccine immunogenicity, as of page 4, right column, second paragraph, and can cause degradation of the composition, as of the paragraph bridging pages 4-5. This would appear to indicate that the relationship between antigens binding (or adsorbing) to aluminum and vaccine effectiveness is more complex than what is asserted by applicant in applicant’s response.
The examiner also notes here that HogenEsch provides a teaching regarding phosphate buffer as of page 5, left column, relevant text reproduced below.
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In view of this, the examiner has cited Iyer et al. (Journal of Pharmaceutical Sciences, Vol. 101, No. 9, September 2012, pages 3078-3090). Iyer et al. (hereafter referred to as Iyer) is drawn to characterization of an aluminum adjuvanted vaccine, as of Iyer, page 3078, title and abstract. Iyer teaches the following, as of page 3089, left column, top paragraph, relevant text reproduced below with annotation by the examiner.
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As such, the art would appear to indicate that sodium phosphate, at least in certain concentrations, would have been expected to have had beneficial effects at the time of filing. Therefore, even if, purely en arguendo, applicant was to present unexpected results showing improved stability of sodium phosphate containing formulations, the examiner would have to consider whether such results would have been expected beneficial results, as per the guidance provided by MPEP 716.02(c)(II).
The examiner clarifies that the above-cited references are not part of the statement of rejection. In contrast, the above-cited references were found by the examiner in order to address an assertion that was first presented in applicant’s response on 18 June 2026.
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.
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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