DETAILED ACTION
Notice of 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 .
Election/Restrictions
Applicant’s election without traverse of Group II in the reply filed on 8/15/2025 is acknowledged. The requirement is still deemed proper and is therefore made FINAL.
Applicant’s election without traverse of a single method in the reply filed on 8/15/2025 is also acknowledged.
The elected species read upon claims 1-6, 8-9, 12, 16-18, 20-22 and 76-79. Claim 7 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Priority
The earliest effective filing date afforded the instantly claimed invention has been determined to be 11/08/2019 as to claims 1-6, 8-9, 12, 16-18, 20 and 76-78, based on the filing date of PRO 62/933,225.
However, PRO 62/933,225 does not provide support for the instantly claimed method wherein the vaccine administered is a recombinant vaccine (claim 21), a SARS-CoV2 vaccine (claim 22), or a recombinant SARS-CoV2 vaccine (claim 79).
As to claims 21-22 and 79, the earliest effective filing date has been determined to be 11/06/2020, based on the filing date of PCT/US2020/59519.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 1-6, 8-9, 12, 16-18, 20 and 76-78 are rejected under 35 U.S.C. 103(a) as being unpatentable over Smith et al (Vaccine 34:4304-4312, 2016) in view of Pearce et al (US 2017/0101624).
Claim 1 is drawn to a method of increasing the effectiveness of a vaccine in a subject, the method comprising administering:
a B cell metabolic reprograming agent (more specifically, Mdivi-1 (claims 2-3 and 76)) to the subject in a dose and scheduled configured to increase the effectiveness of the vaccine; and
the vaccine to the subject.
Smith et al teach that “[o]ne limitation of [vaccine] development has been the inability of conventional vaccines to stimulate an effective antigen-specific CD8+ T cell response, which is critical for protection against many viral diseases” (Page 2) and, as such, “[s]mall-molecule adjuvants that boost and direct adaptive immunity provide a powerful means to increase the effectiveness of vaccines” (Abstract), specifically demonstrating that “pigs vaccinated with antigen comprising the highest dose of adjuvant promoted a 13-fold increase in the percentage of antigen-specific CD3+/CD8+ T cells over pigs vaccinated with antigen alone” (Abstract).
As such, Smith et al teach a method of increasing the effectiveness of a vaccine in a subject comprising administering a small molecule adjuvant and a vaccine to said subject, wherein the small molecule adjuvant is administered in a dose and schedule configured to increase the effectiveness of the vaccine.
However, Smith et al do not teach administration of the B cell metabolic reprograming agent Mdivi-1.
Pearce et al teach “a composition comprising one or more compounds to promote mitochondrial fusion and/or mitochondrial structural remodeling” (Paragraph 0022) – wherein “a compound that promotes mitochondrial fusion may be a compound that inhibits mitochondrial fission” and, “[i]n a specific embodiment, a compound that inhibits mitochondrial fission may be Mdivi-1” (Paragraph 0027) – and “methods of enhancing T cell longevity and/or T cell function by promoting mitochondrial fusion and/or mitochondrial structural remodeling” (Abstract), further teaching that “[i]n yet another aspect, the present disclosure provides a method to improve vaccination strategies” since the “T cells of the disclosure may enhance the activity of vaccines” (Paragraph 0046).
Accordingly, based on Smith et al in view of Pearce et al, it would have been prima facie obvious to administer Mdivi-1 along with a vaccine to a subject in need thereof in a dose and schedule configured to increase the effectiveness of said vaccine, with a reasonable expectation of success. It would have been obvious to do so in the reasonable expectation that administration of Mdivi-1 would enhance T cell longevity and/or T cell function so as to increase the effectiveness of the vaccine.
As such, claims 1-4 and 76 are rejected as prima facie obvious.
Claims 5-6, 9 and 77-78 are drawn to the method of claim 1, wherein the dose is between 1.0 – 50.0 mg/kg (claim 5), more specifically about 2.5 mg/kg (claim 6), and/or wherein the B cell metabolic reprogramming agent is administered at least a day, at least 2 days, or a plurality of times in a regular interval after administering the vaccine (claim 9), more specifically wherein the B cell metabolic reprogramming agent is administered at a dose of 2.5 mg/kg at least a day, at least 2 days, or a plurality of times in a regular interval after administering the vaccine (claim 77), and/or wherein the subject is administered with a second dose of the vaccine at least a day after administering the vaccine (claim 78).
As stated by MPEP 2144.05, “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical” (see also In re Aller (220 F.2d 454 (CCPA): “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…” Indeed, as further discussed by the court, “[s]uch experimentation is no more than the application of the expected skill of the [ordinarily skilled artisan] and failure to perform such experiments would, in our opinion, show a want of the expected skill”; see also In re Peterson, 315 F.3d at 1325 (Fed. Cir. 2005): “[t]he normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages” and “[o]nly if the ‘results of optimizing a variable’ are ‘unexpectedly good’ can a patent be obtained for the claimed critical range” (quoting In re Antonie (559 F.2d 618 (CCPA 1977))).
In the instant case, the concentration of active agent as well as the dosing regimen of said agent in combination with vaccine is clearly a result-effective variable. Accordingly, it would have been customary for an artisan of ordinary skill in the art to determine the optimal dose and regimen of Mdivi-1 and vaccine to administer in order to best achieve the desired results.
As such, claims 5-6, 9 and 77-78 are also rejected as prima facie obvious.
Claims 8, 12, 16-18 and 20 are drawn to the method of claim 1, wherein:
the B cell metabolic reprogramming agent is an immune enhancer for the vaccine (claim 8);
the effectiveness of the vaccine is enhanced by, e.g., increasing a memory B cell population in the subject (claim 12), more specifically wherein the B cell population comprises IgG cells (claim 16), and/or by increasing a TFh cell population in the subject after a rechallenge (claim 17);
the dose and schedule is sufficient to increase antigen-specific antibody titers at least 50% in the subject compared to a subject not receiving the B cell metabolic reprogramming agent or at least 50% in the subject compared to a subject not receiving the B cell metabolic reprogramming agent after a rechallenge (claim 18); and/or
the dose and schedule is sufficient to prevent decreased oxygen consumption of mitochondria in IgG cells in the subject (claim 20).
As stated in In re Best, Bolton, and Shaw (562 F2d 1252 (CCPA 1977)), “[w]here… the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product” (see also In re Fitzgerald 619 F2d 67 (CCPA 1980): the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess characteristic relied on”). This is especially true in cases where the newly discovered, inherent limitation is claimed functionally rather than structurally. For example, in In re Kubin (561 F.3d 1351 (Fed. Cir. 2009)), discussing claims drawn to an isolated nucleic acid molecule encoding a polypeptide “wherein the polypeptide binds CD48”, the court stated that there is “no obligation to predicate [an] obviousness finding on factual findings regarding a prior art teaching of [the polypeptide’s] binding to the CD48 protein” – the limitation is “not an additional requirement imposed by the claims on the [polypeptide], but rather a property necessarily present in” the polypeptide. As stated by the court in Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344 (Fed. Cir. 2012), “[t]o hold otherwise would allow any formulation – no matter how obvious – to become patentable merely by testing and claiming an inherent property” (discussing claims drawn to methods of administering a active agent “wherein upon oral administration… an initial serum concentration of the [active agent] greater than about 0.1 µg / ml is obtained at any time within about 30 minutes after administration” and further noting that “[t]he initial blood serum concentration resulting from administering [the active agent] is an inherent property of the formulation, and an obvious formulation cannot become nonobvious simply by administering it to a patient and claiming the resulting serum concentrations”).
In the instant case, the claimed and prior art product, Mdivi-1, are identical. As such, absent evidence to the contrary, it is asserted that that Mdivi-1 is an immune enhancer for the vaccine and its administration would necessarily enhance the effectiveness of the vaccine, increase antigen-specific titers, and prevent decreased oxygen consumption of mitochondria in IgG cells as claimed. As stated in In re Papesch, 315 F.2d 381 (CCPA 1963), “[f]rom the standpoint of patent law, a compound and all its properties are inseparable”.
As such, claims 8, 12, 16-18 and 20 are rejected as prima facie obvious.
Claims 21-22 and 79 are rejected under 35 U.S.C. 103(a) as being unpatentable over Smith et al (Vaccine 34:4304-4312, 2016) in view of Pearce et al (US 2017/0101624) as applied to claims 1-6, 8-9, 12, 16-18, 20 and 76-78 above, in further view of Keech et al (NEJM 383:2320-2332, published 9/02/2020).
Claims 21-22 and 79 are drawn to the method of claim 1, wherein the vaccine comprises a recombinant vaccine (claim 21), more specifically a SARS-CoV2 vaccine (claim 22), even more specifically a recombinant SARS-CoV2 vaccine (claim 79).
Neither Smith et al nor Pearce et al teach administration of a recombinant SARS-CoV2 vaccine.
Yet, as taught by Keech et al, NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine” (Background) wherein “[t]he addition of adjuvant resulted in enhanced immune responses, was antigen dose-sparing, and induced a T helper (Th1) response” (Results).
In view of all of the foregoing, it would have been prima facie obvious to administer Mdivi-1 along with NVX-CoV2373 to a subject in need thereof in a dose and schedule configured to increase the effectiveness of said vaccine, with a reasonable expectation of success. It would have been obvious to do so in the reasonable expectation that administration of Mdivi-1 would enhance T cell longevity and/or T cell function (as taught by Pearce et al) so as to increase the effectiveness of the vaccine (as taught by Smith et al and Keech et al).
As such, claims 21-22 and 79 are also rejected as prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CRAIG D RICCI whose telephone number is (571) 270-5864. The examiner can normally be reached on Monday through Thursday, and every other Friday, 7:30 am - 5:00 pm ET. 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, Bethany Barham can be reached on (571) 272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611