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 .
Claims Status
Amendments filed 06/27/2024 are entered. Claims 1-37 are pending and under examination.
Priority
The application is a 371 application, filed 06/27/2024, of PCT application PCT/US23/010121, filed 01/04/2023, which claims priority benefits from Provisional No. 63296726, filed 01/05/2022. The effective filing date of this application is 01/05/2022, the filing date of Provisional No. 63296726.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 06/27/2024 is being considered by the examiner.
Claim Objections
Claims 3 and 10 are objected to because of the following informalities: Appropriate correction is required.
In claim 3, “Neiserra” should be spelled “Neisseria” to refer to the bacteria genus.
In claim 10, “CRM197 diphtheria toxin” and “CRM197” as alternatives in a list of carrier proteins, but likely refer to the same molecule. One instance should be deleted to avoid confusion whether they refer to different things.
Claim Rejections - 35 USC § 112(b)
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.
Claims 14 and 15 are 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 14 recites “any combination thereof” of the average diameter ranges (last line). However, it is unclear if that should mean a combination of one possible upper bound option and one possible lower bound option, or if it can be a combination of two upper bound or two lower bound options, leading to a boundless diameter parameter. Is the diameter range simply 50 nm to 950 nm, the lowest lower bound and highest upper bound recited, respectively?
Claim 15 depends on claim 14 and further recites only upper bound diameters, which does not clarify the indefiniteness of claim 14. Therefore, claim 15 inherits the indefiniteness of its parent claim.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 2 is recited to be dependent on itself.
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, 2, 10, 11-18, 20, 21, and 24-31 are rejected under 35 U.S.C. 103 as being unpatentable over Baker et al (US 201200032777 A1, published 01/05/2012) in view of Porro et al (WO 2014118201 A1, published 08/07/2014) and Yang et al (Yang et al, Protective effects of a nanoemulsion adjuvant vaccine (2C-Staph/NE) administered intranasally against invasive Staphylococcus aureus pneumonia, published 2018), as evidenced by Gutnick et al (Gutnick et al, Amphipathic microbial capsules as industrial products, published 1993) and Raso et al (Raso et al, GMMA and Glycoconjugate Approaches Compared in Mice for the Development of a Vaccine against Shigella flexneri Serotype 6, published 2020).
Regarding claim 1, Baker et al teaches an intranasal vaccine composition comprising
an antigen (p. 17, para. 0168)
a nanoemulsion adjuvant, called 60%W805EC (p. 17, para 0169 and p. 19, Table 1), comprising:
droplets having an average diameter of less than about 1000 nm (p. 10, para. 0118),
an aqueous phase (p. 20, para. 0190 and p. 21, para. 0195).
37.67% of the pharmaceutically acceptable oil, soybean oil, USP grade (p. 19, Table 1).
3.55% of the polyoxyethylene nonionic surfactant, polysorbate 80 (p. 19, Table 1), which is a synonym for polyoxyethylene (20) sorbitan monooleate, as evidenced by WHO,
and 4.04% of ethanol (p. 19, Table 1), which is an organic solvent, specifically an alcohol.
Baker et al teaches the nanoemulsion is an oil-in-water nanoemulsion (p. 18, para. 0171). Baker et al teaches the immunogen in examples reduced to practice to be influenza antigens but also envisions the immunogen to comprise of pathogen products, such as polysaccharides (p. 2, para. 0012) and the immunogen is selected from a list that includes bacteria (p. 2-3, para 0016). Baker et al further teaches advantages of a nanoemulsion for vaccine delivery include facilitating delivery of the immunogen to antigen presenting cells without unwanted toxicity.
Baker et al does not explicitly teach the conjugate comprises of one or more polysaccharides from at least one polysaccharide-encapsulated bacteria, conjugated to a carrier protein.
However, Porro et al teaches that conjugate vaccines are the golden standard for measuring success of clinical immunology (p. 1, line 22-23). Porro et al specifically teaches a bacterial vaccine composition comprising of a polysaccharide-antigen conjugate comprising polysaccharides 3, 6A, 7F of polysaccharide-encapsulated bacteria, Streptococcus pneumoniae, covalently conjugated to the carrier protein, CRM197 (p. 38-42, Example 1). Porro et al also teaches commercially available bacterial polysaccharide conjugate vaccines (p 2). Porro et al further teaches the advantages of a multivalent vaccine (p. 10-12), especially in reducing the necessary dose of carrier proteins to reduce "carrier protein-dependent immune-suppression and immune interference" (p. 4, lines 28-29). Porro et al also teaches CRM197 as an ideal helper-T dependent carrier protein and the advantages it confers for conjugations (p. 14).
As evidenced by Raso et al, conjugation of a polysaccharide to a carrier protein converts the polysaccharide from a T-independent to a T-dependent antigen, enabling the induction of immunological memory (p. 20, para. 4).
As evidenced by Gutnick et al, bacterial capsular polysaccharides are amphipathic (e.g. Table 1 and p 126S, section: 2. Amphipathic microbial biopolymers, para. 1).
Porro et al does not explicitly teach the bacterial immunogen vaccine in a nanoemulsion.
However, Yang et al teaches a nanoemulsion adjuvant vaccine comprising of a bacterial adjuvant (Abstract). Yang et al teaches a nanoemulsion comprising of a surfactant, co-surfactant, an oil phase, and an aqueous phase (p. 9997, section: 2.3 Screening and preparation of the NE adjuvant vaccine, para. 1).
Yang et al teaches a bacterial immunogen but does not explicitly teach the immunogen is a bacterial polysaccharide and that it is conjugated to a carrier protein. Yang et al does not explicitly teach ethanol in the nanoemulsion preparation but acknowledges that existing emulsion adjuvants suffer from being thermodynamically unstable due to large sizes greater than 160 nm in diameter (p. 9997, col. 1, para. 2).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to actualize the bacterial polysaccharide immunogen vaccine version of the vaccine nanoemulsion taught by Baker et al using the bacterial polysaccharide conjugate vaccine taught by Porro et al in light of Baker reciting this option and because of the compatibility, advantages, and need of this vaccine formulation. Furthermore, Yang et al teaches an intranasal bacterial vaccine composition comprising of a bacterial antigen in a nanoemulsion adjuvant. Yang et al's invention differs from the instant by the antigen being a bacterial enterotoxin instead of a polysaccharide conjugate, and by the nanoemulsion formulation. However, Porro et al teaches the advantages of a bacterial polysaccharide conjugate, and as evidenced by Raso et al, its ability to act as a T cell antigen. Additionally, it would have been obvious to a skilled artisan that polysaccharide antigens covalently crosslinked with a carrier protein, as taught by Porro et al, is a strategy used successfully in commercial bacterial vaccines. Therefore, it would have been obvious to a skilled artisan to specifically formulate a T cell antigen (i.e. the conjugate vaccine) with the nanoemulsion adjuvant to further improve internalization of this antigen by antigen presenting cells. Baker et al teaches a nanoemulsion prepared ethanol, in addition to surfactants and co-surfactants, to further stabilize the emulsion even at nanoemulsion diameters around 400 nm. The oil-in-water nanoemulsion formulation, 60%W805EC, taught by Baker et al is a compatible carrier and advantageous delivery system for vaccines, including ones made of bacterial polysaccharides, which are generally amphipathic, as evidenced by Gutnick et al. Furthermore, even if Porro et al does not explicitly teach the polysaccharide conjugate vaccine can be delivered intranasally, it would obvious to a skilled artisan that the nanoemulsion confers vaccines the ability to be administer intranasally, making it compatible with mucosal delivery. In summary, the prior art references teach nanoemulsion adjuvants for vaccines and polysaccharide bacterial conjugate vaccines, as well as additional possible adjuvants. The evidentiary references support that the bacterial polysaccharide conjugate vaccine, nanoemulsion adjuvant, and intranasal delivery are compatible, and that the functions claimed are inherent to its mechanism of action.
In addition to being compatible, one skilled in the art, before the effective filing date of the instant application, would be motivated to combine the nanoemulsion and bacterial polysaccharide conjugate vaccine. The bacterial polysaccharide conjugate vaccines trigger both humoral and cell-mediated immune responses. The cell-mediated immune response is dependent on antigen presentation to T cells. There is thus motivation to facilitate the presentation of these immunogens to T cells. The nanoemulsion adjuvant fulfills this role by helping to facilitate internalization of the immunogen by antigen presentation cells (e.g. dendritic cells) so that they can activate T cells towards a cellular immune response. One skilled in the art, before the effective filing date of the instant application, would be motivated to not only formulate a multivalent bacterial polysaccharide conjugate vaccine for its immunogenic advantages but specifically to further formulate it into a nanoemulsion to provide the additional immunogenic advantages. A skilled artisan would be motivated to formulate specifically bacterial vaccines due to the rise in antibiotic resistance.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success because the conjugate vaccine and the nanoemulsion are compatible with each other both functionally and structurally. Structurally, the predominant antigenic component - the polysaccharides - are amphipathic molecules that could be formulated into the oil phase of the oil-in-water emulsion; and functionally, because the conjugate vaccines would still be expected to function as normal, and perhaps better, due to the nanoemulsion's ability to deliver the antigen to antigen presenting cells. The vaccine strategy of Yang et al is conceptually similar to the instant invention but is improved upon by the immunogen strategy of Porro et al and the emulsion strategy of Baker et al.
The teachings of the references regarding the parent claim are incorporated in its entirety for the dependent claims and discussed further below, as is relevant for each claim.
Regarding claim 2, Baker et al further teaches the immunogen can be from a list of pathogens, including a list of bacteria which includes Haemophilus, Neisseria, Streptococcus, Shigella, and Salmonella.
Porro et al further teaches a multivalent vaccine composition comprising a panel of three polysaccharides from different bacterial serotypes from the same bacterial genus and species (p. 2, line 24 - p. 3, line 5). Regarding claims 2-5, as stated previously, they are polysaccharides 3, 6A, 7F of Streptococcus pneumoniae (p. 38, Example 1).
Regarding claim 10, as stated previously, Porro et al teaches the carrier protein is CRM197.
Regarding claim 11, Porro et al further teaches polysaccharides 3, 6A, 7F of Streptococcus pneumoniae are capsular polysaccharides (p. 81, lines 14-19). Porro et al also teaches other capsular polysaccharides of from other bacteria from genera including Haemophilus, Neisseria, Streptococcus, Shigella, and Salmonella (p. 81, line 14 - p. 82, line 4).
Regarding claim 12, Porro et al further teaches the dose of each serotype or serogroup-specific polysaccharide antigen is preferably 1.0 ug (p. 82, lines 30-32). The examples using 0.01 ug or 0.1 ug of each antigen is because 0.01 is the lowest immunogenic dose in mice and the experiments were done in animals (e.g. ferrets) (p. 60, lines 19-21) but the vaccine is intended for humans.
Regarding claim 13, Baker et al further teaches the immunogenic nanoemulsion provides several advantages, such as lack of unwanted toxicity and/or host morbidity (p. 2, para. 0015).
Regarding claims 14 and 15, Baker et al further teaches the size (diameter) distribution, in nanometer, of 100%W805EC (Figure 12, solid line) and 20%W805EC (Figure 13, solid line), showing similar size distributions. Therefore, the nanoemulsion formulation comprises of droplets within these range of sizes. Further, since the 100%W805EC nanoemulsion is made with water as the aqueous phase and since the 60%W805EC formulation is the 100%W805EC nanoemulsion diluted at the appropriate ratio with water (p. 17, para 0170), the 60%W805EC nanoemulsion would reasonably likely have a similar size distribution and therefore similar average diameters as the 100%W805EC nanoemulsion.
Also, Baker et al teaches some experiments using the 20%W805EC formulation, which is the 100%W805EC diluted at the appropriate ratio with PBS (p. 17, para 0171). This shows that the nanoemulsion in both water and PBS as the aqueous phase have similar size distributions, and that the 60%W805EC formulation would reasonably likely have a similar size distribution and therefore similar average diameters as the 20%W805EC formulation also.
To support this, Baker et al further teaches the mean droplet size of the W805EC formulation, without specifying which one, is about 400 nm. It is reasonably likely that all W805EC formulations have a similar size distribution as the size does not seem to change with the aqueous phase (water vs. PBS) but rather whether the nanoemulsion was formulated with ethanol or not (Figure 12-13). Baker et al further teaches in some embodiments, the mean droplet size can also be less than 400 nm (e.g. in the range of 120-400 nm) (p. 10, para. 0116).
Finally, Baker et al teaches that the size of the nanoemulsion droplets (~400 nm) promotes internalization of the loaded antigen into dendritic cells, which are antigen presenting cells (p. 18, para 0181).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that the nanoemulsion formulations in water or PBS spans the size distribution taught by Baker et al, with the mode around 400 nm, and that this size is advantageous for cargo delivery to antigen presenting cells. Therefore, it is obvious to formulate vaccine-loaded nanoemulsions to be around this size range.
One skilled in the art, before the effective filing date of the instant application, would be motivated to formulate the nanoemulsion towards this size range since it is small enough to promote dendritic cell uptake, and therefore, antigen presentation, but large enough to have sufficiently long biodistribution and won't be immediately cleared.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success because the formulation by Baker et al has already been shown to consistently synthesize particles of a predictable size distribution. There is no reason to believe that switching the load will significantly affect the size distribution as the conjugate is expected to be compatible with the oil phase. Further, it is the size of the nanoemulsion, around 400 nm, that is critical to the promotion of cellular uptake of the nanoemulsion. Therefore, the bacterial polysaccharide conjugate loaded nanoemulsion is reasonably likely to maintain the same size distribution and functions.
Regarding claim 16, Baker et al further teaches seroconversion of the subject after a single intranasal dose administration of the vaccine composition comprising of 20%W805EC (e.g. Figure 25 and p. 5, para. 0050). As explained for claims 14-15, the 60%W805EC and 20%W805EC are just diluted forms of the same nanoemulsion, where the 20%W805EC is diluted in PBS for introduction into animal models. In all subjects administered the vaccine encapsulated in W805EC, 100% of subjects responded, compared to incomplete responses in subjects administered only the vaccine or formulations with BPL-inactivated antigens (Figure 25 and p. 24, para. 0220). A "Responder" in Figure 25 is defined as HAI > 40, and "2% seroconversion" is defined as HAI >40 in Figure 26. Therefore, it can be understood that a "Responder" is a subject with seroconversion.
Regarding claims 26-27 and 29, Baker et al teaches a method of inducing an enhanced immunity against disease caused by a pathogen comprising administering the intranasal vaccine composition (p. 24, para. 0219 for the method). Specifically regarding claim 27, Baker et al further teaches seroconversion, i.e. antibody response against the antigen, in the subject after a single intranasal dose administration of the vaccine composition (Figure 25 and p. 5, para. 0050) and specifically regarding claim 29, this seroconversion did not occur to the same degree in those not administered the vaccine composition (Figure 25), meaning the bacteria-specific antibodies titers would be higher in those administered the vaccine.
Regarding claim 28, Baker et al teaches that inducing an immune response primes the host immune system to respond (e.g. to produce a Th1 and/or Th2 type response), thereby providing protective immunity to the immunogen and the disease caused by the immunogen's source pathogen (p. 3, para 0018). Baker et al teaches the nanoemulsions help induce an antibodies directed towards the specific immunogen. Therefore, if loaded with bacteria immunogen, the antibodies would be expected to be specific to the source serotype. Porro et al teaches the immunological results of the bacterial polysaccharide-carrier protein conjugate vaccines, including helper T-dependent immune response (p. 63, lines 14-15), and the successful protective effects of such vaccines in commercial forms (p. 2, lines 5-15).
Regarding claims 30 and 31, Baker et al teaches that the pathogen-specific antibodies comprise systemic IgG antibodies and/or mucosal IgA antibodies responses (p. 3, para. 0019). Specifically regarding claim 31, Baker et al teaches that IgA are secreted in mucosal tissues as first-line defense against many viral and bacterial pathogens and are produced by B cells primed by Th2 help T cells (p. 8, para. 0098). Baker et al teaches that the nanoemulsion immune compositions elicit both antibody responses against the immunogen as well as cytotoxic T cell responses (p. 8, para. 0099).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that the nanoemulsion containing the bacterial immunogen would facilitate the seroconversion of antibodies against these bacterial immunogens and that this leads to protective effects. Specifically, it would be obvious to a skilled artisan that these effects would be the induction of IgG and IgA response because the nanoemulsion and conjugation makes the immunogen into a T-cell-dependent immunogen, which triggers T-cell primed B cell production of antigen-specific antibodies. Intranasal delivery would cause the mucosal IgA response and the eventual systemic IgG response.
One skilled in the art, before the effective filing date of the instant application, would be motivated to achieve seroconversion because it is the fundamental means through which vaccines work and protective effects is the main goal of vaccines. A skilled artisan would be further motivated to achieve a T-cell mediated immune response, which enables a targeted antibody response.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success that the nanoemulsion would function as it normally would and present its loaded immunogen to antigen presenting cells, which then leads to T-cell mediated antibody response against the immunogen.
Regarding claim 17, Baker et al, as previously stated, teaches the alcohol is ethanol (p. 19, Table 1) wherein the ethanol helps the immunogen to localize to the oil phase and stabilizes the emulsion (p. 1, para. 0006).
Regarding claim 18, Baker et al, as previously stated, teaches the oil is soybean oil (p. 19, Table 1).
Regarding claim 20, Baker et al further teaches suitable cationic surfactants include, but are not limited to, a quaternary ammonium compounds (p. 13, para. 0145), and as previously stated, specifically teaches the formulation contains cetylpyridinium chloride (p. 19, Table 1).
Regarding claim 21, Baker et al, as previously stated, teaches the nanoemulsion adjuvant comprises polysorbate 80 (a polyoxyethylene nonionic surfactant) and cetylpyridinium chloride (a cationic surfactant) (p. 19, Table 1).
Regarding claim 24, Baker et al, further teaches the vaccine can comprise a buffer agent (p. 15, para. 0155), such as phosphate buffered saline (p. 16, para. 0155).
Regarding claim 25, Baker et al, further teaches the emulsion was intranasally administered as drops into each nare (Example 10, p. 23, para. 0214), which is inherently a suspension of the emulsion. Baker et al further teaches exemplary dosage forms include aerosols, suspensions, liquids (para. 0110), and can be formulated for immediate release, sustained release, or controlled release (para. 0111).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to formulate the nanoemulsion as Baker et al teaches in Table 1 (p. 19) for the reasons and applications Baker et al presents. Specifically, it is obvious to include ethanol to help load and stabilize the emulsion, soybean oil for its ability to act as the oil phase, and the various surfactants for its ability to form the boundary between the oil and aqueous phase. It would be obvious to choose PBS as the aqueous phase since it is a common physiologically and biologically compatible buffer and is compatible with the nanoemulsion as it does not change the size distribution of the nanoemulsion. It is obvious that the emulsion can be formulated for effective intranasal delivery and that this delivery method is an efficacious method, as evidenced by the response, previously described for claim 16.
One skilled in the art, before the effective filing date of the instant application, would be motivated to use a nanoemulsion already formulated and validated for vaccine delivery. A skilled artisan would be motivated to administer intranasally for its practical ease and apparent effectiveness.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success using this already structurally and functionally validated nanoemulsion formulation to deliver immunogens. Further, a skilled artisan would have reasonable expectation of success that the oil-in-water nanoemulsion would help enable the success of intranasal delivery of vaccines by emulsifying lipophilic or amphipathic molecules into a water-soluble agent compatible with vaccination via the nasal route.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Baker et al (US 201200032777 A1, published 01/05/2012) in view of Porro et al (WO 2014118201 A1, published 08/07/2014) and Yang et al (Yang et al, Protective effects of a nanoemulsion adjuvant vaccine (2C-Staph/NE) administered intranasally against invasive Staphylococcus aureus pneumonia, published 2018), as evidenced by Gutnick et al (Gutnick et al, Amphipathic microbial capsules as industrial products, published 1993), Raso et al (Raso et al, GMMA and Glycoconjugate Approaches Compared in Mice for the Development of a Vaccine against Shigella flexneri Serotype 6, published 2020), as applied to claim 1 above, and further evidenced by WHO (WHO, Polyoxyethylene (20)sorbitan monooleate).
The teachings of the references regarding the parent claims are incorporated in its entirety for the dependent claim and discussed further below, as is relevant for each claim.
Regarding claim 19, Baker et al, as previously stated, teaches the polyoxyethylene nonionic surfactant is polysorbate 80 (p. 19, Table 1), which is a synonym for polyoxyethylene (20) sorbitan monooleate, as evidenced by WHO.
The rationale to use the nanoemulsion formulation by Baker et al is previously presented in the obvious analysis for claim 1.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Baker et al (US 201200032777 A1, published 01/05/2012) in view of Porro et al (WO 2014118201 A1, published 08/07/2014) and Yang et al (Yang et al, Protective effects of a nanoemulsion adjuvant vaccine (2C-Staph/NE) administered intranasally against invasive Staphylococcus aureus pneumonia, published 2018), as evidenced by Gutnick et al (Gutnick et al, Amphipathic microbial capsules as industrial products, published 1993) and Raso et al (Raso et al, GMMA and Glycoconjugate Approaches Compared in Mice for the Development of a Vaccine against Shigella flexneri Serotype 6, published 2020), as applied to claim 3 above, and further in view of Raso et al, as evidenced by Invivogen (Invivogen, Alhydrogel® adjuvant 2%).
The teachings of the references regarding the parent claims are incorporated in its entirety for the dependent claim and discussed further below, as is relevant for each claim.
Regarding claim 7, Baker et al teaches that the bacterial immunogen could be from Shigella dysenteriae (p. 3, para. 0016), since this is a bacteria that causes infections or diseases.
Raso et al specifically teaches glycoconjugate vaccines, which comprises of polysaccharides from against serotype 6 of Shigella flexneri (Abstract and p. 2, para. 4). Raso et al teaches that this glycoconjugates approach, i.e. polysaccharide conjugated to carrier protein, is a well-established bacterial vaccine approach, but can be costly to produce (Abstract). Although Raso et al is comparing this glycoconjugates approach with a new GMMA approach of conjugating antigens to carrier proteins, Raso et al teaches that both are effective methods to varying extents, and are effectively equal when administered loaded onto a hydrogel adjuvant (Alhydrogel) (Abstract). Further, Raso et al teaches multidrug resistance arising against Shigella (p. 2, para. 2) and there are four Shigella species: Shigella boydii, Shigella dysenteriae, Shigella flexneri, and Shigella sonnei, with varying prevalence (p 1-2, section: Introduction, para. 1).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that a Shigella conjugate vaccine is effective and needed. Starting again with a bacterial polysaccharide conjugate and a nanoemulsion for vaccine delivery taught by Baker et al, it is obvious to combine the two for analogous reasons described for combining the Streptococcus pneumoniae vaccine taught by Porro et al with the nanoemulsion taught by Baker et al.
One skilled in the art, before the effective filing date of the instant application, would be motivated to produce a Shigella-specific vaccine for its utility in human health, particularly in light of the rise of antibiotic resistance, as taught by Raso et al. A skilled artisan would be particularly motivated to formulate the vaccine into a nanoemulsion for the added advantages previously explained. Additionally, because Raso et al taught that the glycoconjugates‘ immunological effectiveness was enhanced by its delivery on the Alhydrogel adjuvant (Abstract), which is an aluminum hydroxide wet gel suspension, as evidenced by Invivogen (Invivogen, p. 1, section Description, para. 1). As evidenced by Invivogen, this enhanced effectiveness is likely from the inherent effect that the antigen adsorbed onto the hydrogel matrix are presented as a particulate form, which is more efficiently internalized by antigen presenting cells (p. 1, section Description, para. 1). The hydrogel effectively works as an adjuvant in a similar way as the nanoemulsion, supporting the utility of adding the nanoemulsion technique.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success for analogous reasons as previously presented for the Streptococcus pneumoniae vaccine loaded nanoemulsion and further, for the likely advantage of formulating glycoconjugates vaccines with adjuvants that can present it in a particulate form for more effective cell internalization.
Claims 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Baker et al (US 201200032777 A1, published 01/05/2012) in view of Porro et al (WO 2014118201 A1, published 08/07/2014) and Yang et al (Yang et al, Protective effects of a nanoemulsion adjuvant vaccine (2C-Staph/NE) administered intranasally against invasive Staphylococcus aureus pneumonia, published 2018), as evidenced by Gutnick et al (Gutnick et al, Amphipathic microbial capsules as industrial products, published 1993) and Raso et al (Raso et al, GMMA and Glycoconjugate Approaches Compared in Mice for the Development of a Vaccine against Shigella flexneri Serotype 6, published 2020), as applied to claim 3 above, and further in view of Finn et al (Finn et al, Bacterial polysaccharide–protein conjugate vaccines, published 2004).
The teachings of the references regarding the parent claims are incorporated in its entirety for the dependent claim and discussed further below, as is relevant for each claim.
Regarding claims 6 and 8, Baker et al teaches that the bacterial immunogen could be from Neisseria gonorrhea and Salmonella typhimurium (p. 3, para. 0016), since these are bacteria that causes infections or diseases.
Further regarding claim 6, Finn et al teaches Neisseria meningitides causes bacterial meningitis in children. Finn et al teaches Neisseria meningitides polysaccharide antigen from serogroup C conjugated to CRM197 as licensed vaccines (Table 1), leading to bacteria-specific antibody responses (p. 7, para. 2).
Further regarding claim 8, Finn et al Salmonella typhi causes enteric fever and teaches a vaccine consisting of capsular polysaccharide from Salmonella typhi that was shown to be efficacious in a large study in children, and teaches the logical extension of this would be to an immunogenic conjugate vaccine to make it T-cell dependent, as has been done with other bacteria polysaccharides (p. 10, para. 1). Finn et al teaches that hindrances to the development of these bacterial vaccines seem not to be with its efficaciousness but with making it affordable and available (p. 10, para. 1). Further, antibiotic resistance has spurred renewed necessity for these vaccines (p. 10, para. 1).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that a Neisseria meningitides and, separately, a Salmonella typhimurium conjugate vaccine is effective and needed. Starting again with a bacterial polysaccharide conjugate, taught by Finn et al in this instance, and a nanoemulsion for vaccine delivery taught by Baker et al, it is obvious to combine the two for analogous reasons described for combining the Streptococcus pneumoniae vaccine taught by Porro et al with the nanoemulsion taught by Baker et al.
One skilled in the art, before the effective filing date of the instant application, would be motivated to repurpose this vaccination formulation for other bacterial pathogens that cause human illnesses, such as Neisseria gonorrhea and Salmonella typhimurium, especially in light of the licensed or promising bacterial polysaccharide-based vaccine strategies already developed.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success for analogous reasons as previously presented for the Streptococcus pneumoniae vaccine loaded nanoemulsion.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Baker et al (US 201200032777 A1, published 01/05/2012) in view of Porro et al (WO 2014118201 A1, published 08/07/2014) and Yang et al (Yang et al, Protective effects of a nanoemulsion adjuvant vaccine (2C-Staph/NE) administered intranasally against invasive Staphylococcus aureus pneumonia, published 2018), as evidenced by Gutnick et al (Gutnick et al, Amphipathic microbial capsules as industrial products, published 1993) and Raso et al (Raso et al, GMMA and Glycoconjugate Approaches Compared in Mice for the Development of a Vaccine against Shigella flexneri Serotype 6, published 2020), as applied to claim 3 above, and further in view of Jong et al (Jong et al, Feasibility and therapeutic strategies of vaccines against Porphyromonas gingivalis, published 2010).
The teachings of the references regarding the parent claims are incorporated in its entirety for the dependent claim and discussed further below, as is relevant for each claim.
Regarding claim 9, Jong et al teaches Porphyromonas gingivalis capsular polysaccharide conjugate as a vaccine to protect against periodontitis, leading to induction of serum antibodies and reduced infection severity (Abstract and p. 195, Table 1, section: Capsule). Jong et al teaches vaccines of capsular polysaccharides (referred to as CPS) should be further tested in oral or nasal vaccines to test its ability to induce mucosal immune responses (p. 197, column 1, section: Immunization with CPS, para. 2), potentially further improving its function.
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that a Porphyromonas gingivalis conjugate vaccine is effective and needed. Starting again with a bacterial polysaccharide conjugate, taught by Jong et al in this instance, and a nanoemulsion for vaccine delivery taught by Baker et al, it is obvious to combine the two for analogous reasons described for combining the Streptococcus pneumoniae vaccine taught by Porro et al with the nanoemulsion taught by Baker et al.
One skilled in the art, before the effective filing date of the instant application, would be motivated to repurpose this vaccination formulation for other bacterial pathogens that cause human illnesses, such as Porphyromonas gingivalis, especially in light of the effective bacterial polysaccharide-based vaccines strategies already developed.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success for analogous reasons as previously presented for the Streptococcus pneumoniae vaccine loaded nanoemulsion.
Claim 22 and 23 is rejected under 35 U.S.C. 103 as being unpatentable over Baker et al (US 201200032777 A1, published 01/05/2012) in view of Porro et al (WO 2014118201 A1, published 08/07/2014) and Yang et al (Yang et al, Protective effects of a nanoemulsion adjuvant vaccine (2C-Staph/NE) administered intranasally against invasive Staphylococcus aureus pneumonia, published 2018), as evidenced by Gutnick et al (Gutnick et al, Amphipathic microbial capsules as industrial products, published 1993) and Raso et al (Raso et al, GMMA and Glycoconjugate Approaches Compared in Mice for the Development of a Vaccine against Shigella flexneri Serotype 6, published 2020), as applied to claim 1 above, and further in view of Sun et al (Sun et al, Polysaccharides as vaccine adjuvants, published 2018).
The teachings of the references regarding the parent claims are incorporated in its entirety for the dependent claim and discussed further below, as is relevant for each claim.
Regarding claims 22 and 23, Sun et al teaches polysaccharide adjuvants confer many advantages in nano vaccines applications, specifically chitosan and glucan, in addition to a few other natural polysaccharides (Abstract). Sun et al teaches the advantages and disadvantages of each common polysaccharide adjuvant (Table 1) Sun et al teaches chitosan and glucan are good adjuvants. Disadvantages for chitosan circle around poor solubility, i.e. it is slightly hydrophobic (p. 5229, section: 2.2 Chitosan-based NP, para. 1), which likely leads to the other disadvantages. However, Sun et al teaches modifying chitosan with the quaternary ammonium groups to help solubilize it (p. 5229, section: 2.2 Chitosan-based NP, para. 1). Further, since the nanoemulsion as taught by Baker et al is an oil-in-water, chitosan incorporated into this emulsion would also reasonably likely improve the delivery of chitosan. Disadvantages for glucan are side effects with NSAIDs and asthma symptoms but these drugs or patient population can be avoided or symptoms can be managed.
In contrast, the disadvantages of other polysaccharide adjuvants are limited immunogenicity and limited compatible with antigens or difficulty of analyzing the effects (Table 1), implying a deficiency with their baseline immunogenicity potential, which is comparatively harder to overcome than the avoidable disadvantages of chitosan and glucan.
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to add an adjuvant, particularly a polysaccharide adjuvant, and further particularly, chitosan or glucan, to the vaccine formulation for the known advantages to vaccines that adjuvants offer (Abstract), since not all immunogens are strongly immunogenic. It would be obvious to particularly use a polysaccharide adjuvant as it would localize similarly to the polysaccharide immunogens within the nanoemulsion and be simultaneously internalized by antigen-presenting cells. It would be obvious to add chitosan or glucan, specifically, for the advantages chitosan and glucan offer over other adjuvants, as previously discussed.
One skilled in the art, before the effective filing date of the instant application, would be motivated to add chitosan or glucan for its adjuvant activity and compatibility with the nanoemulsion, and would have reasonable expectation of success because the immunogen and the adjuvant would be in proximity within the nanoemulsion and the adjuvant would reasonably be expected to enhance the immunogenicity of the immunogen as usual.
Claims 32-37 are rejected under 35 U.S.C. 103 as being unpatentable over Baker et al (US 201200032777 A1, published 01/05/2012) in view of Porro et al (WO 2014118201 A1, published 08/07/2014) and Yang et al (Yang et al, Protective effects of a nanoemulsion adjuvant vaccine (2C-Staph/NE) administered intranasally against invasive Staphylococcus aureus pneumonia, published 2018), as evidenced by Gutnick et al (Gutnick et al, Amphipathic microbial capsules as industrial products, published 1993) and Raso et al (Raso et al, GMMA and Glycoconjugate Approaches Compared in Mice for the Development of a Vaccine against Shigella flexneri Serotype 6, published 2020), as applied to claim 1 above, and further evidenced by Bailey et al (Bailey et al, Th17 cells in cancer: the ultimate identity crisis, published 2014).
The teachings of the references regarding the parent claims are incorporated in its entirety for the dependent claim and discussed further below, as is relevant for each claim.
Regarding claims 32-37, Baker et al teaches that the nanoemulsion induces helper T cell mediated responses, which includes the release of Th1-specific cytokines (e.g. IFN-gamma, TNF-alpha) and/or Th2-specific cytokines (e.g. IL-4, IL-5) (p. 3-4, para 0020). Baker et al further teaches that the host immune response is specific for the antigen co-administered with the nanoemulsion, dictating the extent of the helper T response (p. 4, para 0020).
Further regarding claims 32-37, Yang et al teaches the bacterial immunogen nanoemulsion adjuvant vaccine induced a potent protective effect in a pneumonia disease model, specifically a strong mucosal response with high levels of IgA and IL-17A in bronchoalveolar lavage fluid (BALF) samples, which is from the lung (Abstract), showing that intranasal vaccination of the bacterial immunogen nanoemulsion vaccine induced a strong Th17-based cellular response (p. 10004, column 2, para. 2). Yang et al teaches elevated serum IL-17 and IFN-gamma after administration of their vaccine (p. 10004, column 2, para. 2). Yang et al also teaches elevated IFN-gamma and IL-17A in splenocytes from sepsis models when administered the vaccine, showing higher levels for formulations comprising the immunogen in the nanoemulsion adjuvant without aluminum compared to the immunogen with an aluminum-based adjuvant (p. 10004, column 2, para. 2).
As evidenced by Bailey et al, a Th1 response is in response to intracellular pathogens, and a Th2 and Th17 response is in response to extracellular pathogens and bacteria, respectively. As such, the type of pathogen will dictate the type of helper T response and the cytokines released.
Regarding claim 32 specifically, Yang et al teaches elevated serum IFN-gamma in subjects administered the nanoemulsion vaccine compared to those not administered, as previously discussed.
Regarding claim 33 specifically, Baker et al teaches, depending on the antigen, Th1 responses, including the secretion of TNF-alpha, as previously discussed.
Regarding claims 34 and 35 specifically, Baker et al teaches, depending on the antigen, Th1 responses, including the secretion of IL-4 and IL-5, as previously discussed.
Regarding claims 36 and 37 specifically, elevated serum IL-17 in subjects administered the nanoemulsion vaccine compared to those not administered, as previously discussed, and elevated IL-17 levels from lung BALF samples, as previously discussed.
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that the conjugate and nanoemulsion strategy converts the antigen into a T-cell-dependent antigen, inducing helper T cell (Th) responses, leading to humoral and cellular immune responses, but the specific type of helper T cell response depends on the antigen, as taught by Baker et al. The type of antigen then dictates the cytokines that are produced and where they are produced. I.e. antigens from pathogens infecting the lungs will cause elevated levels of cytokines in the lungs, and also systemically in the serum and in the spleen where B cells are produced. Therefore, it would be obvious to a skilled artisan that the secretion of these Th1, Th2, or Th17 cytokines are all inherent, depending on the specific bacteria antigen. Particularly, the elevated levels of these cytokines can be measured in the serum and spleen due to systemic immune response, and the lungs, due to the intranasal delivery leading to a strong mucosal effect directed to the lungs.
One skilled in the art, before the effective filing date of the instant application, would be motivated to induce elevated levels of these helper T-cell cytokines as it is an indicator of successful helper T cell induction and for immunological response against the immunogen.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success because these vaccines are formulated for these desired and known helper T cell response.
Nonstatutory Double Patenting
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.
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Patent No. US 9,492,525 B2
Claims 1-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 7-25 of U.S. Patent No. US 9,492,525 B2 in view of Baker et al (US 201200032777 A1, published 01/05/2012), Porro et al (WO 2014118201 A1, published 08/07/2014), Yang et al (Yang et al, Protective effects of a nanoemulsion adjuvant vaccine (2C-Staph/NE) administered intranasally against invasive Staphylococcus aureus pneumonia, published 2018), Finn et al (Finn et al, Bacterial polysaccharide–protein conjugate vaccines, published 2004), Jong et al (Jong et al, Feasibility and therapeutic strategies of vaccines against Porphyromonas gingivalis, published 2010), and Sun et al (Sun et al, Polysaccharides as vaccine adjuvants, published 2018), as evidenced by Gutnick et al (Gutnick et al, Amphipathic microbial capsules as industrial products, published 1993), Raso et al (Raso et al, GMMA and Glycoconjugate Approaches Compared in Mice for the Development of a Vaccine against Shigella flexneri Serotype 6, published 2020), WHO (WHO, Polyoxyethylene (20)sorbitan monooleate), Invivogen (Invivogen, Alhydrogel® adjuvant 2%), and Bailey et al (Bailey et al, Th17 cells in cancer: the ultimate identity crisis, published 2014).
Patent No. ‘525 claims recite an intranasal vaccine composition comprising of a nanoemulsion adjuvant and an immunogen. The nanoemulsion adjuvant formulation reads on the instant nanoemulsion adjuvant formulation, diameter claims, and lack of toxicity or minimal inflammation to the subject.
Patent No. ‘525 claims differ from the instant claims by the immunogen. Patent No. ‘525 claims a respiratory syncytial virus (RSV) strain L19 as the immunogen instead of the bacterial polysaccharide conjugates. Patent No. ‘525 also does not explicitly claim the specific immune response of the instant application (e.g. IgG, IgA, and cytokines).
However, starting with this nanoemulsion adjuvant formulation and method of using it, arriving at the instant invention is obvious in view of the prior art. To summarize the teachings previously set forth in the prior art rejection:
Baker et al teaches this nanoemulsion adjuvant, its properties and functions, and envisions its use with bacterial polysaccharide immunogens. Baker et al teaches the composition successfully effective with intranasal administration, showing the nanoemulsion is compatible with mucosal delivery. Baker et al teaches the nanoemulsion facilitates cargo immunogen delivery to and internalization by antigen presenting cells, enhancing the immunogenicity of the immunogen.
Porro et al, Finn et al, and Jong et al, teach various bacterial polysaccharide conjugate vaccines, their commercial success, the advantage of multivalent vaccines, and the advantage of conjugation in converting a T cell independent immunogen, solely triggering the humoral response, into also a T cell dependent immunogen, unlocking the cell-mediated immune response.
Yang et al teaches an intranasal bacterial vaccine in a nanoemulsion adjuvant but uses a bacterial enterotoxin as the immunogen. Yang et al teaches the concept that bacterial immunogen, particularly for mucosal vaccines, may not be sufficiently immunogenic, and can benefit from adjuvants, motivating the combination of bacterial vaccine and nanoemulsion adjuvants.
Sun et al teaches why chitosan and glucan are reasonable and motivated adjuvants that could be added.
The evidentiary references support that the bacterial polysaccharide conjugate vaccine, nanoemulsion adjuvant, and intranasal delivery are compatible, and that the functions claimed are inherent to its mechanism of action.
In addition to being compatible, there is motivation to combine them. The bacterial polysaccharide conjugate vaccines trigger both humoral and cell-mediated immune responses. The cell-mediated immune response is dependent on antigen presentation to T cells. There is thus motivation to facilitate the presentation of these immunogens to T cells. The nanoemulsion adjuvant fulfills this role by helping to facilitate internalization of the immunogen by antigen presentation cells (e.g. dendritic cells) so that they can activate T cells towards a cellular immune response.
Starting from the nanoemulsion and bacterial polysaccharide conjugate vaccines, the complete teachings and rationale for combining are previously discussed in the prior art rejection. The teachings and rationale for combining other instant claim limitations are also previously discussed in the prior art rejection.
Patent No. US 9,561,271 B2
Claims 1-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6-11, 16-23 of U.S. Patent No. US 9,561,271 B2 in view of Baker et al (US 201200032777 A1, published 01/05/2012), Porro et al (WO 2014118201 A1, published 08/07/2014), Yang et al (published 2018), Finn et al (published 2004), Jong et al (published 2010), and Sun et al (published 2018), as evidenced by Gutnick et al, Raso et al, WHO, and Bailey et al.
Patent No. ‘271 claims recite a vaccine composition comprising of a nanoemulsion adjuvant and an immunogen. The nanoemulsion adjuvant formulation reads on the instant nanoemulsion adjuvant formulation, diameter claims, and lack of toxicity or minimal inflammation to the subject.
Patent No. ‘271 claims a respiratory syncytial virus (RSV) antigen as the immunogen instead of the bacterial polysaccharide conjugates. Patent No. ‘271 also does not explicitly claim the specific immune response of the instant application (e.g. IgG, IgA, and cytokines).
However, starting with this nanoemulsion adjuvant formulation and method of using it, arriving at the instant invention is obvious in view of the prior art as described in the previous double patenting rejection.
Patent No. US 10,206,996 B2
Claims 1-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-9, 15-18, 23-24, and 28 of U.S. Patent No. US 10,206,996 B2 in view of Baker et al (US 201200032777 A1, published 01/05/2012), Porro et al (WO 2014118201 A1, published 08/07/2014), Yang et al (published 2018), Finn et al (published 2004), Jong et al (published 2010), and Sun et al (published 2018), as evidenced by Gutnick et al, Raso et al, WHO, and Bailey et al.
Patent No. ‘996 claims recite a vaccine composition comprising of a nanoemulsion adjuvant and an immunogen. The nanoemulsion adjuvant formulation reads on the instant nanoemulsion adjuvant formulation, diameter claims, and lack of toxicity or minimal inflammation to the subject.
Patent No. ‘996 claims a herpes simplex virus (HSV) antigen as the immunogen instead of the bacterial polysaccharide conjugates. Patent No. ‘996 also does not explicitly claim the specific immune response of the instant application (e.g. IgG, IgA, and cytokines).
However, starting with this nanoemulsion adjuvant formulation and method of using it, arriving at the instant invention is obvious in view of the prior art as described in the previous double patenting rejection.
Patent No. US 11,147,869 B2
Claims 1-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 20-28 of U.S. Patent No. US 11,147,869 B2 in view of Baker et al (US 201200032777 A1, published 01/05/2012), Porro et al (WO 2014118201 A1, published 08/07/2014), Yang et al (published 2018), Finn et al (published 2004), Jong et al (published 2010), and Sun et al (published 2018), as evidenced by Gutnick et al, Raso et al, WHO, and Bailey et al.
Patent No. ‘869 claims recite a vaccine composition comprising of a nanoemulsion adjuvant and an immunogen. The nanoemulsion adjuvant formulation reads on the instant nanoemulsion adjuvant formulation, diameter claims, and lack of toxicity or minimal inflammation to the subject.
Patent No. ‘869 claims a herpes simplex virus (HSV) antigen as the immunogen instead of the bacterial polysaccharide conjugates. Patent No. ‘869 also does not explicitly claim the specific immune response of the instant application (e.g. IgG, IgA, and cytokines).
However, starting with this nanoemulsion adjuvant formulation and method of using it, arriving at the instant invention is obvious in view of the prior art as described in the previous double patenting rejection.
Patent No. US 11,642,405 B2
Claims 1-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 9-17 of U.S. Patent No. US 11,642,405 B2 in view of Baker et al (US 201200032777 A1, published 01/05/2012), Porro et al (WO 2014118201 A1, published 08/07/2014), Yang et al (published 2018), Finn et al (published 2004), Jong et al (published 2010), and Sun et al (published 2018), as evidenced by Gutnick et al, Raso et al, WHO, and Bailey et al.
Patent No. ‘405 claims recite a vaccine composition comprising of a nanoemulsion adjuvant and an immunogen. The nanoemulsion adjuvant formulation reads on the instant nanoemulsion adjuvant formulation, diameter claims, and lack of toxicity or minimal inflammation to the subject.
Patent No. ‘405 claims a mycobacterial antigen as the immunogen instead of the bacterial polysaccharide conjugates. Patent No. ‘405 also does not explicitly claim the specific immune response of the instant application (e.g. IgG, IgA, and cytokines).
However, starting with this nanoemulsion adjuvant formulation and method of using it, arriving at the instant invention is obvious in view of the prior art as described in the previous double patenting rejection.
Application No. 17292714
Claims 1-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 31-34 of copending Application No. 17292714 (reference application) in view of Baker et al (US 201200032777 A1, published 01/05/2012), Porro et al (WO 2014118201 A1, published 08/07/2014), Yang et al (published 2018), Finn et al (published 2004), Jong et al (published 2010), and Sun et al (published 2018), as evidenced by Gutnick et al, Raso et al, WHO, and Bailey et al. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
App No. ‘714 claims recite a vaccine composition comprising of a nanoemulsion adjuvant and an immunogen. The nanoemulsion adjuvant formulation reads on the instant nanoemulsion adjuvant formulation.
App No. ‘714 claims a genera of antigens as the immunogen, including bacterial antigens, instead of specifically bacterial polysaccharide conjugates. App No. ‘714 also does not explicitly claim the specific immune response of the instant application (e.g. IgG, IgA, and cytokines).
However, starting with this nanoemulsion adjuvant formulation and method of using it, arriving at the instant invention is obvious in view of the prior art as described in the previous double patenting rejection.
Application No. 18133238
Claims 1-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7-14, 17, 20-21, 24 of copending Application No. 18133238 (reference application) in view of Baker et al (US 201200032777 A1, published 01/05/2012), Porro et al (WO 2014118201 A1, published 08/07/2014), Yang et al (published 2018), Finn et al (published 2004), Jong et al (published 2010), and Sun et al (published 2018), as evidenced by Gutnick et al, Raso et al, WHO, and Bailey et al. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
App No. ‘238 claims recite a vaccine composition comprising of a nanoemulsion adjuvant and an immunogen. The nanoemulsion adjuvant formulation reads on the instant nanoemulsion adjuvant formulation.
App No. ‘238 claims influenza antigens as the immunogen instead of bacterial polysaccharide conjugates.
However, starting with this nanoemulsion adjuvant formulation and method of using it, arriving at the instant invention is obvious in view of the prior art as described in the previous double patenting rejection.
Conclusion
No claims are allowed.
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/BONIRATH CHHAY/Examiner, Art Unit 1645 June 9, 2026
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 June 10, 2026
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