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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on February 9, 2024 has been considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, see paragraph [0323] of the instant published application, USPgPub 2025/0281601. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of at least the following terms, TWEEN®, SPAN®, MYRJ®, SOLUTOL®, BRIJ®, POLOXAMER®, GLYDANT PLUS®, PHENONIP®, , GERMALL® 115, GERMABEN® II, NEOLONE™, KATHON™, and EUXYL®, which are trade names or a marks used in commerce, has been noted in this application in at least paragraphs [0095 and 0096]. All of the terms should be accompanied by generic terminology and should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. While some of the trade names or marks recited in the instant disclosure follow these requirements under MPEP § 2173.05(u), the remainder do not.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Applicant is required to properly annotate all trade names and/or marks present in the instant specification, if any additional trade names and/or marks are discovered. Applicant' s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
The substitute specification filed May 23, 2024 has not been entered because it does not conform to 37 CFR 1.125(b) and (c) because: the substitute specification does not comply with MPEP § 2414.02 (2):
(2) An amendment to the specification to incorporate by reference the material in the "Sequence Listing XML" by reciting in a separate paragraph of the specification the name of the file, the date of creation, and the size of the file in bytes (37 CFR 1.835(a)(2) and 37 CFR 1.835(c))
The substitute specification filed May 23, 2024 states that the sequence listing has a size in KB.
Applicant is reminded that the incorporation of essential material in the specification by reference to a foreign application or patent, or to a publication is improper. Instant paragraph [0078] of the instant published application refers to cap structures incorporated by reference from Kore et al. Bioorganic & Medicinal Chemistry 2013 21:4570-4574. Claim 34 requires at least one 5’-cap region. Therefore, 5’-cap structures are essential material as a component required in claim 34. Instant paragraphs [0221 and 0530] incorporate CN103495161 by reference. Claim 1 requires a bacterial antigen. CRM197 of CN103495161 is highly antigenic and is encompassed by claim 1. Incorporation of essential material, by reference to Kore et al. Bioorganic & Medicinal Chemistry 2013 21:4570-4574 and CN103495161, is improper under 37 CFR § 1.57(d). Applicant is required to amend the disclosure to include the material incorporated by reference. 37 CFR § 1.57. The amendment must be accompanied by an affidavit or declaration executed by the applicant, or a practitioner representing the applicant, stating that the amendatory material consists of the same material incorporated by reference in the referencing application. See In re Hawkins, 486 F.2d 569, 179 USPQ 157 (CCPA 1973); In re Hawkins, 486 F.2d 579, 179 USPQ 163 (CCPA 1973); and In re Hawkins, 486 F.2d 577, 179 USPQ 167 (CCPA 1973). Furthermore, if the recited materials in the instant claims, was not set forth in the specification as filed, and was not publicly available at the time the application was filed, the amendment will be treated as an attempt to introduce new matter (similar to attempts to incorporate essential material by reference to unpublished material).
Claim Objections
Claim 33 is objected to because of the following informalities: “comprising mRNA comprises” and “is replaced with SARS-CoV-2 antigen” are ungrammatical.
Claim 34 is objected to because of the following informalities: “composition comprising mRNA comprises a mRNA” is ungrammatical.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1, 2, 4, 8-10, 14-19, 21, 27, and 29-34 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.
Instant claim 1 requires an antigen “derived from” an infectious disease-causing bacteria and an antigen “derived from” a betacoronavirus. Claim 17 requires polysaccharides “derived from” N. meningitidis. It is not clear what is intended by an antigen “derived from” a source. Are the derived antigens intended to be fragments or do the antigens claimed share structural components and/or a similar functional characteristic to the native antigens? The instant disclosure provides discussions for the full length SARS-CoV-2 spike glycoprotein mRNA SEQ ID NOs: 1 and 2, specific Neisseria meningitidis capsular polysaccharides, MenA, MenC, MenW, and MenY, SEQ ID NOs: 3 and 4 N. meningitidis polypeptides, Clostridium difficile toxin A or C and c-terminal portions thereof, and S. pneumoniae capsular polysaccharides in paragraphs [0031, 0125, 0165, 0172, 0216, 0217, 0245, 0815, and 0816 of the instant published disclosure, USPgPub 2025/0281601. Therefore, it is determined that the claims intend for particular whole antigens obtained from specific bacteria and SARS-CoV-2. However, an amendment clarifying the subject matter is required. This rejection affects all dependent claims.
Instant claim 1 requires co-administering to a human subject “an effective dose” of a first immunogenic composition comprising an antigen derived from a bacterium and an immunogenic composition comprising mRNA encoding an antigen derived from a betacoronavirus. MPEP § 2173.05(c) III discusses the test for determining whether “an effective amount” is indefinite, i.e., whether or not one skilled in the art could determine specific values for the amount based on the disclosure. See In re Mattison, 509 F.2d 563, 184 USPQ 484 (CCPA 1975). In the instant case, the skilled artisan would not determine specific values for the effective amount required because there is no discussion or examples provided in the instant disclosure for what an effective amount is. This rejection affects all dependent claims.
Claims 10 and 14 state that the first composition comprises SEQ ID NO: 1. Antecedent basis for the “first immunogenic composition” is provided in claim 1, which requires that the first immunogenic composition comprises an antigen from a bacterium. SEQ ID NO: 1 is a SARS-CoV-2 spike protein in paragraph [0048]. Claim 14 also requires the polypeptide of SEQ ID NO: 2. SEQ ID NO: 2 is the putative sequence of the vaccine SARS-CoV-2 spike mRNA-1273 in paragraph [0032]. The mixed characterizations of a bacterial antigen required in a first composition of claim 1 comprising SARS-CoV-2 spike mRNA sequences in claims 10 and 14 is confusing. Both SEQ ID NOs: 1 and 2 are required to be lipidated in claim 14. However, instant SEQ ID NOs: 1 and 2 are mRNA sequences according to the instant sequence listing and of the instant published application and Figures 2 and 3. In the interest of compact prosecution, claims 10 and 14 are interpreted as polypeptides comprising the amino acid sequence, SEQ ID NOs: 3 and 4, since the polypeptides of SEQ ID NOs: 3 and 4 are the only lipidated polypeptides disclosed in paragraphs [0242 and 0243] and are identified as Neisseria meningitidis polypeptides in the sequence listing, in agreement with the first composition comprising bacterial antigens. However, this courtesy does not preempt the requirement for a clarifying amendment.
Claims 16 and 32 contain the trademark/trade names TRUMENBA® and Comirnaty®, respectively. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a meningococcal group B vaccine and a FDA-approved mRNA SARS-CoV-2 vaccine, respectively, and, accordingly, the identification/description is indefinite.
Claim 33 is drawn to immunogenic composition comprising an mRNA sequence having residues 1-102 of SEQ ID NO:1 and residues 103-4284 of SEQ ID NO:1. Is this phrase intended to recite specific fragments of SEQ ID NO: 1? The full length of SEQ ID NO: 1 is 4284 residues. Since all of the residues are recited, this section of the claim is interpreted to mean all of SEQ ID NO: 1 is required. Claim 33 additionally requires wherein the sequence for the SARS-CoV-2 antigen of SEQ ID NO:1 is replaced with SARS-CoV-2 antigen of a variant strain. Therefore, lines 1-3 of the claim require SEQ ID NO: 1, but lines 4-5 require replacement of SEQ ID NO: 1. Due to this contradiction, it cannot be determined whether SEQ ID NO: 1 required or not in claim 33. In the interest of compact prosecution, the claim is interpreted as requiring SEQ ID NO: 1 since Laha et al. (Infection, Genetics and Evolution. 2020 Nov 1; 85:104445) show sequence structure stability of the spike glycoprotein among different SARS-CoV-2 strains, see Table 1, Table 2, and Figure 1.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 4, 8-10, 14-19, 21, 27, and 29-34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Instant claim 1 requires an antigen “derived from” an infectious disease-causing bacteria and an antigen “derived from” a betacoronavirus. Claim 17 requires polysaccharides “derived from” N. meningitidis. It is not clear what is intended by an antigen “derived from” a source. Are the derived antigens intended to be fragments or do the antigens claimed share structural components and/or a similar functional characteristic to the native antigens? The instant disclosure provides discussions for the full length SARS-CoV-2 spike glycoprotein, i.e., SEQ ID NOs: 1 and 2, specific Neisseria meningitidis polypeptides, SEQ ID NOs: 3 and 4, Neisseria meningitidis capsular polysaccharides, MenA, MenC, MenW, and MenY, Clostridium difficile toxin A or C and c-terminal portions thereof, and S. pneumoniae capsular polysaccharides in paragraphs [0031, 0125, 0165, 0172, 0216, 0217, 0245, 0815, and 0816 of the instant published disclosure, USPgPub 2025/0281601. Therefore, while the instant disclosure provides written support for whole, specific antigens obtained from Neisseria meningitidis, Clostridium difficile, S. pneumoniae, and SARS-CoV-2, there is no written description for any antigen “derived from” any infectious disease-causing bacteria and any antigen “derived from” any betacoronavirus, encompassed by the instant claims.
The skilled artisan would not recognize any antigen derived from any bacteria, administered at an effective dose to a human to elicit an immune response against an infectious disease-causing bacterium, as asserted. Cavaillon (Toxicon. 2018; 149: 45-53) review exotoxins and endotoxins from various bacteria, including Neisseria meningitidis, Clostridium difficile, and S. pneumoniae, leading to the production of IFNγ and chemokines, resulting in a cytokine storm, sepsis, toxic shock syndrome, and mortality. See the abstract, Table 1, Sections 2, 4, and Figures 1 and 2, depicting enhanced release of cytokines upon first contact with an endotoxin and/or exotoxin superantigen.
The instant disclosure provides no written support for any and all antigens from the broad genus of betacoronaviruses. Llanos et al. (International Journal of Molecular Sciences. June 2020; 21: 4546) reviews betacoronavirus genomes, divided into five subgenera by the International Committee on Taxonomy of Viruses (ICTV): Embecovirus, Sarbecovirus, Merbecovirus, Nobecovirus and Hibecovirus, see Table 1 and Figure 1. The skilled artisan would not recognize any antigen derived from any betacoronavirus, administered at an effective dose to a human to elicit an immune response against a betacoronavirus, as asserted. Hurtado-Tamayo et al. (Frontiers in Cellular and Infection Microbiology. 2023; 13: 1166839) describe accessory proteins encoded by betacoronaviruses associated with virulence, see “Interference of deadly HCoV accessory proteins with the inflammatory response”. Therefore, while accessory proteins of betacoronaviruses are antigenic, expression promotes pathogenesis.
The applicable standard for the written description requirement can be found in MPEP 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc., 63 USPQ2d 1609; Vas- Cath Inc. v. Mahurkar, 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004). To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the only factors present in the specification are SARS-CoV-2 mRNA sequences SEQ ID NOs: 1 or 2, specific Neisseria meningitidis polypeptides, SEQ ID NOs: 3 and 4, Neisseria meningitidis capsular polysaccharides, MenA, MenC, MenW, and MenY, Clostridium difficile toxin A or C and c-terminal portions thereof, and S. pneumoniae capsular polysaccharides. There is no disclosure of sufficient characteristics of the claimed genus of betacoronavirus and bacteria antigens allowing persons skilled in the art to recognize that applicants were in possession of the claimed genus of betacoronavirus and bacteria antigens claimed. In the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of betacoronavirus and bacteria antigens. A definition by function alone is not sufficient because it is only an indication of what a thing does, rather than what it is. Eli Lily, 119 F.3 at 1568, 43 USPQ2d at 1406.
The court clearly states in Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not clearly allow persons of ordinary skill in the art to recognize that the inventors invented what is claimed. As discussed above, the skilled artisan cannot envision the distinguishing, identifying characteristics of the encompassed genus of betacoronavirus and bacteria antigens. The claims do not meet the written description provision of 35 U.S.C. 112, first paragraph.
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.
Claims 1, 2, 4, 8, 15, 30-32, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Maeda et al. (PNAS. 15 April 2021; 118 (18): e2025622118), Polack et al. (New England journal of medicine. 2020 Dec 31; 383 (27):2603-2615), and Dubensky et al. (USPgPub 2013/0315950), as evidenced by Vogel et al. (BioRxiv. 2020 Sep 8: 2020-09).
Maeda et al. teach inducing an immune response against a Killed Whole-Cell Vaccine (KWCV) genome-reduced E. coli expressing SARS-COV-2 S2, see the abstract, the paragraph bridging the columns on page 2, “Successful Surface Expression of SARS-CoV-2 FP and PEDV FP on Genome-Reduced E. coli, Production and Characterization of Candidate Vaccines”, “SARS-CoV-2 FP and PEDV FP Vaccines Induce Low Anti-FP Humoral Response but Potent Anamnestic Responses after Virus Challenge”, and “Vaccines Potentiate Interferon-γ Response in Vaccinated Pigs”. Therefore, Maeda et al. teach inducing an immune response against antigens derived from E. coli and SARS-CoV-2, as required by instant claims 1, 8, and 30. Maeda et al. teach human volunteers immunized with a KWCV enterotoxigenic E. coli (ETEC) vaccine, resulted in no adverse effects in the paragraph bridging page 1, denoting an effective dose administered to humans, as required by instant claim 1.
Maeda et al. do not teach an mRNA encoded SARS-CoV-2 antigen or BNT162b2, as required by instant claims 1 and 32.
Polack et al. teach safety, immune responses, and efficacy of the BNT162b2 mRNA vaccine administered at an effective dose in humans, see “Participants”, Figures 2-3, and Tables 1-3. Vogel et al. teach the BNT162b2 mRNA vaccine comprises a nucleoside-modified mRNA (required in instant claim 31) that encodes the spike glycoprotein captured in its prefusion conformation with a 5’cap1 analog at the 5’UTR and a 3′ UTR poly(A) tail stabilizing region, as required by instant claim 34, see the abstract, “In vitro transcription and purification of RNA”, and the first paragraph of the Discussion. Therefore, the BNT162b2 mRNA vaccine of Polack et al. possesses the regions recited in instant claim 34.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have administered the mRNA encoded SARS-CoV-2 BNT162b2 vaccine of Polack et al. in combination with the KWCV E. coli expressing SARS-COV-2 S2 of Maeda et al. to induce high SARS-CoV-2 neutralizing titers, strong TH1-biased CD4+, IFNγ+, and IL-CD8+ T cell responses in humans against SARS-CoV-2 with greater tolerability, see the last two paragraphs on page 8 of Polack et al. and to protect against enterotoxigenic E. coli, see the introduction of Maeda et al. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have administered the mRNA encoded SARS-CoV-2 BNT162b2 vaccine of Polack et al. in combination with the KWCV E. coli expressing SARS-COV-2 S2 of Maeda et al. because Dubensky et al. teach heterologous prime-boost with nucleic acids and bacterial antigens, see paragraphs [0055, 0068, 0120, 0133] and Figures 1 and 2. In addition, Polack et al. teach safety and efficacy in human subjects ranging between 16 to over 55 years old, see Tables 1 and 3 and Maeda et al. teach an ETEC oral KWCV along with a cholera B toxin subunit adjuvant was studied in children and found to be safe, see the paragraph bridging the columns on page 1.
Neither Maeda et al. nor Polack et al. suggest concurrent administration of the bacterial and viral compositions, recited in claim 2 or suggest the bacterial and viral compositions are administered within 24 hours, as required in claim 4, or combining alum with the bacterial composition, as recited in instant claim 15.
Dubensky et al. discusses relative timing of a prime-boost vaccination in paragraph [0090]. Dubensky et al. teach that initiation of the boost administration can be administered prior to the peak of stimulated expansion of antigen-specific immune cells resulting from the prime dose. In paragraph [0089], Dubensky et al. teach that the prime-boost compositions are administered in one dose (concurrently) or spaced within one minute and up to 24 hours. Paragraph [0083] of Dubensky et al. discusses combining alum with the composition.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have added an alum adjuvant, taught by Dubensky et al., to the composition of Maeda et al. and Polack et al. to enhance the immunostimulation of the composition.
In view of the teachings of Dubensky et al., temporal booster doses range from concurrent administrations to doses separated by any number of incremental hours up to 24, see paragraphs [0089 and 0090]. Absent evidence of criticality, the timing of each administration with respect to the claimed compositions are adjustable. Therefore, it would have been prima facie obvious for a person having ordinary skill in the art prior to the effective filing date to routinely optimize the timing of booster administrations. MPEP 2144.05 states, “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 optimization.”
Claims 9, 10, 14, 16, 17, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al. as applied to claims 1, 2, 4, 8, 15, 30-32, and 34 above, and further in view of Jansen et al. (USPgPub 2018/0214532), instant SEQ ID NO: 3 alignment with Geneseq db access no BAT08834 Sept 2013, and instant SEQ ID NO: 4 alignment with Geneseq db access no ADE44816 Jan 2004.
Examiner note: In the interest of compact prosecution, claims 10 and 14 are interpreted as polypeptides comprising the amino acid sequence, SEQ ID NOs: 3 and 4, since the polypeptides of SEQ ID NOs: 3 and 4 are the only lipidated polypeptides disclosed in paragraphs [0242 and 0243] and are identified as Neisseria meningitidis polypeptides in the instant sequence listing.
See the teachings of Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al. above. None of the references mention N. meningitidis polysaccharides as the bacterial antigen, as required in claims 9 and 17, or that the N. meningitidis antigens are Neisseria meningitidis serogroup A (MenA) capsular saccharide conjugated to an adipic acid dihydrazide (ADH) linker by 1-cyano-4- dimethylamino pyridinium tetrafluoroborate, wherein the linker is conjugated to tetanus toxoid (TT) by carbodiimide chemistry (MenAAH-TT conjugate); ii) a Neisseria meningitidis serogroup C (MenC) capsular saccharide conjugated to an ADH linker by 1-cyano-4-dimethylamino pyridinium tetrafluoroborate, wherein the linker is conjugated to tetanus toxoid (TT) by carbodiimide chemistry (MenCAH-TT conjugate); iii) a Neisseria meningitidis serogroup W135 (MenW) capsular saccharide directly conjugated to tetanus toxoid (TT) by 1-cyano-4-dimethylamino pyridinium tetrafluoroborate, in the absence of a linker (MenW-TT conjugate); and iv) a Neisseria meningitidis serogroup Y (MenY) capsular saccharide directly conjugated to tetanus toxoid (TT) by 1-cyano-4-dimethylamino pyridinium tetrafluoroborate, in the absence of a linker (MenY-TT conjugate), in a lyophilized composition that is reconstituted with a liquid, recited in claim 18(b).
Jansen et al. teach a lyophilized composition comprising a Neisseria meningitidis serogroup A (MenA) capsular saccharide conjugated to an adipic acid dihydrazide (ADH) linker by 1-cyano-4-dimethylamino pyridinium tetrafluoroborate chemistry, wherein the linker is conjugated to tetanus toxoid carrier protein (TT) by carbodiimide chemistry (MenAAH-TT conjugate); a Neisseria meningitidis serogroup C (MenC) capsular saccharide conjugated to an ADH linker by 1-cyano-4-dimethylamino pyridinium tetrafluoroborate chemistry, wherein the linker is conjugated to tetanus toxoid carrier protein (TT) by carbodiimide chemistry (MenCAH-TT conjugate); a Neisseria meningitidis serogroup W135 (MenW) capsular saccharide directly conjugated to tetanus toxoid carrier protein (TT) by 1-cyano-4-dimethylamino pyridinium tetrafluoroborate chemistry, in the absence of a linker (MenW-TT conjugate); and a Neisseria meningitidis serogroup Y (MenY) capsular saccharide directly conjugated to tetanus toxoid carrier protein (TT) by 1-cyano-4-dimethylamino pyridinium tetrafluoroborate chemistry, in the absence of a linker (MenY-TT conjugate) that is reconstituted with a liquid, see paragraph [0102]. These teachings satisfy the requirements of instant claims 9, 17, and 18(b). Therefore, Jansen et al. teach equivalent components comprised by TRUMENBA®, recited in instant claim 16. Jansen et al. also teach a liquid composition comprising a first lipidated polypeptide and a second lipidated polypeptide in paragraph [0102].
Jansen et al. do not teach or suggest the lipidated polypeptides are SEQ ID NOs: 3 and 4, as (probably intended to be) required in instant claims 10 and 14.
Geneseq database access no: BAT08834 shares 100% identity with instant SEQ ID NO: 3. Geneseq database access no: ADE44816 Jan 2004 shares 100% identity with instant SEQ ID NO: 4. See the alignments provided.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have administered the Neisseria meningitidis vaccine comprising lipidated polypeptides of Geneseq database access no: BAT08834, Geneseq database access no: ADE44816 and capsular saccharide conjugates from serogroups A, C, W135, and Y of Jansen et al. with the composition of Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al., to elicit an immune response against N. meningitidis homologous and heterologous strains that express factor H binding protein (fHBP) variants in the multi-component composition and effectively elicit an immune response in children aged 12 months and above, see paragraph [0101] of Jansen et al. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have administered the Neisseria meningitidis vaccine comprising lipidated polypeptides and capsular saccharide conjugates from serogroups A, C, W135, and Y of Jansen et al. with the composition of Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al. because Jansen et al. teach co-administration of virus vaccines with the meningococcal vaccine in paragraph [0289].
Claims 19, 21, 27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al. as applied to claims 1, 2, 4, 8, 15, 30-32, and 34 above, and further in view of Tussey et al. (USPgPub 2016/0166671).
See the teachings of Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al. above. None of the references mention the bacterium as C. difficile comprising the C-terminal domain of a wild-type C. difficile toxin A or the C-terminal domain of a wild-type C. difficile toxin B, comprising a fusion protein, administered to a human aged 55 or older, as required in instant claims 19, 21, 27, and 29.
Tussey et al. teach a fusion protein comprising the C-terminal domain of a wild-type C. difficile toxin A (TcdA) and the C-terminal domain of a wild-type C toxin B (TcdB) as fusion proteins, see Figures 1A-1B and paragraphs [0038-0044 and 0052-0058]. Paragraph [0035] of Tussey et al. teach seroconversion in elderly ≥65 years old upon administration of a C. difficile vaccine.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have administered the C. difficile vaccine of Tussey et al. with the composition of Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al., to elicit an immune response against C. difficile in the young (6 years old and younger), elderly (at least 49 to about 65 years old), and humans aged 13-18 years old, see claims 31-37 of Tussey et al. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have administered the C. difficile vaccine of Tussey et al. with the composition of Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al. because Tussey et al. teach co-administration of a virus component with the C. difficile vaccine in claim 44.
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al. as applied to claims 1, 2, 4, 8, 15, 30-32, and 34 above, and further in view of instant SEQ ID NO: 1 alignment with SEQ ID NO: 26907 of Issued_Patents_NA db in US 12,194, 089, hereinafter, “ ’089”.
Examiner note: Due to ambiguity in the claim noted above, claim 33 is interpreted as requiring SEQ ID NO: 1.
See the teachings of Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al. above. None of the references teach SEQ ID NO: 1.
SEQ ID NO: 26907 of Issued_Patents_NA db in US 12,194, 089 shares 99.9% (rounding to 100%) identity with instant SEQ ID NO: 1, see the alignment provided.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have used the mRNA sequence of ‘089 encoding the SARS-CoV-2 antigen of Maeda et al., Polack et al., and Dubensky et al., as evidenced by Vogel et al. with a reasonable expectation of success because SEQ ID NO: 26907 of ‘089 is characterized as an mRNA SARS -CoV-2/Wuhan/WlV05/ 2019_ spike protein coronavirus vaccine, see the alignment provided.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHANON A FOLEY whose telephone number is (571)272-0898. The examiner can normally be reached M-F, generally 5:30 AM-5 PM, flexible.
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/Shanon A. Foley/Primary Examiner, Art Unit 1671