DETAILED ACTION
Disposition of Claims
Claims 1-2, 4-5, 8-15, 17-19, 22-23, and 27-28 are pending.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20240173399A1, Published 05/30/2024.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Optional Authorization to Initiate Electronic Communications
The Applicant’s representative may wish to consider supplying a written authorization in response to this Office action to correspond with the Examiner via electronic mail (e-mail). This authorization is optional on the part of the Applicant’s representative, but it should be noted that the Examiner may not initiate nor respond to communications via electronic mail unless and until Applicant’s representative authorizes such communications in writing within the official record of the patent application. A sample authorization is available at MPEP § 502.03, part II. If Applicant’s representative chooses to provide this authorization, please ensure to include a valid e-mail address along with said authorization.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/04/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color, or reference to a drawing executed in color (See e.g. ¶[0028-0029] for the figure legends for Figs. 16-17 which reference color in the figures.) Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. Alternatively, the reference to color in the drawings can be removed from the specification, with the specification and/or figures updated accordingly to show the referenced data in black and white drawings.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claim 1 is objected to because of the following informalities: the definition of the abbreviation “SARS-CoV-2” is not provided. For clarity, it is requested that the first recitation of an abbreviation within a claim set be preceded by its full-length name (i.e. … severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)...).
Appropriate correction is required.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1 is drawn to an immunogenic composition, comprising:
i) a severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) protein comprising a SARS-COV-2 Spike 1 (S1) protein comprising at least 80%, least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 2, 3, 4, 5, 6, 12 or 15;
ii) a SARS-COV-2 S2 protein comprising at least 80%, least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 9, 13 or 16; or
iii) a SARS-COV-2 Spike (S) protein comprising at least 80%, least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 1, 11 or 14, or to amino acids 16-1208 of SEQ ID NO: 1, amino acids 16-1205 of SEQ ID NO: 11, or amino acids 16-1206 of SEQ ID NO: 14; and
at least one adjuvant, wherein the at least one adjuvant is selected from the group consisting of: CpG oligodeoxynucleotide, Poly I:C, IL-15, or any combination thereof.
Further limitations on the immunogenic composition of claim 1 are wherein the immunogenic composition comprises CpG oligodeoxynucleotide, Poly I:C and IL-15 (claim 2); further comprising a pharmaceutically acceptable carrier (claim 4); and wherein the SARS-CoV-2 S protein, S1 protein, or S2 protein is from SARS-CoV-2 variant alpha; beta; delta; gamma; epsilon; eta (B.1.525); iota (B.1.526); kappa (B.1.617.1); 1.617.3; mu (B.1.621, B.1.621.1), zeta (P.2), or omicron (B.1.1.529)(claim 28).
Claim 5 is drawn to a nanoparticle, comprising:
i) a SARS-CoV-2 Spike (S) protein comprising a SARS-COV-2 S1 protein comprising at least 80%, least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 2, 3, 4, 5, 6, 12 or 15;
ii) a SARS-COV-2 S2 protein comprising at least 80%, least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 9, 13 or 16; or
iii) a SARS-COV-2 S protein comprising at least 80%, least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 1, 11 or 14, or to amino acids 16-1208 of SEQ ID NO: 1, amino acids 16-1205 of SEQ ID NO: 11, or amino acids 16-1206 of SEQ ID NO: 14; and
at least one adjuvant, wherein the at least one adjuvant is selected from the group consisting of: CpG oligodeoxynucleotide, Poly I:C, IL-15, or any combination thereof.
Further limitations on the nanoparticle of claim 5 are wherein the nanoparticle comprises poly(d,l-lactide-co-glycolide) (PLGA) or 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOTAP)(claim 8);
Claim 9 is drawn to an immunogenic composition comprising the nanoparticle of claim 5 and a pharmaceutically acceptable carrier.
Claim 10 is drawn to a glass vial, plastic vial, or syringe, comprising the immunogenic composition of claim 1.
Claim 11 is drawn to a method of eliciting an immune response against SARS-CoV-2 in a subject, comprising: administering to the subject an effective amount of a prime dose of the immunogenic composition comprising a SARS-CoV-2 S protein, S1 protein, or S2 protein and an adjuvant; and subsequently administering to the subject an effective amount of one or more booster doses of the immunogenic composition of claim 9; thereby eliciting the immune response.
Further limitations on the method of claim 11 are wherein a first booster dose is administered at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 9 months, at least 12 months, at least 18 months, at least 24 months, or at least 36 months after administering the prime dose (claim 13); wherein the one or more booster doses comprises 2, 3, 4, 5, 6, 7, 8, 9 or 10 booster doses (claim 14); wherein the immune response inhibits or prevents SARS-CoV-2 infection in the subject; inhibits or prevents severe COVID19 disease in the subject; reduces the risk of transmission of SARS-CoV-2 to other subjects; increases production of dimeric IgA specific for SARS-CoV-2 S1 and IFNa; provides 100% protection against subgenomic viral RNA from SARS-CoV-2 viral challenges in the subject, for example in the upper and lower respiratory tracts; induces a neutralizing antibody titer of at least 100, at least 200, at least 300, at least 350; or combinations thereof (claim 15); wherein administering the priming dose comprises intramuscular administration and wherein administering the one or more booster doses comprises intranasal administration (claim 17); wherein generating the immune response inhibits replication of the SARS-CoV-2 in the subject (claim 18); and wherein the method is further comprising administering to the subject a COVID-19 treatment, wherein the COVID-19 treatment is selected from the group consisting of remdesivir, galidesivir,lenzilumab, molnupiravir, hydroxychloroquine, dexamethasone, arbidol, favipiravir, baricitinib, lopinavir/ritonavir, zinc ions, and interferon beta-lb (claim 27).
Claim 12 is drawn to a method of eliciting an immune response against SARS-CoV-2 in a subject, comprising: administering to the subject an effective amount of a prime dose of a SARS-CoV-2 vaccine; and subsequently administering to the subject an effective amount of one or more booster doses of the immunogenic composition of claim 9; thereby eliciting the immune response.
Further limitations on the method of claim 12 are wherein the SARS-CoV-2 vaccine is: an mRNA vaccine, a chimpanzee adenovirus-vectored vaccine, a protein vaccine, an adenovirus serotype 26 vectored vaccine, or a DNA vaccine; wherein the mRNA vaccine is BNT162b2 or mRNA-1273; wherein the chimpanzee adenovirus-vectored vaccine is ChAdOx1 nCoV-19 (AZC 1222); wherein the protein vaccine is NVX-CoV2373; wherein the adenovirus serotype 26 vectored vaccine is JNJ-78436735; and wherein the DNA vaccine is INO-4800 (claim 19).
Claim 22 is drawn to a method of eliciting an immune response against SARS-CoV-2 in a subject, comprising: administering to the subject an effective amount of a primary dose an immunogenic composition comprising the SARS-CoV-2 S1 protein of SEQ ID NO: 2, and alum; and subsequently administering to the subject an effective amount of one or more booster doses of nanoparticles comprising the SARS-CoV-2 S1 protein of SEQ ID NO: 2, CpG oligodeoxynucleotide, Poly I:C, and IL-15.
Further limitations on the method of claim 22 are wherein nanoparticles in a first booster dose comprise PLGA or DOTAP (claim 23).
Claim Rejections - 35 USC § 112(b); Second Paragraph
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 and 5 and dependent claims 2, 4, 8-15, 17-19, and 27-28 thereof 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.
Claims 1 and 5 both recite in part (b) of the claim the limitation “CpG oligodeoxynucleotide, Poly I:C and IL-15; or CpG oligodeoxynucleotide, Poly I:C, IL-15, or combinations thereof.” What is attempting to be claimed in this Markush group is unclear, as it is unclear if the combination of all 3 adjuvants must be present or if one or more of the adjuvants may be present, as the wording of “or CpG oligodeoxynucleotide, Poly I:C, IL-15, or combinations thereof” already encompasses the previously recited limitation of “CpG oligodeoxynucleotide, Poly I:C and IL-15”. One suggested amendment is to recite “b) CpG oligodeoxynucleotide, Poly I:C, and/or IL-15” or “b) at least one adjuvant, wherein the at least one adjuvant is selected from the group consisting of: CpG oligodeoxynucleotide, Poly I:C, IL-15, or any combination thereof.”
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 1 and 5 are rejected on the grounds of being indefinite. Claims 2, 4, 8-15, 17-19, and 27-28 are also rejected since they depend from claim 1 or 5, but do not remedy these deficiencies of claim 1 or 5.
Claim 11 and dependent claims 13-15 and 27 thereof 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 11 recites the limitation "the immunogenic composition" in lines 3-4. There is insufficient antecedent basis for this limitation in the claim. It is unclear if “the immunogenic composition” intended to refer back to one of the previously recited immunogenic compositions in claims 1-2, 4-5, or 8-10, as later in the claim, the immunogenic composition of claim 9 is recited.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 11 is rejected on the grounds of being indefinite. Claims 13-15 and 27 are also rejected since they depend from claim 11, but do not remedy these deficiencies of claim 11.
Claim 13 is 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 13 recites the limitation "primary dose" in line 5. There is insufficient antecedent basis for this limitation in the claim. It appears as though reference is being made to the ”prime dose” of line 3 in claim 11. Therefore, for proper antecedence, it should refer back to the “prime dose” or “priming dose”.
Claim 15 is 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.
Regarding claim 15, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 17 and 18 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.
Both claim 17 and 18 recite the limitation "method of claim 1" in line 1. There is insufficient antecedent basis for this limitation in the claims. It is believed the preamble intended to recite the “method of claim 11” and will be interpreted as such, but the claims must be amended to provide proper antecedent basis.
Claim 17 is 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 17 recites the limitation "primary dose" in line 2. There is insufficient antecedent basis for this limitation in the claim. As claim 17 is being interpreted as depending upon claim 11, it appears as though reference is being made to the ”prime dose” of line 3 in claim 11. Therefore, for proper antecedence, it should refer back to the “prime dose” or “priming dose”.
Claim 19 is 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 19 contains the trademarks/trade names PFIZER, BIONTECH, MODERNA, ASTRAZENECA, NOVAVAX, JOHNSON AND JOHNSON, and INOVIO. 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 specific biopharmaceutical companies and their related SARS CoV-2 vaccines and, accordingly, the identification/description is indefinite.
Additionally, regarding claim 19, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is suggested the limitations following “such as” either be written in a separate claim which further depends upon and limits this claim, or that the term “such as” be replaced with an appropriate Markush group (e.g. “…an mRNA vaccine, a chimpanzee adenovirus-vectored vaccine, a protein vaccine, an adenovirus serotype 26 vectored vaccine, or a DNA vaccine; wherein the mRNA vaccine is BNT162b2 or mRNA-1273; wherein the chimpanzee adenovirus-vectored vaccine is ChAdOx1 nCoV-19 (AZC 1222); wherein the protein vaccine is NVX-CoV2373; wherein the adenovirus serotype 26 vectored vaccine is JNJ-78436735; and wherein the DNA vaccine is INO-4800.”)
For at least these reasons, claim 19 is rejected on the grounds of being indefinite.
Claim 27 is 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.
Regarding claim 27, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). One suggestion is to amend the claim to read along the lines of “27. The method of claim 1, further comprising administering to the subject a COVID-19 treatment, wherein the COVID-19 treatment is selected from the group consisting of remdesivir, galidesivir,lenzilumab, molnupiravir, hydroxychloroquine, dexamethasone, arbidol, favipiravir, baricitinib, lopinavir/ritonavir, zinc ions, and interferon beta-lb.”
For at least these reasons, claim 27 is rejected on the grounds of being indefinite.
Claim Rejections - 35 USC § 112(a); First Paragraph
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.
Claim 15 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of inhibiting a SARS CoV-2 infection in a host, or preventing SARS CoV-2-related disease or disorder in a host, does not reasonably provide enablement for prevention of infection from SARS CoV-2. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Nature of the invention/Breadth of the claims. The claims are drawn to a method for treating or preventing SARS CoV-2 infection in a subject. The recitation of “preventing” a SARS CoV-2 infection in a subject is interpreted to encompass the complete blockade of any individual cell within the subject from a SARS CoV-2 infection.
State of the prior art/Predictability of the art. The art has not yet recognized the ability of a subunit antigen vaccine to prevent the complete blockade of a virus from entering any cell of a host. In fact, the principle of vaccination with subunit antigens depends upon a host becoming minimally infected with a virus, with said vaccination having “primed” the host to mount a faster, more effective immune response against wild-type viral challenge and inhibiting viral dissemination and/or spread, thus inhibiting symptomatic infection, viremia, and/or disease. Therefore, while infection from a virus cannot necessarily be prevented through the use of standard subunit protein vaccines, symptoms of infection or disease resulting from infection can be prevented from the use of a vaccine.
Working examples. No working example is disclosed in the specification that show prevention of all cells from infection. Rhesus macaques were inoculated intramuscularly (IM) or mucosally. For IM immunization, each vaccine contained 100 μg of recombinant SARS-CoV-2 (2019-nCoV) Spike S1 protein (Val 16-Arg685 of SEQ ID NO: 1). 100 μl of Adju-Phos® adjuvant (Aluminum phosphate gel, InvivoGen) was used as adjuvant. For mucosal immunization, the same S1 protein was used with CP15 adjuvant, which was a combination of 200 μg per dose of D-type CpG oligodeoxynucleotide, 1 mg per dose of PolyI:C, and 200 μg per dose of recombinant human IL-15 (¶[0182]). In the mucosal vaccine, the S1 protein was further integrated into nanoparticles with PLGA or DOTAP (¶[0182]). Viral challenge after inoculation was examined using SARS CoV-2 virus (USA-WA1/2020 strain; ¶[0191]), and neutralization assays and immunogenic titers within the animal models was assessed (¶[0183-0190]). While the challenge studies showed the vaccinated animals could quickly clear the virus, viral infection and replication clearly occurred and only further shedding and symptom from disease was prevented (¶0205-0207]).
Guidance in the specification. The specification provides guidance towards methods of inhibiting infection from a SARS CoV-2, or treatment/prevention of disease associated with a SARS CoV-2 infection, but does not provide guidance towards prevention of infection from SARS CoV-2.
Amount of experimentation necessary. Additional research is required in order to determine how effective the compositions and methods would be in preventing infection from any SARS CoV-2 strain, variant, or mutant.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to make and/or use the claimed methods.
Claims 1-2, 4-5, 8-15, 17-19, 22-23, and 27-28 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.
The instant claims are directed to immunogenic compositions comprising a S1, S2, or full-length S protein from SARS CoV-2 with at least 80% identity to the claimed sequences for each of the three noted antigens, wherein the immunogenic compositions further comprise at least one adjuvant, wherein the adjuvant is one or more of IL-15, CpG, or poly I:C; the instant claims are also drawn to methods of using said immunogenic compositions in methods of raising therapeutic and/or prophylactic immune responses in a subject. The claim limitation does not require that the S1, S2, or full-length S protein to possess any particular distinguishing feature or conserved structure, but only that it has at least 80% identity to the sequences claimed in instant claims 1 and 5. Said protein can therefore be any S1, S2, or full-length S protein which is comprised within any other sequence, so long as said sequence is at least 80% identical to those sequences claimed, which is including chimeric proteins, fusion proteins, muteins and variants comprising an antigenic or immunogenic region of any size of any polypeptide, so long as it has the 80% identity claimed. It is the examiner’s position that the disclosure of the instant application does not convey applicant’s possession of the claimed genus of SAR CoV-2 S proteins, especially those which would be useful in immunogenic compositions, and even more especially those which would be useful in vaccine methods to therapeutically or prophylactically treat SARS CoV-2 infections.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings or structural chemical formulas, or by disclosure of relevant, identifying characteristics, i.e., complete/partial structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, by predictability in the art, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
In Regents of the University of California v. Eli Lilly and Co. 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997), the Court decided that adequate written description of genetic material '"requires a precise definition, such as by structure, formula, chemical name, or physical properties,' not a mere wish or plan for obtaining the claimed chemical invention." Id. 43 USPQ2d at 1404 (quoting Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606). The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter of the claim. Id. 43 USPQ2d at 1406. A description of what the genetic material does, rather than of what it is, does not suffice, ld. While the instant claims are drawn to immunogenic compositions which comprise the breadth of SARS CoV-2 proteins present in any concentration along with one or more of the three cited adjuvants present in any concentration along with any other unclaimed carriers, excipients, or vehicles, the cited case law is relevant because there is limited disclosure of the structure, formula, or physical properties of the "immunogenic composition" and there is only a disclosure of what the “composition" does (composition which is immunogenic, especially in order to raise a therapeutic and/or prophylactic immune response), rather than of what it is.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus. Regents of the University of California v. Eli Lilly& Co., 199 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly & Co., the court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. A "representative number of species" means that the species that are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. MPEP §2163 II.A.3a.ii. Further, even in cases were multiple species with in a claimed genus have been disclosed, such does not necessarily demonstrate possession of the genus. See, In re Smyth, 178 U.S.P.Q. 279 at 284-85 (CCPA 1973) (stating "where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus or combination claimed at a later date in the prosecution of a patent application."); and University of California v. Eli Lilly and Co., 43 USPQ2d 1398, at 1405 (Fed Cir 1997)(citing Smyth for support). Where there is uncertainty in the operability of undisclosed embodiments, an application may be found not to have provided adequate descriptive support for a claimed genus.
The specification discloses the reduction to practice of only compositions which comprised 100 ug of SARS CoV-2 S1 proteins within the claimed genus (e.g. each vaccine composition contained 100 μg of recombinant SARS-CoV-2 (2019-nCoV) Spike S1 protein (Val 16-Arg685 of SEQ ID NO: 1; ¶[0182].) If the S1 protein was delivered via IM injection, it further comprised alum adjuvant, while those compositions delivered mucosally comprised 200 μg per dose of D-type CpG oligodeoxynucleotide, 1 mg per dose of PolyI:C, and 200 μg per dose of recombinant human IL-15. The mucosal vaccine incorporated S1 protein with CP15, formulated in nanoparticles either in PLGA or in DOTAP (100 μl per dose; ¶[0182]). This S1 polypeptide composition does not reflect the entirety of structures of SARS CoV-2 S proteins, mutants, variants, or immunogenic fragments/antigens within each polypeptide sequence. Further, the only combination of adjuvants tested appeared to be either alum alone, or the combination of IL-15, CpG, and poly I:C. It is not clear as to the criticality of parameters for the S protein sequences, variants, mutants, and/or fragments thereof, nor is it clear as to whether or not other combinations of adjuvants are tolerated or are immunogenic with the breadth of S proteins claimed. With respect to the methods, it is not clear as to the dosage and the specific delivery routes that are tolerated, beyond intranasal delivery, and the methods clearly show that the intranasal inoculation is a boosting dosage that follows an intramuscular S1 protein+Alum vaccine priming (Example 2 at ¶[0196]). Consequently, there is no information about which and how many amino acids of the S1, S2, and/or full-length S proteins that are required for raising an immune response, whether or not the full-length S protein is in a prefusion or postfusion conformation, which critical sequences or epitopes may/may not be included in the S protein, which combination of adjuvants at what concentration are tolerated, or which mucosal delivery routes are acceptable.
With respect to the breadth of S proteins and fragments claimed, it is clear that these portions of the S protein have different immunogenic potentials. In one study, when comparing the immunogenic properties of SARS-CoV-2 full-length spike (S) ectodomain, S1 with receptor binding domain, and S2 with fusion domain, full-length S was more immunogenic and effective in inducing IgG antibodies after low dose vaccination, compared to the S1 subunit. Both S1 and S2 subunit domain vaccines were similarly immunogenic, and adjuvant effects were significant for effective induction of IgG1 and IgG2a isotypes, neutralizing and receptor-binding inhibiting antibodies, and antibody-secreting B cell and interferon-γ secreting T cell immune responses (Kim KH, et. al. Vaccines (Basel). 2021 Mar 29;9(4):316.). Another study reported superior immunogenicity of SARS-CoV-2 S1 subunit over a fragment of the S1 protein, namely the receptor binding domain (RBD) domain (Wang Y, et. al. J Med Virol. 2021 Feb;93(2):892-898. Epub 2020 Oct 5.) In contrast, another study demonstrated that a higher neutralizing titer was induced by RBD than that by S1 and full-length S (Ravichandran S, et. al. Sci Transl Med. 2020 Jul 1;12(550):eabc3539. Epub 2020 Jun 8.) A full-length S protein is large (~1300 amino acid residues) and often encounters production difficulties. Vaccine dosage effects by different versions (S, S1, S2) of S protein antigens remain unknown, which is an important parameter in vaccine immunogenicity comparison. Therefore, there is great uncertainty in the art when it comes to the immunogenicity of the S protein and domains, mutants, variants, and fragments thereof.
Furthermore, and in general, it is known for proteins, albeit not in all cases, that amino acid addition(s), substitution(s) or deletion(s) can destroy the function of the epitope, abolish its ability to be immunogenic, or paradoxically make the immune response worse in response to viral challenge. This lack of predictability of the relationship between the protein sequence and the immunogenic epitope function is well documented by Mateu et al. (Mateu MG, et. al. Eur J Immunol. 1992 Jun;22(6):1385-9.) and Greenspan et al. (Greenspan NS, Di Cera E. Defining epitopes: It's not as easy as it seems. Nat Biotechnol. 1999 Oct;17(10):936-7.). Certain viruses, such as SARS CoV-2, have pre-existing antibodies resulting from infections of different sub-types that may recognize but not effectively neutralize the virus, which may result in paradoxically worse disease in a mechanism known as antibody-dependent enhancement (ADE)(Karthik K, et. al. Hum Vaccin Immunother. 2020 Dec 1;16(12):3055-3060. Epub 2020 Aug 26.). Poorly-neutralizing antibodies are undesirable as they may not protect the host from future exposures and thus lead to reinfection. This neutralization ‘escape’ dynamic occurs, for example, in the case of influenza A strains and SARS-CoV-2 variants featuring mutations in vulnerable epitopes resulting in reinfection of hosts whose antibodies developed during prior infection or vaccination no longer effectively recognize the mutated epitopes (Miller NL, Raman R, Clark T, Sasisekharan R. Complexity of Viral Epitope Surfaces as Evasive Targets for Vaccines and Therapeutic Antibodies. Front Immunol. 2022 Jun 17;13:904609.) The effects of these changes are largely unpredictable as to which ones have a significant effect versus not. Thus, the specification fails to adequately describe at least a substantial number of members of compositions which would be immunogenic and comprise the breadth of SARS CoV-2 S proteins as claimed along with the adjuvants as claimed, especially when it comes to administering said compositions in any fashion to elicit an immune response, especially a therapeutic and/or prophylactic immune response.
In summary, one of skill in the art would not accept the disclosure of the immunogenic compositions comprising SARS CoV-2 S proteins and adjuvants in the Examples as representative of all compositions comprising S proteins from all sources and any fragments, homologs, or variants thereof having immunogenic activity, along with any combination of the adjuvants claimed, especially when used in clinically therapeutic methods of treating SARS CoV-2 infections. The specific adjuvants are claimed broadly, as “CpG oligodeoxynucleotides” are a general class of adjuvants that act like toll-like receptor 9 (TLR9) agonists, and include CpG 1018, CpG ODN 7909, CpG ODN 2006, CpG ODN 2935, and CpG ODN 2216 to name just a few which are used in different immunogenic compositions. Likewise, “poly I:C” is a synthetic dsRNA analog (polyinosinic-polycytidylic acid) that is found in various forms and derivatives to act as TLR3 agonists (e.g. poly ICLC, poly IC12U, poly(I:C)-PLL). Finally, it is unclear if the IL-15 is a specific form, sequence, or species that is helpful in said composition to elicit the desired immune response. It is unclear which singular adjuvant or combination thereof is required in combination with which SARS CoV-2 S protein to elicit the immunogenic immune response, especially the desired therapeutic immune response. Based on the lack of knowledge and predictability in the art, those of ordinary skill in the art would not conclude that the applicant was in possession of the claimed genera of all SARS CoV-2 S proteins and all claimed genera of adjuvants to result in an immunogenic composition, especially such compositions that would be useful in methods to therapeutically or prophylactically treat or inhibit SARS CoV-2 challenge or infection based on the disclosure of the instant application. In conclusion, the specification, taken together with the pre-existing knowledge and the lack of predictability in the art, fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph, with respect to claims 47-55.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (page 1115).
Claims 1-2, 4-5, 8-15, 17-19, 22-23, and 27-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for SARS CoV-2 S1 protein-adjuvant-nanoparticle compositions, wherein the S1 protein is V16-R685 of SEQ ID NO: 1, and the adjuvant is CP15, and the nanoparticles comprise either DOTAP or PLGA, and methods of using said compositions in intranasal boosting immune responses in hosts primed with other SARS CoV-2 S protein immunogenic compositions, does not reasonably provide enablement for any SARS CoV-2 S1, S2, or full-length S protein of at least 80% identity to the S proteins claimed in use with any of the combination of adjuvants claimed and in any delivery method in any of the methods of inoculation claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to an immunogenic composition, comprising:
i) a severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) protein comprising a SARS-COV-2 Spike 1 (S1) protein comprising at least 80%, least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 2, 3, 4, 5, 6, 12 or 15;
ii) a SARS-COV-2 S2 protein comprising at least 80%, least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 9, 13 or 16; or
iii) a SARS-COV-2 Spike (S) protein comprising at least 80%, least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 1, 11 or 14, or to amino acids 16-1208 of SEQ ID NO: 1, amino acids 16-1205 of SEQ ID NO: 11, or amino acids 16-1206 of SEQ ID NO: 14; and
at least one adjuvant, wherein the at least one adjuvant is selected from the group consisting of: CpG oligodeoxynucleotide, Poly I:C, IL-15, or any combination thereof.
The claims are further drawn to said composition comprising nanoparticles, and to methods of using said compositions in methods of eliciting an immune response against SARS-CoV-2 in a subject, comprising: administering to the subject an effective amount of a prime dose of any SARS-CoV-2 vaccine, such as one comprising any SARS CoV-2 full-length S protein, S1 protein, or S2 protein or a composition comprising S1 + alum, and subsequently administering to the subject an effective amount of one or more booster doses of the immunogenic composition comprising the claimed SARS CoV-2 S protein+adjuvant+nanoparticle composition. The breadth of the S1, S2, and full-length S proteins claimed in the product claims is drawn to any protein with at least 80% identity to those sequences claimed, which includes any mutant or variant with said percent identity, which includes fusion proteins, chimeric proteins, substitutions, insertions, or deletion proteins, so long as they have at least 80% identity to those proteins sequences claimed. The breadth of “IL-15” includes the IL-15 cytokine from any source, and is found in most jawed vertebrates, including humans, mice, rats, cows, horses, pigs, cats, dogs, rabbits, hedgehogs, naked mole-rats, and fish. “CpG oligodeoxynucleotides” (ODNs) are synthetic DNA molecules containing unmethylated CpG motifs that stimulate the immune system via TLR9. They are primarily classified into four types—A, B, C, and P—based on their structural characteristics (phosphorothioate or phosphodiester backbones, palindromic sequences, and poly-G tails) and their specific effects on immune cell activation. While hundreds of ODNs have been studied and generated, the only ODN that appears to be formally FDA approved as an adjuvant is CpG 1018. There are different formulations of poly I:C (polyinosinic:polycytidylic acid) designed to balance immune-stimulating potency with reduced toxicity and increased stability. Key variations include stabilized derivatives like Poly-ICLC and Poly-IC12U, as well as different molecular weight, transfection, and nanoparticle-based formulations. The immunological effects of poly I:C vary based on molecular weight, with Low Molecular Weight (LMW) tending to elicit stronger antiviral and cytokine responses in myeloid cells, producing cytokines like TNF-α, IL-8, and IFN-β, while High Molecular Weight (HMW) shows greater stimulation in fibroblasts but reduced responses in myeloid cells.
Turning to the methods, the methods are allowing any delivery method for any of the claimed immunogenic compositions in any dosage, so long as said dosage is an “effective amount.” While certain methods point to the specific immunogenic compositions of claim 9, the other compositions in the methods can be reasonably drawn to any known immunogenic composition/vaccine comprising any SARS CoV-2 S/S1/S2 protein and any adjuvant. The method of claim 22 is the only method which narrows the priming and boosting compositions to more specifically comprise one type of SARS CoV-2 S protein antigen and adjuvant. The “subject” may be any subject, and is not drawn to any specific species, group, or demographic.
State of the prior art/Predictability of the art. As detailed supra in the 35 USC 112a written description rejection, the art is unpredictable with respect to those SARS CoV-2 S protein antigens and immunogenic compositions thereof which are additionally useful in methods of raising an immune response in a host. The art has shown differences in the immune responses raised by S1, S2, and full-length S protein compositions, and varies with the antigens or delivery systems used in conjunction with said antigen.
Similar to influenza vaccines, the developed SARS CoV-2 vaccines which primarily deliver nucleic acid encoding full-length prefusion stabilized S protein in lipid nanoparticles or viral vectors, have been shown to elicit limited protection against heterologous variants, requiring seasonal booster shots with updated sequences to elicit protective responses in a host. Immune responses raised by the compositions can also have unwanted side effects, from ADE discussed supra to myocarditis (inflammation of the heart tissue) and pericarditis (inflammation of the pericardial sac around the heart) (Yaamika H, et. al. J Taibah Univ Med Sci. 2023 Sep 5;18(6):1646-1661.; Cao X, et. al. Sci Transl Med. 2025 Dec 10;17(828):eadq0143. Epub 2025 Dec 10.) Additionally, some reports show that SARS CoV-2 S protein can interact with its cognate receptor, ACE2, and raise autoantibodies against ACE2, causing widespread tissue and organ damage in the host (Beduleva L, et. al. Sci Rep. 2025 Oct 24;15(1):37315.).
Working examples. The working examples disclosed in the specification compare the inoculation of Rhesus macaques with two different subunit S1-based vaccines. Rhesus macaques were inoculated intramuscularly (IM) or mucosally (intranasally, IN). For IM immunization, each vaccine contained 100 μg of recombinant SARS-CoV-2 (2019-nCoV) Spike S1 protein (Val 16-Arg685 of SEQ ID NO: 1), wherein 100 μl of ADJU-PHOS® adjuvant (Aluminum phosphate gel) was used as adjuvant. For mucosal immunization, the same S1 protein was used with three adjuvants and a nanoparticle delivery system; the adjuvants used in what was labeled the “CP15 adjuvant” were a combination of 200 μg per dose of D-type CpG oligodeoxynucleotide (D-type ODNs are retained for long periods in early endosomes, allowing them to activate the MyD88/IRF-7 signaling pathway, they are also called “A type” (CpG-A ODN), and include ODN 2216 or ODN D35), 1 mg per dose of Poly I:C, and 200 μg per dose of recombinant human IL-15 (¶[0182]), while the nanoparticles were formulated with PLGA or DOTAP (¶[0182]). The specific type of CpG oligonucleotide adjuvant is not clear, the IL-15 was recombinant human IL-15 (SEQ ID NO: 7, ¶[0048]), and the poly I:C appeared to be an average size of 1.5-8 kb (¶[0182]). The vaccination regimen was performed in SARS CoV-2 naïve animals, wherein the animals were either given the S1+alum via IM injection at weeks 0, 3, and 16, while the S1+CP15+nanoparticle group were given S1+alum via IM at week 0, then boosted at weeks 3 and 6 with S1+CP15+PLGA and at week 16 with S1+CP15+DOTAP (¶[0182]). It is not clear what other components were within the noted nanoparticles. It does not appear as though any other SARS CoV-2 S proteins were tested, including any other S1 variants or mutants, or any S2 or full-length S proteins. It appears as though only the CP15 triple adjuvant system was used; it does not appear that any S proteins were tested with only one or more of the three adjuvants in the CP15 system (e.g. CpG alone, CpG and IL-15, IL-15 and poly I:C, etc.) No seropositive or previously vaccinated subjects were tested for any of these compositions, as all animals appeared to be naïve to both the SARS CoV-2 virus and vaccines.
Viral challenge after inoculation was examined using SARS CoV-2 virus (USA-WA1/2020 strain; ¶[0191]), and neutralization assays and immunogenic titers within the animal models was assessed (¶[0183-0190]). While the challenge studies showed the vaccinated animals could quickly clear the virus, viral infection and replication clearly occurred and only further shedding and symptom from disease was prevented (¶0205-0207]). It is not clear that the animals were challenged with any other viral strains, variants, or isolates.
Guidance in the specification. The specification provides guidance towards the use of the S1+CP15+DOTAP/PLGA nanoparticle formulations as intranasal boosting mucosal vaccination systems. It is not clear from the guidance in the specification that the composition may be used in methods for priming a naïve or seropositive subject. It is not clear if the DOTAP or PLGA nanoparticles may be interchangeable in the system, as the specification notes the PLGA nanoparticles were difficult to suspend, which is why the nanoparticle system was switched to DOTAP in the final IN vaccination (¶[0200]). It is not clear that any other S1 proteins which are at least 80% identical to those sequences claimed would be useful in such a system, nor were any other S2 or full-length S proteins tested with 80% identity to said proteins claimed for their immunogenicity or effectiveness in any vaccine regimen.
Amount of experimentation necessary. Additional research is required in order to determine how effective any composition comprising any S1, S2, or full-length S protein of SARS CoV-2 with at least 80% identity to the sequences claimed would be in the adjuvant system claimed (e.g. at least one of any IL-15, any CpG oligonucleotide, and any poly I:C), especially in methods of inoculating through any route in the methods as claimed in order to raise a therapeutic or prophylactic immune response in a subject.
In light of the Supreme Court decision in Amgen Inc. et al. v. Sanofi et al., 143 S. Ct. 1243 (2023) (hereafter Amgen), updated guidelines were provided regarding the assessment of enablement (Federal Register, pp. 1563-1566; Pub. Jan. 10, 2024.) In Amgen, the Supreme Court unanimously affirmed that a genus of monoclonal antibodies were not enabled because when a range within a genus is claimed, there must be reasonable enablement of the scope of the range. The Court found in Amgen that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality. In the instantly claimed invention, the breadth of claimed antigens (e.g. any SARS CoV-2 S1, S2, or full-length S protein with at least 80% identity to the sequences claimed for each respective protein) combined with the breadth of claimed adjuvants (e.g. any IL-15, any average size of poly I:C, any known CpG oligonucleotide, in any combination of one or more of those said adjuvants) creates an extreme burden to determine which combinations would be immunogenic. Additionally, it would require undue experimentation to determine which of these permutations would be useful in any delivery method (e.g. IM, IN, subcutaneous injection, inhalation, oral, etc.) and provide the desired therapeutic or prophylactic immune response.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to make the claimed compositions and to use said composition in the claimed methods.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4-5, 9-15, 18-19, and 28 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Meinke et. al. (US20230038284A1; Priority 03/01/2020; hereafter “Meinke”.)
The Prior Art
Meinke teaches CpG-adjuvanted SARS-CoV-2 vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof (entire document; see abstract.) Meinke teaches the vaccine comprises inactivated SARS CoV-2 particles which comprise S proteins having at least 95% amino acid identity to SEQ ID NO: 3, and comprises a CpG-containing oligodeoxynucleotide (CpG-ODN) (reference claims 1, 19). Under broadest reasonable interpretation, a SARS CoV-2 particle is a “nanoparticle”. Meinke teaches the adjuvant may be alone or with other adjuvants, such as alum (¶[0016][0042-0044]). Instant SEQ ID NO: 1 is 100% identical to reference SEQ ID NO: 3 (SARS CoV-2 S protein, GenBank: QHD43416); see alignment below; instant claims 1, 5.) Meinke teaches the composition may comprise pharmaceutically acceptable excipients (¶[0131-0132]; instant claims 4, 9). Meinke teaches vials, syringes, and containers which comprise the composition (¶[0011][0141][0170]; instant claim 10). Meinke teaches the different strains and variants which can generate the particle of the instant claims (e.g. B.1.1.7 is an alpha strain; ¶[0146]; instant claim 28).
Meinke teaches that the composition may be administered to a subject in need thereof in a prime dose followed by a second dose at least 28, 60, 70, 80, 90, or 120 days after the first dose (¶[0136]; instant claims 11-12), or the composition can be used only as a booster dose following a different priming dose of a SARS CoV-2 vaccine, wherein the different vaccine may be a subunit vaccine, a recombinant viral vector vaccine, or an mRNA vaccine (¶0137]; instant claims 13-14, 19.) Meinke teaches the composition would inhibit SARS CoV-2 infection and prevent related COVID-19 disease (¶[00122][0125]), wherein the immune response generates antigen-specific antibodies (¶[0126]), and the amount of subgenomic viral RNA is decreased (¶[0020][0030-0031]; Figs. 9, 19-20; instant claims 15, 18.) Meinke teaches the dosage can be administered subcutaneously, intramuscularly (¶[0135]). As instant SEQ ID NO: 2 is aa 16-685 of instant SEQ ID NO: 1, Meinke teaches a composition which comprises SEQ ID NO: 2 and alum.
For at least these reasons, Meinke teaches the limitations of instant claims 1, 4-5, 9-15, 18-19, and 28, and anticipates the invention encompassed by said claims.
US-18-275-925-1
Query Match 100.0%; Score 6722; DB 1; Length 1273;
Best Local Similarity 100.0%;
Matches 1273; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 60
Qy 61 NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV 120
Qy 121 NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE 180
Qy 181 GKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQT 240
Qy 241 LLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETK 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETK 300
Qy 301 CTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN 360
Qy 361 CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD 420
Qy 421 YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPC 480
Qy 481 NGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVN 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 NGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVN 540
Qy 541 FNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITP 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 FNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITP 600
Qy 601 GTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSY 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSY 660
Qy 661 ECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTI 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 ECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTI 720
Qy 721 SVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQE 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 SVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQE 780
Qy 781 VFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 VFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDC 840
Qy 841 LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAM 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAM 900
Qy 901 QMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALN 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 QMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALN 960
Qy 961 TLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRA 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 TLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRA 1020
Qy 1021 SANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPA 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 SANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPA 1080
Qy 1081 ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDP 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDP 1140
Qy 1141 LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDL 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDL 1200
Qy 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDD 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDD 1260
Qy 1261 SEPVLKGVKLHYT 1273
|||||||||||||
Db 1261 SEPVLKGVKLHYT 1273
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure and is listed below.
WO2011026111A1, Teaches coronaviruses and SARS CoV antigens, combination of antigens with the adjuvants of IL-15, CpG, and poly I:C.
Sui Y, et. al. J Clin Invest. 2019 Mar 1;129(3):1314-1328. Epub 2019 Feb 18. Teaches the use of viral surface glycoproteins in conjunction with IL-15, CpG, and poly I:C adjuvants for intramucosal vaccination.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671