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 .
Disposition of Claims
Claims 515-534 are pending and will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2023/0226173 A1 , Published 20 July 2023. Applicant’s amended Specifications as presented on 23 March 2023 and 06 April 2023 are acknowledged and entered.
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.
Priority
Applicant is advised that Claims 527 and 529 do not have support in Provisional Applications # 63/084,421, filed on 28 September 2020, and 63/009,907, filed on 14 April 2020, to which this application claims domestic benefit. As such, the effective filing date for these claims is the same as the PCT Filing Date, 14 April 2021.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statements (IDSes) submitted on 09 January 2023, 04 June 2024, 09 September 2024, 28 October 2024, 09 January 2025, and 14 July 2025 have been considered, as a whole, by the examiner. Any individual references with strikethroughs, however, have not been considered.
Drawings
The Drawings are objected to for containing references to colors. Specifically, Figures 2A, 5, 9, 10, and 14 all refer to colors (i.e., red, blue, green, brown) in the figure legend within the Specification. Additionally, Paragraphs 0244, 0259, 0268, and 0278 also refer to colors within the Figures. 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. 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.”
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). The objection to the drawings will not be held in abeyance. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action.
Drawings and Specification; Sequence Disclosure Requirements
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth below or on the attached Notice To Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures.
The drawings and specification are objected to because Figures 1, 5, 6A, 9, 10, 11A, 14, 15A, 17, 24, and 27 all comprise sequences that do not identify said sequences with corresponding SEQ ID NOs within the figures themselves or within the figure legends of the specification.
Also, Paragraphs 0215 and 0283 comprise sequences that do not identify said sequences with a corresponding SEQ ID NO in the Sequence Listing. The sequences in question are GPGPG, RRAR, and QQAQ.
The sequences in question all have at least 4 specifically defined and enumerated amino acid residues or at least 10 specifically defined and enumerated nucleotide positions, as applicable. Therefore, they are required to have SEQ ID NOs. If the sequences in question correspond to existing sequences in the Sequence Listing, then each sequence should be associated with its corresponding SEQ ID NO each and every time it appears throughout the disclosure. If the sequences in question do not correspond to existing sequences in the Sequence Listing, then each one is required to have its own unique SEQ ID NO.
Additionally, instant SEQ ID NOs: 108 and 173 are 100% identical to each other and the exact same length. The same applies to instant SEQ ID NOs: 114 and 178; instant SEQ ID NOs: 7 and 21; and instant SEQ ID NOs: 35 and 49. These pairs of sequences are duplicates of each other. The sequence alignments have been attached to this Office Action.
The duplicate sequences must be removed from the Sequence Listing. Examiner also kindly requests that Applicant review the Sequence Listing and remove all instances of duplicate sequences.
The objection to the drawings will not be held in abeyance. Applicants must comply with sequence rules in order to be considered a complete response to this Office Action; a complete response would be to either submit corrected drawing sheets as noted below or to amend the specification to include the SEQ ID NO:s within the figure legend.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action.
Specification
The abstract of the disclosure is objected to because the first sentence is a sentence fragment or incomplete sentence. It is suggested that it say “Pan-coronavirus recombinant vaccine compositions…at least one of which is derived from a non-spike protein, are described.” A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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://, www., or other browser-executable code. The hyperlink in question is: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.htmWConsequence (Paragraph 0007). See MPEP § 608.01.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 516-534 are objected to because of the following informalities: In Claim 516, it is suggested that it say “wherein the human coronavirus is the SARS-CoV-2 original strain”.
In Claim 517, it is suggested that it say “wherein the non-spike protein[[s]] [[are]] is…or is the Envelope protein, the Membrane protein, or the Nucleocapsid protein”.
In Claim 518, it is suggested that it say “…or derived from…”.
In Claims 519, 522, and 534, it is suggested that all instances of “SEQ ID NO:” which are present when multiple sequences are recited should be replaced with “SEQ ID NOs:”. There should be an “s” before the colon.
In Claims 519-521, it is suggested that they say “selected from [[a]] the group consisting of”.
In Claim 522, it is suggested that it say “wherein the one or more coronavirus B-cell target epitopes”.
In Claim 523, it is suggested that it say “in [[a]] the spike (S) protein”.
In Claim 524, it is suggested that it say “in [[a]] the nucleocapsid (N) protein”.
In Claim 525, it is suggested that it say “in [[an]] the Envelope (E) protein”.
In Claim 526, it is suggested that it say “in [[a]] the protein encoded by ORF3a”.
In Claim 527, it is suggested that it say “in [[a]] the protein encoded by ORF7a”.
In Claim 528, it is suggested that it say “in [[a]] the protein encoded by ORF8”.
In Claim 529, it is suggested that it say “in [[a]] the protein encoded by ORF10”.
In Claim 530, it is suggested that it say “in [[a]] the protein encoded by ORF1b
In Claim 531, it is suggested that it say “in [[a]] the protein encoded by ORF1a ” instead of “in a protein encoded by ORF1a protein”.
In Claims 532-533, it is suggested that they say “The composition of claim 515, further comprising”. There should be commas after “515”.
Appropriate correction is required.
Claims are only allowed to have one period, as stated in MPEP § 608.01(m). The claim which does not adhere to this rule is Claim 515. Regarding Claim 515, parts a-c should utilize parentheses instead of periods to separate them from the claim language itself. As such, Claim 515 is objected to.
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.
Claim 515, and dependent claims 516-534 thereof, 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 515, it recites the limitation “the composition comprising at least two of: a) one or more coronavirus B-cell target epitopes; b) one or more coronavirus CD4+ T cell target epitopes; c) one or more coronavirus CD8+ T cell target epitopes; wherein at least one epitope has a mutation as compared to its corresponding epitope in SARS-CoV-2 isolate Wuhan-Hu-1, wherein the epitopes are derived from a human coronavirus, an animal coronavirus, or a combination thereof; wherein at least one epitope is derived from a non-spike protein”. The claim recites options a-c, but does not include any connecting word, such as “and”, “and/or”, or “or” between options b and c. This, along with the claim language used, renders the claim indefinite. The claim, as currently written, can be reasonably interpreted to only require two epitopes and that both are from the same group of epitopes (i.e., only B-cell target epitopes, for instance). Another interpretation is that the at least two target epitopes are from different groups (i.e., one B-cell target epitope and one CD4+ T cell target epitope).
Additionally, there is no connecting word between the wherein clauses in the latter portion of the claim. As such, it is unclear if those limitations are being claimed in the alternative or if all are required elements of the claim. It is suggested that the claim be amended to clarify Applicant’s intention, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 515 is rejected on the grounds of being indefinite. Claims 516-534 are also rejected since they depend upon Claim 515, but do not remedy the deficiencies of Claim 515.
Claim 515, and dependent claims 516-534 thereof, 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 515, it recites the limitation “A coronavirus recombinant vaccine composition”. It appears that the word “recombinant” is modifying the word “vaccine” and phrase “vaccine composition”, as currently written. It is unclear how a vaccine composition can be recombinant, rendering the claim indefinite. It is suggested that the claim be amended so that it recites “A recombinant coronavirus vaccine composition”, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 515 is rejected on the grounds of being indefinite. Claims 516-534 are also rejected since they depend upon Claim 515, but do not remedy the deficiencies of Claim 515.
Claim 520 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 520, it recites the limitation “wherein target epitopes are derived from a SARS-CoV-2 protein selected from a group consisting of: proteins encoded by ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10, or an Envelope protein, a Membrane protein, a Nucleocapsid protein, and a Spike protein”. The use of the word “proteins” in “proteins encoded by” conflicts with the phrase “a SARS-CoV-2 protein” as only one protein is recited in the first portion of the claim. This renders the claim indefinite.
Additionally, the use of “an”/”a” with Envelope protein, Membrane protein, Nucleocapsid protein, and Spike protein also renders the claim indefinite because the use of the indefinite articles “an”/”a” appears to imply that there are different types or version of each protein that can be expressed by the virus and that only one is being selected from each type of protein. This renders the claim indefinite. It is suggested that the claim be amended so that it recites “wherein target epitopes are derived from a SARS-CoV-2 protein selected from a group consisting of: a protein[[s]] encoded by ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10, or [[an]] the Envelope protein, [[a]] the Membrane protein, [[a]] the Nucleocapsid protein, and [[a]] the Spike protein”, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 520 is rejected on the grounds of being indefinite.
Claim 522 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 522, as noted above, some of the claimed sequences are duplicates of each other, specifically SEQ ID NOs: 173/108, 178/114, 7/21, and 35/49. As such, it is unclear which other sequences were meant to be referenced in place of the duplicate sequences, and this lack of clarity renders the claim indefinite. It is suggested that the claim be amended by removing all duplicate sequences, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 522 is rejected on the grounds of being indefinite.
Claims 523-524, 528, and 531 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.
Regarding Claims 523, 524, 528, and 531, they all recite mutated epitopes some of which do not recite a specific mutation. For instance, Claim 523 recites Y144-, Claim 524 recites S2-, and Claim 531 recites S3675-. It is unclear what the minus is meant to represent as it is not further explained within the claim set and there is no definition provided in the Specification. Similarly, Claim 528 recites Q27*. It is unclear what the asterisk is meant to represent as it is not further explained within the claim set and there is no definition provided in the Specification. This lack of clarity renders the claims indefinite. It is suggested that the claims be amended by reciting specific mutations or by clarifying what the terms used in the claims mean, as long as said clarification is supported by the originally-filed disclosure, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 523-524, 528, and 531 are rejected on the grounds of being indefinite.
Claims 523-524 and 530-531 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.
Regarding Claims 523-524 and 530-531, they each recite multiple mutations for the claimed mutated residues. Several of the mutations, however, are recited multiple times in their respective claim. In Claim 523, Y144- is recited twice, for instance. In Claim 524, M234I is recited twice, for instance. In Claim 530, R2613C is recited twice. In Claim 531, T265I and L3352F are each recited twice, while S3675-, G3676-, and F3677- are each recited five times. It is unclear if this was intentional or if these are merely typographical or copy/paste errors. If it was done in error, it is unclear which other mutations were meant to be recited. This lack of clarity renders the claims indefinite. It is suggested that the claims be amended by removing the duplicate recitations of the claimed mutations, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 523-524 and 530-531 are rejected on the grounds of being indefinite.
Claim Interpretation
In light of the issues raised above, the claims are being interpreted as reading upon the following:
Claim 515 is drawn to a recombinant coronavirus vaccine composition, the composition comprising at least two of: a) one or more coronavirus B-cell target epitopes; b) one or more coronavirus CD4+ T cell target epitopes; c) one or more coronavirus CD8+ T cell target epitopes; wherein at least one epitope has a mutation as compared to its corresponding epitope in SARS-CoV-2 isolate Wuhan-Hu-1, wherein the epitopes are derived from a human coronavirus, an animal coronavirus, or a combination thereof; wherein at least one epitope is derived from a non-spike protein.
Further limitations on the recombinant coronavirus vaccine composition according to Claim 515 are:
516. The composition of claim 515, wherein the human coronavirus is the SARS-CoV-2 original strain or a SARS-CoV-2 variant and wherein the animal coronavirus is a bat coronavirus, a pangolin coronavirus, a civet cat coronavirus, a mink coronavirus, a camel coronavirus, or a coronavirus from another animal susceptible to coronavirus infection.
517. The composition of claim 515, wherein the non-spike proteins are encoded by ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10, or are the Envelope protein, the Membrane protein, or the Nucleocapsid protein.
518. The composition of claim 515, wherein one or more of the at least two target epitopes is in the form of a large sequence, wherein the large sequence is a whole protein expressed by SARS-CoV-2 or a SARS-CoV-2 variant, or derived from a partial protein sequence expressed by SARS-CoV-2 or a SARS-CoV-2 variant, or a combination thereof.
519. The composition of claim 518, wherein the large sequence is selected from the group consisting of SEQ ID NOs: 143-151.
520. The composition of claim 515, wherein target epitopes are derived from a SARS-CoV-2 protein selected from the group consisting of: a protein encoded by ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10, or the Envelope protein, the Membrane protein, the Nucleocapsid protein, and the Spike protein.
521. The composition of claim 515, wherein the mutated epitopes are derived from one or more of: one or more SARS-CoV-2 human strains or variants in current circulation; one or more coronaviruses that have caused a previous human outbreak; one or more coronaviruses isolated from animals selected from the group consisting of bats, pangolins, civet cats, minks, camels, and other animals receptive to coronaviruses; or one or more coronaviruses that cause the common cold, wherein the one or more SARS-CoV-2 human strains or variants in current circulation are selected from: strain B.1.177; strain B.1.160, strain B.1.1.7; strain B.1.351; strain P.1; strain B.1.427/B.1.429; strain B.1.258; strain B.1.221; strain B.1.367; strain B.1.1.277; strain B.1.1.302; strain B.1.525; strain B.1.526, strain S:677H, and strain S:677P, and wherein the one or more coronaviruses that cause the common cold are selected from: 229E alpha coronavirus, NL63 alpha coronavirus, OC43 beta coronavirus, and HKU1 beta coronavirus.
522. The composition of claim 515, wherein the one or more coronavirus CD8+ T cell target epitopes are selected from: SEQ ID NOs: 2-29, SEQ ID NOs: 30-57, SEQ ID NO: 153, or a combination thereof, wherein the one or more coronavirus CD4+ T cell target epitopes are selected from: SEQ ID NOs: 58-73, SEQ ID NOs: 74-105, SEQ ID NO: 154, or a combination thereof, and wherein the one or more coronavirus B-cell target epitopes are selected from: SEQ ID NOs: 106-116, SEQ ID NOs:117-138, SEQ ID NOs: 155, SEQ ID NOs: 172-178, or a combination thereof.
523. The composition of claim 515, wherein the mutated epitope is in a spike (S) protein, wherein the mutation is one or a combination of A22V, S477N, H69-, V70-, Y144-, N501Y, A570D, P681H, D80A, D215G, L241-, L242-, A243-, K417N, E484K, A701V, L18F, K417T, H655Y, S13I, W152C, L452R, S439K, S98F, D80Y, A626S, V1122L, A67V, Q677H, F888L, L5F, T95I, D253G, or Q677P.
524. The composition of claim 515, wherein the mutated epitope is in a nucleocapsid (N) protein, wherein the mutation is one or a combination of A220V, M234I, A376T, R203K, G204R, T205I, P80R, P199L, S186Y, D377Y, S2-, D3Y, A12G, or P67S.
525. The composition of claim 515, wherein the mutated epitope is in an Envelope (E) protein, wherein the mutation is P71L.
526. The composition of claim 515, wherein the mutated epitope is in a protein encoded by ORF3a, wherein the mutation is one or a combination of Q38R, G172R, V202L, or P42L.
527. The composition of claim 515, wherein the mutated epitope is in a protein encoded by ORF7a, wherein the mutation is R80I.
528. The composition of claim 515, wherein the mutated epitope is in a protein encoded by ORF8, wherein the mutation is Q27*, T11I, or a combination thereof.
529. The composition of claim 515, wherein the mutated epitope is in a protein encoded by ORF10, wherein the mutation is V30L.
530. The composition of claim 515, wherein the mutated epitope is in a protein encoded by ORF1 b protein, wherein the mutation is one or a combination of A176S, V767L, K1141R, E1184D, D1183Y, P255T, Q1011H, N1653D, R2613C, or N1653D.
531. The composition of claim 515, wherein the mutated epitope is in a protein encoded by ORF1a protein, wherein the mutation is one or a combination of S3675-, G3676-, F3677-, I4205V, 12501T, T9451, T15671, Q3346K, V3475F, M38621, T265I, or L3352F.
532. The composition of claim 515, further comprising a T cell attracting chemokine, wherein the T cell attracting chemokine is CCL5, CXCL9, CXCL10, CXCL11, or a combination thereof.
533. The composition of claim 515, further comprising a composition that promotes T cell proliferation and T-cell memory, wherein the composition that promotes T cell proliferation and memory is IL-7, IL-2, or IL-15.
534. The composition of claim 515, wherein the composition comprises one of SEQ ID NOs: 139-141.
Note: for the purposes of examining the claims on their merits, Claims 523, 524, 528, and 531 will be interpreted such that the minus and asterisk represent any amino acid (i.e., any amino acid substitution at the recited residues will read upon the instant claims). Regarding Claim 515, it will be interpreted such that the recited elements, a-c and the wherein clauses, are all being claimed in the alternative and that the at least two epitopes can be selected from the same group of epitopes (i.e., only B-cell target epitopes, for instance). Regarding Claims 519 and 522, they will be interpreted such that the claimed sequences are limited only to the amino acids present (i.e., any prior art sequences must be 100% identical and the exact same length as the claimed sequences).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 515-533 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. While the claimed composition does fall into one of the statutory categories (i.e., composition of matter), it recites a judicial exception, specifically a natural phenomenon. The claims recite a natural phenomenon because, as currently written, mutations compared to the SARS-CoV-2 Wuhan-Hu-1 isolate appear in nature and any coronavirus with a different sequence from the Wuhan isolate at its corresponding epitope would count as a “mutation”. For instance, a pangolin coronavirus would meet the limitations of instant Claims 515-517. This judicial exception is not integrated into a practical application because, as written, the claims do not provide a particular treatment or prophylaxis for a disease or medical condition. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claimed invention, as written, recites a “vaccine” but there are no additional elements comprised by said vaccine recited in the claims, such as an adjuvant.
Applicant is free to amend the claims as they deem necessary or persuasively argue that they are patent eligible.
Claim Rejections - 35 USC § 102
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 515-518, 520-526, 528, 530-531, and 533 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Gaynor et al. (US 2023/0083931 A1) (cited on IDS filed on 09 September 2024)
Gaynor et al. teach an immunogenic composition that comprises T cell and B cell epitopes from SARS-CoV-2 proteins, including ORF1ab, the Spike protein, the Membrane protein, Envelope protein and the Nucleocapsid protein (see Abstract; Paragraphs 0005, 0009, as claimed in instant Claims 515-517 and 520. Gaynor et al. also teach an immunogenic composition comprising epitopes derived from partial SARS-CoV-2 protein sequences (see Paragraphs 0997-0999, 1004). Specifically, Paragraph 0997 defines an epitope as “the collective features of a molecule…that together form a site recognized by, for example, an immunoglobulin, T cell receptor, HLA molecule, or chimeric antigen receptor” and states that throughout the prior art disclosure “epitopes may be referred to in some cases as peptides or peptide epitopes”. Paragraph 0998 states that “proteins or peptides that comprise an epitope or an analog…are still within the bounds of the invention” and that in “certain embodiments, the peptide comprises a fragment of an antigen”. Paragraph 0999 discloses the limitations on the length of a peptide in the prior art reference, stating that in “order to avoid the definition of a epitope from reading, e.g., on whole natural molecules, there is a limitation on the length of any region that has 100% identity with a native peptide sequence” and that “for a peptide comprising an epitope described herein and a region with 100% identity with a native peptide sequence, the region with 100% identity to a native sequence generally has a length of” less than or equal to 600 amino acid residues and ranging down to less than or equal to 50 amino acid residues. This paragraph also states that in “certain embodiments, an ‘epitope’ described herein is comprises by a peptide having a region with less than 51 amino acid residues that has 100% identity to a native peptide sequence, in any increment down to 5 amino acid residues” ranging from as many as 50 to as few as 1. Paragraph 1004 defines the term “isolated”, stating that it refers to material which substantially or essentially free from components which normally accompany the material as it is found in its native state” and that an “’isolated’ epitope refers to an epitope that does not include the whole sequence of the antigen from which the epitope was derived”. Paragraph 1004 also states that “the ‘isolated’ epitope does not have attached thereto additional amino acid residues that result in sequence that has 100% identity over the entire length of a native sequence” and that the “native sequence can be a sequence such as a viral antigen from which the epitope is derived”. As such, the prior art reference discloses epitopes derived from a partial protein sequence expressed by SARS-CoV-2 or a SARS-CoV-2 variant, as claimed in instant Claim 518.
Gaynor et al. also teach an immunogenic composition comprising epitopes from SARS-CoV-2 variants, such as B.1.1.7, as well as mutated epitopes in the Spike protein, such as S477N, H69-, V70-, and E484K, mutated epitopes in the Nucleocapsid protein, such as M234I, R203K, and G204R, mutated epitopes in the Envelope protein, specifically P71L, mutated epitopes in the ORF3a protein, such as P42L, mutated epitopes in the ORF8 protein, such as Q27* and T11I, mutated epitopes in the ORF1b protein, such as D1183Y and Q1011H, and mutated epitopes in the ORF1a protein, such as S3675-, G3676-, and F3677- (see Table A; Paragraph 1044), as claimed in instant Claims 521, 523-526, 528, and 530-531.
Additionally, Gaynor et al. teach an immunogenic composition further comprising interleukins, such as IL-2 (see Paragraph 1176), as claimed in instant Claim 533.
Furthermore, Gaynor et al. teach an immunogenic composition comprising CD4+ T cell epitopes, CD8+ T cell epitopes, and/or B cell epitopes. Specifically, Gaynor et al. teach SEQ ID NO: 11747, which is 100% identical to instant SEQ ID NO: 2 and SEQ ID NO: 52, which is 100% identical to instant SEQ ID NO: 79 (see Sequence Listing), as claimed in instant Claim 522.
For at least these reasons, Gaynor et al. teach the limitations of instant Claims 515-518, 520-526, 528, 530-531, and 533 and anticipate the invention encompassed by said claims.
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 519 and 532 are rejected under 35 U.S.C. 103 as being unpatentable over Gaynor et al. (US 2023/0083931 A1) as applied to claims 515-518, 520-526, 528, 530-531, and 533 above, and further in view of Rauch et al. (US 2024/0277830 A1) and Scholler et al. (US 2012/0258126 A1)
While Gaynor et al. teach the limitations of a majority of the instant claims, as summarized above, Gaynor et al. does not teach a coronavirus vaccine composition wherein the large sequence is selected from the group consisting of SEQ ID NOs: 143-151 or a composition further comprising a T cell attracting chemokine, wherein the T cell attracting chemokine is CCL5, CXCL9, CXCL10, CXCL11, or a combination thereof.
Rauch et al. teach a coronavirus vaccine composition comprising an antigenic peptide or protein wherein said antigenic peptide or protein comprises a spike protein S1 fragment. Specifically, Rauch et al. teach SEQ ID NO: 13243 (see Paragraphs 0100, 0250; Sequence Listing), which is 100% identical to instant SEQ ID NO: 144, as claimed in instant Claim 519.
Scholler et al. teach that vaccine compositions can further comprise additional immunologically active molecules (see Paragraph 0190), including chemokines, such as CCL5, CXCL9, CXCL10, and CXCL11 (see Paragraph-0216). Thus, Scholler et al. teach the limitations of instant Claim 532.
A person having ordinary skill in the art would have been motivated to modify the teachings of Gaynor et al. with those of Rauch et al. and Scholler et al.in order to develop a recombinant coronavirus vaccine composition. Modifying the coronavirus vaccine composition of Gaynor et al. with the spike protein S1 fragment of Rauch et al. would allow for the composition to comprise an S1 fragment with neutralizing epitopes while avoiding the potential problems of using the full-length spike protein in the composition, as disclosed by Rauch et al. Adding the chemokines of Scholler et al. to the vaccine composition of Gaynor et al. would enhance the therapeutic effectiveness of the vaccine composition and lead to the development of a more protective vaccine.
Such modifications, combining prior art elements according to known methods in order to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing dates of the claimed invention. For at least these reasons, instant Claims 519 and 532 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
Claims 527 and 529 are rejected under 35 U.S.C. 103 as being unpatentable over Gaynor et al. (US 2023/0083931 A1) as applied to claims 515-518, 520-526, 528, 530-531, and 533 above, and further in view of Miao et al. (2021) and Hoffman et al. (WO 2022/167571 A1)
While Gaynor et al. teach the limitations of a majority of the instant claims, as summarized above, Gaynor et al. does not teach a coronavirus vaccine composition wherein the mutated epitope is in the protein encoded by ORF7a, wherein the mutation is R80I, or a composition wherein the mutated epitope is in the protein encoded by ORF10, wherein the mutation is V30L.
Miao et al. teach a SARS-CoV-2 variant with the V30L mutation in the ORF10 protein (see Page 8, Paragraphs 2-3; Page 9; Table 2), as claimed in instant Claim 529.
Hoffman et al. teach a SARS-CoV-2 variant with the R80I mutation in the ORF7a protein (see Page 9, Line 16), as claimed in instant Claim 527.
A person having ordinary skill in the art would have been motivated to modify the teachings of Gaynor et al. with those of Miao et al. and Hoffman et al. in order to develop a recombinant coronavirus vaccine composition. Modifying the coronavirus vaccine composition of Gaynor et al. with the ORF10 V30L mutation disclosed by Miao et al. and/or the ORF7a R80I mutation disclosed by Hoffman et al. would allow for the targeting of a specific SARS-CoV-2 variant or multiple variants in order to protect against infection in areas where such a variant is/variants are rapidly spreading and increasing in prevalence or to prevent it/them from gaining a foothold in areas where said variant(s) is/are not common.
Such modifications, combining prior art elements according to known methods in order to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing dates of the claimed invention. For at least these reasons, instant Claims 527 and 529 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 515-517, 520-522, and 532-533 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 and 21 of copending Application No. 18/046,862 (reference application) (cited on IDS filed on 09 September 2024 as US 2023/0146932 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets read upon each other, despite the differences in the claim language used. Both claim sets are drawn to a coronavirus vaccine composition comprising at least two of one or more coronavirus B-cell, CD4+ T cell, or CD8+ T cell target epitopes wherein at least one epitope is derived from a non-spike protein, wherein the non-spike protein is encoded by ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10, or the Envelope protein, the Membrane protein, or the Nucleocapsid protein, and wherein the target epitopes are derived from target epitopes are derived from a SARS-CoV-2 protein selected from a group consisting of: ORF1ab protein, Spike glycoprotein, ORF3a protein, Envelope protein, Membrane glycoprotein, ORF6 protein, ORF7a protein, ORF7b protein, ORF8 protein, Nucleocapsid protein and ORF10 protein. Both claim sets are also drawn to a composition wherein the epitopes are derived from one or more of: target epitopes are derived from a SARS-CoV-2 protein selected from a group consisting of: ORF1ab protein, Spike glycoprotein, ORF3a protein, Envelope protein, Membrane glycoprotein, ORF6 protein, ORF7a protein, ORF7b protein, ORF8 protein, Nucleocapsid protein and ORF10 protein, wherein the one or more SARS-CoV-2 human strains or variants in current circulation are selected from: variant B.1.177; variant B.1.160, variant B.1.1.7 (UK), variant P.1 (Japan/Brazil), variant B.1.351 (South Africa), variant B.1.427 (California), variant B.1.429 (California), variant B.1.258; variant B.1.221; variant B.1.367; variant B.1.1.277; variant B.1.1.302; variant B.1.525; variant B.1.526, variant S:677H; variant S:677P and wherein the one or more coronaviruses that cause the common cold are selected from: 229E alpha coronavirus, NL63 alpha coronavirus, OC43 beta coronavirus, and HKU1 beta coronavirus. Both claim sets are also drawn to a composition further comprising a T cell attracting chemokine, such as CCL5, CXCL9, CXCL10, or CXCL11, and a composition further comprising a composition that promotes T cell proliferation and T-cell memory, such as IL-7, IL-2, or IL-15. Additionally, instant SEQ ID NOs: 2-29 are 100% identical to reference SEQ ID NOs: 2-29, respectively; instant SEQ ID NOs: 30-57 are 100% identical to reference SEQ ID NOs: 30-57, respectively; instant SEQ ID NOs: 58-73 are 100% identical to reference SEQ ID NOs: 58-73, respectively; instant SEQ ID NOs: 74-105 are 100% identical to reference SEQ ID NOs: 74-105, respectively; instant SEQ ID NOs: 106-116 are 100% identical to reference SEQ ID NOs: 106-116, respectively; instant SEQ ID NOs: 117-138 are 100% identical to reference SEQ ID NOs: 117-138, respectively; and SEQ ID NOs: 173 and 178 are 100% identical to reference SEQ ID NOs: 108 and 114, respectively.
The main difference between the instant claims and the reference claims is that the instant claims are drawn to mutated epitopes, while the reference claims are drawn to conserved epitopes. The mutated epitopes of the instant application are in relation to the corresponding epitopes in the original SARS-CoV-2 Wuhan-Hu-1 isolate. The conserved epitopes of the reference application encompass epitopes of SARS-CoV-2 variants, which, by definition, have mutations when compared to the corresponding epitopes of the SARS-CoV-2 Wuhan-Hu-1 isolate. As such, the mutated epitopes of the instant application and the conserved epitopes of the reference application are overlapping in scope and are obvious variants of each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 515-519, 520-521, and 532-533 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of copending Application No. 18/046,875 (reference application) (cited on IDS filed on 09 September 2024 as US 2023/0173060 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets read upon each other, despite the differences in the claim language used. Both claim sets are drawn to a coronavirus vaccine composition comprising at least two of one or more coronavirus B-cell, CD4+ T cell, or CD8+ T cell target epitopes wherein at least one epitope is derived from a non-spike protein, wherein the non-spike protein is encoded by ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10, or the Envelope protein, the Membrane protein, or the Nucleocapsid protein. Both claim sets are also drawn to a composition wherein one or more of the at least two target epitopes is in the form of a large sequence wherein the large sequence is a whole protein expressed by SARS-CoV-2 or derived from a partial protein sequence expressed by SARS-CoV-2. Both claim sets are also drawn to a composition wherein the epitopes or large sequences are derived from one or more of: one or more SARS-CoV-2 human strains or variants in current circulation; one or more SARS-CoV-2 variants identified in the future; one or more coronaviruses that has caused a previous human outbreak; one or more coronaviruses isolated from animals selected from a group consisting of bats, pangolins, civet cats, minks, camels, and other animal receptive to coronaviruses; or one or more coronaviruses that cause the common cold, wherein the one or more SARS-CoV-2 human strains or variants in current circulation are selected from: variant B.1.177; variant B.1.160, variant B.1.1.7 (UK), variant P.1 (Japan/Brazil), variant B.1.351 (South Africa), variant B.1.427 (California), variant B.1.429 (California), variant B.1.258; variant B.1.221; variant B.1.367; variant B.1.1.277; variant B.1.1.302; variant B.1.525; variant B.1.526, variant S:677H; variant S:677P and wherein the one or more coronaviruses that cause the common cold are selected from: 229E alpha coronavirus, NL63 alpha coronavirus, OC43 beta coronavirus, and HKU1 beta coronavirus. Both claim sets are also drawn to a composition further comprising a T cell attracting chemokine, such as CCL5, CXCL9, CXCL10, or CXCL11, and a composition further comprising a composition that promotes T cell proliferation and T-cell memory, such as IL-7, IL-2, or IL-15. Additionally, instant SEQ ID NOs: 143-150 are 100% identical to reference SEQ ID NOs: 186-193, respectively.
The main difference between the instant claims and the reference claims is that the instant claims are drawn to mutated epitopes, while the reference claims are drawn to conserved epitopes. The mutated epitopes of the instant application are in relation to the corresponding epitopes in the original SARS-CoV-2 Wuhan-Hu-1 isolate. The