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 .
Response to Amendment/Disposition of Claims
Applicant’s Amendment filed on 28 July 2025 has been received and entered. Claims 1-3, 6-12, 15-20, 22, 24-25, 28-31, 43-56, 61-62, 64, 68-69, 78-83, 94-95, 97, 160-163, and 165-170 were pending. No claims were amended. Claims 1-170 have been cancelled. New Claims 171-212 have been added.
Accordingly, Claims 171-212 are currently 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 2023/0083931 A1, Published 16 March 2023. Applicant’s amended Specification as presented on 28 July 2025 is 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.
Response to Arguments
Applicant's arguments filed 28 July 2025 regarding the previous Office action dated 28 January 2025 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
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 statement (IDS) submitted on 14 September 2023 and 28 July 2025 have been considered, as a whole, by the examiner. Any individual references with strikethroughs, however, have not been considered.
Drawings
(Objection withdrawn) – The objection to the drawings for being illegible is withdrawn in light of the amendments to the drawings.
Drawings and Specification; Sequence Disclosure Requirements
(Objection maintained in part) – The objection to the Drawings and Specification for failing to comply with Sequence Disclosure Requirements is maintained in part.
Response to Arguments
Applicant's arguments with respect to the objection to the Drawings and Specification for failing to comply with Sequence Disclosure Requirements have been fully considered but they are not fully persuasive.
In their Response, Applicant argues that they submitted “corrected drawing sheets in accordance with 37 C.F.R. 1.121(d)” (see Page 1 of Remarks, Paragraph 2) and that they submitted “a substitute specification where all sequences corresponding to existing SEQ ID NOs in the Sequence Listing are identified as such each time they occur and any sequences that do not correspond to existing SEQ ID NOs in the Sequence Listing were assigned new and unique SEQ ID NOs” (see Page 1, Paragraph 6). Examiner agrees with the arguments regarding the Drawings, but disagrees with the arguments regarding the Specification. Paragraphs 0029 and 0152, at least, which were listed in the Office Action mailed on 28 January 2025, still list sequences which are not associated with corresponding SEQ ID NOs. These sequences have at least 4 specifically defined and enumerated amino acid residues and therefore must have SEQ ID NOs. As such, the objection to the Drawings for failing to comply with Sequence Disclosure Requirements is withdrawn, but the objection to the Specification for failing to comply with Sequence Disclosure Requirements is maintained.
(New Objection) – The Specification is objected to for failing to comply with Sequence Disclosure Requirements. Specifically, Paragraphs 001142-001143 and 001210, at least, of the substitute Specification filed on 28 July 2025 still comprise sequences which do not have corresponding SEQ ID NOs. Examiner kindly requests that Applicant review the Specification and provide SEQ ID NOs for all applicable sequences present.
(New Objection – necessitated by amendment) – The Specification is objected to for failing to comply with Sequence Disclosure Requirements. Specifically, Paragraph 00146 of the substitute Specification filed on 28 July 2025 lists two different sequences as SEQ ID NO: 15.
Specification
(Objection withdrawn) – The objection to the disclosure for containing embedded hyperlinks and/or other forms of browser-executable code is withdrawn in light of the amendments to the Specification.
(Objection withdrawn) – The objection to the disclosure for containing minor informalities is withdrawn in light of the amendments to the Specification.
(Objection withdrawn) – The objection to the disclosure for containing possible minor errors is withdrawn in light of the amendments to the Specification.
Claim Objections
(Objection withdrawn) – The objection to Claim 1 for containing an undefined abbreviation is withdrawn in light of the cancellation of the claim.
(Objection withdrawn) – The objection to Claim 43 for containing an undefined abbreviation is withdrawn in light of the cancellation of the claim.
(Objection withdrawn) – The objection to Claims 8-9, 19, and 29-31 for containing minor informalities is withdrawn in light of the cancellation of the claims.
(New Objection – necessitated by amendment) – Claims 175 and 200 are objected to because of the following informalities: In Claim 175, the period is missing from the end of the sentence.
In Claim 200, it should say “The polynucleotide of claim[[s]] 199, wherein…” instead of “The polynucleotide of claims 199, wherein…”.
Appropriate correction is required.
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.
(Rejection withdrawn) – The rejection of Claims 1, 6, 9-10, and 15-17, and dependent claims 2-3, 6-12, 15-20, 22, 24-25, 28-31, 43-56, 61-62, 64, 68-69, 160-163, and 169 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn) – The rejection of Claim 1, and dependent claims 2-3, 6-12, 15-20, 22, 24-25, 28-31, 44-56, 61-62, 64, 68-69, 160-163, and 169 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn) – The rejection of Claim 3 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claim.
(Rejection withdrawn) – The rejection of Claims 15-17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn) – The rejection of Claims 43 and 80, and dependent claims 169-170 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn) – The rejection of Claims 43, 80, 97, and 169-170, and dependent claim 170 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn) – The rejection of Claims 49-56, 61-62, and 165-168 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn) – The rejection of Claim 81 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claim.
(New Rejection – necessitated by amendment) - Claim171, and dependent claims 172-212 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 171, it recites the limitation “to a polypeptide of concatenated epitopes, wherein the polypeptide comprises: (i) a sequence comprising an epitope sequence from a SARS-CoV-2 nucleocapsid phosphoprotein (N); (ii) a sequence comprising an epitope sequence from a SARS-CoV-2 ORF1ab; and (iii) a sequence comprising an epitope sequence of a SARS-CoV-2 ORF9b and/or a sequence comprising an epitope sequence from a SARS-CoV-2 ORF3a, wherein each epitope satisfies mass spectrometry (MS)-based HLA-I or HLA-II binding prediction tools trained on mono-allelic HLA immunopeptidome data generated via MS”. The limitation “(ii) a sequence comprising an epitope sequence from a SARS-CoV-2 ORF1ab; and (iii) a sequence comprising an epitope sequence of a SARS-CoV-2 ORF9b and/or a sequence comprising an epitope sequence from a SARS-CoV-2 ORF3a” makes it unclear what is being referenced as the absence of the word “protein” after each orf appears to suggest that the claim language is actually referring to the genes or nucleotide sequences instead of the proteins encoded by said genes. This lack of clarity renders the claim indefinite. It is suggested that the claim be amended by adding the word “protein” after each orf, 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 Claim 171 is rejected on the grounds of being indefinite. Claims 172-212 are also rejected since they depend upon Claim 171, but do not remedy the deficiencies of Claim 171.
(New Rejection – necessitated by amendment) – Claims 173 and 175, and dependent claim 174 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.
Regarding Claim 173, it recites the limitation “wherein the epitopes that satisfy the MS-based HLA-I binding tools (the HLA-I epitopes) have been selected to collectively maximize cumulative coverage in a population coverage based on HLA-I allele frequencies in the population”. Regarding Claim 175, it recites the limitation “wherein the epitopes that satisfy the MS-based HLA-II binding tools (the HLA-II epitopes) score in the top 1% relative to a plurality of reference peptides that includes at least 100,000 reference peptides”. It is unclear if the recited element within parentheses (See e.g. "(the HLA-I epitopes)" and “(the HLA-II epitopes)”) is a required element of the respective claim. It is suggested that the Applicant amend the claims to remove the parentheses or amend the claims to recite the items within the parentheses as additional dependent claims which further limit the independent, parent claims, 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 173 and 175 are rejected on the grounds of being indefinite. Claim 174 is also rejected since it depends upon Claim 173, but does not remedy the deficiencies of Claim 173.
(New Rejection – necessitated by amendment) – Claim 177 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 177, it recites the limitation “wherein the sequence comprising the epitope sequence from ORF1ab is C-terminal to the sequence comprising an epitope sequence from nucleocapsid phosphoprotein (N)”. The use of “an” in “an epitope sequence from nucleocapsid phosphoprotein (N)” renders the claim indefinite because it is unclear if it is meant to reference the same epitope sequence from the nucleocapsid phosphoprotein that is introduced in Claim 171, which claim 177 depends upon, or if it is meant to introduce a different epitope sequence from the nucleocapsid phosphoprotein. “A/An” is an indefinite article, while “the” is a definite article. “The” refers back to a specific molecule from Claim 171, while “a/an” can refer back to any non-specific molecule and is not clear that it is only referencing the molecule of Claim 177. It is suggested that the claim be amended by replacing “an” with “the”, if the claim was meant to reference the same epitope sequence introduced in Claim 171, 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 177 is rejected on the grounds of being indefinite.
(New Rejection – necessitated by amendment) – Claims 190 and 191, and dependent claim 191 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.
Regarding Claims 190 and 191, they recite the limitation “the sequence comprising an epitope sequence from membrane glycoprotein (M)”. The use of the word “an” renders the claims indefinite because it is unclear if they are referencing the same epitope sequence introduced in Claim 189, upon which Claim 190 depends, which Claim 191 in turn depends upon, or if they are meant to introduce different epitope sequences. “A/An” is an indefinite article, while “the” is a definite article. “The” refers back to a specific molecule from Claim 189, while “a/an” can refer back to any non-specific molecule and is not clear that it is only referencing the molecule of Claim 189. It is suggested that the claims be amended by replacing “an” with “the”, if the claims were meant to reference the same epitope sequence introduced in Claim 189, 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 190 and 191 are rejected on the grounds of being indefinite. Claim 191 is also rejected since it depends on Claim 190, but does not remedy the deficiencies of Claim 190.
(New Rejection – necessitated by amendment) – Claims 203-204, and dependent claim 204 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.
Regarding Claims 203 and 204, they both recite the element of a “dEarI-hAg sequence”. It is unclear what this entire phrase refers to. While it appears to refer to a 5’ UTR sequence and that the “hAg” part appears to refer to “human alpha-globin” (see Paragraph 1217 of the instant Specification), the “dEarI” portion is not further clarified in the claim set and no specific definition or reference is provided in the instant Specification. Additionally, a Google search of the term did not yield any conclusive results. Furthermore, while examples of “dEarI-hAg” sequences are disclosed in the instant Specification, none of these sequences are claimed, so a sequence search cannot be performed to provide any additional clarity on what exactly is being claimed. This lack of clarity renders the claims indefinite. It is suggested that the claims be amended to provide clarity on the recited element, 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 203-204 are rejected on the grounds of being indefinite. Claim 204 is also rejected since it depends upon Claim 203, but does not remedy the deficiencies of Claim 203.
(New Rejection – necessitated by amendment) – Claim 208 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 208 recites the limitation "the 3’ UTR of AES" in Line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 208 is dependent upon Claim 206, but Claim 206 does not introduce “a 3’ UTR of amino-terminal enhance of split (AES)”. Claim 207 does introduce this limitation, however. It is suggested that Claim 208 be amended by making it depend upon Claim 207, 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 208 is rejected on the grounds of being indefinite.
(New Rejection – necessitated by amendment) – Claim 211 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 211 recites the limitation "the 3’UTR of AES" in Line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 211 is dependent upon Claim 209, but Claim 209 does not introduce “a 3’ UTR of AES”. It seems that Claim 211 should be dependent upon Claim 210, but Claim 210 does not introduce the limitation of an “AES” either. Claim 210 introduces the limitation of an “mtRNR1”, but Claim 211 does not recite this element. Claim 207 does introduce the limitation of an “AES”, however. It is suggested that Claim 211 be amended by making it dependent upon the appropriate claim to provide proper antecedence and to make sure it recites the correct element, 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 211 is 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 171 is drawn to a polypeptide of concatenated epitopes, wherein the polypeptide comprises: (i) a sequence comprising an epitope sequence from a SARS-CoV-2 nucleocapsid phosphoprotein (N); (ii) a sequence comprising an epitope sequence from a SARS-CoV-2 ORF1ab protein; and (iii) a sequence comprising an epitope sequence of a SARS-CoV-2 ORF9b protein and/or a sequence comprising an epitope sequence from a SARS-CoV-2 ORF3a protein, wherein each epitope satisfies mass spectrometry (MS)-based HLA-I or HLA-II binding prediction tools trained on mono-allelic HLA immunopeptidome data generated via MS.
Further limitations on the polypeptide of concatenated epitopes according to Claim 171 are:
172. The polypeptide of claim 171, wherein each of the epitope sequences elicits a T cell response and has been observed by mass spectrometry as being presented by an HLA molecule.
173. The polypeptide of claim 171, wherein the epitopes that satisfy the MS-based HLA-I binding tools, the HLA-I epitopes, have been selected to collectively maximize cumulative coverage in a population coverage based on HLA-I allele frequencies in the population.
174. The polypeptide of claim 173, wherein the HLA-I epitopes have been selected to provide the coverage with the fewest number of selected epitopes.
175. The polypeptide of claim 171, wherein the epitopes that satisfy the MS-based HLA-II binding tools, the HLA-II epitopes, score in the top 1% relative to a plurality of reference peptides that includes at least 100,000 reference peptides.
176. The polypeptide of claim 171, wherein the polypeptide does not include any exact match to a 8-12mer contiguous amino acid sequence found in the human proteome as defined based on protein-coding transcripts of genes with hg19 annotation.
177. The polypeptide of claim 171, wherein the sequence comprising the epitope sequence from ORF1ab is C-terminal to the sequence comprising the epitope sequence from nucleocapsid phosphoprotein (N).
178. The polypeptide of claim 171, wherein the epitope sequence from ORF1ab comprises 2, 3, 4, 5, 6, 7, 8, 9 or 10 or more epitope sequences from ORF1ab.
179. The polypeptide of claim 171, wherein the epitope sequence from ORF1ab comprises epitope sequences from non-structural proteins (NSP).
180. The polypeptide of claim 179, wherein the epitope sequences from non-structural protein (NSP) comprise epitope sequences from NSP1, NSP2, NSP3, NSP4, or any combinations thereof.
181. The polypeptide of claim 171, wherein the polypeptide comprises the sequence comprising the epitope sequence from ORF9b.
182. The polypeptide of claim 181, wherein the sequence comprising the epitope sequence from ORF9b is C-terminal to the sequence comprising the epitope sequence from nucleocapsid phosphoprotein (N).
183. The polypeptide of claim 181, wherein the sequence comprising the epitope sequence from ORF9b is N-terminal to the sequence comprising the epitope sequence from ORF1ab.
184. The polypeptide of claim 171, wherein the polypeptide comprises the sequence comprising the epitope sequence from ORF3a.
185. The polypeptide of claim 171, wherein the sequence comprising the epitope sequence from ORF3a is C-terminal to the sequence comprising the epitope sequence from nucleocapsid phosphoprotein (N).
186. The polypeptide of claim 184, wherein the sequence comprising the epitope sequence from ORF3a is C-terminal to the sequence comprising the epitope sequence from ORF1ab.
187. The polypeptide of claim 171, wherein the polypeptide comprises the sequence comprising the epitope sequence from ORF9b and the sequence comprising the epitope sequence from ORF3a.
188. The polypeptide of claim 187, wherein the sequence comprising the epitope sequence from ORF9b is N-terminal to the sequence comprising the epitope sequence from ORF3a.
189. The polypeptide of claim 171, further comprising a sequence comprising an epitope sequence from membrane glycoprotein (M), wherein the membrane glycoprotein (M) is from SARS CoV-2.
190. The polypeptide of claim 189, wherein the sequence comprising the epitope sequence from nucleocapsid phosphoprotein (N) is N-terminal to the sequence comprising the epitope sequence from membrane glycoprotein (M).
191. The polypeptide of claim 190, wherein the sequence comprising the epitope sequence from membrane glycoprotein (M) is N-terminal to the sequence comprising the epitope sequence from ORF1ab.
192. The polypeptide of claim 171, wherein the polypeptide further comprises one or more linker sequences.
193. The polypeptide of claim 192, wherein the one or more linker sequences comprise cleavage sequences.
194. The polypeptide of claim 171, wherein the polypeptide further comprises a transmembrane domain sequence.
195. The polypeptide of claim 194, wherein the transmembrane domain sequence is C-terminal to the sequence comprising the epitope sequence from nucleocapsid phosphoprotein (N), the sequence comprising the epitope sequence from ORF1ab, and the sequence comprising the epitope sequence from ORF9b and/or the sequence comprising the epitope sequence from ORF3a.
196. The polypeptide of claim 171, wherein the polypeptide further comprises a secretory sequence.
197. The polypeptide of claim 196, wherein the secretory sequence is N-terminal to the sequence comprising the epitope sequence from nucleocapsid phosphoprotein (N), the sequence comprising the epitope sequence from ORF1ab, and the sequence comprising the epitope sequence from ORF9b and/or the sequence comprising the epitope sequence from ORF3a.
198. The polypeptide of claim 171, wherein each epitope binds to or is predicted to bind to an HLA class I or class II molecule with a KD of 1000 nM or less.
199. A polynucleotide encoding the polypeptide of claim 171.
200. The polynucleotide of claim 199, wherein the polynucleotide is an mRNA.
201. The polynucleotide of claim 199, wherein the polynucleotide comprises a modified nucleoside.
202. The polynucleotide of claim 199, wherein the polynucleotide is a codon optimized sequence for expression in a human.
203. The polynucleotide of claim 199, wherein the polynucleotide comprises a dEarI-hAg sequence.
204. The polynucleotide of claim 203, wherein each T of the dEarI-hAg sequence is a U.
205. The polynucleotide of claim 199, wherein the polynucleotide comprises a Kozak sequence.
206. The polynucleotide of claim 199, wherein the polynucleotide comprises an F element sequence.
207. The polynucleotide of claim 206, wherein the F element sequence is a 3' UTR of amino-terminal enhancer of split (AES).
208. The polynucleotide of claim 207, wherein each T of the 3' UTR of AES is a U.
209. The polynucleotide of claim 199, wherein the polynucleotide comprises an I element sequence.
210. The polynucleotide of claim 209, wherein the I element sequence is a 3' UTR of mitochondrially encoded 12S rRNA (mtRNR1).
211. The polynucleotide of claim 210, wherein each T of the 3' UTR of mtRNR1 is a U.
212. The polynucleotide of claim 199, wherein the polynucleotide comprises a poly A sequence.
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.
(Rejection withdrawn) – The rejection of Claims 1-3, 6-12, 15-20, 22, 24-25, 28-31, 43-56, 61-62, 64, 68-69, 78-83, 94-95, 97, 160-163, and 165-170 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for failing to comply with the written description requirement is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn) – The rejection of Claims 44, 46, and 78 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for failing to comply with the written description requirement is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn) – The rejection of Claims 78-79, 81-83, and 94-95 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for being enabling for treating an infection caused by SARS-CoV-2, or treating or preventing symptoms associated with COVID-19 disease, but not reasonably providing enablement for treating or preventing an infection by any virus or treating any respiratory disease or condition associated with an infection by any virus is withdrawn in light of the cancellation of the claims.
Claim Rejections - 35 USC § 101
(Rejection withdrawn) – The rejection of Claims 1-2, 6-12, 15-17, 22, 24-25, 27-29, 31, 43, 45, 47-48, and 68-69 under 35 U.S.C. 101 for directed to a product of nature without significantly more is withdrawn in light of the cancellation of the claims.
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.
(Rejection withdrawn) – The rejection of Claims 1, 18, and 47-48 under 35 U.S.C. 102(a)(1) as being anticipated by Meulen et al. (US 2007/0128217 A1) is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn) – The rejection of Claims 1-2, 6-12, 15-17, 2, 24-25, 27-29, 31, 43, 45, 47-48, and 68-69 under 35 U.S.C. 102(a)(1) as being Wu et al. (2020) is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn) – The rejection of Claims 1-2, 6-8, 18, 20, 28-29, 31, 43, 45, 47-48, 68-69, and 169 under 35 U.S.C. 102(a)(2) as being anticipated by De Groot and Martin (US 2023/0151061 A1) is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn) – The rejection of Claims 1, 18, 20, 22, 28-31, 45, 47-48, and 68-69 under 35 U.S.C. 102(a)(2) as being anticipated by Rauch et al. (WO 2021/156267 A1) is withdrawn in light of the cancellation of the 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.
(New Rejection – necessitated by amendment) – Claims 171-172, 177-202, and 205-212 are rejected under 35 U.S.C. 103 as being unpatentable over De Groot and Martin (US 2023/0151061 A1) (cited in previous Office Action), Orlandini et al. (WO 2017/060314 A2), Abelin et al. (2017), Wang et al. (US 2023/0109393 A1), and Metkar et al. (US 2021/0228707) (cited in previous Office Action)
De Groot and Martin teach immunogenic T-cell epitope polypeptides comprising concatemeric peptides (see Abstract; Paragraphs 0003, 0009), wherein the polypeptide comprises an epitope derived from the SARS-CoV-2 nucleocapsid, an epitope derived from a SARS-CoV-2 ORF1ab protein, an epitope derived from a SARS-CoV-2 ORF3a protein, and an epitope derived from the membrane protein (see Paragraph 0080), as claimed in instant Claims 171, 184, 189. Specifically, De Groot and Martin teach epitopes derived from non-structural proteins (NSPs) 2-4 (see Paragraph 0080), as claimed in instant Claims 179-180. De Groot and Martin also teach that the concatemeric polypeptide can comprise 10 or more epitopes (see Paragraph 0012), as can be found in any of the disclosed SARS-CoV-2 proteins, including proteins encoded by the ORF1ab gene (see Paragraph 0080), as claimed in instant Claim 178.
Additionally, De Groot and Martin teach a concatemeric polypeptide comprising one or more of the disclosed polypeptides or peptides and optionally 1 to 12 additional amino acids distributed in any ratio on the N-terminus and/or C-terminus and linked, fused, or joined together to an additional peptide or polypeptide. They teach that this additional peptide or polypeptide may be one or more of the disclosed polypeptides or peptides, or may be an additional peptide or polypeptide of interest (see Paragraphs 0011-0013). As such, De Groot and Martin teach all combinations of epitopes linked together, including an orientation wherein the ORF1ab epitope is C-terminal to the nucleocapsid epitope, the ORF3a epitope is C-terminal to the nucleocapsid epitope, the ORF3a epitope is C-terminal to the ORF1ab epitope, the nucleocapsid epitope is N-terminal to the membrane protein epitope, and wherein the M protein epitope is N-terminal to the ORF1ab epitope, as claimed in instant Claims 177, 185, 186, 190, 191.
De Groot and Martin also teach a concatemeric polypeptide wherein each peptide or polypeptide has one or more linkers, wherein said linkers are cleavage sensitive sites (see Paragraph 0012), which reads on instant Claims 192-193, as well as a concatemeric polypeptide comprising at its N-terminus a secretory signal in the form of a heterologous signal sequence (see Paragraph 0132), as claimed in instant Claim 196. Furthermore, De Groot and Martin teach a polynucleotide, such as mRNA, encoding said concatemeric polypeptide (see Paragraphs 0137-0139), as claimed in instant Claims 199-200.
Wang et al. teach SARS-CoV-2 antigenic peptides and peptide immunogen constructs, wherein the antigenic peptides are derived from the Nucleocapsid protein, membrane protein, and proteins encoded by the ORF9b gene, (see Paragraphs 0066-0070; Figures 17, 19, 21), as claimed in instant Claims 171, 181, 189. Wang et al. also teach generating nucleic acids encoding said antigenic peptides and peptide immunogen constructs which have been codon optimized for the organism in which the gene is to be expressed (see Paragraphs 0363, 0443), such as the host to whom the peptide immunogen construct is being administered, including humans (see Paragraph 0376). As such, Wang et al. teach the limitations of instant Claim 202.
Metkar et al. teach immunogenic compositions that comprise an RNA or mRNA that encodes highly immunogenic antigens as well as signal sequences, transmembrane domains, and linkers (see Paragraphs 0003, 0051, 0062), as claimed in instant Claims 192, 194, 196, 199, 200, and wherein said RNA or mRNA comprises modified nucleosides (see Paragraphs 0081-0100), as claimed in instant Claim 201. Metkar et al. also teach nucleic acids encoding the highly immunogenic antigens wherein said nucleic acids comprise a Kozak sequence and a poly A sequence (see Paragraphs 0102, 0111), as claimed in instant Claims 205 and 212.
Orlandini et al. teach 3’ UTR sequences for the stabilization of RNA which can improve stability and translation efficiency (see Abstract). Specifically, they teach a nucleic acid sequence comprising a 3’ UTR of amino-terminal enhance of split (AES) and/or a 3’ UTR of mitochondrially encoded 12S rRNA (mtRNR1) (see Page 126, Lines 32-34 and Page 127, Lines 1-7; Table 2), wherein each T of the 3’UTR sequence is a U (see Page 183, Lines 26-31), as claimed in instant Claims 206-208 and 209-211.
Abelin et al. teach a method for identifying via mass spectrometry epitopes or antigens in the form of peptides which are bound to HLA and implementing a scalable mono-allelic strategy for profiling the HLA peptidome (see Page 1, Paragraph 1; Page 2, Paragraph 1), which reads upon instant Claims 171-172. Abelin et al. also teach a method wherein epitopes bind to or were predicted to bind to HLA molecules with a KD of 500 nm or less (see Page 4, Paragraphs 3-5), as claimed in instant Claim 198.
A person having ordinary skill in the art would have been motivated to modify the teachings of De Groot and Martin with those of Orlandini et al., Abelin et al., Wang et al., and Metkar et al. in order to develop a more effective coronavirus vaccine. Abelin et al. teach that their method can be used to design more effective vaccines for infections (see Page 11, Second Paragraph), which would provide the motivation to apply this method when identifying the epitopes/peptides used by De Groot and Martin. Adding epitopes from proteins encoded by the ORF9b gene, as disclosed by Wang et al., to the concatemeric polypeptide of De Groot and Martin would add additional immunogenic epitopes to the polypeptide, which would enhance the immunogenicity of the polypeptide, which would elicit a stronger immune response. The combination of De Groot and Martin would also teach a polypeptide orientation wherein the ORF9b epitope is C-terminal to the nucleocapsid epitope, the ORF9b epitope is N-terminal to the ORF1ab epitope, and/or the ORF9b epitope is N-terminal to the ORF3a epitope, as claimed in instant Claims 182, 183, 187, 188, as well as an orientation wherein the transmembrane domain sequence is C-terminal to the sequence comprising the epitope sequence from nucleocapsid phosphoprotein (N), the sequence comprising the epitope sequence from ORF1ab, and the sequence comprising the epitope sequence from ORF9b and/or the sequence comprising the epitope sequence from ORF3a and wherein the secretory sequence is N-terminal to the sequence comprising the epitope sequence from nucleocapsid phosphoprotein (N), the sequence comprising the epitope sequence from ORF1ab, and the sequence comprising the epitope sequence from ORF9b and/or the sequence comprising the epitope sequence from ORF3a, as claimed in instant Claims 195 and 197. The N-terminal and C-terminal sequences of Metkar et al. and Orlandini et al. would enhance the stability of the RNA or mRNA molecule encoding the polypeptide and increase the translation efficiency, allowing for more of the polypeptide to be produced, resulting in a more protective and robust immune response upon administration to a subject.
Such modifications, combining prior art elements according to known methods to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the claimed invention. For at least these reasons, instant Claims 171-172, 177-202, and 205-212 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
Response to Arguments
Applicant did not present any arguments regarding the prior art references utilized in the previous Office Action. Applicant instead cancelled all of the then-pending claims. As such, no rebuttal is necessary, even though at least one of the references is utilized in a new rejection in the current Office Action.
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.
(Rejection withdrawn) – The provisional rejection of Claims 1-2, 6-8, 10-12, 15-18, 22-25, 28-31, 43, 45, and 47-48 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6-7, 10, 14-15, 18, 20, 22, 24-25, 27-28, 30, 43, and 51 of copending Application No. 17/912,841 (reference application) is withdrawn in light of the cancellation of the instant claims.
(Rejection withdrawn) – The provisional rejection of Claims 1, 28, 31, 45, 47-48, 68-69, and 169 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 8, 15-18, 54, 67-70, and 148 of copending Application No. 18/694,596 (reference application) is withdrawn in light of the cancellation of the instant claims and the abandonment of the copending application.
(New Rejection – necessitated by amendment) – Claims 171-172, 178-180, 189, 192-194, 199-200, 202, and 206-212 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6-7, 18, 20, 28, 30, 35, 43-44, 78-79 of copending Application No. 17/912,841 (reference application) (cited in previous Office Action as US 2023/0141371 A1) in view of De Groot and Martin, Abelin et al., and Wang et al.
Both claim sets are drawn to a polypeptide comprising T cell epitope sequences from SARS-CoV-2 membrane glycoprotein, nucleocapsid phosphoprotein, and/or derived from the ORF1ab gene, wherein the polypeptide comprises 2-10, or more, epitope sequences from ORF1ab, specifically an NSP, such as NSP1-4, wherein each epitope elicits a T cell response and/or has been observed by mass spectrometry (MS) as being presented by an HLA molecule. Both claim sets are also drawn to a polypeptide comprising linker sequences, wherein said linker sequences can comprise cleavage sequences. Both claim sets are also drawn to a polynucleotide encoding said polypeptide, wherein the polynucleotide is an mRNA and is codon optimized for expression in a human. Both claim sets are also drawn to a polynucleotide comprising a 3’ UTR of amino-terminal enhance of split (AES) and/or a 3’UTR of mitochondrially encoded 12S rRNA (mtRNR1).
The main differences between the instant claims and the reference claims are that the instant claims are only drawn to the polypeptide, which comprises concatenated epitopes, wherein each epitope satisfies MS-based HLA-I or HLA-II binding prediction tools trains on mono-allelic HLA immunopeptidome data generated via MS. The instant claims are also drawn to an epitope derived from the ORF9b gene. The reference claims are drawn to a composition comprising a polypeptide as well as a method of treating or preventing an infection by SARS-CoV-2 or treating a respiratory disease or condition associated with infection by SARS-CoV-2 comprising administering the reference composition. The reference composition and method encompass and/or utilize the instant polypeptide, so it would have been obvious to skilled artisan to use the instant polypeptide in the reference composition and/or method.
The previous teachings of De Groot and Martin, Abelin et al., and Wang et al. have been summarized above.
A person having ordinary skill in the art would have been motivated to modify the teachings of the instant claims with those of De Groot and Martin, Abelin et al., and Wang et al. in order to develop a more effective coronavirus vaccine. Abelin et al. teach that their method can be used to design more effective vaccines for infections, which would provide the motivation to apply this method when identifying the epitopes/peptides used by De Groot and Martin. Adding epitopes from proteins encoded by the ORF9b gene, as disclosed by Wang et al., to the concatemeric polypeptide of De Groot and Martin would add additional immunogenic epitopes to the polypeptide, which would enhance the immunogenicity of the polypeptide, which would elicit a stronger immune response and thus make for a more effective vaccine.
Such modifications, combining prior art elements according to known methods to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the claimed invention. For at least these reasons, Claims 171-172, 178-180, 189, 192-194, 199-200, 202, and 206-212 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6-7, 18, 20, 28, 30, 35, 43-44, 78-79 of the reference application in view of De Groot and Martin, Abelin et al., and Wang et al.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant did not present any arguments regarding the prior art references utilized in the previous Office Action. Applicant instead cancelled all of the then-pending claims. As such, no rebuttal is necessary, even though at least one of the references is utilized in a new rejection in the current Office Action.
Conclusion
No claims are allowed.
The prior art made of record, but not relied upon, and considered pertinent to applicant's disclosure is listed below:
Abelin et al. (2019)
Abelin et al. teach a method that improves HLA-II epitope prediction and therapeutic targeting. This reference has not been utilized, as rejection would have been redundant to those set forth above.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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