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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on May 18, 2026 and July 02, 2024. Claims 1-5, 7-13 and 15-22 are pending. Claims 20-22 are withdrawn. Claims 1-5, 7-13 and 15-19 are currently examined.
Election/Restrictions
Applicant's election Group I (claims 1-5, 7-13 and 15-19) in the reply filed on Aug. 17, 2023, is acknowledged.
As for the species election, Applicant elected SEQ ID NOs: 2 and 4.
Although applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Accordingly, claims 20-22 are withdrawn as being directed to a non-elected invention.
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 1-5, 7-13, 15-16 and 19 are rejected under 35 U.S.C. §101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
These claims are directed a nucleic acid molecule comprising one or more nucleotide sequence encoding one or more antigen, wherein said one or more antigen comprises: a) an established T cell epitope; b) a series of amino acids N-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates; and c) a series of amino acids C-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates, where the claimed the nucleic acid molecule can be from natural occurrence.
In the instant specification, it discloses that a "peptide," "protein," or "polypeptide" as used herein can mean a linked sequence of amino acids and can be natural, synthetic, or a modification or combination of natural and synthetic (See [0049]). The instant specification also discloses that in one embodiment, said established T cell viral epitope of the nucleic acid molecule is derived from one or more virus selected from the group consisting of: Vesicular stomatitis virus (VSV), Hepatitis C virus (HCV), Human immunodeficiency virus 1 (HIV-1), Murine Cytomegalovirus (MCMV), Influenza A virus, Hepatitis B virus (HBV), Murine leukemia virus (MLV), Herpes simplex virus 1 (HSV-1), Herpes simplex virus 2 (HSV-2), and Respiratory syncytial virus (RSV) (See [0007]). Thus, the claimed nucleic acid molecule encoding one or more antigen does not have markedly different characteristics from what occurs in nature, and is a “product of nature” exception.
Accordingly, claims are directed to a judicial exception. Because the claims do not include any additional features that could add significantly more to the exception, the claim does not qualify as eligible subject matter under 35 U.S.C. § 101.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-5, 7-13 and 15-19 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.
The base claim 1 recites the phrases “a series of amino acids N-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates” and “a series of amino acids C-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates” that render the claims indefinite. It is not clear if the “a series of amino acids” is a part of the “established T cell epitope” or it is just a flanked sequence. It is also unclear how many amino acids the “a series of amino acids” is represented for.
Also, the terms “established T cell epitope”, “derived” and “originates” render the claims indefinite. Without a specific epitope structure described, it is unclear how the T cell epitope be established, and how the established T cell epitope “derived” and “originates”.
Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
For purposes of compact prosecution and applying prior art, claim 1 was interpreted herein that the “a series of amino acids N-terminal/a series of amino acids C-terminal” encompass a generic series of amino acids to a generic established T cell epitope derived from any endogenous protein from which the established T cell epitope originates.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Regarding claims 8 and 11, they are indefinite because they lack a reference sequence for the cited “at least 95% identical to a sequence N-terminal to the established T cell viral epitope in the endogenous protein from which the epitopes derives”, and “at least 95% identical to a sequence C-terminal to the established T cell viral epitope in the endogenous protein from which the epitopes derives”. Without a specific reference sequence, one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5, 7-13 and 15-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The base claim 1 is directed to a method a nucleic acid molecule comprising one or more nucleotide sequence encoding one or more antigen, wherein said one or more antigen comprises: a) an established T cell epitope; b) a series of amino acids N-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates; and c) a series of amino acids C-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates.
The applicable standard for the written description requirement can be found in MPEP 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc., 63 USPQ2d 1609; Vas- Cath Inc. v. Mahurkar, 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004).
1). The written description rejection is made because the claims are interpreted as being drawn to a series of amino acids N-terminal/ a series of amino acids C-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates. However, the instant Example 1 discloses that the construct encoding the C-terminally by 11-13 amino acids derived from the endogenous viral protein (33mer) and the same but further encoding the PADRE CD4+ helper epitope (PADRE 33mer) generated robust immune responses for most epitopes (FIG. 2) and generated immune responses against more epitopes than established T cell viral epitopes alone with PADRE (FIG. 3). Thus, the addition of N-terminal and C-terminal amino acid sequences that flank the established epitopes represents a novel strategy to improve the immunogenicity of nucleic acid vaccines (See [0188]). This discloses indicates that the flanking sequence has a length limitation and include the PADRE such as “in one embodiment, the CD4+ helper epitope is Pan DR epitope (PADRE) (See [0025]), where the CD4+ helper epitope is a type of T cell epitope and PADRE is a non-natural epitope. The PADRE can be evidenced by Guercio’s study. Guercio teaches that they described the engineering of synthetic non-natural Pan DR Epitope (PADRE) peptides which bind with high or intermediate affinity (IC50%<500 nM) to nine out of ten common HLA-DR specificities tested (See page 442, left column, paragraph 2).
Therefore, the instant specification does not provide evidence or support to demonstrate that any series of amino acids N-terminal/C-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates.
2). The written description rejection is made because the claims are interpreted as being drawn to “an endogenous protein from which the established T cell epitope originates”. However, the instant specification only shows a viral epitope, and does not provide evidence or support for any T cell epitope originating from any endogenous protein.
The court clearly states in Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.). As discussed above, the skilled artisan cannot envision the nucleic acid molecule comprising a series of amino acids N-terminal/ a series of amino acids C-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates as claimed.
Therefore, the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
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 1-2, 4 and 15-17 and 19 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Yelensky et al. (CA3178115A1, published on Nov. 25, 2021, priority date: May 19, 2020, hereinafter, “Yelensky”).
The base claim 1 is directed to nucleic acid molecule comprising one or more nucleotide sequence encoding one or more antigen, wherein said one or more antigen comprises:
a) an established T cell epitope;
b) a series of amino acids N-terminal to said established T cell epitope derived
from the endogenous protein from which the established T cell epitope originates; and
c) a series of amino acids C-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates.
Yelensky teaches the MHC class I epitope comprises a polypeptide sequence as set forth in Table A and/or Table C or MHC class II epitope comprising a polypeptide sequence as set forth in Table B, wherein the encoded SARS-CoV-2 immunogenic polypeptide is conserved between SARS CoV-2 and a Coronavirus species and/or sub-species other than SARS-CoV-2 (See page 3) and the immunogenic polypeptide comprises a N-terminal linker and/or a C-terminal linker; (ii) optionally, a second promoter nucleotide sequence operably linked to the SARS-CoV-2 derived nucleic acid sequence; and (iii) optionally, at least one MHC class II epitope-encoding nucleic acid sequence (See page 4), and in some aspects, the different antigen cassettes comprise a Spike-encoding cassette and a separate T cell epitope encoding cassette. In some aspects, the different antigen cassettes comprise cassettes encoding distinct epitopes and/or antigens derived from different isolates of SARS-CoV-2 (See [0058]). Here based on the description, Yelensky teaches a SARS-CoV-2 nucleic acid sequence encoding an antigen as spike and an MHC class II epitope/T cell epitope that is derived from the SARS-CoV-2 that teaches the base claim 1 for nucleic acid molecule encoding an antigen and the antigen comprises a T cell epitope (teaches the claim 1 (a)).
As for the base claim 1 (b) and (c), Yelensky teaches claim 1 (b) and (c) by stating that MHC presentation of CTL epitopes can be improved by including synthetic (e.g. poly-alanine) or naturally-occurring flanking sequences adjacent to the CTL epitopes (See [00393]), and Therapeutic epitopes can represent a fixed-length epitope Therapeutic epitopes can represent a variable length epitope, in which the length of the epitope can be varied depending on, for example, the length of the C- or N-flanking sequence. For example, the C-terminal flanking sequence and the N-terminal flanking sequence can each have varying lengths of 2-5 residues, resulting in 16 possible choices for the epitope (See [00410]). Also, in both cases, use of a longer peptide allows endogenous processing by patient cells and may lead to more effective antigen presentation leading to increased T cell responses (See [00250]), and the Spike protein was split at the furin cleavage site for generating candidate CD8+ T-cell epitopes. All 8-11 mer peptides were then generated from the cleaved proteins and the other proteins, flanked by their native N-terminal and C-terminal 5-mers (See [00431]), and T cell response to overlapping peptide pools spanning either Spike, Nucleocapsid, or Orf3a (See [00125]). Here the descriptions of Yelensky disclose the flanked amino acids at both N-terminal and C-terminal to said established T cell epitope derived from the endogenous protein such as the same spike or Nucleocapsid protein from which the established T cell epitope originates.
Regarding claim 2, Yelensky teaches the T cell viral epitope is from SARS-COV-2 virus such as the different antigen cassettes comprise a Spike-encoding cassette and a separate T cell epitope encoding cassette (See [0058]).
Regarding claim 4, Yelensky teaches that at least one polyadenylation poly(A) sequence is a poly(A) sequence of at least 80 consecutive a nucleotides (SEQ ID NO: 27940) provided by the backbone, each N encodes a MHC class I epitope 7-15 amino acids in length (See [0022]) that comprises and I0 amino acids in length as claimed.
Regarding claims15-16, Yelensky teaches that in some aspects, two or more of the at least one SARS-CoV-2 derived nucleic acid sequences are derived from the same SARS-CoV-2 gene. In some aspects, the two or more SARS-CoV-2 derived nucleic acid sequences derived from the same SARS-CoV-2 gene are ordered such that a first nucleic acid sequence cannot be immediately followed by or linked to a second nucleic acid sequence if the second nucleic acid sequence follows first nucleic acid sequence in the corresponding SARS-CoV-2 gene (See [0036]) that teaches claim 15. Yelensky teaches that a linker can also have a cleavage site, such as a TEV or furin cleavage site. Linkers with cleavage sites can be used in combination with other elements, such as those in a multicistronic system (See [00288]) and the Spike protein was split at the furin cleavage site for generating candidate CD8+ T-cell epitopes (See [00431]), which teaches two or more nucleotide sequences are separated by one or more nucleotide sequence encoding a furin cleavage domain in claim 16.
Regarding claim 17, Yelensky teaches that at least one MHC class II epitope-encoding nucleic acid sequence is present and comprises at least one universal MHC class II epitope-encoding nucleic acid sequence, optionally wherein the at least one universal sequence comprises at least one of Tetanus toxoid and PADRE, and/or at least one MHC class II SARS-CoV-2 derived epitope-encoding nucleic acid sequence (See [0039]).
Regarding claim 19, Yelensky teaches that an immunogenic composition, e.g, a vaccine composition, capable of raising a specific immune response, e.g., an infectious disease organism-specific immune response. Vaccine compositions typically comprise one or a plurality of antigens, e.g., selected using a method described herein (See [00264]), and the antigen-based vaccine comprises any one of the pharmaceutical compositions provided herein. In some aspects, the subject expresses at least one HLA allele predicted or known to present a MHC class I or MHC class II epitope encoded by the at least one SARS-CoV-2 derived nucleic acid sequence (See [[20]).
Accordingly, claims 1-2, 4, 15-17 and 19 are anticipated by Yelensky.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 7-8, 10-12 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Knowlden et al. (Pathogens. 2019 Nov 5;8(4):220, hereinafter, “Knowlden”) as evidenced by Wang et al. (Vaccine. 2011 Mar 9;29(12):2328-35), hereinafter, “Wang”).
The base claim 1 is directed to nucleic acid molecule comprising one or more nucleotide sequence encoding one or more antigen, wherein said one or more antigen comprises:
a) an established T cell epitope;
b) a series of amino acids N-terminal to said established T cell epitope derived
from the endogenous protein from which the established T cell epitope originates; and
c) a series of amino acids C-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates.
Knowlden describes that peptide epitope hot spots of CD4 T cell recognition within Influenza Hemagglutinin during the primary response to Infection, and teaches that HA-specific CD4 T cell epitopes cluster in two distinct regions of HA (See Abstract), which teaches the claim 1 (a) of the established T cell epitope. Knowlden also teaches that they analyzed these data in a graphical display (Figure 2B). There are approximately 100 16–17 mer peptides in the overlapping array provided by the supplier, numbered from amino acid 1–94, from amino (‘N”)- to carboxy (C)-terminus (Supplemental Table S2). The peptides were grouped by each decade of HA amino acid sequence (e.g., peptides 1–10, peptides 11–20) (from N to C terminus), indicated on the X-axis (See page 5, paragraph 2). The Figure 3 of Knowlden discloses the stretches of the HA sequence that have distinct regions of CD4 T cell epitope dominance (See Figure 3, page 7 and below), which is flanked by a series of amino acids N-terminal or a series of amino acids C-terminal to the designed T cell epitopes where the T cell epitopes are all from an Influenza hemagglutinin (HA).
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Although Knowlden does not explicitly point out the term “endogenous protein”, Knowlden teaches that the T cell epitopes are derived from the hemagglutinin (HA) protein of influenza virus (See Abstract) and the HA protein is the origin protein that the T cell epitope from. Here the description is comparable to the base claim (b) and (c) as “a series of amino acids N-terminal / a series of amino acids C-terminal to said established T cell epitope derived from the endogenous protein from which the established T cell epitope originates”, where the flanking sequence of the epitope can be considered as the series of amino acids (See Figure 2A, page 6 and below).
In addition, in Knowlden’s study, Knowlden teaches that all the 17-mer peptides overlapping by 11 amino acids to encompass the entire sequence of the HA of influenza virus A/New Caledonia/20/99 (NR-2602) were obtained from BEI Resources, ATCC (See page 10, 4.3 paragraph). It is a common knowledge in the art that all the peptide and HA protein are encoded by the corresponding nucleic acids. This can also be evidenced by Wang. Wang teaches a method for Preparation of recombinant proteins and synthetic peptides by disclosing that the DNA fragment encoding PADRE and multiple CTL epitopes of HBV (HBsAg28-39, HBcAg18-27 and HBcAg141-151) that was synthesized by PCR. The expression plasmid was created by cloning the minigene encoding PADRE and HBV polytopes to the downstream of Hsp65 in pET28a-Hsp65, designated as pET28a-Hsp65-HBV (See page 2329, left column, paragraph 3). Therefore, the nucleic acid molecule comprising one or more nucleotide sequence encoding one or more antigen claimed in the base claim 1 would have been obvious base on the teaching of Knowlden.
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Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding the claims 2-3, Knowlden teaches the viral antigen (teach claim 2) by disclosing that the antigen is form influenza virus (teach claim 3) (See Table 1, page 4).
Regarding claim 7 and 10, the Figure 3 of Knowlden teaches the stretches of the HA sequence that have distinct regions of CD4 T cell epitope dominance. The HA sequence is shown highlighted in regions that contain many dominant epitopes (shown in red), minor epitopes (shown in cream) or devoid of epitopes (shown highlighted in dark grey (See Figure 3 and above), which shows a peptide epitope can be flanked by different series of amino acid sequence with different length at both N-terminal and C-terminal, where one of skilled in the art can include any length of the flanked amino acids including the claimed length in claims 7 and 10 at both end of the T cell epitope based on the need through routine experiment optimization. Therefore, the claimed length between 11 and 13 amino acids in claims 7 and 10 would have been obvious unless there is evidence showing that they produce unexpected results.
Regarding claims 8 and 11, Knowlden teaches their study is performed using a diverse set of mouse strains (See page 2, paragraph 1) and the biggest clusters of CD4 T cell epitopes in HA, recognized by multiple strains of mice (See page 5, paragraph 1; Figure 2A, page 6 and above). It would be obvious that a series of amino acids N-terminal/C-terminal to said established T cell epitope are at least 95% identical to a sequence as claimed to the established T cell viral epitope can be achieved.
Regarding claim 12, Knowlden teaches the specific T cell epitope peptides in the Table 1 (See page 4) and most of them with a C-terminal sequence is directly downstream of the established T cell epitope. For example, the amino acids sequences C-terminal to the established T cell viral epitope “144 TVTGVSASCSHNGKSSF 160” (mouse strain is B10. PL and SJL) in Table 1 is directly downstream of this established T cell epitope (See Figure 2 above).
Regarding claim 17, although Knowlden does not teach the nucleotide sequence encoding a Pan DR CD4+ helper epitope, Wang teaches that BCG Hsp65 and PADRE have been shown to be potent to enhance antigen specific immunity (See Abstract) and the DNA fragment encoding PADRE and multiple CTL epitopes of HBV (HBsAg28-39, HBcAg18-27 and HBcAg141-151) was synthesized by PCR (See page 2329, left column, paragraph 3). It would be obvious for one of ordinary skill in the art to fuse the PARDE into Knowlden’s epitope to increase the specific immunity and the result would be predictable based on the teaching of Knowlden in view of Wang.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Knowlden et al. (Pathogens. 2019 Nov 5;8(4):220, hereinafter, “Knowlden”) as evidenced by Wang et al. (Vaccine. 2011 Mar 9;29(12):2328-35), hereinafter, “Wang”) as applied to claims 1-3, 7-8, 10-12 and 17 above and evidenced by Tamura et al. (J Virol. 1998 Nov;72(11):9404-6).
Claim 4 requires the established T cell viral epitope comprises a peptide between 8 and I0 amino acids in length.
Knowlden teaches that they map individual epitopes from the influenza HA protein, common inbred mice expressing different murine MHC class II molecules (thus having the potential to present different HA-derived peptides) (See Figure Table 1, page 4), and the biggest clusters of CD4 T cell epitopes in HA, recognized by multiple strains of mice were clustered between amino acids 120–190 and 316–414 (See page 5, paragraph 1). Although Knowlden does not specially show a peptide that the length is 8-10 aa, one skilled in the can design a peptide with a claimed length based on the analysis of the “biggest clusters of CD4 T cell epitopes in HA” as taught through routine experimental optimization. This can be evidenced by Tamura’s study. Tamura teaches that they defined the epitopes recognized by three influenza A virus-specific, H-2Kd-restricted CD81 cytotoxic T-lymphocyte (CTL) clones: H1-specific clone A-12, H2-specific clone F-4, and H1- and H2-cross-reactive clone B7-B7. The A-12 and B7-B7 clones recognized the same peptide, which comprises amino acids 533 to 541 (IYSTVASSL) of A/PR/8 hemagglutinin (HA). The F-4 and B7-B7 clones both recognized the peptide which comprise amino acids 529 to 537 (IYATVAGSL) of A/Jap HA (See Abstract), which is a nine amino acids epitope.
Claims 5 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Knowlden et al. (Pathogens. 2019 Nov 5;8(4):220, hereinafter, “Knowlden”) as evidenced by Wang et al. and Tamura et al. as applied to claims 1-4, 7-8, 10-12 and 17 above and in view of Yang et al. (CN105372433A, published on Mar. 02, 2016).
Claims 5 and 13 require a specific sequence of T cell viral epitope (claim 5) and a specific sequence of viral antigen (claim 13).
Knowlden teaches a required a nucleic acid molecule comprising one or more nucleotide sequence encoding one or more antigen comprising the different T cell viral epitope peptides. However, it is silent on a specific sequence as claimed of SEQ ID NNO: 2 and 4.
Yang teaches a test strip for rapidly detecting a vesicular stomatitis virus (VSV) antibody is characterized in that a vesicular stomatitis virus recombinant N protein antigen is fixed on the test strip, and the amino acid sequence of the vesicular stomatitis virus recombinant N protein antigen is represented by SEQ ID No. 1 and provide good specificity, high sensitivity, fast detection, easy operation (See page 1, claims)., where the SEQ ID NO: 1 comprise the identical sequences of the instant SEQ ID NO: 1 and 2 (See Tables A and B).
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It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the teaching of Yang into Knowlden’s study to arrive at an invention as claimed. One of skill in the art would have been motivated to use the known variant of the SEQ ID NO: 1 of Yang to substitute the SEQ ID NOs: 2 and 4 as claimed (See MPEP 2144.06: Substituting equivalents known for the same purpose). There would be a reasonable expectation of success to develop such a nucleic acid molecule comprising one or more nucleotide sequence encoding one or more antigen and encode a T cell viral epitope as claimed.
Claims 15-16 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Knowlden et al. (Pathogens. 2019 Nov 5;8(4):220, hereinafter, “Knowlden”) as evidenced by Wang et al. as applied to claims 1-3, 7-8, 10-12 and 17 above and in view of Yelensky et al. (CA3178115A1, published on Nov. 25, 2021, priority date: May 19, 2020).
Claims 15-16 require nucleic acid molecule of claim 1 comprising the two or more nucleotide sequences encoding two or more antigens, where said two or more nucleotide sequences are separated by one or more nucleotide sequence encoding a furin cleavage domain.
Claim 19 requires an immunogenic composition comprising the nucleic acid molecule of claim 1.
Knowlden teaches a required a nucleic acid molecule comprising one or more nucleotide sequence encoding one or more antigen comprising the different T cell viral epitope peptides. However, it is silent on two or more nucleotide sequences encoding two or more antigens (claim 15) and a furin cleavage domain between them (claim 16), Also, it is not explicitly using the term “immunogenic composition” although Knowlden teaches a T cell viral epitope peptide.
Yelensky teaches vaccine compositions that include SARS-CoV-2 MHC epitope-encoding cassettes and/or full-length SARS CoV-2 proteins. Also disclosed are nucleotides, cells, and methods associated with the compositions including their use as vaccines (See Abstract), and in some aspects, the heterologous prime/boost strategy comprises different antigen cassettes encoded by the same vaccine platform. In some aspects, the heterologous prime/boost strategy comprises different antigen cassettes encoded by different vaccine platforms. In some aspects, the different antigen cassettes comprise a Spike-encoding cassette and a separate T cell epitope encoding cassette. In some aspects, the different antigen cassettes comprise cassettes encoding distinct epitopes and/or antigens derived from different isolates of SARS-CoV-2 (See [0058]), and in some aspects, at least one of the at least one SARS-CoV-2 derived nucleic acid sequences encodes two or more distinct polypeptides predicted or validated to be capable of presentation by at least one HLA allele (See 0033]), which teach claim 15 for two or more antigens as claimed with the boost strategy.
For claim 16, Yelensky teaches that one or more native sequences flanking the antigen derived from the cognate protein of origin and that is at least 2… 20, or 2-20 amino acid residues in length; and (7) a furin or TEV cleavage sequence (See 0031), and the Spike protein was split at the furin cleavage site for generating candidate CD8+ T-cell epitopes (See [00431]).
For claim 19, Yelensky teaches claim 19 by stating that a method for inducing an immune response in a subject, the subject expresses at least one HLA allele predicted or known to present an MHC class I or MHC class II epitope encoded by the at least one SARS-CoV-2 derived nucleic acid sequence. In some aspects, the subject expresses at least one HLA allele predicted or known to present an MHC class I epitope encoded by the at least one SARS-CoV-2 derived nucleic acid sequence, and wherein the MHC class I epitope comprises at least one MHC class I epitope comprising a polypeptide sequence as set forth in Table A (See [0059]).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Knowlden and Yelensky to arrive at an invention as claimed. One of skill in the art would have been motivated to do so to use two or more antigen with furin cleavage site to boost the immunity responses and also develop an immunogenic composition as claimed. There would be a reasonable expectation of success to develop such an antigens/epitopes and composition based on the teaching of Knowlden in view of Yelensky.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Knowlden et al. (Pathogens. 2019 Nov 5;8(4):220, hereinafter, “Knowlden”) as evidenced by Wang et al. as applied to claims 1-3, 7-8, 10-12 and 17 above and in view of Li et al. (WO 2006/015373 A2, published on Feb. 09, 2006).
Claim 18 requires the Pan DR CD4+ helper epitope comprises SEQ ID NO:45.
Knowlden as evidenced by Wang teaches the nucleic acid molecule further comprising a nucleotide sequence encoding a Pan DR CD4+ helper epitope, however, it is silent on the SEQ ID NO:45.
Li teaches that generation of monoclonal antibodies to murine Dkk-1 in mice and rats and One mg of the maleirnide-activated murine Dkk-1 was incubated with 0.5 mg of PADRE peptide (AKFVAAWTLKAAAC; SEQ ID NO: 13) and 0.5 mg of a second PADRE peptide (CAKXVAAWTLKAAA (X =cyclohexyl-alanine); SEQ ID NO:14) at room temperature for 1 hour and 30 then dialyzed against PBS (See Example 1, page 54), where the SEQ ID NO: 13 comprises identical sequence of the instant SEQ ID NO: 45 at AKFVAAWTLKAAA.
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the teaching of Li into Knowlden’s study to arrive at an invention as claimed. One of skill in the art would have been motivated to use the known variant of the SEQ ID NO: 13 of Li to substitute the SEQ ID NO: 45 as claimed (See MPEP 2144.06: Substituting equivalents known for the same purpose). There would be a reasonable expectation of success to develop a nucleic acid molecule comprising the Pan DR CD4+ helper epitope as claimed.
Conclusion
No claims are allowed.
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/RUIXUE WANG/ Examiner, Art Unit 1672
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