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 Aug. 25, 2026. Claims 1, 2, 5, 8, 10, 11, 13-19, 21, 23 and 25 are pending. Claims 21, 23 and 25 are withdrawn. Claims 1, 2, 5, 8, 10, 11 and 13-19 are currently examined.
Election/Restrictions
Applicant's election without traverse of Group I (Claims 1, 2 5, 8, 10, 11, and 13-19), directed to a vaccine comprising or capable of expressing one or more concatemers of epitopes from a viral pathogen, in the reply filed on Aug. 25, 2026, is acknowledged. For the species election requirement, Applicant elects without traverse (1) vaccine that expresses concatemer(s) of epitopes and a nucleic acid-based vaccine, and (2) any one of SEQ ID NOs: 802-807 and 832-835 for claim 10 and 11.
Accordingly, claims 21, 23 and 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group.
Specification – Sequence Compliance
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) as follows:
The specification does not contain sequence identifiers (SEQ ID NO:) in all locations where sequences are disclosed, see at least FIGs 2, 4, 6, 8, 10, and 12-23, tables 1-13, and paragraphs [0101], [0103], and [0104], etc. To correct this, the sequences in figures can be referred to in either the figure or the Brief Description of Drawings. If the prior filed Sequence Listing does not contain updated sequences, Applicant is also required to submit a replacement Sequence Listing that includes all updated sequences.
Full compliance with the sequence rules is required in response to this Office Action. A complete response to this office action should include both compliance with the sequence rules and a response to the Office Action set forth below. Failure to fully comply with both these requirements in the time period set forth in this Office Action will be held non-responsive.
Claim Objections
Claim 17 is objected to because of the following informalities: this claim recites “SAM RNA-based vaccine”. Here, “SAM” appears to be an abbreviation for “self-amplifying” (see [0067]), which should be spelled out the first time it appears in the claims list. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1, 2, 5, 8, 10, 11 and 13-19 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. This rejection has the following grounds.
I. Claim 1 recites “such as a sarbecovirus pathogen”, which renders the claim indefinite since by reciting “such as” it is not clear if this limitation is required or not.
II. Claim 1 is directed to a vaccine comprising or capable of expressing “one or more concatemers of epitopes” from a viral pathogen. Even though, the specification provides embodiments for the “concatemer” of the invention in figures and the sequence listing and uses the term throughout the context, the specification does not clearly and exclusively define the term “concatemer” nor the term “concatemer of epitopes”.
A Google search for the term “concatemer” generates a result indicate that a is a long, continuous DNA or RNA molecule that contains multiple copies of the same sequence linked together in a row (end-to-end), referring to Wikipedia: concatemer (https://en.wikipedia.org/wiki/Concatemer). Although this definition relates to nucleic acid sequences, it appears to require that multiple copies of same sequences must be included in a “concatemer”.
A Google search for the term “concatemer of epitopes” generates a result indicating that a concatemer of epitopes is a single continuous chain of multiple immune-triggering protein segments linked head-to-tail for vaccine design, based on the teachings of Sluder et al. (Front. Immunol. 2022, 13:901372). Sluder teaches that multiple viral vector-based candidate vaccines were generated that express concatemers of selected epitope sequences arranged to minimize potential junctional neo-epitopes. See page 1. It teaches that epitope concatemers were designed from two epitope sets: (a) all 27 selected epitopes (concatemer QVx27) and (b) an 18-epitope subset (QVx18) comprising 14 epitopes associated with particularly strong recall responses (stimulated:unstimulated response ratio >3) in at least 10% of C. burnetii-exposed humans plus the four additional epitopes selected based on antigenic recall responses in C. burnetii-infected mice; and that each epitope set was randomly concatenated and analyzed for non-specific potential immunogenicity at epitope junctions as well as the potential for transmembrane insertion, and rearrangements were made to minimize the potential of both. See page 7, right column, last para.
The teachings of Sluder, however, suggest that multiple peptides of any sequences can be put together to form a concatemer. Indeed, many embodiments of concatemers disclosed in the instant specification include multiple different epitopes including peptide sequences to form a large polypeptide. E.g., Concatemer 1 shown in Fig. 13 (see below) is formed by connecting multiple different peptide sequences by linkers (underlined):
MTYASALWEIQQWDADSKIVPRRARSVRYPQLSEFDWRQCSGVPRRARSVRYPLMWIPDYPRRARSVRYPKILNNLGVDIAANTVIWDPRRARSVRYPTKVDGVDVELFPRRARSVRYPVLGSLAATVPRRARSVRYPCSCGSCCKPRRARSVRYPVLPFNDGVYFAPRRARSVRYPFFSNVTWFHAIHVSPRRARSVRYPSQDLSWSPRRARSVRYPSEAFLIGCNYLPRRARSVRYPAEVQIDRLPRRARSVRYPGSNVFQTRAGCLPRRARSVRYPIKDLPKEITVATSRTLSYYKLGASQRVAPRRARSVRYPTDAVDCALPRRARSVRYPFNCYFPLQSYGFPRRARSVRYPGPKVKYLYFIPRRARSVRYPFEYVSQPFLMPRRARSVRYPLQSLQTYVTQQLIRAAPRRARSVRYPTSACVLAAECTIFKPRRARSVRYPTSCCSCLKPRRARSVRYPRLCAYCCNIVNVSLVKPSFYVYSRVKNLPRRARSVRYPTPLIQPIGALPRRARSVRYPALGKLQDWNQNPRRARSVRYPFTGCVIAWPRRARSVRYPYTELEPPCRFVTDPRRARSVRYPLSPVALRQMSCAAGPRRARSVRYPIQLSSYSLF
According to the description above, the phrase of “concatemer of epitopes” is not clearly and exclusively defined. It appears that the phrase may be interpreted as referring to a polypeptide formed by connecting epitope-containing peptides head-to-tail with or without spacer (linker) sequences. However, based on this interpretation, the phrase “concatemer of epitopes” reads on a naturally occurring antigenic protein or fragment thereof that contains multiple epitopes because such an antigen or fragment thereof can be considered as being formed by the head-to-tail connection of epitope-containing peptides linked directly or by spacer peptides that do not contain epitopes.
III. Claim 2 recites “wherein said vaccine comprises or expresses epitopes for all MHC I and MHC II alleles with a frequency >1% in the target population”. First, this limitation does not have sufficient antecedent basis since the independent claim 1 does not recite a target population. Secondly, it is noted that the claim does specify what the “target population” is. Therefore, without specifying the target population, the limitation “epitopes for all MHC I and MHC II alleles with a frequency >1% in the target population” is not specified, and, therefore, the metes and bounds are subject to change.
IV. Claim 11 recites “A vaccine comprising or capable of expressing one or more concatemers of epitopes set forth in SEQ ID NOs 1-789 or SEQ ID NOs 798-851.” This claim is indefinite because it is not clear how to interpret the limitation “expressing one or more concatemers of epitopes set forth in SEQ ID NOs 1-789 or SEQ ID NOs 798-851”. It is not clear if the “one or more concatemers of epitopes”, as a whole, set forth in in SEQ ID NOs 1-789 or SEQ ID NOs 798-851 is required, or if one or more concatemers of “epitopes set forth in SEQ ID NOs 1-789 or SEQ ID NOs 798-851” is required. The former requires a concatemer (which is currently considered as comprising at least two adjacent epitopes connected by a linker) set forth in the recited sequences, while the latter requires a concatemer comprising the “epitopes set forth” in the recited sequences.
Additionally, the phrase “set forth in SEQ ID NOs 1-789 or SEQ ID NOs 798-851” may cause confusions because it is not clear if phrase “set forth” requires that the recited “one or more concatemers” or “epitopes” must be comprised in SEQ ID NOs 1-789 or SEQ ID NOs 798-851, or if the recited sequences only represent examples.
To facilitate examination, claim 11 is broadly interpreted as reading on a vaccine comprising or capable of expressing one or more concatemers comprising epitopes comprised in any one of SEQ ID NOs: 1-789 or SEQ ID NOs: 798-851.
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.
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, 2, 5, 8, 10, 11, and 13-17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter because it is directed to a judiciary exception.
A claim directed to a judicial exception must be analyzed to determine whether the elements of the claim, considered both individually and as an ordered combination, are sufficient to ensure that the claim as a whole amounts to significantly more than the exception itself. To be patent-eligible, a claim that is directed to a judicial exception must include additional features to ensure that the claim describes a process or product that applies the exception in a meaningful way, such that it is more than a drafting effort designed to monopolize the exception.
As indicated in the 112(b) rejection above, the phrase “concatemer of epitopes” reads on a naturally occurring antigenic protein or fragment thereof containing multiple epitopes. E.g., table 1 if instant specification shows many epitope-containing peptides for the SARS-CoV-2 surface glycoprotein – about 30 peptides are disclosed in Table 1 for the SARS-CoV-2 surface glycoprotein. Therefore, SARS-CoV-2 surface glycoprotein can be considered as comprising multiple concatemers of epitopes. Simply reciting “a vaccine” does not change the structure and/or properties of the SARS-CoV-2 surface glycoprotein and nucleic acid sequence encoding it.
Claims 13-16 read on the genome or a fragment thereof of a virus. E.g., claim 14 reads on an adenovirus genome or fragment thereof, claim 16 reads on an RNA virus genome or fragment thereof. Claim 17 reads on an enveloped RNA virus.
Therefore, the claims read on a naturally occurring product.
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, 5, 8, 10, 13 and 14 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Georges et al. (US 2021/0260180 A1, published Aug. 26, 2021; PCT filed on Feb. 12, 2021).
Base claim 1 is described above. To expediate prosecution, the limitation “one or more concatemers of epitopes from a viral pathogen” is interpreted as a fusion polypeptide comprising a string of epitope-containing peptides connected together in a way different from that in the antigens the epitopes originate from.
Georges teaches that the application of the invention pertains generally to an adenoviral vectored coronavirus antigen pharmaceutical formulation for administration to a mammalian subject that induces an immune response in the subject and optionally provides protection against novel 2019 Coronavirus (SARS-CoV-2). See [0003].
Georges teaches that the invention may involve SARS-CoV-2 immunization vectors comprising one or more peptide-encoding sequences up to 60 amino acids in length (and concatenated if more than one), wherein each peptide comprise at least one CD8+ T cell epitope and/or at least one CD4+ T cell epitope, that, in this case, the concatenated peptide-encoding polynucleotide express a polypeptide where T cell epitopes or T-cell epitope-containing sequences are separated by a spacer sequence containing amino-acids such as glycine, serine or alanine residues, and that the polynucleotide may further comprise polynucleotide sequences coding for ubiquitin or a signal peptide. See [0184].
Georges teaches that, in some preferred embodiments, the vectors can encode multiple epitopes, separately or as part of a single polypeptide (e.g., concatenated, optionally separated by a linker amino acid sequence of two to ten amino acids); and that in some embodiments, the vectors can encode multiple epitopes as in the exemplary groups shown in Table 3B. See [0185]. Part of Table 3B is shown below:
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456
896
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The group of peptides shown above include peptides, assumed to contain T-cell epitopes, from various SARS-CoV-2 antigens. E.g., FIAGLIAIV (SEQ ID NO: 46) is from the spike protein and LALLLLDRL (SEQ ID NO: 35) is from the nucleocapsid protein.
Accordingly, Georges teaches an invention relating to a potential vaccine comprising or capable of expressing one or more concatemers (i.e., strings of concatenated epitope-containing peptide linked together with or without spacers) from a viral pathogen, SARS-CoV-2. Georges teaches that the concatemers can be expressed from an adenoviral vector.
Regarding claims 10 and 11, Georges teaches a number of epitope-containing peptides derived from SARS-CoV-2 viral antigens. E.g., the group 1 peptides shown in Table 3B above include epitope-containing peptides comprised in instant SEQ ID NO: 832. See below (bolded and underlined):
SEQ ID NO: 832
YVRITGLYPTLNISYEPRRARSVRYPTQLYLGGMSYYCKPHKPPISFPLPRRARSVRYPHFPRKGVFVSNPRRARSVRYPGTNLPLQLGFPRRARSVRYPFTSDYYQLYSTQLSTYTGVEHVTFFIYNPRRARSVRYPNYTVSCLPFTINCQEPPRRARSVRYPLQKAAITILDGISQYSLRLIPRRARSVRYPSVELKHFFFAPRRARSVRYPTDTVVEHVTFFIYNPRRARSVRYPNVAFNVVNKGPRRARSVRYPCSNLLLQYGSFCTQLNRPRRARSVRYPSQHTMLVKQFDDYVYLPYPDPSPRRARSVRYPGYLPQNAVVKIYCPACHNSEPRRARSVRYPFQTLLHRSYLTPPRRARSVRYPGCDVTDVTQLYLGGMSYYCKSHKPPISFPLCANGQVFGLPRRARSVRYPIVKFISTCACEIVPRRARSVRYPEPLLKGVKLPRRARSVRYPARDLSLQFPRRARSVRYPRHSLSHFVNLPRRARSVRYPVREVLSDRELHLSWEVPRRARSVRYPREGVFVSNPRRARSVRYPYELKHGTFTCAPRRARSVRYPHWPQIAQFAPSASAFFPRRARSVRYPKGVQIPCTCGKPRRARSVRYPTENLLLYIDPRRARSVRYPILLNKHIDAYKTFPPIEPRRARSVRYPAIPINFTISVTTEILPVSMPRRARSVRYPKFPLKLRGTPRRARSVRYPSVLNDILARLPRRARSVRYPDNVLSTFISAAPRRARSVRYPACIDCSARHIPRRARSVRYPVQQESPFVMMPRRARSVRYPTISVTTEILPVSMAKPRRARSVRYPTSACVLAAECTIFKPRRARSVRYPLFVVEVVDKYFDCYDGGCPRRARSVRYPGFNCYSPLQSYGFQPRRARSVRYPATVAYFNMVYMPASWVPRRARSVRYPAIKCVPQADVEWKPRRARSVRYPLFFFLYENAFLPFVMGIPRRARSVRYPALLAVFHNASPRRARSVRYPYDKLQFTSLEIPRRARSVRYPSSNVANYQPRRARSVRYPSRELKVTFFPRRARSVRYPTTVAAFHQECSLQSCTQHQPYVVDDPCPIHFYSKWYIRVGARPRRARSVRYPDMYSVMLTPRRARSVRYPRKIFVDGVPFVVSTGYPRRARSVRYPYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKPRRARSVRYPTYGVGYQPYRVVVLSPRRARSVRYPKDQVILLNKHIDAYKTFPRRARSVRYPKAVFISPYPRRARSVRYPKLALGGSVAIKITPRRARSVRYPYDKLVSSFPRRARSVRYPITTVAAFHQECSLQPRRARSVRYPLMNVLTLFYKVYYGNAPRRARSVRYPHQPYVVDDPCPIHFYSKWYIRVGPRRARSVRYPLGSLVVRCSFYEDFLEYHDVRVVLPRRARSVRYPLPRVFSAVGNPRRARSVRYPQLALSKGVYFVCNLLLLFVTVYSPRRARSVRYPYDFAVSKGPRRARSVRYPYRLANECAQVLSEIVMCGGSLYVKPGPRRARSVRYPQIGVVREFPRRARSVRYPYLKLRSDVPRRARSVRYPKLNVGDYFVLTSHTVMPLSPRRARSVRYPSFKLKDCVMYPRRARSVRYPPRWYFYYLGTPRRARSVRYPCYDYCIPYNSVTSLIVITSPRRARSVRYPMPVCVETKAPRRARSVRYPGVVQQLPETPRRARSVRYPGVNLVAVPTGYVDPRRARSVRYPSVLLSMQGAVDIPRRARSVRYPRSVASQSIIAYTMPRRARSVRYPVKGLQPSVGPKQAPRRARSVRYPQLSLSKGFHFVCNLLLLFVPRRARSVRYPISSVLNDILSRLDPRRARSVRYPVLYQGVNCTEVPRRARSVRYPFSNVTWFHAIVSPRRARSVRYPRLTLGVYDYLVSTQPRRARSVRYPKESVQTFFKLVPRRARSVRYPNVVIKVCEFQFCNYPFLGVYYHPRRARSVRYPIETISLAGPRRARSVRYPANSVFNICQAVTANVNALLPRRARSVRYPNEFYAYLRKHPRRARSVRYPFPQSAPHGVVFLHVTYVPAQPRRARSVRYPNPVLPFNDGVYFAPRRARSVRYPISDYDYYRYNPRRARSVRYPSLIDLQELPRRARSVRYPLGGMSYYCKSHKPSISFPLCANPRRARSVRYPIQLSSYSLFPRRARSVRYPYVYLPYPDPSRILGAGCFVDPRRARSVRYPETICAPLTVFFPRRARSVRYPQVAVLYQDVNCTEVPVAIHPRRARSVRYPVTGLFKDCSKPRRARSVRYPFFSNVTWFHAIHVSPRRARSVRYPNYTVSCSPFTINCQEPPRRARSVRYPMMFVKHKHAFLPRRARSVRYPGFNCYFPLQPYGFQPRRARSVRYPAAAYYVGYLPRRARSVRYPEFQFCNYPFLGVYHKPRRARSVRYPDGYVMHANYIPRRARSVRYPEHVQIHTIPRRARSVRYPEFQFCNDPFLGVYYHPRRARSVRYPSHGKQVVSDIDYVPLKSATCITRPRRARSVRYPSLRCGACIRRPFLCCKPRRARSVRYPFFSNVTWFH
Therefore, Georges teaches each and every aspect of claims 1, 5, 8, 10, 11, 13, and 14.
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 of this title, 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 2, 5, 8, 10, 11, 21, 23 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Chukwudozie et al. (PLoS ONE 16(3): e0248061; published online Mar. 17, 2021).
These claims are described above.
Chukwudozie teaches a study on immuno-informatics design of a multimeric epitope-peptide-based vaccine targeting SARS-CoV-2 spike glycoprotein. The authors have used a bioinformatic approach to aid in designing an epitope peptide-based vaccine against the spike protein of the SARS-CoV-2 virus. Five antigenic B cell epitopes with viable antigenicity and a total of 27 discontinuous B cell epitopes were mapped out structurally in the spike protein for antibody recognition. They identified eight CD8+ T cell 9-mers and 12 CD4+ T cell 14-15-mer as promising candidate epitopes putatively restricted by a large number of MHC I and II alleles, respectively. The authors used this information to construct an in silico chimeric peptide vaccine whose translational rate was highly expressed when cloned in pET28a (+) vector. With the in silico test, the vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was also characterized by an increase in IgM and IgG and an array of Th1 and Th2 cytokines. Upon in silico challenge with SARS-CoV-2, there was a decrease in antigen levels using their immune simulations. See Abstract.
Chukwudozie teaches that to construct a multi-epitope vaccine, the authors selected CTL, HTL, and B cell linear epitopes linked together with the help of AAV, GPGPG, and KK linkers, respectively. To boost the immunogenic profile of the selected profile epitopes, an adjuvant would be required. The outer membrane protein A (OmpA) (GenBank: AFS89615.1) was retrieved for this purpose because it serves as an agonist to the human immune receptor by interacting with antigen presenting cells [22]. The adjuvant was putatively added through the EAAAK linker, with the B and HTL epitopes linked together through the GPGPG linkers. These complexes were subsequently added to the CTL epitopes through the AAV linkers. The tag (6xHis-tag) was added at the C terminal end of the vaccine construct. The 6xHis-tag is one of the simplest and most widely used purification tags, with six or more consecutive histidine residues. These residues readily coordinate with transition metal ions such as Ni2+ or Co2+ immobilized on beads or resin for purification [23]. The vaccine peptide’s intrinsic solubility properties were conducted using the CamSol tool, which yields a solubility profile where regions (residues) with scores greater than 1 signify soluble regions. In contrast, scores lesser than -1 represents poorly soluble regions [24]. An overall score was generated for the entire sequence, as these amino residue scores are ranked based on their level of solubility. See page 5, para 2.
Chukwudozie teaches that for the maximum expression of the vaccine in the host, a codon optimization was conducted, using the Java Codon Adaptation Tool (JCat) to increase the translational vaccine rate in E. coli K12 system, and that refined nucleotide was cloned into the pET28a (+) vector prototype, utilizing the SnapGene 4.2 tool. See para bridging pages 6 and 7.
Chukwudozie teaches that the entire predicted conjugate vaccine peptide was assessed for their immunogenicity, and immune response attributes using the C-ImmSim online server (http://150.146.2.1/ C-IMMSIM/index.php) [37]. The authors simulated the administration of three injections containing the designed peptide vaccine at an interval of four weeks i.e., days 0. 28 and 56. This prime-booster-booster approach at 4-weeks interval was employed to achieve long-lasting protective immune response based on the assessment of immune readouts from the simulation. See page 7, para 2.
Accordingly, Chukwudozie teaches potential vaccine candidate comprising or capable of expressing one or more concatemers (i.e., strings of concatenated epitope-containing peptide linked together with or without spacers) from a viral pathogen SARS-CoV-2. However, Chukwudozie teaches only an in silico simulation study on the vaccine development, no real-world products and/or processes are disclosed.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to further the study of Chukwudozie to arrive at the invention as claimed. One would have been motivated to do so to verify the in silico simulation results by real-world experiments.
Regarding claim 2, Chukwudozie teaches that the epitopes identified in the study are restricted by various HLA allelles. See e.g. Tables 3-6. It is noted that the claim does specify what the “target population” is. Therefore, without specifying the target population, the limitation “epitopes for all MHC I and MHC II alleles with a frequency >1% in the target population” is not specified and subject to change.
One of skill in the art would have found it obvious to select epitope-containing peptides disclosed in Chukwudozie based on the target population determined for the vaccine candidate so that the resulting vaccine may cover a desired amount MHC I and MHC II alleles as possible, including that as claimed.
Regarding claims 10-11, at least Table 1 of Chukwudozie shows two peptides, No. 4 and No. 5, which are included in the instant SEQ ID NO: 832. See below (bolded and underlined):
SEQ ID NO: 832
YVRITGLYPTLNISYEPRRARSVRYPTQLYLGGMSYYCKPHKPPISFPLPRRARSVRYPHFPRKGVFVSNPRRARSVRYPGTNLPLQLGFPRRARSVRYPFTSDYYQLYSTQLSTYTGVEHVTFFIYNPRRARSVRYPNYTVSCLPFTINCQEPPRRARSVRYPLQKAAITILDGISQYSLRLIPRRARSVRYPSVELKHFFFAPRRARSVRYPTDTVVEHVTFFIYNPRRARSVRYPNVAFNVVNKGPRRARSVRYPCSNLLLQYGSFCTQLNRPRRARSVRYPSQHTMLVKQFDDYVYLPYPDPSPRRARSVRYPGYLPQNAVVKIYCPACHNSEPRRARSVRYPFQTLLHRSYLTPPRRARSVRYPGCDVTDVTQLYLGGMSYYCKSHKPPISFPLCANGQVFGLPRRARSVRYPIVKFISTCACEIVPRRARSVRYPEPLLKGVKLPRRARSVRYPARDLSLQFPRRARSVRYPRHSLSHFVNLPRRARSVRYPVREVLSDRELHLSWEVPRRARSVRYPREGVFVSNPRRARSVRYPYELKHGTFTCAPRRARSVRYPHWPQIAQFAPSASAFFPRRARSVRYPKGVQIPCTCGKPRRARSVRYPTENLLLYIDPRRARSVRYPILLNKHIDAYKTFPPIEPRRARSVRYPAIPINFTISVTTEILPVSMPRRARSVRYPKFPLKLRGTPRRARSVRYPSVLNDILARLPRRARSVRYPDNVLSTFISAAPRRARSVRYPACIDCSARHIPRRARSVRYPVQQESPFVMMPRRARSVRYPTISVTTEILPVSMAKPRRARSVRYPTSACVLAAECTIFKPRRARSVRYPLFVVEVVDKYFDCYDGGCPRRARSVRYPGFNCYSPLQSYGFQPRRARSVRYPATVAYFNMVYMPASWVPRRARSVRYPAIKCVPQADVEWKPRRARSVRYPLFFFLYENAFLPFVMGIPRRARSVRYPALLAVFHNASPRRARSVRYPYDKLQFTSLEIPRRARSVRYPSSNVANYQPRRARSVRYPSRELKVTFFPRRARSVRYPTTVAAFHQECSLQSCTQHQPYVVDDPCPIHFYSKWYIRVGARPRRARSVRYPDMYSVMLTPRRARSVRYPRKIFVDGVPFVVSTGYPRRARSVRYPYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKPRRARSVRYPTYGVGYQPYRVVVLSPRRARSVRYPKDQVILLNKHIDAYKTFPRRARSVRYPKAVFISPYPRRARSVRYPKLALGGSVAIKITPRRARSVRYPYDKLVSSFPRRARSVRYPITTVAAFHQECSLQPRRARSVRYPLMNVLTLFYKVYYGNAPRRARSVRYPHQPYVVDDPCPIHFYSKWYIRVGPRRARSVRYPLGSLVVRCSFYEDFLEYHDVRVVLPRRARSVRYPLPRVFSAVGNPRRARSVRYPQLALSKGVYFVCNLLLLFVTVYSPRRARSVRYPYDFAVSKGPRRARSVRYPYRLANECAQVLSEIVMCGGSLYVKPGPRRARSVRYPQIGVVREFPRRARSVRYPYLKLRSDVPRRARSVRYPKLNVGDYFVLTSHTVMPLSPRRARSVRYPSFKLKDCVMYPRRARSVRYPPRWYFYYLGTPRRARSVRYPCYDYCIPYNSVTSLIVITSPRRARSVRYPMPVCVETKAPRRARSVRYPGVVQQLPETPRRARSVRYPGVNLVAVPTGYVDPRRARSVRYPSVLLSMQGAVDIPRRARSVRYPRSVASQSIIAYTMPRRARSVRYPVKGLQPSVGPKQAPRRARSVRYPQLSLSKGFHFVCNLLLLFVPRRARSVRYPISSVLNDILSRLDPRRARSVRYPVLYQGVNCTEVPRRARSVRYPFSNVTWFHAIVSPRRARSVRYPRLTLGVYDYLVSTQPRRARSVRYPKESVQTFFKLVPRRARSVRYPNVVIKVCEFQFCNYPFLGVYYHPRRARSVRYPIETISLAGPRRARSVRYPANSVFNICQAVTANVNALLPRRARSVRYPNEFYAYLRKHPRRARSVRYPFPQSAPHGVVFLHVTYVPAQPRRARSVRYPNPVLPFNDGVYFAPRRARSVRYPISDYDYYRYNPRRARSVRYPSLIDLQELPRRARSVRYPLGGMSYYCKSHKPSISFPLCANPRRARSVRYPIQLSSYSLFPRRARSVRYPYVYLPYPDPSRILGAGCFVDPRRARSVRYPETICAPLTVFFPRRARSVRYPQVAVLYQDVNCTEVPVAIHPRRARSVRYPVTGLFKDCSKPRRARSVRYPFFSNVTWFHAIHVSPRRARSVRYPNYTVSCSPFTINCQEPPRRARSVRYPMMFVKHKHAFLPRRARSVRYPGFNCYFPLQPYGFQPRRARSVRYPAAAYYVGYLPRRARSVRYPEFQFCNYPFLGVYHKPRRARSVRYPDGYVMHANYIPRRARSVRYPEHVQIHTIPRRARSVRYPEFQFCNDPFLGVYYHPRRARSVRYPSHGKQVVSDIDYVPLKSATCITRPRRARSVRYPSLRCGACIRRPFLCCKPRRARSVRYPFFSNVTWFH
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Georges et al. (US 2021/0260180 A1, published Aug. 26, 2021; PCT filed on Feb. 12, 2021).
Claim 2 is described in the 103 rejection above over Chukwudozie.
Georges also teaches that the epitopes identified in the invention are restricted by various HLA allelles. See e.g. Table 6 and throughout the specification. It is noted that the claim does specify what the “target population” is. Therefore, without specifying the target population, the limitation “epitopes for all MHC I and MHC II alleles with a frequency >1% in the target population” is not specified and subject to change.
One of skill in the art would have found it obvious to select epitope-containing peptides disclosed in Gorges based on the target population determined for the vaccine candidate so that the resulting vaccine may cover a desired amount MHC I and MHC II alleles as possible, including that as claimed.
Claims 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Georges et al. (US 2021/0260180 A1, published Aug. 26, 2021; PCT filed on Feb. 12, 2021) and/or Chukwudozie et al. (PLoS ONE 16(3): e0248061; published online Mar. 17, 2021), as applied in the art rejections above, in view of Ciaramella et al. (US 2019/0008938 A1, published on Jan. 10, 2019) and Geall et al. (PNAS, 2012, 109(36): 14604-14609..
Claim 15 specifies that the vaccine of claim 1 is a nucleic acid-based vaccine. Claim 16 specifies a SAM RNA based vaccine. Claims 17-19 specify that the SAM RNA based vaccine of claim 16 is encapsulated in lipid nanoparticles (LNPs).
Relevance of Georges and Chukwudozie is set forth in the rejections above. However, they are silent on nucleic acid-based vaccines (Goerges teaches adenovirus vectors while Chukwudozie teaches plasmid vectors in expressing the antigen polypeptides, which are not considered here as nucleic acid-based vaccines).
Ciaramella teaches an invention relating to concatemeric peptide epitope RNAs, as well as methods and compositions thereof. mRNA vaccines are also provided according to the invention, including cancer vaccines. See Abstract.
Ciaramella teaches that in one embodiment, the LNP formulation may be used in the disclosed invention, containing PEG-DMG 2000 (l,2-dimyristoyl-sn-glycero-3- phophoethanolamine-N-[methoxy(polyethylene glycol)-2000) which is a cationic lipid known in the art, DSPC and cholesterol; that the LNP formulation may contain PEGDMG 2000, DLin-DMA, DSPC and cholesterol. As another non-limiting example the LNP formulation may contain PEG-DMG 2000, DLin-DMA, DSPC and cholesterol in a molar ratio of 2:40:10:48 (see e.g., Geall et al., Nonviral delivery of self-amplifying RNA vaccines, PNAS 2012; PMID: 22908294; herein incorporated by reference in its entirety). See [0363].
Geall, cited in Ciaramella, teaches a study on nonviral delivery of self-amplifying RNA vaccines. In the study, the authors show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, the results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted. See Abstract.
Figure 1 of Geall shows characterization of self-amplifying RNA vaccines of the study. (A) Schematic illustration of a self-amplifying RNA derived from an alphavirus contains a 5′ cap, nonstructural genes (NSP1–4), 26S subgenomic promoter (grey arrow), the gene of interest (GOI), and a 3′ polyadenylated tail. (B) Schematic illustration of a lipid nanoparticle (LNP) encapsulating self-amplifying RNA, with the percent molar ratios of lipid components as indicated. See Fig. 1A and Fig. 1B below:
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Accordingly, both Ciaramella and Geall teach development of RNA-based vaccine, including SAM-RNA-based vaccines, for delivery of sequences encoding antigen peptides, formulated in lipid nanoparticles (LNPs).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to combine the teachings of Georges and/or Chukwudozie with the teachings of Ciaramella and Geall to arrive at the invention as claimed. One would have been motivated to do so to evaluate the RNA-LNP vaccine platforms disclosed in Ciaramella and Geall in the delivery of concatemeric antigens disclosed in the inventions of Georges and/or Chukwudozie. There is a reasonable expectation of success that a nucleic acid sequence encoding a concatemeric antigen disclosed in the inventions of Georges or Chukwudozie may be incorporated into a RNA molecule, including a SAM RNA molecule, formulated into LNPs, and tested for immunogenicity, based on teachings of the prior art references.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671
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