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 .
Application Status
Applicant’s amendments to the claims filed January 30, 2025 are acknowledged. Claims 1, 5-6, 8, 10, 20-21, 23-24, 27, and 30 were amended, and claims 2, 4, 7, 9, 11, 19, 22, 28-29, and 32-99 were cancelled. Claims 1, 3, 5-6, 8, 10, 12-18, 20-21, 23-27, and 30-31 are pending and under consideration hereinafter.
Priority
Applicant’s priority claims to Application Nos. 63/219,596, 63/219,599, 63/219,587, 63/332,378, and PCT/US22/36367 are acknowledged. Claims 1, 3, 5-6, 8, 10, 12-18, 20-21, 23-27, and 30-31 find support in at least Application No. 63/219,587 filed July 8, 2021. The effective filing date of all claims under examination is July 8, 2021.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO: X” or the like) in accordance with 37 CFR 1.831(c). Specifically, claim 14 sets forth the sequence “Xn-QPFAAA-Xn,” which is not identified by a sequence identifier. Based on the guidance in Example 3(c)-2 of STANDARD ST.26 (page: 3.26.vi.11), when “n” is indeterminate, the peptide cannot be expanded to a definite length, and therefore, “the unexpanded formula must be considered.” The unexpanded formula of the sequence “Xn-QPFAAA-Xn” is XQPFAAA, which appears to correspond to the sequence set forth in SEQ ID NO: 55 of the sequence listing filed January 30, 2025.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The specification is objected to because of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, e.g., “http://www.Atcc.org” (pg. 65). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of terms which are trade names or marks used in commerce has been noted in this application, e.g., “Transporter 5” (pg. 65), “Alexa Fluor” (pg. 65), and “Accutase” (pg. 69). Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. The terms, including the exemplary terms above, should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Appropriate correction is required.
Claim Objections
Claims 1, 8, 12-14, 17, 20-21, 23-24, 26, and 31 are objected to because of the following informalities:
Claim 1 recites “A composition comprising an… oligonucleotide having… and includes….” It would be preferable to amend the claim to recite, for example, “A composition comprising an… oligonucleotide having… and including[[es]]…,” to improve the grammar of the claim.
Claim 8 recites a “chimeric molecule comprising one or more peptide domains and one or more 5’- and/or 3’-untranslated (UTR) sequences or fragments thereof.” Based on the disclosure and content of the claims as a whole, the “chimeric molecule” is a nucleic acid sequence encoding (a) one or more amino acid sequences comprising from 5-20 amino acids (i.e., “peptide domains”), and (b) one or more (i) nucleic acid sequences which are capable of recruiting ribosomes and initiating translation (i.e., “5’ UTR”) and/or (ii) nucleic acid sequences which immediately follow the translation termination codon (i.e., “3’ UTR”). See Figs. 3D, 4A, 20A, definitions of 5’- and 3’- UTRs on pg. 19, and description of nucleic acids encompassed by the disclosure on pg. 42-46.
Accordingly, claim 8 should be amended to recite, for example, “A chimeric molecule comprising a nucleic acid sequence encoding one or more peptide domains and one or more 5’- and/or 3’-untranslated region (UTR) sequences or fragments thereof, wherein the one or more peptide domains comprise from about five amino acids to about twenty amino acids.” Claim 8 is interpreted hereinafter as in the suggested amendment directly above.
Claims 12 and 13 recite “the peptide.” It is clear that this term refers to the “one or more peptide domains” of claim 8; however, it would be preferable to amend the claims to recite “the one or more peptide domains,” so that the terminology is consistent throughout the claims.
Claim 14 recites “the peptide domain.” It is clear that this term refers to the “one or more peptide domains” of claim 8; however, it would be preferable to amend the claim to recite “the one or more peptide domains,” so that the terminology is consistent throughout the claims.
Claim 17 recites “the 5’-UTR and/or 3’-UTR.” It is clear that this phrase refers to the “one or more 5’- and/or 3’-untranslated region (UTR) sequences or fragment thereof” of claim 8, wherein the one or more 5’-UTR sequences or fragments thereof are limited to those derived from one or more viruses as in claims 15-16. However, it would be preferable to amend claim 17 to recite “the one or more 5’-UTR and/or 3’-UTR sequences or fragments thereof,” so that the terminology is consistent throughout the claims.
Claims 20-21, and 23-24 recite “the one or more 5’-UTR nucleic acid sequences or fragments thereof,” and “the one or more 3’-UTR nucleic acid sequences or fragments thereof.” It would be preferable to amend the claims to recite “the one or more 5’-UTR sequences or fragments thereof,” so that the terminology is consistent throughout the claims.
Claims 26 and 31 recite the term “viral transcripts/proteins.” It is reasonably clear that the “/” intends to set forth alternatives. It would be preferable to amend the claims to recite, “viral transcripts[[/]] or proteins,” accordingly.
Appropriate correction is required.
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 8, 10, 12-18, 20-21, 23-27, and 30-31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 8, 10, and 30 recite the term “about.” The term “about” is a relative term which renders the claims indefinite. The term “about” is not defined by the claims. The specification provides that “about” “means within an acceptable error range for the particular value as determined by one of ordinary skill… which will depend in part on how the value is measured or determined… “about” can mean within 1 or more than 1 standard deviation… can mean a range of up to 20%... of a given value or range… can mean within an order of magnitude within 5-fold…” (pg. 12). This does not provide a standard for ascertaining the requisite degree, because the skilled artisan would not know which of the many possible definitions that “about” could mean apply to the number of amino acids encoded by the peptide domains. Because neither the claims nor specification clearly define the requisite degree of “about” which applies to the number of amino acids encoded by the peptide domains, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 12-18, 20-21, 23-27, and 30-31 are rejected for depending from claims 8 or 30 and failing to remedy the indefiniteness. In the interest of compact prosecution, the recited ranges in claims 8, 10, and 30 will be interpreted as “from five to twenty amino acids,” and “seven amino acids.”
Claim 25 recites that the chimeric molecule “further compris[es] one or more biomolecules operably linked to the one or more peptide domains and/or the one or more 5’UTR and/or 3’-UTR sequences.” Claim 26 recites that “the biomolecule [operably linked to the one or more peptide domains and/or the one or more 5’UTR and/or 3’-UTR sequences] comprises: a viral transcript/proteins, vaccines, antibodies, an mRNA, an mRNA vaccine….”
The specification describes that “operably linked” may refer to linkage of nucleic acids on a single nucleic acid fragment, and also to “the products of chimeric genes, such as fusion proteins,” and also to “the linking of a peptide tag to a biomolecule, e.g., peptide of interest to be produced and recovered” (pg. 16-1). Based on the specification, “operably linked” is interpreted as any linkage between two or more elements, e.g., between a fusion protein and an element, between two nucleic acids sequences, or between a peptide tag and a protein of interest.
As described above, the chimeric molecule is interpreted as a nucleic acid sequence. The structures encompassed by the claims are unclear in view of the claim language, the scope of the term “operably linked,” and the structures encompassed by the term “biomolecules” based on claim 26.
Specifically, it is not clear whether the claim encompasses for example, an mRNA (composed of RNA nucleotides), or a viral protein, antibody, or cellular protein (each composed of amino acids), or a virion (a complex structure composed of different chemical species) literally linked to the nucleic acid sequences encoding the one or more peptide domains or UTRs as the claim literally states, or whether the claim intends to encompass operably linking a sequence encoding an mRNA, viral protein, antibody, cellular protein, or element of a virion to the nucleic acid sequences encoding the one or more peptide domains or UTR as described elsewhere in the specification. The structure of a chimeric molecule operably linked to various “vaccines” or “biomimetics” is also unclear, because these terms encompass formulations and materials (e.g., compositions administered to promote immunity, hydrogels, 3D printed biomaterials, etc.), and it is not clear what element(s) of such formulations and materials would be “operably linked” to the nucleic acid sequences encoding the one or more peptide domains or UTRs. Taken together, the structures of the chimeric molecules encompassed by the claims are unclear.
In the interest of compact prosecution, the claims will be interpreted as encompassing chimeric molecules further comprising a polynucleotide or sequence encoding a polypeptide operably linked to the one or more peptide domains and/or the one or more UTRs.
Claim 27 recites “the… biomolecule.” Neither claim 27 nor claim 8 recite a biomolecule. Claim 27 recites several elements which could be considered a biomolecule, e.g., a “chimeric molecule,” or “one or more peptide domains,” but it is not clear which, if any, of these elements correspond to the “biomolecule” recited in claim 27. The term “biomolecule” does not have sufficient antecedent basis in claim 27.
In the interest of compact prosecution, the claim will be interpreted hereinafter as depending from claim 25, which recites the term “one or more biomolecules.”
Claim 30 recites a method comprising "tagging a desired peptide or a nucleic acid sequence with a chimeric molecule." The “chimeric molecule” comprises “one or more peptide domains and one or more 5’- and/or 3’-untranslated (UTR) sequences or fragments thereof.” As stated above, based on the disclosure and content of the claims as a whole, the “chimeric molecule” is a nucleic acid sequence encoding (a) one or more amino acid sequences comprising from 5-20 amino acids (i.e., “peptide domains”), and (b) one or more (i) nucleic acid sequences which are capable of recruiting ribosomes and initiating translation (i.e., “5’ UTR”) and/or (ii) nucleic acid sequences which immediately follow the translation termination codon (i.e., “3’ UTR”). See Figs. 3D, 4A, 20A, definitions of 5’- and 3’- UTRs on pg. 19, and description of nucleic acids encompassed by the disclosure on pg. 42-46.
Claim 30 is confusing, therefore, because it literally encompasses tagging a "desired peptide" with a chimeric molecule, which is a nucleic acid sequence based on the disclosure, and then "expressing the peptide." Means of linking a nucleic acid sequence to an amino acid sequence are known in the art; however, a fusion between a nucleic acid sequence (i.e., the chimeric molecule) and an amino acid sequence (i.e., the desired peptide) would not be "expressed," i.e., produced by transcription and/or translation machinery (pg. 16), because the nucleic acid sequence would not be part of the "expressed" peptide. It is not actually clear what "expressing the peptide" in this context means, given that the peptide is already provided for in the earlier step of the method.
The claim also recites the term "harvesting the protein." While it is clear that the term "peptide" and "protein" may be used interchangeably (pg. 17), such that "the protein" could refer to the previously recited "desired peptide," it is not clear how the term "the protein" relates to the tagged and expressed nucleic acid sequence. For example, it is not clear whether "the protein" refers to an unrecited element which the nucleic acid sequence must comprise, e.g., a sequence encoding a protein, or whether the term refers to the "one or more peptide domains" which the nucleic acid sequence is tagged with, or, for example, whether the term refers to a protein sequence encoded by the nucleic acid sequence, which, by virtue of the tagging, comprises the "one or more peptide domains" which are “the protein,” or whether the term “the protein” does not even apply to the nucleic acid sequence. Taken together, the scope of the claimed method is unclear.
Claim 31 is rejected for depending from claim 30 and failing to remedy the indefiniteness. In the interest of compact prosecution, claim 31 will be interpreted as referring to tagging a nucleic acid sequence, e.g., a nucleic acid sequence encoding a desired peptide, with a chimeric molecule, rather than literally tagging a desired peptide with a chimeric molecule (i.e., a nucleic acid sequence). The method is interpreted as requiring harvesting of the nucleic acid sequence, or a desired peptide expressed from the nucleic acid sequence.
Claim 31 recites “the proteins.” No such “proteins” are explicitly recited in claim 31. Furthermore, as described in the rejection of claim 30 above, even should the term “the proteins” intend to refer to “the protein” of claim 30, it is not clear how or if the term "the protein" relates to the tagged and expressed nucleic acid sequence. The list of elements which “the proteins” may comprise adds even more confusion to the claim. It is not clear how these elements relate to the elements of claim 30, e.g., the peptide, the nucleic acid sequence, or the harvested protein. For example, it is not clear whether the claim intends to require that the desired peptide, nucleic acid sequence, and/or harvested protein “comprise” (e.g., by actually having the element, or by operable linkage, fusion, or the like), and/or encode one of the elements. For example, it is not clear whether the claim encompasses a desired peptide operably linked to an mRNA, or a nucleic acid sequence operably linked to a cellular protein, virion, or antigen. Linkages between amino acid sequences and nucleic acid sequences are known in the art, but as described above it is not clear how or what structures are “expressed” and/or “harvested,” given that, for example, expressing a nucleic acid sequence operably linked to a cellular protein would not necessarily preserve the operable linkage between the nucleic acid sequence and cellular protein. It is also not clear how the desired peptide, nucleic acid sequence, and/or harvested protein can “comprise” (e.g., via operable linkage, fusion, etc.) various “vaccines” or “biomimetics” because these terms encompass various formulations and materials (e.g., compositions administered to promote immunity, hydrogels, 3D printed biomaterials, etc.) as described above.
Taken together, the claim lacks sufficient antecedent basis for the term “the proteins,” and this term, when coupled with the list of elements which “the proteins” may comprise, provide significant uncertainty as to the structures encompassed by the claim.
In the interest of compact prosecution, claim 31 will be interpreted as referring to the harvested nucleic acid sequence, or the desired peptide expressed from a nucleic acid sequence. The harvested nucleic acid sequence may be a polynucleotide, an oligonucleotide, an mRNA, etc., and the desired peptide expressed from the nucleic acid sequence may be a peptide, polypeptide, cellular protein, antigen, etc.
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomena without significantly more. The claim recites a “composition comprising an expression enhancing oligonucleotide having 21 nucleic acid bases and includes a cis-regulatory coding motif that retains in-frame of target gene, wherein the expression enhancing oligonucleotide comprises a nucleic acid sequence comprising… []SEQ ID NO: 7[].” Based on the specification, SEQ ID NO: 7 functions as a cis-regulatory motif that enhances expression when located in-frame in a target gene (see Example 3, pg. 81-100; ). Thus, the term “expression enhancing” and phrase “includes a cis-regulatory coding motif that retains in-frame of a target gene” are understood to be functions inherent to an oligonucleotide comprising SEQ ID NO: 7, which do not further structurally limit the composition. Claim 1, therefore, is directed to a composition comprising an oligonucleotide comprising the sequence of SEQ ID NO: 7.
Laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature. GenBank MW442776.1 (Asterocampa clyton clyton voucher 18LW13006 small subunit ribosomal RNA gene, internal transcribed spacer 1, 5.8S ribosomal RNA gene, internal transcribed spacer 2, and large subunit ribosomal RNA gene, complete sequence, GenBank: MW442776.1, available 12 November 2025) teaches a naturally-occurring oligonucleotide comprising SEQ ID NO: 7. See attached alignment in Appendix I. The oligonucleotide occurs in nature inside the cytosol of a eukaryotic cell as evidenced by GenBank MW442776.1. The composition of claim 1 is not markedly different from its naturally-occurring counterpart, i.e., the cytosol of a eukaryotic cell comprising the oligonucleotide taught by GenBank MW442776.1. Claim 1 recites a nature-based product.
As stated above, the claim also recites the term “expression enhancing” and phrase “includes a cis-regulatory coding motif that retains in-frame of a target gene.” However, these are understood to recite inherent functions, which do not further structurally limit the judicial exception such that it is markedly different from the naturally-occurring product. Accordingly, the judicial exception is not integrated into a practical application and does not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claims 3, and 5-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomena without significantly more. Claim 3 recites a “synthetic oligonucleotide comprising a nucleic acid sequence comprising… []SEQ ID NO: 7[].” The term “synthetic” is interpreted as referring to an artificial, or man-made oligonucleotide. Claims 5-6 recite that the synthetic oligonucleotide encodes a peptide comprising an amino acid sequence having at least 90% identity to, or comprising the amino acid sequence of SEQ ID NO: 1 (i.e., QPRFAAA). The limitations in claims 5-6 are interpreted as functions inherent to the sequence set forth in SEQ ID NO: 7 which do not modify the structure of the synthetic oligonucleotide because, based on the specification, SEQ ID NO: 7 is inherently capable of encoding a peptide comprising SEQ ID NO: 1 (“Exen21 was assigned as a new name for the unique and novel expression-enhancing 21-mer cis-regulatory motif, which encodes an epitope tag (Qα),” pg. 91; Fig. 8H). Thus, claims 3, and 5-6 are directed to a man-made oligonucleotide (i.e., any two or more linked nucleotides) comprising SEQ ID NO: 7.
Laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature. MPEP 2106.04(b)(II) also provides that “product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart.” In other words, the term “synthetic” does not render the product eligible, if the product is structurally identical to a naturally-occurring counterpart. As stated above, GenBank MW442776.1 teaches a naturally-occurring oligonucleotide comprising SEQ ID NO: 7. See attached alignment in Appendix I. The synthetic oligonucleotides of claims 3, and 5-6 are not markedly different from the naturally-occurring counterpart, i.e., the oligonucleotide taught by GenBank MW442776.1. Claims 3, and 5-6 recite a nature-based product.
The claims do not recite any additional elements. Each element is found in the naturally-occurring counterpart as described above. The judicial exceptions are not integrated into a practical application and do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claims 8, 10, 12-14, and 25-27 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomena without significantly more. Claim 8 recites a “chimeric molecule comprising one or more peptide domains and one or more 5’- and/or 3’-untranslated region (UTR) sequences or fragments thereof, wherein the one or more peptide domains comprise from about five amino acids to about twenty amino acids.” The specification does not provide a specific definition for the term “chimeric molecule,” but based on the definition of “chimeric protein” and “chimeric peptide,” the term would reasonably be construed as referring to a molecule “comprising at least two portions, each portion comprising a distinct function” (pg. 15). The term “peptide domain” is also not explicitly defined, but based on the disclosure (e.g., Figs. 3D, 4A, 20A), the term is understood to refer an amino acid sequence comprising from 5-20 linked amino acids. The term “5’ UTR” is interpreted as a “polynucleotide sequence that, when linked to a transcript, is capable of recruiting ribosome complexes and initiating translation of the transcript” (pg. 19). The term “3’ UTR” is interpreted as a “section of… []mRNA[] that immediately follows the translation termination codon” (pg. 19). Accordingly, the “chimeric molecule” of claim 8, is interpreted as a nucleic acid sequence encoding (a) one or more amino acid sequences comprising from 5-20 amino acids (i.e., “peptide domains”), and (b) one or more (i) sequences which are capable of recruiting ribosomes and initiating translation (i.e., “5-UTR”) and/or (ii) sequences which immediately follow the translation termination codon (i.e., “3’-UTR”). The nucleic acid sequence must comprise at least two portions, each portion comprising a distinct function.
Claim 10 is interpreted as requiring a nucleic acid sequence encoding an amino acid sequence comprising 7 amino acids. Claims 12-13 require that “the peptide,” interpreted herein as referring to one of the one or more peptide domains, encode an amino acid sequence at least 90% identical to, or an amino acid sequence comprising, SEQ ID NO: 1. Similarly, claim 14 is interpreted as requiring that one of the one or more peptide domains encode an amino acid sequence with the formula Xn-QPRFAAA-Xn. Claims 25-26 are interpreted as requiring one or more additional “biomolecules,” e.g., an “oligonucleotide,” or “polynucleotide,” operably linked to components (a) and/or (b) above. Claim 27 is interpreted as requiring one or more promoters and/or regulatory sequences, interpreted herein as referring to nucleic acid sequences required for gene expression (pg. 18), operably linked to component (b) above. Thus, claims 25-27 encompass one or more promoters and/or regulatory sequences operably linked to component (b) above.
Laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature. GenBank: AP028215.1 (Cutaneotrichosporon cavernicola HIS019 DNA, chromosome: 4, GenBank: AP028215.1, available 16 November 2023) teaches C. cavernicola HIS019 chromosome 4 DNA. GenBank: KQ087185.1 (Trichosporon oleaginosus strain IBC0246 unplaced genomic scaffold CC85scaffold_9, whole genome shotgun sequence, GenBank: KQ087185.1, available 24 June 2015) teaches T. oleaginosus IBC0246 genomic DNA. The DNA taught by the GenBank entries encodes (a) one or more amino acid sequences comprising 5-20 amino acids, or comprising 7 amino acids. GenBank teaches that portions of the DNA are transcribed (“CDS”) and translated (“/translation =…”), therefore, the DNA must inherently comprise (b) one or more (i) sequences which are capable of recruiting ribosomes and initiating translation and/or (ii) sequences which immediately follow the translation termination codon. GenBank AP028215.1 teaches the C. cavernicola HIS019 chromosome 4 DNA encodes a peptide domain within the gene located at “2746954..2747933,” which encodes the sequence “QPRFAAA,” i.e., instant SEQ ID NO: 1, which is bordered by amino acids so as to meet the formula Xn-QPRFAAA-Xn (“PGQPRFAAASY”). Similarly, GenBank: KQ087185.1 teaches T. oleaginosus IBC0246 genomic DNA encodes a peptide domain within the gene located at “complement(join(156680..156801,156857..157152, 157231..157655)),” which encodes the sequence “QPRFAAA,” i.e., instant SEQ ID NO: 1, which is bordered by amino acids so as to meet the formula Xn-QPRFAAA-Xn (“PGQPRFAAASY”). Because the DNA is transcribed (“CDS”), the DNA must inherently comprise a promoter and/or regulatory sequences, operably linked to the one or more sequences which are capable of recruiting ribosomes and initiating translation. Finally, the DNA comprises at least two portions (e.g., the coding regions, and the regulatory sequences), each portion comprising a distinct function (e.g., coding for an amino acid sequence, facilitating transcription, translation, etc.). The chimeric molecules of claims 8, 10, 12-14, and 25-27 are not markedly different from their naturally-occurring counterparts, i.e., the DNA taught by GenBank: AP028215.1 and the DNA taught by GenBank: KQ087185.1. The claims recite nature-based products.
The claims do not recite any additional elements. Each element is found in the naturally-occurring counterpart as described above. The judicial exceptions are not integrated into a practical application and do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claims 8, 10, 15-18, 20-21, and 23-27 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomena without significantly more. The interpretation of claims 8, 10, and 25-27 is described above and applied hereinafter. Claims 15-18, 20-21, and 23-24 encompass chimeric molecules wherein the one or more 5’ UTR sequences and/or one or more 3’ UTR sequences comprise a SARS-CoV-2 5’-UTR or 3’-UTR. Accordingly, the “chimeric molecule” of claims 15-18, 20-21, and 23-24 encompass a nucleic acid sequence encoding (a) one or more amino acid sequences comprising from 5-20 amino acids, or comprising 7 amino acids (i.e., “peptide domains”), and (b) one or more (i) sequences which are capable of recruiting ribosomes and initiating translation (i.e., “5’-UTR”) and/or (ii) sequences which immediately follow the translation termination codon (i.e., “3’-UTR”), wherein the sequences (i) and (ii) comprise a SARS-CoV-2 5’-UTR or 3’-UTR. The nucleic acid sequence must comprise at least two portions, each portion comprising a distinct function.
Brant (Brant et al., 2021, Cell & Bioscience, (2021) 11:136, pg. 1-17) teaches the SARS-CoV-2 genome comprises a nucleic acid sequence encoding (a) one or more amino acid sequences comprising from 5-20 amino acids, or 7 amino acids (i.e., protein-coding sequences and portions thereof in Fig. 1), and (b) one or more (i) sequences which are capable of recruiting ribosomes and initiating translation and/or (ii) sequences which immediately follow the translation termination codon, wherein the sequences (i) and (ii) comprise a SARS-CoV-2 5’-UTR or 3’-UTR (“The 5’ untranslated region (UTR)… is 265-nt long… The 3’ UTR of the SARS-CoV-2 genome is 337-nt long,” pg. 4). Brant teaches the SARS-CoV-2 genome comprises a promoter and/or regulatory sequences, operably linked to the one or more sequences which are capable of recruiting ribosomes and initiating translation and/or one or more sequences which immediately follow the translation termination codon (“The SARS-CoV-2 genome… has a ~30-60-nt-long… poly-A tail on its 3’ end,” pg. 4). As evidenced by Brant, the SARS-CoV-2 genome comprises at least two portions (e.g., the coding regions, and the regulatory sequences), each portion comprising a distinct function (e.g., coding for an amino acid sequence, facilitating transcription, translation, etc.)(Fig. 1; pg. 4). The chimeric molecules of claims 8, 10, 15-18, 20-21, and 23-27 are not markedly different from their naturally-occurring counterpart, i.e., the SARS-CoV-2 genome as evidenced by Brant. The claims recite nature-based products.
The claims do not recite any additional elements. Each element is found in the naturally-occurring counterpart as described above. The judicial exceptions are not integrated into a practical application and do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claim Rejections - 35 USC § 102 – GenBank: KQ087185.1
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.
Claims 8, 10, 12-14, and 25-27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by GenBank: KQ087185.1 (Trichosporon oleaginosus strain IBC0246 unplaced genomic scaffold CC85scaffold_9, whole genome shotgun sequence, GenBank: KQ087185.1, available 24 June 2015).
The chimeric molecule of claim 8 is interpreted as a nucleic acid sequence encoding (a) one or more amino acid sequences comprising from 5-20 amino acids (i.e., “peptide domains”), and (b) one or more (i) sequences which are capable of recruiting ribosomes and initiating translation (i.e., “5-UTR”) and/or (ii) sequences which immediately follow the translation termination codon (i.e., “3’-UTR”). The nucleic acid sequence must comprise at least two portions, each portion comprising a distinct function.
Regarding claims 8, 10, and 12-14, GenBank: KQ087185.1 teaches T. oleaginosus IBC0246 genomic DNA. The DNA encodes (a) one or more amino acid sequences as evidenced by each GenBank entry (“/translation=…”). GenBank teaches that portions of the DNA are transcribed (“CDS”) and translated (“/translation =…”), therefore, the DNA must inherently encode (b) one or more (i) sequences which are capable of recruiting ribosomes and initiating translation and/or (ii) sequences which immediately follow the translation termination codon. The DNA taught by GenBank comprises at least two portions (e.g., the coding regions, and the regulatory sequences), each portion comprising a distinct function (e.g., coding for an amino acid sequence, facilitating transcription, translation, etc.), and therefore, is a “chimeric molecule” as interpreted herein.
The one or more amino acid sequences encoded by the DNA comprise from 5-20 amino acids, or comprise 7 amino acids. Specifically, and with respect to claims 12-14, GenBank: KQ087185.1 teaches T. oleaginosus IBC0246 genomic DNA encodes a peptide domain within the gene located at “complement(join(156680..156801,156857..157152, 157231..157655)),” which encodes the sequence “QPRFAAA,” i.e., instant SEQ ID NO: 1, which is bordered by amino acids so as to meet the formula Xn-QPRFAAA-Xn (“PGQPRFAAASY”).
Regarding claim 25, GenBank teaches the DNA is transcribed (“CDS”), therefore, the DNA must inherently comprise one or more promoters and/or regulatory sequences, operably linked to the one or more peptide domains and/or the one or more 5’-UTR and/or 3’-UTR sequences which are capable of recruiting ribosomes and initiating translation.
Regarding claim 26, as stated above, GenBank teaches the DNA is transcribed (“CDS”), therefore, the DNA must inherently comprise one or more promoters and/or regulatory sequences (i.e., an “oligonucleotide,” or “polynucleotide”), operably linked to the one or more peptide domains and/or the one or more 5’-UTR and/or 3’-UTR sequences which are capable of recruiting ribosomes and initiating translation.
Regarding claim 27, as described above, GenBank teaches the DNA is transcribed (“CDS”), therefore, the DNA must inherently comprise one or more promoters and/or regulatory sequences, operably linked to the one or more 5’-UTR and/or 3’-UTR sequences which are capable of recruiting ribosomes and initiating translation.
Claim Rejections - 35 USC § 102 - Chaturvedi
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)(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 8, 10, 15-18, 20-21, and 23-27 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Chaturvedi (Chaturvedi et al., WO 2021/216979 A2, effectively filed 23 April 2021).
As described above, the chimeric molecule of claim 8 is interpreted as a nucleic acid sequence encoding (a) one or more amino acid sequences comprising from 5-20 amino acids (i.e., “peptide domains”), and (b) one or more (i) sequences which are capable of recruiting ribosomes and initiating translation (i.e., “5-UTR”) and/or (ii) sequences which immediately follow the translation termination codon (i.e., “3’-UTR”). The nucleic acid sequence must comprise at least two portions, each portion comprising a distinct function.
Regarding claims 8 and 10, Chaturvedi teaches chimeric molecules (“SARS-CoV-2 TIP1,” “SARS-CoV-2 TIP2”) encoding (a) one or more amino acid sequences (“part of ORF1ab,” Fig. 7A; “part of ORF1ab,” “part of N/ORF10 protein,” Fig. 7B), and (b) one or more (i) sequences which are capable of recruiting ribosomes and initiating translation (“5’UTR,” Fig. 7A-B) and/or (ii) sequences which immediately follow the translation termination codon (“3’UTR,” Fig. 7A-B)(see Figs. 7A-B; “FIG. 7A-7B,” pg. 7; description of portions of SARS-CoV-2 genome in TIP1 and TIP2 in “Example 2: SARS-CoV-2 Therapeutic Interfering Particles (TIPs),” pg. 75-76; and descriptions of portions of the SARS-CoV-2 genome which correspond to each ORF, 5’- and 3’-UTR in “SARS-CoV-2 virus,” pg. 33-59). As shown in Fig. 7A-B, the chimeric molecules comprise at least two portions (e.g., various coding regions, “part of ORF1ab,” “part of N/ORF10 protein,” “mCherry,” and regulatory regions, “5’UTR,” “3’UTR,” “IRES”), each portion comprising a distinct function (encoding an amino acid sequence, facilitating transcription, translation, etc.).
As stated above, the chimeric molecules comprise nucleic acid sequences encoding “part of ORF1ab” (Fig. 7A-B). The part of ORF1ab encoded by the chimeric molecules comprises from 5-20 amino acids, or comprises 7 amino acids, i.e., the sequence MESLVPGFNE (“positions 266-21555 of the SEQ ID NO: 1 sequence, where this open reading frame is referred to as ORF1ab polyprotein and has SEQ ID NO: 2, shown below… 1 MESLVPGFNE,” pg. 48; “SEQ ID NO: 1… 241… ATGGA GAGCCTTGTC… 281 CCTGGTTTCA ACGAG…,” pg. 33; “the 5’ SARS-CoV-2 sequences in TIP1 are as shown below (SEQ ID NO: 28)… 241… ATGGA GAGCCTTGTC… 281 CCTGGTTTCA ACGAG,” pg. 75; “The 5’ SARS-CoV-2 sequences in TIP2 are as shown below (SEQ ID NO: 30)… 241… ATGGA GAGCCTTGTC… 281 CCTGGTTTCA ACGAG,” pg. 76).
Regarding claims 15-18, 20-21, and 23-25, the chimeric molecules comprise one or more 5’-UTR and 3’-UTR sequences, wherein the nucleic acid sequences of the one or more 5’-UTR and 3’-UTR sequences comprise a SARS-CoV-2 5’-UTR and SARS-CoV-2 3’-UTR, respectively (Figs. 7A-B; “FIG. 7A-7B,” pg. 7; description of portions of SARS-CoV-2 genome in TIP1 and TIP2 in “Example 2: SARS-CoV-2 Therapeutic Interfering Particles (TIPs),” pg. 75-76; and descriptions of portions of the SARS-CoV-2 genome which correspond to each ORF, 5’- and 3’-UTR in “SARS-CoV-2 virus,” pg. 33-59).
Regarding claim 25, the chimeric molecules comprise one or more “biomolecules” operably linked to the one or more peptide domains and/or the one or more 5’-UTR and/or 3’-UTR sequences (“Kozak sequence,” “IRES,” “mCherry,” Fig. 7A-B).
Regarding claim 26, the chimeric molecules comprise one or more oligonucleotides or polynucleotides (“Kozak sequence,” “IRES”), or one or more sequences encoding a polypeptide (“mCherry”), operably linked to the one or more peptide domains and/or the one or more 5’-UTR and/or 3’-UTR sequences (Figs. 7A-B).
Regarding claim 27, the chimeric molecules comprise one or more promoters and/or regulatory sequences operably linked to the UTRs (“Kozak sequence,” “IRES,” Fig. 7A-B).
Claim Rejections - 35 USC § 102 – Cohen-Zontag
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.
Claims 30-31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cohen-Zontag (Cohen-Zontag et al., 1 July 2019, PLOS Genetics, 15(7): e1008248).
Regarding claim 30, Cohen-Zontag teaches a method of enhancing production of biomolecules, wherein the method comprises tagging a nucleic acid sequence (i.e., an altered 3’ UTR sequence of GAS1 that contains SECReTE), with a chimeric molecule by conjugation or cloning (“SECReTE addition affects secretion of an exogenous naïve protein… we employed a GFP transcript construct bearing the encoded signal sequence (SS) of Gas1… at the 5’ end. SSGas1 addition enables the secretion of GFP protein to the medium… we added an altered 3’UTR sequence of GAS1 that contained SECReTE…,” pg. 16). Cohen-Zontag’s chimeric molecule (i.e., the construct comprising a GFP transcript bearing the encoded signal sequence (SS) of Gas1 at the 5’ end) encodes (a) one or more amino acid sequences comprising 5-20 amino acids (i.e., the one or more nucleic acid sequences encoding GFP). Cohen-Zontag’s chimeric molecule also must inherently comprise one or more 5’-UTR sequences or fragments thereof (i.e., a polynucleotide sequence capable of recruiting ribosome complexes and initiating translation), because as shown in Fig. 5G, the construct produces translated protein (Fig. 5G). Cohen-Zontag teaches expressing the nucleic acid sequence and harvesting the peptide encoded by the nucleic acid sequence (see Fig. 5G, which shows harvested, expressed “ssGAS-GFP- GAS13’UTR(+)SECReTE”).
Regarding claim 31, the harvested peptide comprises a polypeptide (i.e., GFP).
Conclusion
No claims allowed.
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/JENNA L PERSONS/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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